In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2
)-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that ...integrated key structural elements essential for DNA damage
direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles
and
in addition to 4-(4-chlorophenyl)imidazoles
and
would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds
and
against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than
, respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
•A green-house test was led to examine the efficacy of heavy metal-tolerant plant growth promoting bacterial.•Using bacterial strains (HMT-PGPB) to alleviate the heavy metal’s toxic effects on ...sorghum plant.•The oxidative enzymes, photosynthetic pigments, growth characteristics, were estimated in sorghum cultivated.•Also, heavy metals uptake and heavy metals translocation factor (TF) were tested in sorghum cultivated in soil.•This soil contaminated with heavy metals under green-house conditions.
A green-house experiment was conducted to investigate the efficiency of three heavy metal-tolerant plant growth promoting bacterial strains (HMT-PGPB) (Alcaligenes faecalis MG257493.1, Bacillus cereus MG257494.1 and Alcaligenes faecalis MG966440.1 to alleviate the heavy metal’s toxic effects on sorghum plant (Sorghum bicolor, L.) in addition to their ability to enhance plant growth. The oxidative enzymes, photosynthetic pigments, growth characteristics, heavy metals uptake and heavy metals translocation factor (TF) were estimated in sorghum cultivated in soil contaminated with heavy metals under green-house conditions. Results showed that the application of these HTM-PGPB strains as biofertilizer of sorghum help plant to ignore the toxic effects of heavy metals and enhance growth characteristics.
Acute myeloid leukemia (AML) is one of the cancers that grow most aggressively. The challenges in AML management are huge, despite many treatment options. Mutations in FLT3 tyrosine kinase receptors ...make the currently available therapies less responsive. Therefore, there is a need to find new lead molecules that can specifically target mutated FLT3 to block growth factor signaling and inhibit AML cell proliferation. Our previous studies on FLT3-mutated AML cells demonstrated that β-elemene and compound
showed strong inhibition of proliferation by blocking the mutated FLT3 receptor and altering the key apoptotic genes responsible for apoptosis. Furthermore, we hypothesized that both β-elemene and compound
could be therapeutically effective. Therefore, combining these drugs against mutated FLT3 cells could be promising. In this context, dose-matrix combination-based cellular inhibition analyses, cell morphology studies and profiling of 43 different apoptotic protein targets via combinatorial treatment were performed. Our studies provide strong evidence for the hypothesis that β-elemene and compound
combination considerably increased the therapeutic potential of both compounds by enhancing the activation of several key targets implicated in AML cell death.
Bone is the second most common site of metastasis in patients with thyroid cancer (TC) and dramatically impacts overall survival and quality of life with no definitive cure, yet there is no extensive ...study of the demographic and clinical risk factors in the recent literature. Data regarding 120,754 TC patients with bone metastasis were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analyses were used to identify the risk factors of bone metastasis occurring in various histologies of TC. Cox regression was performed to analyze the influence of bone metastasis on overall survival. Hazard ratios were computed to analyze the association between bone metastasis and the primary outcomes. Of the 120,754 records collected from the SEER database from 2000 to 2019, 976 (0.8%) presented with bone metastasis, with occurrence being the greatest in patients of age ≥ 55 years (OR = 5.63, 95%CI = 4.72-6.71), males (OR = 2.60, 95%CI = 2.27-2.97), Blacks (OR = 2.38, 95%CI = 1.95-2.9) and Asian or Pacific Islanders (OR = 1.90, 95%CI = 1.58-2.27), and single marital status. TC patients presenting with bone metastasis (HR = 2.78, 95%CI = 2.34-3.3) or concurrent bone and brain metastases (HR = 1.62, 95%CI = 1.03-2.55) had a higher mortality risk. Older age, gender, race, and single marital status were associated with bone metastasis and poorer prognosis in TC patients at initial diagnosis. Understanding such risk factors can potentially assist clinicians in making early diagnoses and personalized treatment plans, as well as researchers in developing more therapeutic protocols.
Two structurally novel series of histone deacetylase inhibitors (HDACIs) involving two potential surface recognition moieties; 3′,4′-dihydro-2′H-spiroimidazolidine-4,1′-naphthalene-2,5-dione (in ...series I) and 1-(3-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamide (in series II) were designed, synthesized, and evaluated for their anti-proliferative activities, HDAC inhibitory activities, and their binding modes to HDAC protein. Compounds 5f and 10e showed comparable HDAC inhibitory activity to SAHA.
Series II have been also demonstrated as potential HDAC-tubulin dual inhibitors, promoted with structural similarities between (1-(3-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamide) nucleus, of series II, and Combretastatin A4.
The tubulin inhibitory activities of series II members, together with their docking into colchicine binding site of β-tubulin were performed. Compound 9a showed remarkable cytotoxicity. Hybrid 10e behaved as potent HDAC-tubulin dual inhibitor. It showed better tubulin inhibition than CA4 as well as its effectiveness against HDAC.
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•Two novel series of histone deacetylase inhibitors (HDACIs) involving two potential surface recognition moieties; 3′,4′-dihydro-2′H-spiroimidazolidine-4,1′-naphthalene-2,5-dione and 1-(3-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamide were synthesized.•Novel compounds were evaluated for their anti-proliferative activities.•The mechanism was proved by evaluation of HDAC inhibitory activities.•Molecular Modeling studies were done to demonstrate binding modes to HDAC protein.•Series II have been also demonstrated as potential HDAC-tubulin dual inhibitors.
The protective and therapeutic anti-inflammatory and antioxidant potency of Malapterurus electricus (F. Malapteruridae) skin fish methanolic extract (FE) (300 mg/kg.b.wt/day for 7 days, orally) was ...tested in monosodium urate(MSU)-induced arthritic Wistar albino male rats’ joints. Serum uric acid, TNF-α, IL-1β, NF- B, MDA, GSH, catalase, SOD, and glutathione reductase levels were all measured. According to the findings, FE significantly reduced uric acid levels and ankle swelling in both protective and therapeutic groups. Furthermore, it has anti-inflammatory effects by downregulating inflammatory cytokines, primarily through decreased oxidative stress and increased antioxidant status. All the aforementioned lesions were significantly improved in protected and treated rats with FE, according to histopathological findings. iNOS immunostaining revealed that protected and treated arthritic rats with FE had weak positive immune-reactive cells. Phytochemical analysis revealed that FE was high in fatty and amino acids. The most abundant compounds were vaccenic (24.52%), 9-octadecenoic (11.66%), palmitic (34.66%), stearic acids (14.63%), glycine (0.813 mg/100 mg), and alanine (1.645 mg/100 mg). Extensive molecular modelling and dynamics simulation experiments revealed that compound 4 has the potential to target and inhibit COX isoforms with a higher affinity for COX-2. As a result, we contend that FE could be a promising protective and therapeutic option for arthritis, aiding in the prevention and progression of this chronic inflammatory disease.
Since silica goes under the category of amorphous materials, it is difficult to investigate important processes such as second harmonic generation (SHG) in silica-based fibers. In this paper, we ...proposed a method for SHG relaying on cladding modes as pump modes. Cladding modes are introduced in optical fibers through tilted long period grating (T-LPG), where power of core mode is transferred into cladding modes. By functionalizing T-LPG with nonlinear coating, the interaction occurs between cladding modes and the coating material, consequently second harmonic signal (SHS) is generated with efficiency up to 0.14%.
Nutritional deficits in one’s diet have been established as the key risk factor for T2DM in recent years. Nutritional therapy has been demonstrated to be useful in treating T2DM. The current study ...was carried out to assess the nutritional composition of bovine (12 months), chicken (4 months), sheep (13 months), and goat (9 months) femur bone extracts, as well as their potential therapeutic effects on T2DM regression in a Wistar albino rat model (500 mg/kg b.wt.). The proximate composition of the different extracts, their fatty acid composition, their amino acids, and their mineral contents were identified. In vivo data indicated considerably improved T2DM rats, as seen by lower serum levels of TL, TG, TC, ALT, AST, ALP, bilirubin, creatinine, urea, IL-6, TNF-α, sICAM-1, sVCAM-1, and MDA. Low levels of HDL-C, GSH, and total proteins were restored during this study. Histological investigations of liver and pancreatic tissue revealed that the distribution of collagen fibers was nearly normal. The bovine extract, on the other hand, was the most active, followed by the sheep, goat, and finally chicken extract. This research could result in the creation of a simple, noninvasive, low-cost, and reliable method for T2DM control, paving the way for potential early therapeutic applications in T2DM control.
BACKGROUND AND AIMS:Gastroesophageal reflux disease (GERD) is a common prevalent disease. We aimed to assess the dynamic changes in the peripheral T lymphocytes and lymphocytes infiltrating the ...esophageal mucosa after treatment with proton-pump inhibitor (PPI) in patients with GERD.
PATIENTS AND METHODS:A total of 200 patients who presented with upper GIT symptoms were included in this prospective study. All patients were subjected to full history taking, clinical examination, and complete blood count. Upper endoscopy was performed to detect the grade of GERD, followed by 4 quadrant biopsies before and 1 month after acid suppressive drug therapy. Histopathologic and immunohistochemical examination were carried out for all biopsies. Flow cytometry analysis for the peripheral T lymphocytes and cytokine profile assay before therapy and after therapy were also carried out.
RESULTS:In total, 200 patients comprising 132 male individuals (66%) and 68 female individuals (34%) with a mean age of 47.9±18.3 were included. The risk factors for development of GERD were smoking in 87 (43.5%), spicy food intake in 26 (13%), analgesics in 46 (23%), excessive tea and coffee in 35 (17.5%), and nondetected risk factors in 6 (3%). Endoscopic examination using Los Angeles grading system revealed that 102 patients (51%) were grade A, 57 patients (28.5%) were grade B, 38 patients (19%) were grade C, and 3 patients (1.5%) were grade D. No statistically significant differences could be detected in HGB levels and WBC, PLT, monocyte, granulocyte, and eosinophil counts before and after treatment with PPI. Histopathologic examination of esophageal biopsies showed significant posttreatment improvement in 132 cases (66%); however, 66 cases (33%) including the 2 cases (1%) of Barrett’s esophagus showed nonsignificant pathologic improvement compared with the pretreatment picture. Immunohistochemical staining of esophageal biopsies with CD3 (T-cell marker) and CD20 (B-cell marker), before and 1 month after treatment, showed the presence of a very large number of infiltrating B cells in the esophageal mucosa (700±30/10 HPF) with large aggregations; in contrast, T-cell infiltration appeared less marked (570±23/10 HPF), and they formed smaller aggregates than those of B cells in pretreated patients, with P<0.01. However, 1 month after treatment with PPI, esophageal biopsies revealed a marked decrease in the number of both B (10±2/10 HPF) and T (290±12/HPF) cells in 66% of patients, with a P<0.01 in comparison with the pretherapy pattern. However, the remaining 33% of patients still showed a significantly high number of T cells (490±28/HPF), with a P <0.05 in comparison with the responder group that formed small aggregates with larger cell sizes, indicating their activation. Cytokine profiles before and after treatment revealed significant posttreatment reduction in their levels in the 132 cases with improvement in their clinical manifestations, and endoscopic and histopathologic findings, but there is no obvious change in the measured cytokine levels in 66 patients who simultaneously had no improvement in their endoscopic, histopathologic findings and mild improvement in their clinical manifestations. Moreover, significant posttreatment reduction of IL-8 and IL-1β in the 98 (49%) patients with Los Angeles grading B, C, and D was observed. With regard to serum levels of IL-10 and IL-4, there were no statistically significant differences before and after treatment with PPI. Peripheral blood immunologic parameters revealed a statistically significant reduction of the total CD3 absolute count, T-helper lymphocyte (CD4/CD3) percentage, T-helper lymphocyte absolute count, and the percentage and absolute cytotoxic T-lymphocyte count (CD8/CD3) after treatment with PPI. Moreover, the same significant difference of peripheral blood lymphocytes was detected after exclusion of patients with Los Angeles grade A, which may be considered normal.
CONCLUSIONS:Acid-induced T-cell–related cytokine production plays an important role in inflammation occurring in patients with GERD. Mucosal and peripheral inflammation reduces with PPI use.
•Parents of children without epilepsy had better knowledge score than parents of children with epilepsy.•Better attitude noticed among parents of children without epilepsy.•Better percentage of level ...of knowledge is a positive predictor to more positive attitude and good practices skills.•There is a statistically significant association between level of education and knowledge and attitude score percent.•Parents of children with epilepsy treated with more than one drug have good practice skills than those treated with one drug.
Epilepsy is one of the most common neurological disorders affecting children. As a chronic disease, it affects not only the child but also the entire family. The attitudes towards the children suffering from epilepsy and the skills required to deal with acute seizures are influenced by the level of knowledge the parents have about that disease.
To evaluate the knowledge, attitudes, and skills toward epilepsy among parents of children diagnosed with epilepsy in comparison to parents of children without epilepsy.
Data collected through a structured questionnaire that was designed, translated into Arabic, and analyzed statistically in a cross-sectional study for a total of 534 Egyptian parents as two groups, group I (n = 223) consist of parents with children with epilepsy and group II (n = 311) of parents with children without epilepsy. Parents with children with epilepsy were recruited from the Paediatric Neurology Outpatient Clinic of Alexandria University Children’s Hospital (AUCH). Parents with children without epilepsy were recruited from other outpatient clinics or wards of AUCH.
This study showed a poor knowledge score percentage of (89.7 %) among parents with children with epilepsy and (83.3 %) among parents with children without epilepsy. The difference between both groups was statistically significant with fewer knowledge scores among parents of children with epilepsy. Parents of both groups showed a negative attitude score percentage; (69.5 %) of group I and (62.7 %) of group II. The difference between both groups was statistically significant with a more negative attitude score percentage among parents with children without epilepsy. Parents of both groups had poor practice score percentage of (66.8 %) of group I and (74.3 %) of group II having poor practice skills needed for emergency management of acute seizures. A high level of education was significantly associated with fair knowledge score percentage and positive attitude score percentage.
Poor knowledge, negative attitudes, and poor skills required for the management of acute seizures were found among both parents of children with epilepsy and those with children without epilepsy. Educational programs are needed to eliminate all the misconceptions and myths and to change attitudes of the Egyptian parents towards epilepsy.
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