Integration of measurable residual disease by WT1 gene expression and flow cytometry identifies pediatric patients with high risk of relapse in acute myeloid leukemia.

Background: Molecular testing plays a pivotal role in monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML), aiding in the refinement of risk stratification and treatment guidance. Wilms tumor gene 1 (WT1) is frequently upregulated in pediatric AML and serves as a potential molecular marker for MRD. This study aimed to evaluate WT1 predictive value as an MRD marker and its impact on disease prognosis. Methods: Quantification of WT1 expression levels was analyzed using the standardized European Leukemia Network real-time quantitative polymerase chain reaction assay (qRT-PCR) among a cohort of 146 pediatric AML patients. Post-induction I and intensification I, MRD response by WT1 was assessed. Patients achieving a ≥2 log reduction in WT1MRD were categorized as good responders, while those failing to reach this threshold were classified as poor responders. Results: At diagnosis, WT1 overexpression was observed in 112 out of 146 (76.7%) patients. Significantly high levels were found in patients with M4- FAB subtype (p=0.018) and core binding fusion transcript (CBF) (RUNX1::RUNX1T1, p=0.018, CBFB::MYH11, p=0.016). Following induction treatment, good responders exhibited a reduced risk of relapse (2-year cumulative incidence of relapse [CIR] 7.9% vs 33.2%, p=0.008). Conversely, poor responders' post-intensification I showed significantly lower overall survival (OS) (51% vs 93.2%, p<0.001), event-free survival (EFS) (33.3% vs 82.6%, p<0.001), and higher CIR (66.6% vs 10.6%, p<0.001) at 24 months compared to good responders. Even after adjusting for potential confounders, it remained an independent adverse prognostic factor for OS (p=0.04) and EFS (p=0.008). High concordance rates between WT1-based MRD response and molecular MRD were observed in CBF patients. Furthermore, failure to achieve either a 3-log reduction by RT-PCR or a 2-log reduction by WT1 indicated a high risk of relapse. Combining MFC-based and WT1-based MRD results among the intermediate-risk group identified patients with unfavorable prognosis (positive predictive value [PPV] 100%, negative predictive value [NPV] 85%, and accuracy 87.5%). Conclusion: WT1MRD response post-intensification I serves as an independent prognostic factor for survival in pediatric AML. Integration of WT1 and MFC-based MRD results enhances the reliability of MRD-based prognostic stratification, particularly in patients lacking specific leukemic markers, thereby influencing treatment strategies.

Hematopoietic effect of echinochrome on phenylhydrazine-induced hemolytic anemia in rats.

Background: Hemolytic anemia (HA) is a serious health condition resulting from reduced erythrocytes' average life span. Echinochrome (Ech) is a dark-red pigment found in shells and spines of sea urchins. Aim: Studying the potential therapeutic effect of Ech on phenylhydrazine (PHZ)-induced HA in rats. Methods: Eighteen rats were divided into three groups (n = 6): the control group, the phenylhydrazine-induced HA group and the Ech group, injected intraperitoneally with PHZ and supplemented with oral Ech daily for 6 days. Results: Ech resulted in a considerable increase in RBCs, WBCs, and platelets counts, hemoglobin, reduced glutathione, catalase, and glutathione-S-transferase levels, and a significant decrease in aspartate & alanine aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, creatinine, urea, urate, malondialdehyde & nitric oxide levels in anemic rats. Histopathological examination of liver and kidney tissue samples showed marked improvement. Conclusion: Ech ameliorated phenylhydrazine-induced HA with a hepatorenal protective effect owing to its anti-inflammatory and antioxidant properties.

Evaluation of the Therapeutic Effect of Curcumin-Conjugated Zinc Oxide Nanoparticles on Reserpine-Induced Depression in Wistar Rats.

Depression, a devastating brain illness, necessitates the exploration of novel antidepressant treatments. We evaluated the antidepressant effects of free curcumin, zinc oxide nanoparticles (ZnO NPs), and curcumin-conjugated zinc oxide nanoparticles (Zn(cur)O NPs). The nanoformulations were extensively characterized using advanced techniques. An acute toxicity study ensured the safety of Zn(cur)O NPs. Rats were assigned to one of five groups: control, reserpine-induced depression model, treatment with ZnO NPs, free curcumin, or Zn(cur)O NPs. Behavioral assessments (forced swimming test [FST] and open-field test [OFT]) and neurochemical analyses were conducted. Zn(cur)O NPs exhibited superior efficacy in ameliorating reserpine-induced behavioral and neurochemical effects compared to free curcumin and ZnO NPs. The reserpine-induced model displayed reduced motor activity, swimming time, and increased immobility time in the FST and OFT. Treatment with Zn(cur)O NPs 45 mg/kg significantly improved motor activity and reduced immobility time. Furthermore, Zn(cur)O NPs decreased malondialdehyde (MDA) levels while increasing reduced glutathione (GSH) and catalase (CAT) levels. Additionally, concentrations of serotonin (5-HT) and norepinephrine (NE) increased. In conclusion, curcumin-conjugated zinc oxide nanoparticles demonstrate potent antidepressant effects, alleviating depressive-like behavior in rats. These findings support Zn(cur)O NPs as a promising therapeutic strategy for depression management, warranting further investigation and clinical validation.

Assessment of Waste Marble Powder on the Mechanical Properties of High-Strength Concrete and Evaluation of Its Shear Strength.

Currently, the costs of building materials, especially cement, are increasing. Waste marble powder (WMP) could be used as a cement replacement material to produce environmentally friendly concrete to help preserve resources and reduce environmental pollution. The study's goals are (1) to evaluate the effects of using marble powder in place of cement in high-strength concrete (HSC) on the material's mechanical properties and durability characteristics. (2) The study is expanded to assess the effect of using partial WMP on the shear behavior of HSC beams under static loads. Eight half-scale simply supported reinforced beams with and without WMP have been tested. Each beam's cross-section was 120 × 200 mm, and each beam had a total length of 1000 mm. The ratios of the used WMP were 0%, 2.5%, 5%, 7.5% by weight, and two different stirrup ratios, 0% and 0.47%, were used. When applied to HSC beams with and without WMP, the shear strength provisions of two of the most used codes, such as the locally used Egyptian Code (ECP 207) and the internationally used American Concrete Institute's (ACI-2019), were examined. Using the ABAQUS software, the experimental results were compared to the findings of the nonlinear finite element analysis. The results established that partial replacement of cement by WMP led to increases in the concrete's compressive and tensile strengths of about 15% and 16%, respectively. When tested specimens were exposed to acid attack, there were slight losses in weight and compressive strength (1.25% to 2.47%) for both with and without the addition of WMP. Both the concrete with and without WMP showed the same level of water absorption. Additionally, WMP led to an enhancement in the shear capacities for all beams. Increasing the WMP ratio from 0% to 2.5%, 5%, and 7.5% increased the shear capacity by about 13%, 20%, and 28%, respectively, for beams without stirrups, while for beams with stirrups, the shear capacity improved by 12%, 19%, and 25%, respectively. The enhancement in the beams' shear capacities could be attributed to the advanced concrete matrix produced by WMP's extremely small particle size.

Novel lipid-coated mesoporous silica nanoparticles loaded with thymoquinone formulation to increase its bioavailability in the brain and organs of Wistar rats.

AIMS: The Blood-Brain Barrier (BBB) is a filter for most medications and blocks their passage into the brain. More effective drug delivery strategies are urgently needed to transport medications into the brain. This study investigated the biodistribution of thymoquinone (TQ) and the effect on enzymatic and non-enzymatic oxidative stress indicators in different brain regions, either in free form or incorporated into nanocarriers as mesoporous silica nanoparticles (MSNs). Lipid bilayer-coated MSNs. MATERIALS AND METHODS: MSNs and LB-MSNs were synthesized and characterized using a transmission electron microscope and dynamic light scattering to determine the particle size and zeta potential. TQ encapsulation efficiency and TQ's release profile from LB-MSNs were also examined. The impact of loading LB-MSNs with TQ-on-TQ delivery to different brain areas was examined using chromatographic measurement. Furthermore, nitric oxide, malondialdehyde (MDA), reduced glutathione, and catalase were evaluated as oxidant and antioxidant stress biomarkers. KEY FINDINGS: The LB-MSNs formulation successfully transported TQ to several areas of the brain, liver, and kidney, revealing a considerable increase in TQ delivery in the thalamus (81.74%) compared with that in the free TQ group and a considerable reduction in the cortex (-44%). The LB-MSNs formulation had no significant effect on TQ delivery in the cerebellum, striatum, liver, and kidney. SIGNIFICANCE: TQ was redistributed in different brain areas after being encapsulated in LB-MSNs, indicating that LB-MSNs have the potential to be developed as a drug delivery system for selective clinical application of specific brain regions. CONCLUSIONS: LB-MSNs are capable nanoplatforms that can be used to target medications precisely to specific brain regions.

Modulatory effect of Ovothiol-A on myocardial infarction induced by epinephrine in rats.

Myocardial infarction (MI) is one of the most prevalent disorders seen in clinical practice, and its prevalence has risen dramatically in the last decade. Ovothiol-A is a natural product isolated from sea urchin eggs and display unusual antioxidant properties. The present study investigates the therapeutic effect of Ovothiol-A against MI stimulated in rats by epinephrine injection. Subcutaneous injection of 2 mg/kg epinephrine for 2 days caused MI in rats. The rats divided into three groups; control, MI, and MI treated with Ovothiol-A (500 mg/kg, orally) for 7 days. The treatment with Ovothiol-A restored ST-segment near normal, ameliorated the changes in cardiac troponin T, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, total proteins, creatinine, uric acid, urea, malondialdehyde, nitric oxide, reduced glutathione, catalase, glutathione-S-transferase, hemoglobin, RBCs, WBCs, platelet/lymphocyte ratio, and neutrophil/lymphocyte ratio. The histological investigation revealed that Ovothiol-A-treated group showed marked improvement in the examined cardiac muscles, liver and kidney in numerous sections. Ovothiol-A possessed a therapeutic effect against epinephrine-induced myocardial infarction. Ovothiol-A improves cardiac, liver, and kidney biomarkers and restores the typical pattern of EEG. PRACTICAL APPLICATIONS: Eggs of sea urchins are rich in potent antioxidant molecule (Ovothiol-A). The current study reveals the ability to use Ovothiol-A in the treatment of myocardial infarction.

Echinochrome pigment extracted from sea urchin suppress the bacterial activity, inflammation, nociception, and oxidative stress resulted in the inhibition of renal injury in septic rats.

The current study aimed to evaluate the antibacterial, anti-inflammatory, analgesic, and renoprotective effects of echinochrome pigment extracted from sea urchin. The disk diffusion method was used for the antibacterial activity of echinochrome against four different bacterial strains; Salmonella typhimurium, Pseudomonas aeroginosa, Staphylococcus aureus, and Listeria monocytogenes. While, acetic acid-induced writhing, formalin-induced licking, and hot plate latency assays evaluate the analgesic activity. The biochemical and oxidative stress markers of kidneys, as well as the histopathological examination, were measured to evaluate the renoprotective activity of echinochrome for cecal ligation and puncture-induced renal injury in rats. Echinochrome pigment exhibited in vitro antibacterial activity against all aforementioned bacterial species besides a powerful anti-inflammatory impact in vitro by the effective stabilization of the RBCs membrane and in vivo by decrease levels of serum IL6 and TNF-α. What's more, echinochrome showed a notable analgesic efficacy as well as an enhancement of the kidney's biochemical markers, oxidative stress status, and histopathological screening. Ech attenuated cecal ligation and puncture-induced renal injury by improving renal biomarkers, suppressing reactive oxygen species propagation as well as its antibacterial, anti-inflammatory, and anti-nociceptive activities. PRACTICAL APPLICATIONS: Sea urchins are rich in pharmacologically important quinone pigments, specifically echinochrome. The current study aimed to evaluate the role of echinochrome as a renal protective remedy in sepsis and clarify its biological activities. Echinochrome exhibited antibacterial activity in vitro against Salmonella typhimurium, Pseudomonas aeroginosa, Staphylococcus aureus, and Listeria monocytogenes. Our results revealed that echinochrome protects the kidney against damage caused by sepsis in rats. Echinochrome can use in the treatment of sepsis as an antibacterial, anti-inflammatory, and antioxidant agent.

Freshwater Clam as a Potential Bioindicator for Silver/Saponin Nanocomposites Toxicity.

Despite the progress in using silver nano products in many fields, including medicine, food, and industry, their effects on the environment need more attention. Therefore, the current study aimed to assess the effect of silver/saponin nanocomposites (Ag/S NCs) for the first time on the aquatic environment by using freshwater clam, Caelatura aegyptiaca, as a fundamental bioindicator in the freshwater system. Following the preparation and characterization of Ag/S NCs by using atomic absorption spectrophotometer, UV-Vis spectrophotometer, X-ray diffraction, transmission electron microscopy, and acute toxicity study, we exposed the clam to three different doses of Ag/S NCs (12.5, 25 and 50 mg L-1) for consecutive 6 days. All Ag/S NCs concentrations caused a significant increase in malondialdehyde and nitric oxide while induced a notable decrease in glutathione and catalase levels in all studied organs. Moreover, the histological alternations were observed in gills, labial palp, and foot tissues, particularly at dose 50 mg L-1. From the results of our work, we concluded that toxicity of Ag/S NCs on freshwater clam leads to an oxidative stress response as well as histopathological changes. Besides, we assumed that Coelatura aegyptiaca could be used as a sensitive bioindicator for monitoring water pollution caused by different nanoparticles. Therefore, we do recommend performing further studies by using fresh clam to provide a better assessment for our aquatic environment to prevent water pollution locally and globally.

Sodium pentobarbital dosages for exsanguination affect biochemical, molecular and histological measurements in rats.

Rodents are widely used for animal research in Egypt. Pentobarbital is the most common anesthetic agent; however overdoses may affect the experimental outcomes and limit the use of tissues. To investigate the effects of sodium pentobarbital overdoses during exsanguination, three groups (6 rats/group) of male and female rats were injected i.p. with 50, 100 and 150 mg/kg of sodium pentobarbital, then carotid exsanguination was performed immediately after loss of consciousness. Hypoxia-inducible factor 1-alpha (Hif1a) and tumor necrosis factor-alpha (Tnfa) mRNA expressions in liver and kidney organs were evaluated. As well as, serum aminotransferase activities (AST&ALT), glucose, urea, creatinine, malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT) levels were determined. The histological alterations in liver, kidney and spleen were studied. It was found that Hif1a and Tnfa were significantly overexpressed in the studied organs and serum AST, glucose, creatinine and urea levels were significantly increased after sodium pentobarbital overdoses (100 and 150 mg/kg) compared to 50 mg/kg dose. Similarly, significant increase in MDA and GSH levels of liver, kidney and spleen were noticed. Results showed gender difference where Hif1a and Tnfa levels were significantly overexpressed at high dose of sodium pentobarbital of liver and kidney organs in female more than male rats. Since euthanasia protocol may influence the physiological variables and affect genes' expression, it is recommended to avoid sodium pentobarbital overdose during euthanasia as it may interfere with the biochemical, molecular and histological measurements.

Hepatotoxicity effect of short-term Bradykinin potentiating factor in cholestatic rats.

BACKGROUND: Drug-induced hepatotoxicity is an extremely widespread condition and is responsible for a variety of pathological effects on the liver. It was reported that hepatotoxicity induced by angiotensin converting enzyme inhibitors (ACEIs) is cholestasis mediated hepatitis. Bradykinin-potentiating factor (BPF) is one of the natural ACEIs. Although prolonged treatment with ACEIs provides protection against liver injury, the effect of short-term treatment with ACEIs has not been fully elucidated before. Thereby, the present study sought to determine if transient ACE inhibition may exacerbate the hepatotoxicity caused by bile duct ligation (BDL) in rats. METHODS: Twenty one Wistar rats were divided into 3 groups: Sham-operated group, bile duct ligated (BDL) rats, and BDL rats treated for short-term with BPF (1 µg/kg body weight) day after day for one week and biochemical parameters were measured. Also, we assessed expression level of ACE1 and detection of hepatotoxicity in the liver tissues of different groups. RESULTS: There was a significant increase in liver enzymes, bilirubin levels, and oxidative stress in the BDL group after treatment with BPF as compared to BDL group. We found overexpression of ACE1 gene in BDL group compared to BPF and Sham-operated control group. Histopathological examination of liver treated with BPF showed severe degeneration hepatic architecture and hepatocytes as compared to BDL group. Collagen deposition increased after BPF treatment as compared to BDL groups. CONCLUSION: The present investigation suggests and recommends that short- term ACE inhibition pathway potentiates liver fibrosis during cholestasis disease.

Hepatoprotective Effect of Echinochrome Pigment in Septic Rats.

BACKGROUND: Sepsis is an inevitable stage of bacterial invasion characterized by the deregulated inflammatory response, resulting in multiorgan dysfunction syndrome. Acute liver injury is a common and serious complication in patients with severe sepsis. The most of conventional antibiotics in managing sepsis are effective, but they are accompanied by undesirable side effects. Therefore, the ongoing study aimed to evaluate the efficacy of echinochrome (Ech) pigment isolated from sea urchins on sepsis-induced liver damage using cecal ligation and puncture (CLP) model. MATERIALS AND METHODS: Male albino rats were randomly divided into three groups: sham group, CLP-induced sepsis, and septic rats treated with Ech. The estimation of liver function markers and oxidative status were analyzed. RESULTS: The results demonstrated that Ech administration significantly improved liver function, as indicated by the decreased liver enzyme activities such as alanine transaminase, gamma-glutamyl transferase, lactate dehydrogenase, aspartate transaminase, and alkaline phosphatase, as well as the increase of albumin content. Moreover, Ech could counteract the hepatic oxidative stress induced by CLP via a marked increment in glutathione content and antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-s-transferase), as well as downregulation of malondialdehyde, nitric oxide, and hydrogen peroxide formation. In addition, the Ech treatment repaired, to some extent, the abnormal architecture of hepatic tissues induced by polymicrobial infection. CONCLUSIONS: In conclusion, Ech could be used as a potential alternative antiseptic remedy via oxidative damage attenuation.

Effects of 3 Rodent Beddings on Biochemical Measures in Rats and Mice.

Components of bedding might interact with experimental treatments and affect the outcome of various experiments. Here we studied the biochemical effects of 3 rodent bedding materials that are commonly used in Egypt. Male and female rats and mice were assigned randomly into 4 single-sex and single-species groups (10 animals per group). Three types of bedding-rice straw, wheat straw, and pine wood shavings-were evaluated. After 4 wk, animals were euthanized, and biochemical parameters were measured. In male and female rats given wood shavings, serum ALT activity and malondialdehyde concentration increased whereas catalase activity decreased compared with levels in the wheat straw group. In contrast, ALT activity and malondialdehyde concentrations decreased but CAT activity increased in rats housed on rice straw compared with wheat straw. Serum AST and ALT activities increased in male and female mice exposed to rice straw, whereas the malondialdehyde concentration increased and catalase decreased in the wood shavings group relative to the wheat straw group. In mice exposed to wheat straw, AST and ALT activities and malondialdehyde concentrations decreased and CAT activity increased compared with the other groups. Because our results showed that exposure to wood shavings affects some biochemical parameters of rats and mice, we do not recommend its use as laboratory animal bedding. We consider that, of the materials tested, rice straw bedding is the best bedding material for rats, whereas wheat straw is best for mice.

Antioxidant Effect of Sepia Ink Extract on Extrahepatic Cholestasis Induced by Bile Duct Ligation in Rats.

OBJECTIVE: The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligation. METHODS: Rattus norvegicus rats were divided into 3 groups: Sham-operated group, model rats that underwent common bile duct ligation (BDL), and BDL rats treated orally with sepia ink extract (200 mg/kg body weight) for 7, 14, and 28 d after BDL. RESULTS: There was a significant reduction in hepatic enzymes, ALP, GGT, bilirubin levels, and oxidative stress in the BDL group after treatment with sepia ink extract. Collagen deposition reduced after sepia ink extract treatment as compared to BDL groups, suggesting that the liver was repaired. Histopathological examination of liver treated with sepia ink extract showed moderate degeneration in the hepatic architecture and mild degeneration in hepatocytes as compared to BDL groups. CONCLUSION: Sepia ink extract provides a curative effect and an antioxidant capacity on BDL rats and could ameliorate the complications of liver cholestasis.

Holoturia arenicola extract modulates bile duct ligation-induced oxidative stress in rat kidney.

BACKGROUND: Acute Renal Failure (ARF) in patients with cirrhosis is one of the most frequently encountered complications of obstructive jaundice. Marine organisms from the Mediterranean Coast of Egypt are considered potential sources of bioactive molecules. The present study was undertaken to explore the curative effects of Holothuria arenicola extract (HaE) against renal injury induced by bile duct ligation in male albino rats. METHODS: Fifty four male Wistar albino rats were assigned into two main groups, the Sham-operated control (received distilled water only for 28 days) and bile duct ligated (BDL) group, which divided into 2 subgroups, animals of these subgroups treated for 28 consecutive days as follow: Subgroup I (BDL), rats of this subgroup administered distilled water orally. Subgroup II, animals of this subgroup treated orally with HaE (200 mg/kg body weight). RESULTS: BDL induced marked alteration on renal functions as manifested by a significant increase in the kidney function markers, serum creatinine, urea and uric acid. In addition, BDL caused significant increase in MDA level and significant decrease in GSH level as well as antioxidant enzymes activities (GST, SOD and CAT). However, administration of HaE for consecutive 28 days significantly reversed these changes, suggesting that the renal curative effect of HaE against oxidative stress- induced injury might be involved in decreasing lipid peroxide generation and stimulating antioxidant status. CONCLUSION: The present study revealed that HaE had a profound effect against BDL-induced oxidative stress in the kidney tissues which is the common feature of choestasis in the liver.

Protective and curative effects of the sea cucumber Holothuria atra extract against DMBA-induced hepatorenal diseases in rats.

Oxidative stress is a common mechanism contributing to the initiation and progression of hepatic damage. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present study is to evaluate the efficacy of Holothuria atra extract (HaE) as an antioxidant against 7,12-dimethylbenz[a]anthracene- (DMBA-) induced hepatorenal dysfunction. Experimental animals were divided into two main groups: protective and curative. Each group was then divided into five subgroups pre- or posttreated either with distilled water (DMBA subgroups) or with HaE (200 mg/kg body weight) for seven and fourteen days. Single oral administration of DMBA (15 mg/kg body weight) to Wistar rats resulted in a significant increase in the serum liver enzymes and kidney function's parameters. DMBA increased level of liver malondialdehyde (MDA), decreased levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) in the liver tissue, and induced liver histopathological alterations. Pre- or posttreatment with HaE orally for 14 days significantly reversed the hepatorenal alterations induced following DMBA administration. In conclusion, HaE exhibits good hepatoprotective, curative, and antioxidant potential against DMBA-induced hepatorenal dysfunction in rats that might be due to decreased free radical generation.