Investigating causes and risk factors of pre-chemotherapy viremia in acute lymphoblastic leukemia pediatric patients.

BACKGROUND: Leukemia patients are immune-compromised even before starting chemotherapy because the malignant cells invade the bone marrow and destroy WBC precursors. Leukemic patients are more susceptible to infection by a wide range of microorganisms. Viral infections and reactivations are common and may result in severe complications. The aim of this study is to investigate different causes of viremia in ALL pediatric patients as well as the clinical and the laboratory characteristics associated with viral infections. METHODS: Qualitative real-time PCR was used to detect (polyoma BK, parvo B19 and herpes simplex virus) DNA in the blood of ALL patients and routine hospital records were used to provide the data of hepatitis B & C virus infection. RESULTS: Polyoma BK was the most common detected virus (51.2%) followed by herpes simplex (30.2%). Viremia by single virus was found in 16 (37.2%) cases, while viremia by multiple viruses was found in 15 (34.8%) cases. The most frequent co-detected viruses were herpes simplex and polyoma BK (11.6%) followed by herpes simplex, parvo B19 and polyoma BK (9.3%). CONCLUSION: There is a high frequency of viremia by single virus and viremia by multiple viruses at the time of diagnosis of acute lymphoblastic leukemia in pediatric patients admitted to South Egypt Cancer Institute (SECI) compared to studies in other regions. Polyoma BK is the most common detected virus and is mainly associated with lymphopenia. It was also significantly associated with herpes simplex viremia. HCV infection was associated with increased incidence of CNS leukemia.

Grass carp IL-20 binds to IL-20R2 but induces STAT3 phosphorylation via IL-20R1.

IL-20 is a pleiotropic cytokine that belongs to the IL-10 family and has a variety of biological functions in tissue homeostasis and regulation of host immune defenses. It signals through a heterodimeric receptor composed of a subunit with a long intracellular domain (R1 type receptor) and a subunit with a short intracellular domain (R2 type receptor). In this study, the R1 type receptor (CiIL-20R1/CRFB8) and the R2 type receptor (CiIL-20R2/CRFB16) were identified in grass carp Ctenopharyngodon idella. Expression analysis revealed that IL-20R2 was highly expressed in the gills and skin in healthy fish. Infection with Flavobacterium columnare resulted in the downregulation of both receptors in the gill at 48 and 72 h, whilst infection with grass carp reovirus induced their expression in the head kidney and spleen at 72 h. In the primary head kidney leucocytes, the expression levels of IL-20R1 and IL-20R2 were decreased after stimulation with 250 ng/mL IL-1ß but not affected by IFN-γ. Co-immunoprecipitation analysis showed that CiIL-20R2/CRFB16 but not CiIL-20R1/CRFB8 bound to CiIL-20L. Furthermore, it was shown that CiIL-20R1/CRFB8 was responsible for activating the phosphorylation of STAT3, whilst CiIL-20R2/CRFB16 was not involved. Structural modeling analysis showed that key residues involved in the interaction between IL-20 and receptors were highly conserved between grass carp and humans, suggesting that the signal transduction and functions of IL-20/IL-20R axis are evolutionarily conserved.

Curcumin loaded liposome formulation: Enhanced efficacy on performance, flesh quality, immune response with defense against Streptococcus agalactiae in Nile tilapia (Orechromis niloticus).

Application of novel trend comprising antioxidant phytogenics is aiming to minimize the stress related factors and associated diseases in intensive fish culturing. Today, the concept of exploiting and protecting natural antioxidants represents a paradigm shift for the aqua feed industry. Therefore, our principal goal targeting liposome as a novel nanocarrier for curcumin is directed to attain superior performance, fillet antioxidant stability and bacterial resistance in Nile tilapia. A total of 500 Nile tilapia fingerlings (average body weight, 10.27 ± 0.10 g) assigned into five experimental groups in 25 glass aquaria of 120 L capacity at the density 20 fish/aquaria. The experimental groups were supplemented with varying doses of liposomal curcumin-NPs, LipoCur-NPs (0, 5, 15, 25 and 35 mg/kg diet) were reared for 12 weeks and later Streptococcus agalactiae (S. agalactiae) challenged model was performed. Inclusion of LipoCur-NPs (25 and 35 mg/kg diet) had the most prominent impact on Nile tilapia growth rate and feed conversion ratio. The immune boosting outcomes post supplementing 35 mg/kg diet of LipoCur-NPs were evidenced by higher myeloperoxidase, lysozyme and total immunoglobulin levels. Even after 4 weeks frozen storage, LipoCur-NPs at the dose of 35 mg/kg diet prominently increased (P < 0.05) the fillet scavenging capability for free radicals (1,1-diphenyl-2-picrylhydrazyl and 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) with an inverse reduction in lipid peroxidation biomarker (malondialdehyde). Notably, upregulation of GSH-Px, CAT, and SOD genes in fillet of 35 mg/kg LipoCur-NPs fed fish coordinated with higher T-AOC and lower oxidative markers (ROS and H2O2). Post S. agalactiae challenge, higher supplementation levels of LipoCur-NPs (35 mg/kg diet) greatly attenuated the expression of its vital virulence genes (cfb, fbsA and cpsA) with higher expression of Igm, CXC-chemokine and MHC genes. Concordantly, downregulation of inflammatory markers (IL-1ß, TNF-α and IL-8) and upregulation of anti-inflammatory ones (IL-10 and TGF-ß) were remarkably documented. Based on these findings, the innovative curcumin loaded liposome was considered a novel multitargeting alternative not only playing an imperative role in Nile tilapia growth promotion and fillet stability upon storage, but also protecting efficiently against S. agalactiae.

Genotoxicity, DNA damage and sperm defects induced by vinblastine.

BACKGROUND: The treatment with chemotherapy may develop secondary tumors as a result of chemo genotoxicity. Sperm defects is another complication associated with chemo treatment. In this study the genotoxicity of vinblastine (VB) was estimated in both somatic and germ cells. MATERIALS: 85 mice were taken. Four single doses of VB at 3, 4.5, 6 and 10 mg/kg and three successive doses at 3, 4.5 and 6 mg/kg were taken for estimation of chromosomal aberrations (CAs). Four single doses of VB were involved in estimating the DNA fragmentation, and comet assay. For sperm abnormalities mice were injected with three successive doses of VB at 3, 4.5, and 6 mg/kg. RESULTS: The results demonstrated a significant frequency of DNA fragmentation in spleen cells and in the percentage of CAs in bone marrow. Numerical and structural aberrations were recorded with a pronounced number of polyploidy metaphases which reached (11.60%) after treatment with 6 mg/kg for three successive days vs zero for control. VB also induced a significant percentage of CAs in spermatocytes in the form of univalent. Sperm defects in the form of coiled tail, absence of acrosome and shapeless head and a significant DNA damage in the testes were recorded. The frequency of sperm abnormalities reached 11.06 ± 0.14 after treatment with highest tested dose (6 mg/kg) vs 3.04 ± 0.19 for control. CONCLUSION: VB is genotoxic in somatic and germ cells. Sperm defects induced by VB are of serious concern to future generations and may affect the fertility of cancer survivors.

Toxoplasmosis and cytomegalovirus infection and their role in Egyptian autistic children.

Autism is a neurodevelopmental disorder with a significantly increased incidence rate across the world over the past few years. Toxoplasmosis and cytomegalovirus (CMV) infection are globally prevalent and have been associated with diverse neurological and psychiatric disorders. A few studies have demonstrated the role of toxoplasmosis and CMV as potential etiological factors for autism. Accordingly, this study was performed to estimate the relationship between toxoplasmosis and CMV infection in children with autism as well as to assess their impact on the Childhood Autism Rating Scale (CARS) score. A total of 45 autistic children (6 girls, 39 boys) and 45 (21 girls, 24 boys) healthy control children were enrolled in our study. Their blood samples were collected and tested for the presence of Toxoplasma and CMV (IgG and IgM) antibodies and DNA by ELISA and real-time PCR (RT-PCR), respectively. Toxoplasmosis was detected in 11 (24.4%) autistic children through the ELISA [10 (22.2%) IgG + /IgM - and 1 (2.2%) IgG + /IgM +]; however, RT-PCR assay recorded only 1 positive case (2.2%), while it was detected in 10 (22.2%) control children through ELISA [9 (20%) IgG + /IgM - and 1 (2.2%) IgG + /IgM +] and 1 (2.2%) by RT-PCR. On the other hand, CMV infection was detected in all autistic children with 44 (97.8%) testing positive by ELISA [24 (53.3%) IgG + /IgM - , 18 (40%) IgG + /IgM + and 2 (4.4%) IgG - /IgM +] and 25 (55.6%) testing positive by RT-PCR assay. In addition, ELISA assay recorded 43 (95.6%) [19 (42.2%) IgG + /IgM + and 22 (48.9%) IgG + /IgM - and 2 (4.4%) IgG-/IgM +] and RT-PCR recorded 21 (46.7%) positive samples in control children with CMV. No significant difference was noted between autistic and control children for the overall prevalence of Toxoplasma or/and CMV infection. Similarly, the CARS score indicated a non-significant difference with Toxoplasma or/and CMV infection. Our data does not show an association between autism and toxoplasmosis or/and CMV infection. Nevertheless, considering that autistic children are at a high risk of contracting these infections, further studies with a larger sample size are recommended.

Impact of atorvastatin and mesenchymal stem cells combined with ivermectin on murine trichinellosis.

Trichinellosis is one of the global food-borne parasitic diseases that can cause severe tissue damage. The traditionally used drugs for the treatment of trichinellosis have limited efficacy against the encysted larvae in the muscular phase of the disease. Therefore, this study aimed to evaluate the role of atorvastatin and mesenchymal stem cells combined with ivermectin against different phases of Trichinella in experimentally infected mice. A total of 120 male Swiss albino mice were divided into two major groups (n = 60 of each), intestinal and muscular phases. Then, each group was subdivided into 10 subgroups (n = 6); non-infected control, infected non-treated control, infected ivermectin treated, infected atorvastatin treated, infected mesenchymal stem cells treated, infected combined ivermectin and atorvastatin treated, infected combined mesenchymal stem cells and ivermectin treated, infected combined mesenchymal stem cells and atorvastatin treated, infected combined mesenchymal stem cells and a full dose of (ivermectin and atorvastatin) treated, and infected combined mesenchymal stem cells and half dose of (ivermectin and atorvastatin) treated. Mice were sacrificed at days 5 and 35 post-infection for the intestinal and muscular phases, respectively. The assessment was performed through many parameters, including counting the adult intestinal worms and muscular encysted larvae, besides histopathological examination of the underlying tissues. Moreover, a biochemical assay for the inflammatory and oxidative stress marker levels was conducted. In addition, levels of immunohistochemical CD31 and VEGF gene expression as markers of angiogenesis during the muscular phase were investigated. The combined mesenchymal stem cells and atorvastatin added to ivermectin showed the highest significant reduction in adult worms and encysted larvae counts, the most noticeable improvement of the histopathological changes, the most potent anti-inflammatory (lowest level of IL-17) and anti-angiogenic (lowest expression of CD31 and VEGF) activities, and also revealed the highly effective one to relieve the oxidative stress (lowest level of SOD, GSH, and lipid peroxidase enzymes). These observed outcomes indicate that adding mesenchymal stem cells and atorvastatin to ivermectin synergistically potentiates its therapeutic efficacy and provides a promising candidate against trichinellosis.

Formation of Gold Nanoclusters from Goldcarbonyl Chloride inside the Metal-Organic Framework HKUST-1.

Gas-phase infiltration of the carbonylchloridogold(I), Au(CO)Cl precursor into the pores of HKUST-1 ([Cu3(BTC)2(H2O)2], Cu-BTC) SURMOFs (surface-mounted metal-organic frameworks; BTC = benzene-1,3,5-tricarboxylate) leads to Au(CO)Cl decomposition within the MOF through hydrolysis with the aqua ligands on Cu. Small Aux clusters with an average atom number of x ≈ 5 are formed in the medium-sized pores of the HKUST-1 matrix. These gold nanoclusters are homogeneously distributed and crystallographically ordered, which was supported by simulations of the powder X-ray diffractometric characterization. Aux@HKUST-1 was further characterized by scanning electron microscopy (SEM) and infrared reflection absorption (IRRA) as well as Raman spectroscopy, time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma optical emission spectroscopy (ICP-OES).

Hybridization from Guest-Host Interactions Reduces the Thermal Conductivity of Metal-Organic Frameworks.

We experimentally and theoretically investigate the thermal conductivity and mechanical properties of polycrystalline HKUST-1 metal-organic frameworks (MOFs) infiltrated with three guest molecules: tetracyanoquinodimethane (TCNQ), 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ), and (cyclohexane-1,4-diylidene)dimalononitrile (H4-TCNQ). This allows for modification of the interaction strength between the guest and host, presenting an opportunity to study the fundamental atomic scale mechanisms of how guest molecules impact the thermal conductivity of large unit cell porous crystals. The thermal conductivities of the guest@MOF systems decrease significantly, by on average a factor of 4, for all infiltrated samples as compared to the uninfiltrated, pristine HKUST-1. This reduction in thermal conductivity goes in tandem with an increase in density of 38% and corresponding increase in heat capacity of ∼48%, defying conventional effective medium scaling of thermal properties of porous materials. We explore the origin of this reduction by experimentally investigating the guest molecules' effects on the mechanical properties of the MOF and performing atomistic simulations to elucidate the roles of the mass and bonding environments on thermal conductivity. The reduction in thermal conductivity can be ascribed to an increase in vibrational scattering introduced by extrinsic guest-MOF collisions as well as guest molecule-induced modifications to the intrinsic vibrational structure of the MOF in the form of hybridization of low frequency modes that is concomitant with an enhanced population of localized modes. The concentration of localized modes and resulting reduction in thermal conductivity do not seem to be significantly affected by the mass or bonding strength of the guest species.

Multigene Panel Sequencing Reveals Cancer-Specific and Common Somatic Mutations in Colorectal Cancer Patients: An Egyptian Experience.

This study aims at identifying common pathogenic somatic mutations at different stages of colorectal carcinogenesis in Egyptian patients. Our cohort included colonoscopic biopsies collected from 120 patients: 20 biopsies from patients with inflammatory bowel disease, 38 from colonic polyp patients, and 62 from patients with colorectal cancer. On top of this, the cohort included 20 biopsies from patients with non-specific mild to moderated colitis. Targeted DNA sequencing using a customized gene panel of 96 colorectal related genes running on the Ion Torrent NGS technology was used to process the samples. Our results revealed that 69% of all cases harbored at least one somatic mutation. Fifty-seven genes were found to carry 232 somatic non-synonymous variants. The most frequently pathogenic somatic mutations were localized in TP53, APC, KRAS, and PIK3CA. In total, 16 somatic mutations were detected in the CRC group and in either the IBD or CP group. In addition, our data showed that 51% of total somatic variants were CRC-specific variants. The average number of CRC-specific variants per sample is 2.4. The top genes carrying CRC-specific mutations are APC, TP53, PIK3CA, FBXW7, ATM, and SMAD4. It seems obvious that TP53 and APC genes were the most affected genes with somatic mutations in all groups. Of interest, 85% and 28% of the APC and TP53 deleterious somatic mutations were located in Exon 14 and Exon 3, respectively. Besides, 37% and 28% of the total somatic mutations identified in APC and TP53 were CRC-specific variants, respectively. Moreover, we identified that, in 29 somatic mutations in 21 genes, their association with CRC patients was unprecedented. Ten detected variants were likely to be novel: six in PIK3CA and four variants in FBXW7. The detected P53, Wnt/ßcatenin, Angiogenesis, EGFR, TGF-ß and Interleukin signaling pathways were the most altered pathways in 22%, 16%, 12%, 10%, 9% and 9% of the CRC patients, respectively. These results would contribute to a better understanding of the colorectal cancer and in introducing personalized therapies for Egyptian CRC patients.

Is there a relation between long non-coding RNA MALAT-1 and miRNA-9 in Egyptian patients with Vitiligo?

To conduct a clinical biochemical study that aids in investigation of some non-coding RNA expressions and polymorphisms (including long non-coding RNAs and miRNAs) namely, MALAT-1 and miR-9 in attempt to provide new diagnostic biomarkers in vitiligo patients for Egyptians. Twenty patients having vitiligo and other twenty apparently controls were included in this study. Serum and biopsy were taken where patients were classified into lesional and peri-lesional groups. Laboratory and pathological investigations were assessed. Serum miR-9 and long-non coding MALAT-1 were measured. Vitiligo patients had a mean age of 36.40±13.75. The mean serum miR-9 level in patients group (4.28 ± 1.70) was significantly higher than in the control (1.05 ± 0.12) (p = 0.001). The MALAT-1 level in vitiligo patients was (3.65 ± 1.30) significantly higher than control (1.45 ± 0.15) (p = 0.001). There was a positive association between the expression levels of MALAT-1and miR-9in serum and tissue as well where p-value <0.05. miR-9 as well as long non-coding MALAT-1 may be considered as biomarkers for vitiligo susceptibility which may provide a new direction for treatment.

Protective role of Codiaeum variegatum against genotoxicity induced by carmustine in somatic and germ cells of male mice.

BACKGROUND: Carmustine (Cr) is an important chemotherapeutic drug, widely used in the treatment of brain tumors. Herein, the protective role of Codiaeum variegatum leaves ethyl acetate fraction was determined against genotoxicity of Cr. The technique HPLC-qTOF-MS/MS was used to identify the constituents in C. variegatum. MATERIALS: 90 male mice were used to evaluate micronuclei (MPCEs) in bone marrow, chromosomal aberration (CAs) in bone marrow and mouse spermatocytes, sperm abnormalities, and gene expression (qRT-PCR). The following groups were included, I: Negative control (ethanol 30%), II: Positive control (i.p injected once with 30 mg/kg Cr), III: Control orally treated with C. variegatum at 500 mg/kg, four days. IV-VI: treated with 100, 300, and 500 mg/kg of the plant (4 days) plus a single dose of Cr. RESULTS: In bone marrow, Cr induced significant increase in MPCEs and CAs by 3 and 7-folds respectively over the control. Cr also induced a significant percentage of CAs in spermatocytes in meiosis in the form of univalent (X-Y and autosomal univalent) and also a significant percentage of morphological sperm abnormalities was recorded. A large number of coiled tail abnormalities were detected indicating the effect of Cr in sperm motility. Cr induced an overexpression of p53 gene. C. variegatum mitigated all deleterious genotoxic effects of Cr. Chemical analysis showed that flavones (35.21%) and phenolic acids (17.62%) constitute the main components. CONCLUSIONS: The results indicated that Cr is genotoxic in both somatic and germ cells. The active components in C. variegatum together participate in the obtained protective role.

Identification of a promising hit from a new series of pyrazolo[1,5-a]pyrimidine based compounds as a potential anticancer agent with potent CDK1 inhibitory and pro-apoptotic properties through a multistep in vitro assessment.

A new series of sixteen new 2-arylamino-5,7-disubstituted-N-aryl-pyrazolo[1,5-a]pyrimidine-3-carboxamide derivatives was designed and synthesized. The antitumor activities of the new compounds were initially screened through the developmental therapeutics program at NCI-USA 60 cell line panel. 2-((2,4-dimethoxyphenyl)amino)-5,7-diphenylpyrazolo[1,5-a]pyrimidine-3-carboxamide (7a) was identified as a potential hit with a mean percentage of growth inhibition of 48.5% over the 60-NCI cancer cell lines whereas the other fifteen compounds ranged from 0.5 to 10.72%. In MTT assay, compound 7a exhibited IC50 of 6.28 ± 0.26 µM and 17.7 ± 0.92 µM against HCT-116 colorectal cancer and WI-38 human lung fibroblast normal cell lines, respectively. In cell cycle analysis, compound 7a arrested cell cycle at G2/M phase. It was able to inhibit CDK1 (Cyclin-Dependent Kinase 1)/Cyc B (Cyclin B) complex at IC50 161.2 ± 2.7 nM. The apoptosis-inducing ability of compound 7a was assessed through apoptosis detection flow-cytometry and gene expression analysis of apoptosis markers and caspase cascade which revealed that compound 7a exerts pro-apoptotic effect and increased expression of p53, Bax, cytochrome c, caspases (-3,-8, and-9), and decreased expression of Bcl-2. This suggests that the pro-apoptotic effect is exerted through the intrinsic pathway. The molecular docking study revealed a unique binding mode at the ATP binding pocket of CDK1/Cyc B/Cks2 through its 2,4-dimethoxyphenyl-amino. These results suggest that compound 7a could be a promising hit as a targeted protein kinase inhibitor which exerts its antitumor effect through CDK1 inhibition and pro-apoptotic action.

Growth Inhibition and Apoptotic Effect of Pine Extract and Abietic Acid on MCF-7 Breast Cancer Cells via Alteration of Multiple Gene Expressions Using In Vitro Approach.

In vitro anti-proliferative activity of Pinus palustris extract and its purified abietic acid was assessed against different human cancer cell lines (HepG-2, MCF-7 and HCT-116) compared to normal WI-38 cell line. Abietic acid showed more promising IC50 values against MCF-7 cells than pine extract (0.06 µg/mL and 0.11 µM, respectively), with insignificant cytotoxicity toward normal fibroblast WI-38 cells. Abietic acid triggered both G2/M cell arrest and subG0-G1 subpopulation in MCF-7, compared to SubG0-G1 subpopulation arrest only for the extract. It also induced overexpression of key apoptotic genes (Fas, FasL, Casp3, Casp8, Cyt-C and Bax) and downregulation of both proliferation (VEGF, IGFR1, TGF-ß) and oncogenic (C-myc and NF-κB) genes. Additionally, abietic acid induced overexpression of cytochrome-C protein. Furthermore, it increased levels of total antioxidants to diminish carcinogenesis and chemotherapy resistance. P. palustris is a valuable source of active abietic acid, an antiproliferative agent to MCF-7 cells through induction of apoptosis with promising future anticancer agency in breast cancer therapy.

Functional characterization of an interleukin 20 like homologue in grass carp Ctenopharyngodon idella.

IL-20 is a pleiotropic cytokine that belongs to the IL-10 family and plays an important biological role in tissue homeostasis and regulation of host immune defenses. IL-20 homologues have recently been discovered in fish, but their functions have not been studied. In this study, an IL-20 like (IL-20L) cytokine was cloned in grass carp (Ctenopharyngodon idella) and its bioactivities were investigated. Expression analysis showed that the CiIL-20L gene was constitutively expressed in tissues with the highest expression detected in the head kidney. It was upregulated in the head kidney after infection with Flavobactrium columnare (F. cloumnare) and grass carp reovirus II (GCRV II). The recombinant CiIL-20L produced in E. coli cells was shown to be effective in inducing the expression of Th cytokine genes (IFN-γ, IL-4/13A, IL-4/13B and IL-10), macrophage marker genes (arginase 2, IRF4, KLF4 and SOCS3) and inflammatory genes (IL-1ß, IL-6, IL-8 and TNFα) in the head kidney leukocytes when stimulated at 12 h. Long term culture (6 days) of head kidney macrophages in the presence of CiIL-20L leads to high expression of IRF4, TGFß1 and arginase 2. Our data suggest that IL-20 may play regulatory roles in promoting Th responses, macrophage differentiation and inflammation.

Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition.

The use of natural compounds is promising in approaches to prevent and treat cancer. The long-term application of most currently employed chemotherapy techniques has toxic side effects. Eugenol, a phenolic phytochemical extracted from certain essential oils, has an anti-cancer effect. The modulation of autophagy can promote either the survival or apoptosis of cancer cells. Triple-negative (MDA-MB-231) and HER2 positive (SK-BR-3) breast cancer cell lines were treated with different doses of eugenol. Apoptosis was detected by a flow-cytometry technique, while autophagy was detected by acridine orange. Real-time PCR and Western blot assays were applied to investigate the effect of eugenol on the gene and protein expression levels of autophagy and apoptotic genes. Treating cells with different concentrations of eugenol significantly inhibited cell proliferation. The protein levels of AKT serine/threonine kinase 1 (AKT), forkhead box O3 (FOXO3a), cyclin dependent kinase inhibitor 1A (p21), cyclin-dependent kinase inhibitor (p27), and Caspase-3 and -9 increased significantly in Eugenol-treated cells. Eugenol also induced autophagy by upregulating the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and downregulating the expression of nucleoporin 62 (NU p62). Eugenol is a promising natural anti-cancer agent against triple-negative and HER2-positive breast cancer. It appears to work by targeting the caspase pathway and by inducing autophagic cell death.

An investigative study of antitumor properties of a novel thiazolo[4,5-d]pyrimidine small molecule revealing superior antitumor activity with CDK1 selectivity and potent pro-apoptotic properties.

New thiazolo[4,5-d]pyrimidine analogues were synthesized and biologically assessed in-vitro for their antineoplastic activity. The growth inhibitory effects of these compounds were assessed through the National Cancer Institute-United States of America (NCI-USA) anticancer screening program. Compound5(7-Chloro-3-(2,4-dimethoxyphenyl)-5-methylthiazolo[4,5-d]pyrimidine-2(3H)-thione) was found to have a potent and broad-spectrum cytotoxic action against NCI panel with GI50 (50% growth inhibition concentration) mean graph midpoint (MG-MID) = 2.88 µM. MTT assay was used to determine IC50 values of the most potent agent against HCT-116 colorectal carcinoma and WI-38 human lung fibroblast cell lines; 5.33 µM ± 0.69 and 21.69 µM ± 1.04, respectively. Flow cytometric analysis revealed that compound5triggered apoptosis and G2/M cell cycle arrest. The ability of compound5to inhibit CDK1 (Cyclin-Dependent Kinase 1)/Cyclin B complex was evaluated, and its IC50 value was 97 nM ± 2.33. Moreover, according to the gene expression analysis, compound5up-regulated p53, BAX, cytochrome c, caspases-3,-8 and-9 besides down-regulated Bcl-2. In conclusion, compound5exerted a potent pro-apoptotic activity through the activation of the intrinsic apoptotic pathway and arrested the cell cycle at the G2/M phase.

Inhibitory activity of black mulberry (Morus nigra) extract against testicular, liver and kidney toxicity induced by paracetamol in mice.

Black mulberry (Morus nigra) leaves is broadly used in traditional medicine worldwide. However, there are no scientific reports regarding testicular protection, hepato-and nephroprotective activities of M. nigra leaves. The present investigation was assessed the protective mechanism by which methanol extract from M. nigra leaves suppressed the damaging effects induced by paracetamol (APAP) in different mouse tissues. Male mice were orally given APAP (500 mg/kg) with or without M. nigra extract (150, 300, and 500 mg/kg) for four consecutive days. The results showed that crude extract possessed potent antioxidant activity (EC50 = 42.97 µg extract/mL) due to the presence of a high amount of polyphenol and flavonoid compounds. Gallic acid, chlorogenic acid, catechin, and rutin were isolated from the n-butanol fraction of M. nigra extract. Unexpectedly, oral administration of APAP did not induce chromosomal aberrations in mouse bone marrow; however, it produced damaging effects on testis, liver, and kidney tissues. Interestingly, M. nigra extract suppressed APAP-induced genotoxicity by lowering meiotic chromosomal aberrations in spermatocytes, morphological sperm abnormalities, and % DNA damage in comet tail in the liver and kidney tissues. The altered levels of glutathione S transferase activity, lipid peroxidation, liver, and kidney functions were significantly reversed when M. nigra was given to APAP group. The restoring of the histo-architectural distortions and decreasing over-expression of p53 protein as determined by immunohistochemistry in the liver, kidney, and testis sections were strengthened the protective activity of M. nigra extract. Conclusion, the bioactive components in the leaves of black mulberry appear to be a good candidate for genetic protection, treatment of oxidative stress-induced organotoxicity.

Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report.

BACKGROUND: Human pegivirus (HPgV) is structurally similar to hepatitis C virus (HCV) and was discovered 20 years ago. Its distribution, natural history and exact rule of this viral group in human hosts remain unclear. Our aim was to determine, by deep next-generation sequencing (NGS), the entire genome sequence of HPgV that was discovered in an Egyptian patient while analyzing HCV sequence from the same patient. We also inspected whether the co-infection of HCV and HPgV will affect the patient response to HCV viral treatment. To the best of our knowledge, this is the first report for a newly isolated HPgV in an Egyptian patient who is co-infected with HCV. CASE PRESENTATION: The deep Next Generation Sequencing (NGS) technique was used to detect HCV sequence in hepatitis C patient's plasma. The results revealed the presence of HPgV with HCV. This co-infection was confirmed using conventional PCR of the HPgV 5' untranslated region. The patient was then subjected to direct-acting-antiviral treatment (DAA). At the end of the treatment, the patient showed a good response to the HCV treatment (i.e., no HCV-RNA was detected in the plasma), while the HPgV-RNA was still detected. Sequence alignment and phylogenetic analyses demonstrated that the detected HPgV was a novel isolate and was not previously published. CONCLUSION: We report a new variant of HPgV in a patient suffering from hepatitis C viral infection.

ADRB3 polymorphism rs4994 (Trp64Arg) associates significantly with bodyweight elevation and dyslipidaemias in Saudis but not rs1801253 (Arg389Gly) polymorphism in ARDB1.

BACKGROUND: In some populations, obesity and body weight related disorders show a correlation with polymorphisms in three subtypes of beta-adrenoceptor (ß1, ß2, and ß3) [ADRB1, ADRB2 and ADRB3] genes. We scanned for the polymorphism of Arg389Gly (rs1801253) in ADRB1 and Trp64Arg (rs4994) in ADRB3 genes in Saudi population to determine association, if any, of these polymorphisms with obesity and related disorders. METHODS: We studied 329 non-related adults (33.1% men and 66.9% women), aged 18-36 years. Anthropometric measurements were recorded, and Body mass index (BMI) and waist/hip ratio were calculated; leptin, insulin, lipidogram, and glucose concentrations were determined. ADRB1 and ADRB3 polymorphisms (Arg389Gly and Trp64Arg, respectively) were screened by DNA sequencing. The subjects were divided into three groups according to BMI: normal weight (BMI < 25 kg/m2), overweight (BMI ≥25.1-29.9 kg/m2) subjects, and obese (≥30 kg/m2). RESULTS: In the age-matched groups of the normal weight, overweight and obese male and female subjects, all anthropometric parameters were found to be significantly higher, and in the obese group, all biochemical parameters were significantly elevated compared to the normal weight controls. The allelic frequency of Gly389 ADRB1 did not differ amongst the three groups, whereas the frequency of Arg64 of ADRB3 gene was significantly higher in the overweight and obese subjects, compared with the normal weight subjects. In addition, subjects carrying Arg64 allele regardless of their BMI had a greater waist and hip circumference, W/H ratio, plasma cholesterol, triglyceride, LDL, leptin, insulin, and glucose level compared to those with the wild-type Trp allele. CONCLUSION: The results of this study have shown a significant association between the Trp64Arg polymorphism in ADRB3 gene and the development of overweight and obesity in Saudi populations. It also has an influence on the levels of lipid, insulin, leptin, and glucose, whereas, Arg389Gly polymorphism in ADRB1 is not associated with overweight, obesity or dyslipidaemias in Saudis.

A versatile program for the calculation of linear accelerator room shielding.

This work aims at designing a computer program to calculate the necessary amount of shielding for a given or proposed linear accelerator room design in radiotherapy. The program (Shield Calculation in Radiotherapy, SCR) has been developed using Microsoft Visual Basic. It applies the treatment room shielding calculations of NCRP report no. 151 to calculate proper shielding thicknesses for a given linear accelerator treatment room design. The program is composed of six main user-friendly interfaces. The first enables the user to upload their choice of treatment room design and to measure the distances required for shielding calculations. The second interface enables the user to calculate the primary barrier thickness in case of three-dimensional conventional radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT) and total body irradiation (TBI). The third interface calculates the required secondary barrier thickness due to both scattered and leakage radiation. The fourth and fifth interfaces provide a means to calculate the photon dose equivalent for low and high energy radiation, respectively, in door and maze areas. The sixth interface enables the user to calculate the skyshine radiation for photons and neutrons. The SCR program has been successfully validated, precisely reproducing all of the calculated examples presented in NCRP report no. 151 in a simple and fast manner. Moreover, it easily performed the same calculations for a test design that was also calculated manually, and produced the same results. The program includes a new and important feature that is the ability to calculate required treatment room thickness in case of IMRT and TBI. It is characterised by simplicity, precision, data saving, printing and retrieval, in addition to providing a means for uploading and testing any proposed treatment room shielding design. The SCR program provides comprehensive, simple, fast and accurate room shielding calculations in radiotherapy.