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Mohammed Saied Bakeer,1 Mohamed Ibrahim Youssef,1 Helmy M Elshazly,2 Mohamed Abdel-Samiee,2 Abdelaleem A El-Gendy,3 M Abouzed,4 Warda Othman,2 Mervat Abdelkareem,2 Mai Abozeid,2 Samah Mohammed Awad,5 Fatma O Khalil,5 Hanan M Bedair,6 Karema A Diab,6 A S Seif,7 Marwa F Youssef,8 Ayman Ahmed Sakr,9 Eman Abdelsameea21Internal Medicine Department, Al-Azhar University, Cairo, Egypt; 2Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt; 3Clinical Pathology Department, Al-Azhar University, Cairo, Egypt; 4Psychiatry Department, Al-Azhar University, Cairo, Egypt; 5Clinical Microbiology and Immunology and Molecular Microbiology in Liver and GIT Department, National Liver Institute, Menoufia University, Menoufia, Egypt; 6Clinical Pathology Department, National Liver Institute, Menoufia University, Menoufia, Egypt; 7Tropical Medicine Hepatology and Gastroenterology Department, Shebin Elkom Teaching Hospital, Menoufia, Egypt; 8Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia, Egypt; 9Tropical Medicine Department, Faculty of Medicine, Menoufia University, Menoufia, EgyptCorrespondence: Mohamed Abdel-SamieeHepatology and Gastroenterology Department, National Liver Institute, Menoufia University, 32511 Shebin El-kom, Menoufia, EgyptEmail drmohammed100@yahoo.comBackground: As physicians in a referral hospital, we observed the association between history of enteric fever and somatic disorders associated with low mood. At the Al-Hussein University Hospital, Cairo and the National Liver Institute Hospital, Menoufia, we receive patients from all over Egypt, including rural areas where enteric fever is endemic.Aim: Here in, 60 Egyptian patients referred to us for evaluation of different somatic disorders are reported.Methods: After extensive evaluations, the patients’ symptoms were function-related. Also, their typhoid carrier states were documented, and the severity of depression using Hamilton-D (HAM-D) questionnaire was evaluated and recorded. All patients were treated with ceftriaxone, 2 gm, IV, daily for 15 days. The clinical evaluation and Hamilton score were reassessed at the end of the treatment and 6 weeks thereafter. The patients did not receive any anti-depressant nor anti-anxiety treatment during their course. Typhoid carrier was defined by documenting the history of typhoid fever that was diagnosed by culturing the Salmonella species, and not by serology, isolated from stool culture along with febrile condition, plus the absence of fever in the past 3 weeks. The Widal test was not accepted as a criterion for enrollment.Results: Patients showed clinically significant improvement in the somatic complaints, and their HAM-D score immediately post-treatment that was consolidated for 6 weeks post-treatment completion.Conclusion: In this study, the typhoid carrier was associated with the psychosomatic depression that improved by antibiotic therapy.Keywords: psychosomatic, depression, typhoid carriers, Egypt

Diabetic cardiomyopathy (DCM) is a serious common complication of diabetes. Unfortunately, there is no satisfied treatment for those patients and more studies are in critical need to cure them. Therefore, we aimed to carry out our current research to explore the role of two novel therapeutic approaches: one a biological drug aimed to block inflammatory signaling of the IL 1beta (IL1β) axis, namely, anakinra; the other is provision of anti-inflammatory regenerative stem cells. Wistar male rats were allocated into four groups: control group: type 2 diabetes mellitus (DM) induced by 6-week high-fat diet (HFD) followed by a single-dose streptozotocin (STZ) 35 mg/kg i.p., then rats were allocated into: DM: untreated; DM BM-MSCs: received a single dose of BM-MSCs (1 × 10 6 cell/rat) into rat tail vein; DM-Anak received Anak 0.5 μg/kg/day i.p. for 2 weeks. Both therapeutic approaches improved cardiac performance, fibrosis, and hypertrophy. In addition, blood glucose and insulin resistance decreased, while the antioxidant parameter, nuclear factor erythroid 2-related factor 2 (Nrf2) and interleukin 10 (IL10), and anti-inflammatory agent increased. Furthermore, there is a significant reduction in tumor necrosis factor alpha (TNFα), IL1β, caspase1, macrophage marker CD 11b, inducible nitric oxide synthase (iNOS), and T-cell marker CD 8. Both Anak and BM-MSCs effectively ameliorated inflammatory markers and cardiac performance as compared to non-treated diabetics. Improvement is mostly due to anti-inflammatory, antioxidant, anti-apoptotic properties, and regulation of TNFα/IL1β/caspase1 and Nrf2/IL10 pathways., (© 2024. The Author(s).)

Aim: This study focused on designing and synthesizing novel derivatives of 3,5,8-trisubstituted coumarin. Results: The synthesized compounds, particularly compound 5 , exhibited significant cytotoxic effects on MCF-7 cells, surpassing staurosporine, and reduced toxicity toward MCF-10A cells, highlighting potential pharmacological advantages. Further, compound 5 altered the cell cycle and significantly increased apoptosis in MCF-7 cells, involving both early (41.7-fold) and late stages (33-fold), while moderately affecting necrotic signaling. The antitumor activity was linked to a notable reduction (4.78-fold) in topoisomerase IIβ expression. Molecular modeling indicated compound 5 's strong affinity for EGFR, human EGF2 and topoisomerase II proteins. Conclusion: These findings highlight compound 5 as a multifaceted antitumor agent for breast cancer.

According to data provided by the World Health Organization (WHO), a total of 2.3 million women across the globe received a diagnosis of breast cancer in the year 2020, and among these cases, 685,000 resulted in fatalities. As the incidence of breast cancer statistics continues to rise, it is imperative to explore new avenues in the ongoing battle against this disease. Therefore, a number of new indolyl-hydrazones were synthesized by reacting the ethyl 3-formyl-1 H -indole-2-carboxylate 1 with thiosemicarbazide, semicarbazide.HCl, 4-nitrophenyl hydrazine, 2,4-dinitrophenyl hydrazine, and 4-amino-5-(1 H -indol-2-yl)-1,2,4-triazole-3-thione to afford the new hit compounds, which were assigned chemical structures as thiosemicarbazone 3 , bis (hydrazine derivative) 5 , semicarbzone 6 , Schiff base 8, and the corresponding hydrazones 10 and 12 by NMR, elemental analysis, and X-ray single-crystal analysis. The MTT assay was employed to investigate the compounds' cytotoxicity against breast cancer cells (MCF-7). Cytotoxicity results disclosed potent IC 50 values against MCF-7, especially compounds 5 , 8 , and 12, with IC 50 values of 2.73 ± 0.14, 4.38 ± 0.23, and 7.03 ± 0.37 μM, respectively, compared to staurosproine (IC 50 = 8.32 ± 0.43 μM). Consequently, the activities of compounds 5 , 8 , and 12 in relation to cell migration were investigated using the wound-healing test. The findings revealed notable wound-healing efficacy, with respective percentages of wound closure measured at 48.8%, 60.7%, and 51.8%. The impact of the hit compounds on cell proliferation was assessed by examining their apoptosis-inducing properties. Intriguingly, compound 5 exhibited a significant enhancement in cell death within MCF-7 cells, registering a notable increase of 39.26% in comparison to the untreated control group, which demonstrated only 1.27% cell death. Furthermore, the mechanism of action of compound 5 was scrutinized through testing against kinase receptors. The results revealed significant kinase inhibition, particularly against PI3K-α, PI3K-β, PI3K-δ, CDK2, AKT-1, and EGFR, showcasing promising activity, compared to standard drugs targeting these receptors. In the conclusive phase, through in vivo assay, compound 5 demonstrated a substantial reduction in tumor volume, decreasing from 106 mm³ in the untreated control to 56.4 mm³. Moreover, it significantly attenuated tumor proliferation by 46.9%. In view of these findings, the identified leads exhibit promises for potential development into future medications for the treatment of breast cancer, as they effectively hinder both cell migration and proliferation.

Breast cancer is a global health concern, with increasing disease burden and disparities in access to healthcare. Late diagnosis and limited treatment options in underserved areas contribute to poor outcomes. In response to this challenge, we developed a novel family of 2-substituted-quinoxaline analogues, combining coumarin and quinoxaline scaffolds known for their anticancer properties. Through a versatile synthetic approach, we designed, synthesized, and characterized a set of 2-substituted quinoxaline derivatives. The antiproliferative activity of the synthesized compounds was assessed toward the MCF-7 breast cancer cells. Our investigations showed that the synthesized compounds exhibit considerable antiproliferative activity toward MCF-7 cells. Notably, compound 3b, among examined compounds, displayed a superior inhibitory effect (IC 50 = 1.85 ± 0.11 μM) toward the growth of MCF-7 cells compared to the conventional anticancer drug staurosporine (IC 50 = 6.77 ± 0.41 μM) and showed minimal impact on normal cells (MCF-10A cell lines, IC 50 = 33.7 ± 2.04 μM). Mechanistic studies revealed that compound 3b induced cell cycle arrest at the G1 transition and triggered apoptosis in MCF-7 cells, as evidenced by increasing the percentage of cells arrested in the G2/M and pre-G1 phases utilizing flow cytometric analysis and Annexin V-FITC/PI analysis. Moreover, compound 3b was found to substantially suppress topoisomerase enzyme activity in MCF-7 cells. Molecular modeling studies further supported the potential of compound 3b as a therapeutic candidate by demonstrating significant binding affinity to the active sites of both topoisomerase II and EGFR proteins. Taken together, the presented 2-substituted-quinoxaline analogues, especially compound 3b, show promise as potential candidates for the development of effective anti-breast cancer drugs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Cancer is the most severe disease worldwide. Every year, tens of millions of people are diagnosed with cancer, and over half of those people will ultimately die from the disease. Hence, the discovery of new inhibitors for fighting cancer is necessary. As a result, new indolyl-triazole hybrids were synthesized to target breast and liver cancer cells. The synthetic strategy involves glycosylation of the 4-aryltriazolethiones 3a - b with acetyl-protected α-halosugars in the presence of K 2 CO 3 in acetone to give a mixture of β- S -glycosides 6a-b , 7a-b , and β-N -glycosides 8a-b , 9a-b . Chemo-selective S -glycosylation was achieved using NaHCO 3 in ethanol. The migration of glycosyl moiety from sulfur to nitrogen ( S → N glycosylmigration) was achieved thermally without any catalyst. Alkylation of the triazole-thiones with 2-bromoethanol and 1-bromopropan-2-ol in the presence of K 2 CO 3 yielded the corresponding S -alkylated products. The synthesized compounds were tested for their cytotoxicity using an MTT assay and for apoptosis induction targeting PARP-1 and EGFR. Compounds 12b , 13a , and 13b exhibited cytotoxic activities with promising IC 50 values of 2.67, 6.21, 1.07 μM against MCF-7 cells and 3.21, 8.91, 0.32 μM against HepG2 cells compared to Erlotinib (IC 50 = 2.51, 2.91 μM, respectively) as reference drug. Interestingly, compounds 13b induced apoptosis in MCf-7 and HepG2 cells, arresting the cell cycle at the G2/M and S phases, respectively. Additionally, the dual enzyme inhibition seen in compound 13b against EGFR and PARP-1 is encouraging, with IC 50 values of 62.4 nM compared to Erlotinib (80 nM) and 1.24 nM compared to Olaparib (1.49 nM), respectively. The anticancer activity was finally validated using an in vivo SEC-cancer model; compound 13b improved both hematological and biochemical analyses inhibiting tumor proliferation by 66.7% compared to Erlotinib's 65.7%. So, compound 13b may serve as a promising anticancer activity through dual PARP-1/EGFR target inhibition., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objectives: To compare the effects of 3 ventilation strategies during cardiopulmonary bypass (CPB) on arterial oxygenation and postoperative pulmonary complications (PPCs)., Design: A prospective, randomized, controlled study., Setting: A single-center tertiary teaching hospital., Participants: One hundred twenty pediatric patients undergoing elective repair of congenital acyanotic heart diseases with CPB., Interventions: Patients were assigned randomly into 3 groups according to ventilation strategy during CPB as follows: (1) no mechanical ventilation (NOV), (2) continuous positive airway pressure (CPAP) of 5 cmH 2 O, (3) low tidal volume (LTV), pressure controlled ventilation (PCV), respiratory rate (RR) 20-to-30/min, and peak inspiratory pressure adjusted to keep tidal volume (Vt) 2 mL/kg., Measurements and Main Results: The PaO 2 /fraction of inspired oxygen (F I O 2 ) ratio and PaO 2 were higher in the 5 minutes postbypass period in the LTV group but were nonsignificant. The PaO 2 /F I O 2 ratio and PaO 2 were significant after chest closure and 1 hour after arrival to the intensive care unit with a higher PaO 2 /F I O 2 ratio and PaO 2 in the LTV group. Regarding the oxygenation index, the LTV group was superior to the NOV group at the 3 time points, with lower values in the LTV group. There were no significant differences in the predictive indices among the 3 groups, including the extubation time, and postoperative intensive care unit stays days. The incidence of PPCs did not significantly differ among the 3 groups., Conclusions: Maintaining ventilation during CPB was associated with better oxygenation and did not reduce the incidence of PPCs in pediatric patients undergoing cardiac surgery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Diabetes mellitus (DM) is a multisystem endocrine disorder affecting the brain. Mesenchymal stem cells (MSCs) pretreated with Melatonin have been shown to increase the potency of MSCs. This work aimed to compare Melatonin, stem cells, and stem cells pretreated with Melatonin on the cognitive functions and markers of synaptic plasticity in an animal model of type I diabetes mellitus (TIDM). Thirty-six rats represented the animal model; six rats for isolation of MSCs and 30 rats were divided into five groups: control, TIDM, TIDM + Melatonin, TIDM + Stem cells, and TIDM + Stem ex vivo Melatonin. Functional assessment was performed with Y-maze, forced swimming test and novel object recognition. Histological and biochemical evaluation of hippocampal Neuroligin 1, Sortilin, Brain-Derived Neurotrophic Factor (BDNF), inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2), Tumor necrosis factor-alpha (TNF-α), and Growth Associated Protein 43 (GAP43). The TIDM group showed a significant decrease of hippocampal Neuroligin, Sortilin, and BDNF and a significant increase in iNOS, TNF-α, TLR2, and GAP43. Melatonin or stem cells groups showed improvement compared to the diabetic group but not compared to the control group. TIDM + Stem ex vivo Melatonin group showed a significant improvement, and some values were restored to normal. Ex vivo melatonin-treated stem cells had improved spatial working and object recognition memory and depression, with positive effects on glucose homeostasis, inflammatory markers levels and synaptic plasticity markers expression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Amin, Sharawy, El Tablawy, Elberry, Youssef, Abdelhady, Rashed and Hassan.)

Gold nanoparticles (GNPs) have been proposed as carriers for drugs to improve their intrinsic therapeutic activities and to overcome pharmacokinetic problems. In this study, novel nanosystems constituted by a model β-diketo acid (DKA) grafted to the surface of GNPs were designed and synthesized following the "multivalent high-affinity" binding strategy. These first nanoscale DKA prototypes showed improved inhibition of HIV-1 integrase (HIV-1 IN) catalytic activities as compared with free DKA ligands., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Background and Objectives: Myelosuppression is the most common toxicity encountered in the oncology clinic today. This study was planned to investigate the possible protective and therapeutic role of the traditional Chinese Medicinal Herb; Astragalus Membranaceus (AM), on chemotherapy-induced myelosuppression., Methods and Results: This study was carried out on thirty six adult male albino rats. They were divided into: Group I Control Group (n=6) received a vehicle of phosphate buffered saline (PBS) solution. Group II (n=12) were injected I.P. with cyclophosphamide (CY) for 3 days (gIIa n =6) and continued for one more week to receive AM orally (gIIb n=6). Group III (n=6) received CY I.P. together with AM orally for 3 days. Group IV (n=12) received AM orally for one week (gIVa n=6) and continued for extra three days receiving CY I.P. with AM orally (gIVb n=6). Blood samples were analysed for Total Leucocytic Count and Lymphocytic Count. Counting of CD34 +ve cells in bone marrow was performed by flowcytometry. Bone marrow sections were subjected to H&E stain as well as immunohistochemical staining for anti- CD20 antibody. The mean area % of cellular bone marrow regions occupied by developing haemopoietic cells, mean area of fat cells and mean number of CD20 immunopositive B lymphocytes in the bone marrow were measured by histomorphometric studies and statistically compared. AM proved to have a myelo-protective and myelo-therapeutic capacity, evidenced at both laboratory and morphological levels., Conclusions: The greatest myelo-potentiating effect of AM was achieved when supplied before and together with CY therapy.

Background: There are limited data about the influence of hypothyroidism and hyperthyroidism on the connective tissue component and smooth muscle cells of the thoracic aorta. The aim was to study the histological changes of the wall of the thoracic aorta in the hypothyroid and hyperthyroid rats. Morphometric measurements were also done., Materials and Methods: Thirty adult rats were used. They were divided into control, hyperthyroid, and hypothyroid groups. Each group consisted of 10 rats. The animals were sacrificed at the end of 8 weeks and the descending aorta was excised. Sections were stained with haematoxylin and eosin, orcein and Masson's trichrome stains. Themorphometric measurement included: number of smooth muscle cell nuclei, number of the elastic lamellae, thickness of the tunica media, elastic fibre optic density, and relative collagen area., Results: Atheromatous plagues had been observed in the hyperthyroid group. Thinning and rupture of the elastic lamellae had been observed in the hypothyroid group; these were accompanied with intimal ulceration and aortic dissection. The average number of smooth muscle cell nuclei in the hyperthyroid group had doubled and tripled compared to their fellows in the control and hypothyroid groups, respectively. The thickness of the tunica media increased in the hyperthyroid and hypothyroid groups by 75% and 35%. In addition, the relative collagen area increased in the previously mentioned groups by 142% and 120%, respectively. On the other hand, the mean elastic fibre optic density decreased in both groups by 30%., Conclusions: Structure wall affections of the intima and media of the descending aorta were associated with the thyroid hormone dysfunctions. These changes were more severe in the hypothyroid group.

Background: The hippocampus is a key brain area for many forms of learning and memory and is particularly sensitive to changes in glucose homeostasis., Aim of the Work: To investigate in experimentally induced type 1 and 2 diabetes mellitus in rat model the effect of  diabetes mellitus on cognitive functions and related markers of hippocampal synaptic plasticity, and the possible impact of blocking N-methyl-D-aspartic acid (NMDA) receptors by memantine., Materials and Methods: Seven rat groups were included: non-diabetic control and non-diabetic receiving memantine; type-1 diabetic groups - untreated, treated with insulin alone and treated with insulin and memantine; and type 2 diabetic groups - untreated and memantine treated. Cognitive functions were assessed by the Morris Water Maze and passive avoidance test. Biochemical analysis was done for serum glucose, serum insulin and insulin resistance. Routine histological examination was done, together with immunohistochemistry for detection of the hippocampal learning and memory plasticity marker, namely activity regulated cytoskeletal-associated protein (Arc), and the astrocytes reactivity marker, namely glial fibrillary acidic protein (GFAP). , Results: Both type 1 and 2 untreated diabetic groups showed significantly impaired cognitive performance compared to the non-diabetic group. Treating the type 1 diabetic group with insulin alone significantly improved cognitive performance, but significantly decreased GFAP and Arc compared to the untreated type 1 group. In addition, the type 2 diabetic groups showed a significant decrease in hippocampus GFAP and Arc compared to the non-diabetic groups. Blocking NMDA receptors by memantine significantly increased cognitive performance, GFAP and Arc in the type 1 insulin-memantine group compared to the type 1-insulin group and significantly increased Arc in the type 2-memantine group compared to the untreated type 2 diabetic group. The non-diabetic group receiving memantine was, however, significantly adversely affected., Conclusion: Cognitive functions are impaired in both types of diabetes mellitus and can be improved by blockage of NMDA receptors which may spark a future therapeutic role for these receptors in diabetes-associated cognitive dysfunction.

Background and Objectives: The rapidly increasing number of diabetic patients across the world drew the attention to develop more effective therapeutic approaches. Recent investigations on newly differentiated insulin producing cells (IPCs) revealed that they could be derived from embryonic, adult mesenchymal and hematopoietic stem cells. This work was planned to evaluate the role of StemEnhance (Aphanizomenon flos-aquae [AFA] plant extract) in mobilizing naturally occurring bone marrow stem cells as well as in improving streptozotocin-induced diabetic rats., Methods and Results: Twenty adult male albino rats were divided into four groups namely the control, the diabetic, the positive control-StemEnhance and the diabetic-StemEnhance groups. After diabetes induction by streptozotocin (STZ), rats received StemEnhance for four weeks. The mean number of blood CD34 immunopositive cells was measured by flowcytometry and random blood sugar was measured weekly. The pancreas was removed from the sacrificed rats and processed for staining with H&E and immunohistochemical staining for CD34+ve and insulin +ve cells. CD34+ve cells increased in the blood after introduction of StemEnhance. CD34+ve cells were observed in the pancreas and the insulin producing cells in the islets of Langerhans were increased from the second to the fourth week of treatment. Blood glucose level improved but it was still higher than the control level after four weeks of StemEnhance treatment., Conclusions: This work points to the significant role of StemEnhance in stem cell mobilization and the improvement of diabetes mellitus.