Bioinformatics is a branch of science that uses computers, algorithms, and databases to solve biological problems. To achieve more accurate results, researchers need to use large and complex ...datasets. Sequence alignment is a well-known field of bioinformatics that allows the comparison of different genomic sequences. The comparative genomics field allows the comparison of different genomic sequences, leading to benefits in areas such as evolutionary biology, agriculture, and human health (e.g., mutation testing connects unknown genes to diseases). However, software engineering best practices, such as software performance engineering, are not taken into consideration in most bioinformatics tools and frameworks, which may lead to serious performance problems. Having an estimate of the software performance in the early phases of the Software Development Life Cycle (SDLC) is beneficial in making better decisions relating to the software design. Software performance engineering provides a reliable and observable method to build systems that can achieve their required performance goals. In this paper, we introduce the use of the Palladio Component Modeling (PCM) methodology to predict the performance of a sequence alignment system. Software performance engineering was not considered during the original system development. As a result of the performance analysis, an alternative design is proposed. Comparing the performance of the proposed design against the one already developed, a better response time is obtained. The response time of the usage scenario is reduced from 16 to 8.6 s. The study results show that using performance models at early stages in bioinformatics systems can help to achieve better software system performance.
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•Design & synthesis of new hybridized quinoxalines.•Antibacterial activity against bacterial, fungal and multi-drug resistant strains.•Enzyme assay: DNA Gyrase inhibitory ...activity.•Investigating the Immunomodulatory effect.•Molecular docking studies are also performed in this research work.
2,3-Dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonyl chloride 1 was prepared via reaction of o-phenylene diamine with oxalic acid followed by chlorosulfonation with excess chlorosulfonic acid. A series of new sulfonylquinoxaline derivatives 2–6 were obtained upon reacting compound 1 with different types of amines. 2,3-Dichloro-6-morpholinosulfonylquinoxaline derivative 6 was subjected to further chemical reactions to afford many derivatives of 6-morpholino 2,3-disubstitutedquinoxalines, thus reaction of compound 6 with different secondary amines yielded mono and di secondary aminoquinoxaline derivatives 7–10 depending on the reactivity difference of the two chlorine atoms. Hydrazinolysis of compound 7 furnished hydrazino quinoxaline derivatives 11a-c. Additionally triazolo and pyrazolyl quinoxaline derivatives 12–14 were obtained through the reaction of compound 11a with phenyl isothiocyanate, formylpyrazole and ethyl acetoacetate. All the synthesized compounds were screened for their antibacterial and antifungal activities. Compounds 7a, 9b, 10a, 10c, 10f and 11c showed good to moderate antimicrobial activity against the tested Gram-positive, Gram-negative bacteria and fungi with MIC values ranging from 2.44 to 180.14 μM. Their MBC values were also evaluated using the same tested microorganisms. Moreover, screening against multi-drug resistant strains revealed the promiscuity of these new derivatives, especially compound 7a that showed comparable antibacterial activity (MIC 4.91–9.82 μM) with Norfloxacin (MIC 2.44–9.80 µM). Furthermore, these compounds were evaluated as DNA Gyrase inhibitors and the obtained results were in the range of 15.69–23.72 µM. Immunomodulatory effect was also investigated and compounds 7a, 11c, 10f, 10c, 10a and 9b showed high immunostimulatory action with ratio (142.6 ± 0.4, 135.7 ± 0.5, 117.8 ± 0. 39, 112.5 ± 0. 83, 86.4 ± 0. 47, 72.8 ± 0. 77) respectively. Molecular docking studies of the promising derivatives into DNA Gyrase binding site proved the usefulness of hybridizing quinoxaline scaffold with SO2 and morpholine moieties as a hopeful strategy in designing new DNA Gyrase binding molecules.
Transglutaminase (TG) isoforms control diverse normal and pathophysiologic processes through their capacity to cross-link extracellular matrix (ECM) proteins. Their functional and signalling roles in ...cardiac fibrosis remain poorly understood, despite some evidence of TG2 involvement in abnormal ECM remodelling in heart diseases. In this study, we investigated the role of TG1 and TG2 in mediating fibrotic signalling, collagen cross-linking, and cell proliferation in healthy fibroblasts by siRNA-mediated knockdown. siRNA for TG1, TG2 or negative control was transfected into cultured neonatal rat ventricular fibroblasts and cardiomyocytes. mRNA expression of TGs and profibrotic, proliferation and apoptotic markers was assessed by qPCR. Cell proliferation and soluble and insoluble collagen were determined by ELISA and LC-MS/MS, respectively. TG1 and TG2 were both expressed in neonatal rat cardiomyocytes and fibroblasts before transfection. Other TGs were not detected before and after transfection. TG2 was predominantly expressed and more effectively silenced than TG1. Knocking down TG1 or TG2 significantly modified profibrotic markers mRNA expression in fibroblasts, decreasing connective tissue growth factor (CTGF) and increasing transforming growth factor-β1 compared to the negative siRNA control. Reduced expression of collagen 3A1 was found upon TG1 knockdown, while TG2 knockdown raised α-smooth muscle actin expression. TG2 knockdown further increased fibroblast proliferation and the expression of proliferation marker cyclin D1. Lower insoluble collagen content and collagen cross-linking were evidenced upon silencing TG1 or TG2. Transcript levels of collagen 1A1, fibronectin 1, matrix metalloproteinase-2, cyclin E2, and BCL-2-associated X protein/B-cell lymphoma 2 ratio were strongly correlated with TG1 mRNA expression, whereas TG2 expression correlated strongly with CTGF mRNA abundance. These findings support a functional and signalling role for TG1 and TG2 from fibroblasts in regulating key processes underlying myocardial ECM homeostasis and dysregulation, suggesting that these isoforms could be potential and promising targets for the development of cardiac fibrosis therapies.
Chronic diabetic foot ulcers (CDFUs) are complex pathological processes involving persistent inflammation, significantly impacting a patient's quality of life. Resveratrol (RES), recognized for its ...potent antioxidant and anti-inflammatory properties, faces challenges regarding its permeability. This study aimed to develop Resveratrol glycerosomal nanovesicles (RES-GLY-NVs) for topical application to enhance skin permeation. The optimized formulation was integrated into a 2 % HPMC gel and subjected to comprehensive physicochemical characterization, skin deposition, in vitro release, microbiological, antioxidant, and in vivo assessments. Results revealed RES-GLY-NVs with particle size ranging from 82.19 ± 6.51 nm to 145.70 ± 1.39 nm with PDI less than 0.5, encapsulation efficacy ranging from 89.14 ± 1.39 % to 96.09 ± 2.13 % and a zeta potential ranging from −27.93 ± 6.47 mV to −49.33 ± 1.89 mV. The release profile of RES was obviously ranging from % 54.40 ± 1.71 to 77.47 ± 0.54 % after 8 h. In vitro cell assessment revealed that RES-GLY-NVs have no cytotoxicity on normal cells. The optimized RES-GLY-NVs-HPMC gel displayed pseudoplastic rheological behavior and significantly enhanced RES flux and permeability through excised rat skin compared to plain gel. The In vivo study and histological evaluation of diabetic rats ensured that RES-GLY-NVs-HPMC gel acts as a more effective healing adjunct compared to free RES and conventional therapy. These findings encourage the utilization of RES-GLY-NVs-HPMC gel as a wound-healing drug delivery system in chronic diabetes-related wounds and ulcers.
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•Preparation of Mn(II), Co(II), Pd(II) Zn(II) and Cd(II) complexes of salen ligand.•Theoretical studies for the isolated compounds were computed using DFT technique.•Fluorescence studies of Co(II) ...and Zn(II) complexes have been measured.•Cyclic voltammetric study of Cd(II)-complex has been estimated.•Biological activities of the compounds have been determined.
2,2′-((1E,1′E)-(ethane-1,2-diylbis(azanylylidiene))bis(methanylylidene))diphenol (H2L) ligand and its Mn(II), Co(II), Pd(II) Zn(II) and Cd(II) chelates have been isolated and characterized by conventional and spectroscopic techniques including FTIR spectrum, 1HNMR , 13CNMR , powder X-ray diffraction PXRD, UV–visible, mass spectroscopy besides elemental analyses, and magnetic susceptibility measurements. The DMOL3 tool in the material studio package was also used to optimize the structures. The ligand behaves as binegative N2O2 tetradentate in Pd(II) and Zn(II) complex, neutral N2 bidentate in Mn(II), Co(II) and Cd(II)-complexes. Horowitz–Metzger and Coats–Redfern approaches were used to estimate the various kinetic and thermodynamic parameters. Zeta Potentials for the H2L ligand and its Pd(II), Cd(II) and Co(II) complexes in ethanol as a dispersive medium were measured. Ligand and its complexes were tested for their biological potency as anti-bacterial activity against gram (-) E. coli, P. aeruginosa, and gram (+) B. subtilis, S. aureus bacteria as well as antifungal activity against C. albicans. The antioxidant potentials of the isolated compounds were also screened by using DPPH scavenging methods. The isolated compounds were examined for cytotoxic activity using the MTT assay on MDA-MB-231 and HepG2 cell lines, and the results were verified using molecular docking simulations.
Abstract Melanoma is the third highest rated cancer in prevalence. Surgery, radiotherapy and targeted/biological therapies in addition to chemotherapy are available options for management of this ...cancer. Met is an appealing target for management of this type of cancer, since it targets many cancer vital processors, such as angiogenesis, cell growth, scattering and differentiation. In this review, we provide an overview about pathway abnormalities associated with melanoma. We also provide a summary about the events involved in Met signaling and related signaling molecules. We also show the evidence of the importance of Met signaling pathway as a target in cancer management. We also summarize clinical evidence about the use of Met signaling in management of cancer and summarize available trials related to targeting Met in other cancers.
Most fungal bone and joint infections (arthritis) are caused by Mucormycosis (
). These infections may be difficult to treat and may lead to chronic bone disorders and disabilities, thus the use of ...new antifungal materials in bone disorders is vital, particularly in immunocompromised individuals, such as those who have contracted coronavirus disease 2019 (COVID-19). Herein, we reported for the first time the preparation of nitrogen-doped carbon quantum dots (N/CQDs) and a nitrogen-doped mesoporous carbon (N/MC) using a quick micro-wave preparation and hydrothermal approach. The structure and morphology were analysed using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and surface area analyser. Minimum inhibitory concentration (MIC), disc diffusion tests, minimum fungicidal concentration (MFC) and antifungal inhibitory percentages were measured to investigate the antifungal activity of N/CQDs and N/MC nanostructures. In addition to the
antifungal activity in rats as determined by wound induction and infection, pathogen count and histological studies were also performed. According to
and
testing, both N/CQDs with small size and N/MC with porous structure had a significant antifungal impact on a variety of bone-infecting bacteria, including Mucor infection. In conclusion, the present investigation demonstrates that functional N/CQDs and N/MC are effective antifungal agents against a range of microbial pathogenic bone disorders in immunocompromised individuals, with stronger and superior fungicidal activity for N/CQDs than N/MC
and
studies.
Royal jelly (RJ) is a multifunctional bee product with a unique composition and wide-ranging biological properties, including antioxidant, anti-inflammatory and antiproliferative activities. Still, ...little is known about the possible myocardial protective properties of RJ. Considering that sonication could enhance RJ bioactivity, this study aimed to assess the effects of non-sonicated (NS) and sonicated (S) RJ on fibrotic signaling, cell proliferation, and collagen production in cardiac fibroblasts. S-RJ was produced by ultrasonication at 20 kHz. Ventricular fibroblasts isolated from neonatal rats were cultured and treated with different concentrations of NS-RJ or S-RJ (0, 50, 100, 150, 200, and 250 µg/well). S-RJ significantly depressed the expression levels of transglutaminase 2 (TG2) mRNA across all the concentrations tested and was inversely associated with the expression of this profibrotic marker. S-RJ and NS-RJ displayed distinct dose-dependent effects on mRNA expression of several other profibrotic, proliferation, and apoptotic markers. Unlike NS-RJ, S-RJ elicited strong negative dose-dependent relationships with the expression of profibrotic markers (TG2, COL1A1, COL3A1, FN1, CTGF, MMP-2, α-SMA, TGF-β1, CX43, periostin), as well as proliferation (CCND1) and apoptotic (BAX, BAX/BCL-2) markers, indicating that RJ dose-response effects were significantly modified by sonification. NS-RJ and S-RJ increased the content of soluble collagen, while decreasing collagen cross-linking. Collectively, these findings show that S-RJ has a greater range of action than NS-RJ for downregulating the expression of biomarkers associated with cardiac fibrosis. Reduced biomarker expression and collagen cross-linkages upon cardiac fibroblast treatment with specific concentrations of S-RJ or NS-RJ suggests putative roles and mechanisms by which RJ may confer some protection against cardiac fibrosis.
•Royal jelly (RJ) displayed antifibrogenic activity in cultured ventricular fibroblasts.•RJ administration reduced collagen cross-linking in fibroblasts.•RJ altered the expression of key profibrotic, proliferation, and apoptotic markers.•Sonication enhanced RJ bioactivity in downregulating cardiac fibrosis signaling.•Sonicated RJ also showed superior potential for reducing fibroblast proliferation.
Cardiac tumors are a rare condition that typically presents with nonspecific symptoms. Among the histologic patterns, myxoid sarcomas are rarely identified and may have a less favorable prognosis. ...Reporting a case of this type of cardiac tumor can increase awareness about this condition and aid in early diagnosis, potentially leading to better outcomes.
We are presenting a case of a 41-year-old female with left atrial myxoid sarcoma, which was presented with a cardiogenic shock picture. She underwent surgical excision of the mass and was discharged in good condition. After discharge, she deteriorated and was found to have lung metastases.
Primary cardiac sarcomas, due to their rarity and poor prognosis, are often diagnosed at an advanced stage of the disease and lack sufficient data to establish a standard course of treatment. The cornerstone of therapy is surgical resection. However, novel therapeutic approaches must be developed.
Primary cardiac tumors should be suspected in adult patients with progressive dyspnea, and a biopsy should also be done to determine the histopathological pattern of the mass and estimate the overall prognosis and outcomes.
Abstract Objective The aim of this study was to compare the efficacy and tolerability of iron amino acid chelate (IAAC) and ferrous fumarate (FF) in treatment of iron deficiency anemia (IDA) with ...pregnancy. Study design A total of 150 pregnant women having iron deficiency anemia (IDA) were randomized to receive either IAAC or FF for 12 weeks. Hemoglobin, red cell indices, serum iron, and serum ferritin were measured at baseline and then 4, 8, and 12 weeks after treatment. Adverse effects were questioned in both groups. Results The mean values of hemoglobin, red cell indices, serum iron, and serum ferritin were not significantly different between both groups after 12 weeks of treatment. However, the rise in hemoglobin level after 4, 8, and 12 weeks of treatment was significantly faster in the IAAC group ( p = <0.001). Constipation and abdominal colicky pain were significantly more common in the FF group ( p = 0.022 and 0.031 respectively). Conclusion IAAC and FF are comparable in curing IDA with pregnancy; however, IAAC has the advantage of providing a faster rate of improvement of hemoglobin level and is better tolerated by the patients.
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