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Quorum sensing inhibitor (QSI) has been attracting attention as anti-virulence agent which disarms pathogens of their virulence rather than killing them. QSI marking cyclic peptide-mediated QS in Gram-positive bacteria is an effective tool to overcome the crisis of antibiotic-dependent chemotherapy due to the emergence of drug resistance strain, e.g., methicillin resistant Staphylococcus aureus (MRSA) and Vancomycin resistant Enterococci (VRE). From a semi-large-scale screening thus far carried out, two Epoxide compounds, Ambuic acid and Synerazol, have been found to efficiently block agr and fsr QS systems, suggesting that the Epoxide group is involved in the mode of action of these QSIs. To address this notion, known natural Epoxide compounds, Cerulenin and Fosfomycin were examined for QSI activity for the agr and fsr systems in addition to in silico and SAR studies. As a result, most of investigated Epoxide containing antibiotics correlatively interfere with QSI activity for the agr and fsr systems under sublethal concentrations. [ABSTRACT FROM AUTHOR]

Thrombosis is the leading cause of illness and mortality worldwide, posing a serious risk to human health and life. Because antithrombotic drugs can prevent the beginning and progression of thrombotic disorders, they are essential in the management of thrombotic diseases. The substantial side effects and unsatisfactory efficacy of present antithrombotic drugs stimulate the search for novel, effective, and safer antithrombotic therapies. Natural and synthetic coumarins have been shown to have antithrombotic action, specifically anticoagulation, and antiplatelet aggregation. In particular, coumarin-based medications like warfarin, phenprocoumon, and cloricromen have long been used to treat thrombosis in clinical settings. The favored structure for creating novel antithrombotic medications with diverse modes of action is coumarin, which has low toxicity. The goal of the current review is to consolidate recent findings on the development of coumarins as antithrombotic agents, with a focus on the connection between these compounds' chemical compositions and therapeutic potency. It aims to offer promising suggestions for the identification of new coumarin compounds with potent antithrombotic properties. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), also known as hepatoma, is the most prevalent type of primary liver cancer. It begins in the hepatocytes, the liver's major cell type. Cancer that began in another region of the body but has spread to the liver is known as secondary cancer of life; several still unmet demands for better, less toxic therapy to treat this malignant tumor. Several novel pyrazolo[1,5-a]pyrimidine derivatives were synthesized as part of our goal to develop promising anticancer drugs. All the synthesized hybrids have been screened for their cytotoxicity effect against three cancer cell lines which are; HepG-2, HCT-116, and MCF-7. The liver cancer cells were found to be the most sensitive to the effect of the new molecules. A subsequent set of in vitro biological evaluation studies has been conducted on the most promising derivatives to identify their effect on such a cancer type. In HepG-2 cells, four derivatives (8a, 8b, 10c, and 11b) demonstrated good anticancer activity. The most efficacious compounds were 8b and 10c, which had IC50 values of 2.36 ± 0.14 and 1.14 ± 0.063 μM, respectively, higher than the reference medication Imatinib. The latter's putative molecular effect has been investigated further by looking at its influence on the cell cycle, EGFR, and specific apoptotic and anti-apoptotic markers in HepG-2 cells. These findings indicated that 8b and 10c could trigger apoptosis by upregulating BAX and caspase-3 and cell cycle at the Pre-G1 and G2-M stages. The compounds 8b and 10c showed high potency for EGFR with IC50 equal to 0.098 and 0.079 μM, respectively. Compound 10c had the most effective inhibitory activity for EGFR L858R-TK with IC50 (36.79 nM). Additionally, in silico ADMET and docking studies were done for the most active hits, representing good results. [ABSTRACT FROM AUTHOR]

Physiotherapy (PT) is a profession that includes education and close contact for long periods of time with patients for treatment sessions. Globally, smoking is prevalent and is expected to increase in the next decades; thus, smoking cessation (SC) is an important management strategy to mitigate further escalation. Little is known about PT practice in SC, and therefore, this study aimed to systematically review and discuss the published literature about the role of physiotherapists in smoking cessation management, opinions, and prevalence of SC counselling in physiotherapy practice; and to explore barriers towards smoking cessation counselling within physiotherapy practice. A systematic search was conducted through EBSCO, and articles were included if they assessed the role of PTs in SC management. The databases were searched for studies published between 1 January 1970 to 1 April 2022. Articles were excluded if they did not include PTs, if they did not include assessment of SC management/counselling, if they were not cross-sectional studies, if they were not written in the English language, or if they were conference abstracts. Seven studies were included in the review. The search identified no studies that have investigated the role of PTs in vaping cessation. It was found that PTs are not addressing SC counselling and management enough in their practice. In addition, the search revealed that lack of training, time, and knowledge are the most common barriers against including SC counselling in physiotherapy practice and rehabilitation programs. Exploring possibilities of including SC counselling according to the clinical guidelines is encouraged. Additionally, establishing solutions to overcome barriers against SC counselling as part of physiotherapy practice is essential. [ABSTRACT FROM AUTHOR]

A new set of 1,2,3-triazoles was designed and synthesized to evaluate their potential to inhibit the growth of cancer cells. Thiazole, thiazolone, and hydrazine as effective fragments present in certain anticancer molecules were incorporated in the structure of the new molecules given that they have been suggested to enhance the cytotoxic activity. The growth inhibition (GI) of all the compounds was evaluated by the National Cancer Institute against a panel of sixty human cancer cells of nine different types. Three compounds showed mild to moderate growth inhibition activity against lung, renal, and prostate cancerous cells. The best GI activity was observed for triazole derivative 14 against EKVX, RXF-393, and UO-31 with GI of 37.59%, 33.76%, and 29.49%, respectively. Additionally, thiazolone-linked triazole derivative 21 exhibited relatively good activity with GI of 28.89%, 32.87%, and 22.26% against HOP-92, RXF-393, and UO-31, respectively. Additionally, docking and pharmacokinetic profiling studies were performed to examine the probable mechanistic effect of these cytotoxic derivatives and evaluate their potential as good drug candidates. [ABSTRACT FROM AUTHOR]

The first outbreak in Wuhan, China, in December 2019 was reported about severe acute coronaviral syndrome 2 (SARS-CoV-2). The global coronavirus disease 2019 (COVID-19) pandemic in 2020 resulted in an extremely high potential for dissemination. No drugs are validated in large-scale studies for significant effectiveness in the clinical treatment of COVID-19 patients, despite the worsening trends of COVID-19. This study aims to design a simple and efficient cyclo-condensation reaction of 6-aminouracil derivatives 2a–e and isatin derivatives 1a–c to synthesize spiro-oxindoles 3a–d, 4a–e, and 5a–e. All compounds were tested in vitro against the SARS-CoV-2. Four spiro[indoline-3,5′-pyrido[2,3-d:6,5-d']dipyrimidine derivatives 3a, 4b, 4d, and 4e showed high activities against the SARS-CoV-2 in plaque reduction assay and were subjected to further RNA-dependent-RNA-polymerase (RdRp) and spike glycoprotein inhibition assay investigations. The four compounds exhibited potent inhibitory activity ranging from 40.23 ± 0.09 to 44.90 ± 0.08 nM and 40.27 ± 0.17 to 44.83 ± 0.16 nM, respectively, when compared with chloroquine as a reference standard, which showed 45 ± 0.02 and 45 ± 0.06 nM against RdRp and spike glycoprotein, respectively. The computational study involving the docking studies of the binding mode inside two proteins ((RdRp) (PDB: 6m71), and (SGp) (PDB: 6VXX)) and geometrical optimization used to generate some molecular parameters were performed for the most active hybrids. [ABSTRACT FROM AUTHOR]

Anti-virulence agents are non-bacteriostatic and non-bactericidal emerging therapeutic options which hamper the production of virulence factors in pathogenic flora. In Staphylococcus aureus and Enterococcus faecalis, regulation of virulence genes' expression occurs through the cyclic peptide-mediated accessory gene regulator (agr) and its ortholog fsr quorum sensing systems, respectively. In the present study, we screened a set of 54 actinomycetales secondary metabolites as novel anti-virulence compounds targeting quorum sensing system of the Gram-positive bacteria. The results indicated that four compounds, Phenalinolactones A–D, BU–4664LMe, 4,5-dehydrogeldamycin, and Questinomycin A, potentially inhibit the agr quorum sensing system and hemolytic activity of S. aureus. On the other hand, Decatromicin A and B, Okilactomycin, Rishirilide A, Abyssomicin I, and Rebeccamycin selectively blocked the fsr quorum sensing system and the gelatinase production in E. faecalis at sub-lethal concentrations. Interestingly, Synerazol uniquely showed the capability to inhibit both fsr and agr quorum sensing systems. Further, in silico molecular docking studies were performed which provided closer insights into the mode of action of these compounds and proposed that the inhibitory activity of these compounds could be attributed to their potential ability to bind to the ATP-active site of S. aureus AgrA. Taken together, our study highlights the potential of actinomycetales secondary metabolites with diverse structures as anti-virulence quorum sensing inhibitors. [ABSTRACT FROM AUTHOR]

Several coumarin-containing substitute nitrogen heterocycles have recently received considerable importance due to their diverse pharmacological properties. One-pot and rapid synthesis of coumarin derivatives was achieved via reactions of acetyl-coumarin with p-chloro-benzaldehyde and malononitrile to provide compound 2-containing cyano-amine using conventional heating. Compound 2 was condensed with different carbon electrophiles triethyl orthoformate, phenyl isocyanate, carbon disulfide, benzoyl chloride, and acetyl chloride that afforded the corresponding chromene derivatives 3–17. All the newly synthesized compounds were characterized by elemental and spectroscopic evidences. All of the synthesized compounds were tested for antimicrobial activity against S. Pneumoniae, S. Epidermidis, S. Aureus, and E. coli as Gram + ve Bacteria, K. Pneumoniae, S. Paratyphi as Gram -ve Bacteria, P. Italicum, A. Fumigatus representative for Fungi. The preliminary screening results showed that most of the compounds had moderate to high activity against all tested organisms. The most potent four compounds were subjected to further investigation against E. Coli DNA gyrase and topoisomerase IV inhibitory activity, and the results showed that all of these derivatives inhibit DNA gyrase and thus cell division. Also, in silico studies were done for the most active compounds which showed good results. [ABSTRACT FROM AUTHOR]

The targeted approach of protein kinases (PKs), as PKs are the main regulators of cell survival and proliferation, has been a promising strategy for cancer treatments. Here we analyse the potential of quinoline-carboxamide derivatives for four cell lines: MCF-7, CACO, HepG-2 and HCT-116 as anticancer agents. 3e, 4b, 11b and 13d derivatives showed good anti-proliferative activities in comparison to the reference standard Doxorubicin, against the four cell lines tested. They have been chosen for further studies. First of all, the IC50 value surveys were carried out to ensure the protection of our hits and demonstrate that the cytotoxic effect (IC50 > 113 μM) is highly selective on normal human cells (WI-38). Secondly, apoptosis was accomplished by down-regulation of Bcl-2 and up-regulation of BAX and Caspase-3 by these active compounds. Also, the Pim-1 inhibitory activity of the active hybrids was done, which indicates that compound 3e was the most active with the percentage of inhibition 82.27% and IC50 equals 0.11 when compared to SGI-1776 as a reference standard. In addition, by in silico assessment of ADME properties, all of the strongest compounds are orally bioavailable without blood–brain barrier penetration. [ABSTRACT FROM AUTHOR]

PURPOSE: Down Syndrome (DS) is characterized by intellectual disability, hypotonia, and joint laxity. Physical disability can be an additional problem and manifests as reduced lower limb muscle strength and impaired balance. The objectives of this study were to characterize DS dynamic foot-ground contact area and to study its relationship with balance impairment among adolescents with DS. METHODS: Twenty-eight children and adolescents with DS and 28 non-DS adolescents/children were matched for age and sex. The Oxford Ankle Foot Questionnaire (parents' version) was used to measure disability related to ankle/foot problems in all subjects. A pressure-sensitive mat was used to assess the contact area and arch index. Also, a Biodex balance system was used for measuring postural stability. RESULTS: There were significant differences between both groups in all domains of the Oxford Ankle Foot Questionnaire, overall contact area, and arch index (p < 0.05). Overall postural stability index was significantly decreased in subjects with DS (p < 0.05). There was a nonsignificant correlation between contact area and postural stability (p > 0.05). CONCLUSION: Adolescents with DS exhibited larger mid-foot and forefoot contact areas with respect to non-DS matched children. Impairment of balance in adolescents with DS is a multifactorial problem not related to changes in the foot contact area. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Plant Production is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Electrode impedance measures resistance encountered by electric current passing through wires, electrodes and biological tissue. This study was designed mainly to evaluate changes in electrode impedance values and psycho-electric parameters changes (i.e. threshold levels, comfortable levels, and dynamic range) in cochlear implant patients over time. Methods: It was a prospective study encompassing 20 patients implanted by MED-EL device programd using behavioral programs. Electrical stimulation levels and electrode impedance values were examined at 0, 1, 3 and 6 months after the first fitting session. Results: Electrode impedance values were reduced from the time of activation to the 6 months visit. Most comfortable levels increased and dynamic range widened until the 6 months visit. There was an inverse correlation between impedance values and most comfortable level as well as dynamic range, over time. Conclusion: Frequent monitoring of electrode impedance (for device and electrodes problems) and electric stimulation levels (for better performance, mapping and habituation) during the first 6 months of implant use is recommended. [ABSTRACT FROM AUTHOR]

Copyright of Zagazig Journal of Agricultural Research is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A novel series of coumarin-pyridine/fused pyridine hybrids were designed and synthesized. Their anticancer activity was evaluated against human cancer cell lines MCF-7, HCT-116, HepG-2, and A549. Compounds 9, 10, and 11 showed the most potent growth inhibitory activities with IC50 values ranging from 1.1 to 2.4 μM, against MCF-7 cell line. Flow cytometric analysis revealed that these compounds induced cell cycle arrest in the G2/M phase followed by apoptotic cell death. Consistent with these results, the activity of caspase-3 in MCF-7 cells was tested. The results indicated that compounds 9, 10, and 11 increased caspase-3 activity significantly compared to control group. Moreover, their binding affinity for caspase-3 was confirmed by docking study. Taking all these data together, it is suggested that these coumarin derivatives may be potential antiproliferative agents. [ABSTRACT FROM AUTHOR]

3,5-Diamino-4-(3-trifluoromethylphenyldiazenyl)-1H-pyrazole was used as a starting scaffold for the synthesis of new pyrazole-based heterocycles to study their effects on the proliferation of three human cancer cell lines; human liver carcinoma cell line (HepG-2), colon cancer cell line (HCT-116) and human breast cancer cell line (MCF-7) using MTT assay. The synthesized compounds were characterized on the basis of IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis results. Cytotoxicity assay results revealed that some of the compounds showed potent growth inhibition against all the cell lines tested, with IC50 values in the range of 0.64-7.73 μg/mL. Breast cancer cells were used for further detailed studies to understand the mechanism of cell growth inhibition and apoptosis-inducing effect of the most active compounds. The results indicated that compounds 3a, 10b and 11a arrested MCF-7 cells at G2/M phase of the cell cycle and might induce apoptosis via caspase-3-dependent pathway. Molecular modeling and binding mode analysis of the most active compounds to caspase 3 active site further provide a synergistic mechanism for their pro-apoptotic effects. In order to explore the structural requirements controlling the observed cytotoxic properties, 3D pharmacophore model was generated. [ABSTRACT FROM AUTHOR]

Derivatives of isatin have been reported to possess cytotoxic effects against different human carcinoma cell lines. A series of new isatin-linked chalcones was synthesized starting from isatin. Most of the newly synthesized compounds were screened for their in vitro anticancer activity against human breast (MCF-7), liver (HepG-2), and colon (HCT-116) cancer cell lines. All the tested compounds exhibited antitumor activity, with IC ranging from 2.88 to 62.88 μM in comparison to the reference drug used in this study, Imatinib. Compounds 2- 5 were the most active, with IC ranging from 2.88 to 18.12 μM for the three cell lines, while compound 7b also showed moderate activity against HepG-2, MCF-7 and HCT-116 with IC 13.95, 31.66 and 11.78 μM, respectively. Furthermore, compound 7d showed high activity against HepG-2 cells with IC 12.84 μM. Compound 4 was shown to be the most potent against both HepG-2 and HCT-116 cell lines, while compound 2 is the most potent against MCF-7. The compounds were also screened for their cytotoxic activity against normal breast cell line MCF-12A, and were found to possess mild cytotoxicity. A docking study was performed for the most active compounds in this study, 2- 5, inside the active site of CDK2. All the docked compounds have shown favorable binding interactions and energy scores. Compound 4 has proved to be the best in binding interactions and energy score. These findings may explain the cytotoxic activity of the target compounds. Graphical Abstract: A novel series of isatin-linked chalcones was synthesized. The target compounds were evaluated for their cytotoxic activity towards human breast (MCF-7), liver (HepG-2), colon (HCT-116) cancer cell lines and (MCF-12A) normal breast cell line. [ABSTRACT FROM AUTHOR]

This review describes the synthesis and reactions of naproxen derivatives and highlights the effects of compounds containing the naproxen moiety in important biological applications. [ABSTRACT FROM AUTHOR]

Background: Uracil derivatives have a great attraction because they play an important role in pharmacological activities. Pyrimidodiazepines, lumazines, triazolopyrimidines and xanthines have significant wide spectrum activities including anticancer, antiviral as well as antimicrobial activities. Results: A newly synthesized compounds pyrimido[4,5- b][1, 4]diazepines 5a- e, 6a- d, lumazines 7a- d, triazolo[4,5- d]pyrimidine 8 and xanthines 9, 10 was prepared in a good yields. The antimicrobial and antioxidant activities of compounds 5a, 5b, 6a, 6d and 8 exhibited a wide range activity against the pathogenic tested microbes ( Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans, and Saccharomyces cerevisiae). Compound 8 showed activity against the fungus Aspergillus niger. The highest antioxidant activity was noticed for compound 5a. Conclusions: A series of novel pyrimido[4,5- b][1, 4]diazepines 5a- e, 6a- d, lumazines 7a- d, triazolo[4,5- d]pyrimidine 8 and xanthines 9, 10 was prepared from 5,6-diamino-1-(2-chlorobenzyl)uracil 3 in good yields. Compounds 5a- e, 6a- d were prepared by sequential manipulation of 3 with α, β-unsaturated ketones. Lumazines 7a- d were obtained from 3 by treatment with phenacyl bromides in the presence of TEA. Compound 8 was prepared by treatment of 3 with HNO, while xanthines 9, 10 were obtained from 3 by consecutive acetylation then intramolecular cyclodehydration or heating with malononitrile under solvent-free condition. The antimicrobial and antioxidant activity of this series was evaluated in vitro and they showed either weak or moderate activities. [ABSTRACT FROM AUTHOR]

BACKGROUND:Most stroke patients experience hand impairments that can result in persistent limitations in daily activities. OBJECTIVE: This study aimed at estimating the immediate and retention effects of task specific training and wrist/fingers extension splint on hand joints range of motion and function after stroke. METHODS: Twenty-four right handed patients with first ever stroke represented the sample of the study. The participants were randomly assigned into two equal groups. The study group received task specific exercises five times a week for an hour concurrently with wrist/fingers extension splint which was used two hours for each three hours (day and night) excluding exercises and sleeping hours for 16 weeks. The control group received traditional passive stretch and range of motion exercises. Manual dexterity and upper limb function were assessed by nine holes peg test and Fugl-Meyer upper extremity and hand. Goniometry was used for measuring wrist, metacarpophalangeal, thumb carpometacarpal joints active range of motion. RESULTS: Significant improvements were observed in nine holes peg test, Fugl-Meyer upper extremity and hand scores and ranges of motion at post-intervention and follow-up compared to pre-intervention at P⩽0.05. CONCLUSIONS: The results of this study provide an evidence that task specific training and wrist/fingers extension splint are effective in improving fingers dexterity, upper extremity function and wrist/hand range of motion. [ABSTRACT FROM AUTHOR]

Simple one-pot syntheses of indenopyrrolopyrimidines and indolopyrrolopyrimidines were achieved via the cyclocondensation of 6-aminouracils and, respectively, ninhydrin and isatin in the presence of catalytic amounts of glacial acetic acid. Similarly, 5,6-diaminouracil derivatives were used as starting materials for the synthesis of indenopteridines and indolopteridines via their reaction with ninhydrin and isatin, respectively. The synthesised compounds were evaluated for antitumour activity against a human hepatocellular carcinoma cell line (HepG2), some showing antitumour activity comparable with 5-fluorouracil and imatinib. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Physical Medicine & Rehabilitation / Turkiye Fiziksel Tip ve Rehabilitasyon Dergisi is the property of Turkish Society of Physical Medicine & Rehabilitation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Objectives. Postural changes are frequent and disabling complications of Parkinson’s disease (PD). Many contributing factors have been evident either related to disease pathology or to adaptive changes. This study aimed at studying the postural changes in subjects with Parkinson’s disease and its relation to duration of illness and disease severity. Methods. Eighteen patients with PD and 18 healthy matched volunteers represented the sample of the study. The patients were at stage 1 or 1.5 according to the Modified Hoehn and Yahr Staging with duration of illness between 18 and 36 months. Three-dimensional analysis of the back surface was conducted to explore the postural changes in the sagittal and frontal planes in both the patients and the healthy subjects. Results. Kyphotic angle, lordotic angle, fleche cervicale, fleche lombaire, scoliotic angle, and associated vertebral rotation and pelvic obliquity were significantly increased in patients with PD compared to the healthy subjects (P≤0.05). There was no association between the measured postural changes and duration of illness as well as the severity of the IPD (P≤0.05). Conclusion. Postural changes start in the early stages of idiopathic PD and they have no relationship to the duration of illness and disease severity. [ABSTRACT FROM AUTHOR]

Background and Purpose. Equinovarus foot is a common sign after stroke. The aim of this study is to investigate the effect of task specific exercises, gait training, and visual biofeedback on correcting equinovarus gait among individuals with stroke. Subjects and Methods. Sixteen subjects with ischemic stroke were randomly assigned to two equal groups (G1 and G2). All the patients were at stage 4 of motor recovery of foot according to Chedoke-McMaster Stroke Assessment without any cognitive dysfunction. E-med pedography was used to measure contact time, as well as force underneath hind and forefoot during walking. Outcome measures were collected before randomization, one week after the last session, and four weeks later. Participants in G1 received task specific exercises, gait training, and visual biofeedback and a traditional physical therapy program was applied for participants in G2 for 8 weeks. Results. Significant improvement was observed among G1 patients (P ≤ 0.05) which lasts one month after therapy termination. On the other hand, there were no significant differences between measurements of the participants in G2. Between groups comparison also revealed a significant improvement in G1 with long lasting effect. Conclusion. The results of this study showed a positive long lasting effect of the task specific exercises, gait training, and visual biofeedback on equinovarus gait pattern among individuals with stroke. [ABSTRACT FROM AUTHOR]