Investigation of the Effect of Imatinib and Hydroxyurea Combination Therapy on Hematological Parameters and Gene Expression in Chronic Myeloid Leukemia (CML) Patients

(1) Background: Chronic myeloid leukemia is defined as the neoplastic development of mostly myeloid cells in the bone marrow. Several treatments, including chemotherapy, radiation, hormone treatment, and immunological therapy, can be used to control this condition. The therapeutic impact on leukemic individuals varies, and the response to therapy varies between patients due to disease heterogeneity. The primary goal of this study is to compare the effects of single and Imatinib (IM) and Hydroxyurea (HU) combined treatment on hematological parameters and gene expression in CML patients. (2) Methods: This study was conducted on 51 patients, with chronic myeloid leukemia, who were admitted to Al-Basher hospital in Amman, Jordan, for follow-up. Their hematological parameters were checked and gene expression was measured for (BCL2, PP2A, CIP2A, and WT1). (3) Results: The BCL2 gene was found to be less expressed in both IM and (HU + IM) treatments as compared to the HU group alone, while PP2A gene expression was raised. Such a thing indicates that the outcome of the combined therapy method is not ideal, since PP2A activation causes CML cells to move toward the blast crisis stage. Furthermore, CIP2A gene expression revealed that IM and (HU + IM) had the same therapeutic effect and were more successful in CML patients than HU alone. With regards to the treatment effect on hematological parameters, notably in CML patients in later stages, the combination therapy (HU + IM) raised lymphocyte count, indicating a greater response to the treatment. When compared to single medicines, the combination treatment reduced the proportion of neutrophils to normal reference ranges. Platelet counts, on the other hand, dramatically decreased in both IM and (HU + IM). (4) Conclusion: Because the studied genes (BCL2, PP2A, CIP2A, and WT1) are participating in cell proliferation and death, the findings show that the examined genes are significant to understand the efficacy of various therapies. Furthermore, it was found that there was a clear effect of the clinic-based strategic treatment on hematological indicators such as WBCs, lymphocytes, neutrophils, and platelet counts.Financial support was offered by Al-Ahliyya Amman University/Jordan. Open Access funding provided by the Qatar National Library (QNL)

The Antiglycation Effect of Monomethyl Branched Chained Fatty Acid and Phytochemical Compounds and their Synergistic Effect on Obesity Related Colorectal Cancer Cell Panel

Background and aims: monomethyl branched chain fatty acids (mmBCFA) and phytochemicals including: Hydroxycitric Acid, Chlorogenic Acid and Piperine have been considered as an interesting agent for researches due to their role in diabetes and cancer. The present study examines the antiglycation effect of mmBCFA and phytochemicals and investigate their Synergistic effect on different colorectal cancer cell lines

Comparison between Smoking and Nonsmoking Palestinian Medical Students in the Health-Promoting Behaviors and Lifestyle Characteristics

Objectives. This study was aimed at comparing the predictors of health-promoting lifestyle behaviors between smoking and nonsmoking medical students at An-Najah National University located in Palestine. Methods. A descriptive cross-sectional study was performed during the academic year 2017/2018. Medical students were asked to complete a self-reported questionnaire that involved the predictors of Health-Promoting Lifestyle Profile-II. With the use of a suitable available sample composed of a total of 430 medical students, 400 had successfully completed the questionnaire and were included in the study. The data was analyzed by using SPSS version 24 software. Results. The sample included 400 medical students with a mean age of 18.7 years, 311 (77.7%) were females, and 89 (22.3%) were males. The prevalence of smokers in the sample was 110 (27.5%). For the health status of over half the students, 211 (52.8%) were excellent. The total HPLP-II score for smoking students resulted to be significantly lower in comparison to nonsmoking students (131.2 versus 135.7). This significant difference was clear in the interpersonal relation subscale (25.6 versus 26.8) for smoking and nonsmoking students, respectively. The score differences in other subscales were generally lower in smoking students. However, these differences were not consistent with statistical significance. Conclusion. The significant lower total Health-Promoting Lifestyle Profile-II score in smoking students necessitates the urgent need for awareness programs, not only towards smoking but also on how to enhance student health-promoting lifestyle behaviors

Evaluation of Pancreatic and Extra Pancreatic Effects of Branched Amino Acids

Background and aims: Leucine, Isoleucine, and Valine collectively known as Branched-chain amino acids (BCAAs), can be closely associated with metabolic dysregulates and with insulin resistance. We aimed to explore the role of BCAAs as potential treatment option for diabetes

The Ability of Rhizopus stolonifer MR11 to Biosynthesize Silver Nanoparticles in Response to Various Culture Media Components and Optimization of Process Parameters Required at Each Stage of Biosynthesis

One of the most important roles for nanotechnology concerns is the development of optimizable experimental protocols for nanomaterials synthesis. The formation of silver nanoparticles (AgNPs) was supported by Rhizopus stolonifer MR11, which was isolated from olive oil mill soil samples. The ability of R. stolonifer MR11 to biosynthesize silver nanoparticles in response to various components of different culture media was tested. Furthermore, the conditions under which the reducing biomass filtrate was obtained, as well as the conditions of the bio-reduction reaction of AgNO3 into AgNPs, were investigated. The fungal biomass filtrate of the strain Rhizopus stolonifer MR11 was capable of converting silver nitrate into AgNPs, as evidenced by the color change of the fungal filtrates. UV-Vis spectrophotometer, TEM, Zeta potential, Zeta sizer, FT-IR, and XRD analyses were used to characterize the AgNPs. TEM analysis revealed that the silver nanoparticles were 1–35 nm in size. R. stolonifer MR11 produced the maximum AgNPs when grown for 18 hours at 36 °C in media with starch and yeast extract as the sole carbon and nitrogen sources, respectively. The reducing biomass filtrate was obtained by incubating 5 g mycelial biomass in deionized water with a pH of 6 for 48 hours at 30 °C. The optimal reduction conditions of the biosynthesis reaction were determined by adding 1.0 mM AgNO3 to a pH 5 buffered mycelial filtrate and incubating it for 72 hours at 33 °C. The current study’s findings highlighted the importance of process parameters at each stage for optimal AgNPs biosynthesis

Antioxidant and Antihyperglycemic Effects of <i>Ephedra foeminea</i> Aqueous Extract in Streptozotocin-Induced Diabetic Rats

Background: Ephedra foeminea is known in Jordan as Alanda and traditionally. It is used to treat respiratory symptoms such as asthma and skin rashes as an infusion in boiling water. The purpose of this study was to determine the antidiabetic property of Ephedra foeminea aqueous extract in streptozotocin-induced diabetic rats. Methods: The aqueous extract of Ephedra foeminea plant was used to determine the potential of its efficacy in the treatment of diabetes, and this extract was tested on diabetic rats as a model. The chemical composition of Ephedra foeminea aqueous extract was determined using liquid chromatography–mass spectrometry (LC-MS). Antioxidant activity was assessed using two classical assays (ABTS and DPPH). Results: The most abundant compounds in the Ephedra foeminea extract were limonene (6.3%), kaempferol (6.2%), stearic acid (5.9%), β-sitosterol (5.5%), thiamine (4.1%), riboflavin (3.1%), naringenin (2.8%), kaempferol-3-rhamnoside (2.3%), quercetin (2.2%), and ferulic acid (2.0%). The antioxidant activity of Ephedra foeminea aqueous extract was remarkable, as evidenced by radical scavenging capacities of 12.28 mg Trolox/g in ABTS and 72.8 mg GAE/g in DPPH. In comparison to control, induced diabetic rats treated with Ephedra foeminea extract showed significant improvement in blood glucose levels, lipid profile, liver, and kidney functions. Interleukin 1 and glutathione peroxidase levels in the spleen, pancreas, kidney, and liver of induced diabetic rats treated with Ephedra foeminea extract were significantly lower than in untreated diabetic rats. Conclusions: Ephedra foeminea aqueous extract appears to protect diabetic rats against oxidative stress and improve blood parameters. In addition, it has antioxidant properties that might be very beneficial medicinally

Thymoquinone Enhances Apoptosis of K562 Chronic Myeloid Leukemia Cells through Hypomethylation of <i>SHP-1</i> and Inhibition of JAK/STAT Signaling Pathway

The epigenetic silencing of tumor suppressor genes (TSGs) is critical in the development of chronic myeloid leukemia (CML). SHP-1 functions as a TSG and negatively regulates JAK/STAT signaling. Enhancement of SHP-1 expression by demethylation provides molecular targets for the treatment of various cancers. Thymoquinone (TQ), a constituent of Nigella sativa seeds, has shown anti-cancer activities in various cancers. However, TQs effect on methylation is not fully clear. Therefore, the aim of this study is to assess TQs ability to enhance the expression of SHP-1 through modifying DNA methylation in K562 CML cells. The activities of TQ on cell cycle progression and apoptosis were evaluated using a fluorometric-red cell cycle assay and Annexin V-FITC/PI, respectively. The methylation status of SHP-1 was studied by pyrosequencing analysis. The expression of SHP-1, TET2, WT1, DNMT1, DNMT3A, and DNMT3B was determined using RT-qPCR. The protein phosphorylation of STAT3, STAT5, and JAK2 was assessed using Jess Western analysis. TQ significantly downregulated the DNMT1 gene, DNMT3A gene, and DNMT3B gene and upregulated the WT1 gene and TET2 gene. This led to hypomethylation and restoration of SHP-1 expression, resulting in inhibition of JAK/STAT signaling, induction of apoptosis, and cell cycle arrest. The observed findings imply that TQ promotes apoptosis and cell cycle arrest in CML cells by inhibiting JAK/STAT signaling via restoration of the expression of JAK/STAT-negative regulator genes

Effectiveness of Anodal otDCS Following with Anodal tDCS Rather than tDCS Alone for Increasing of Relative Power of Intrinsic Matched EEG Bands in Rat Brains

Background: This study sought to determine whether (1) evidence is available of interactions between anodal tDCS and oscillated tDCS stimulation patterns to increase the power of endogenous brain oscillations and (2) the frequency matching the applied anodal otDCS’s frequency and the brain’s dominant intrinsic frequency influence power shifting during stimulation pattern sessions by both anodal DCS and anodal oscillated DCS. Method: Rats received different anodal tDCS and otDCS stimulation patterns using 8.5 Hz and 13 Hz state-related dominant intrinsic frequencies of anodal otDCS. The rats were divided into groups with specific stimulation patterns: group A: tDCS–otDCS (8.5 Hz)–otDCS (13 Hz); group B: otDCS (8.5 Hz)–tDCS–otDCS (13 Hz); group C: otDCS (13 Hz)–tDCS–otDCS (8.5 Hz). Acute relative power changes (i.e., following 10 min stimulation sessions) in six frequency bands—delta (1.5–4 Hz), theta (4–7 Hz), alpha-1 (7–10 Hz), alpha-2 (10–12 Hz), beta-1 (12–15 Hz) and beta-2 (15–20 Hz)—were compared using three factors and repeated ANOVA measurement. Results: For each stimulation, tDCS increased theta power band and, above bands alpha and beta, a drop in delta power was observed. Anodal otDCS had a mild increasing power effect in both matched intrinsic and delta bands. In group pattern stimulations, increased power of endogenous frequencies matched exogenous otDCS frequencies—8.5 Hz or 13 Hz—with more potent effects in upper bands. The power was markedly more potent with the otDCS–tDCS stimulation pattern than the tDCS–otDCS pattern. Significance: The findings suggest that the otDCS–tDCS pattern stimulation increased the power in matched intrinsic oscillations and, significantly, in the above bands in an ascending order. We provide evidence for the successful corporation between otDCS (as frequency-matched guidance) and tDCS (as a power generator) rather than tDCS alone when stimulating a desired brain intrinsic band (herein, tES specificity)

Synergistic Effects of AgNPs and Biochar: A Potential Combination for Combating Lung Cancer and Pathogenic Bacteria

The synthesis of reliable biological nanomaterials is a crucial area of study in nanotechnology. In this study, Emericella dentata was employed for the biosynthesis of AgNPs, which were then combined with synthesized biochar, a porous structure created through biomass pyrolysis. The synergistic effects of AgNPs and biochar were evaluated through the assessment of pro-inflammatory cytokines, anti-apoptotic gene expression, and antibacterial activity. Solid biosynthesized AgNPs were evaluated by XRD and SEM, with SEM images revealing that most of the AgNPs ranged from 10 to 80 nm, with over 70% being less than 40 nm. FTIR analysis indicated the presence of stabilizing and reducing functional groups in the AgNPs. The nanoemulsion’s zeta potential, hydrodynamic diameter, and particle distribution index were found to be −19.6 mV, 37.62 nm, and 0.231, respectively. Biochar, on the other hand, did not have any antibacterial effects on the tested bacterial species. However, when combined with AgNPs, its antibacterial efficacy against all bacterial species was significantly enhanced. Furthermore, the combined material significantly reduced the expression of anti-apoptotic genes and pro-inflammatory cytokines compared to individual treatments. This study suggests that low-dose AgNPs coupled with biochar could be a more effective method to combat lung cancer epithelial cells and pathogenic bacteria compared to either substance alone