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Cigarette smoking exacerbates respiratory diseases, while plant-derived polyphenols offer antioxidant and anti-inflammatory benefits. This study explores the effects of Rhoifolin (ROF), a polyphenol from Jordanian Teucrium polium, on lung health in rats exposed to tobacco smoke. Male rats were divided into two groups: one exposed to cigarette smoke (CS), and the other to ROF treatment alongside smoke exposure (ROF/CS). ROF was administered orally for 21 days before smoke exposure. Results showed smoke-induced lung inflammation and oxidative stress, mitigated by ROF treatment. Histological examination revealed smoke-related morphological changes in lung tissue. ROF treatment reduced oxidative stress and inflammation, as evidenced by decreased proinflammatory cytokines. In silico docking demonstrated ROF's potential as an inhibitor. This study suggests the therapeutic potential of ROF and similar polyphenols in mitigating the harmful effects of cigarette smoke on lung health.
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Levofloxacin (LVX) is among the fluoroquinolones antibiotics that has also been studied in vitro and in vivo for its anticancer effects. In this study, we used LVX and novel LVX thionated derivatives; compounds 2 and 3, to evaluate their antioxidant activity, aldehyde dehydrogenase (ALDH) enzymes activity inhibition, and anticancer activity. Combination treatments with doxorubicin (DOX) were investigated as well. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to determine the antioxidant activity. The NADH fluorescence spectrophotometric activity assay was used to determine the ALDH inhibitory effects. Resazurin dye method was applied for cell viability assays. Molecular Operating Environment software was used for the molecular docking experiments. Compared to ascorbic acid, DPPH assay showed that compound 3 had the highest antioxidant activity among the tested compounds with approximately 35% scavenging activity. On ALDH enzymes, compound 3 showed a significant ALDH activity inhibition compared to compound 2 at 200 µM. The IC50 values for the tested compounds were approximately 100 µM on A549 cell line, a non-small cell lung cancer (NSCLC) cell line. However, significant enhancement of cytotoxicity and reduction of IC50 values were observed by combining DOX and synergism was achieved with LVX with a combination index value of 0.4. The molecular docking test showed a minimum binding energy with a good affinity for compound 3 towards ALDH enzymes. Thionated LVX derivatives, may be repurposed for NSCLC therapy in combination with DOX, taking into account the antioxidant activity, ALDH activity inhibition, and the molecular docking results of compound 3.
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The purpose of this research was to evaluate how much the people in the Jazan region know about the care and healing of surgical wounds. Proper care of surgical wounds is very important to achieve the best treatment outcomes and to avoid negative consequences. However, factors like obesity, diabetes, and certain medications can impair wound healing, with surgical site infections being a major problem in the healthcare system. Therefore, this study aimed to determine public awareness and perceptions of surgical wound care to help improve education and raise awareness of the importance of proper wound care for better results. We run an observational cross-sectional study among adults above 18 years in the Jazan region. An online self-administered questionnaire was used in the collection of data. Simple random sampling was the used technique and 384 participants were calculated. The study used Statistical Package for the Social Sciences (SPSS) for data analysis and employed descriptive statistics, independent t test, Analysis of Variance (ANOVA), Pearson's correlation, and multivariate logistic regression to identify factors associated with knowledge of surgical site infection and wound care. This study analyzed 599 participants' knowledge, attitude, and practice about surgical site infection and wound management. While participants had a strong general understanding of surgical wounds, only 17% had a high degree of knowledge about surgical site infection and wound management. Medical students had the highest degree of knowledge, and being a medical student was the only significant predictor of having a high level of knowledge about surgical site infection (SSI) and wound care. The study emphasizes the necessity of enhanced patient education and investment in medical education quality. The participants in this study had high overall knowledge regarding surgical wounds but lacked particular knowledge concerning surgical site infection and wound management. Medical education was discovered to be a strong predictor of having a high level of knowledge about surgical site infection and wound management. Healthcare professionals should take the lead in giving accurate and reliable information regarding wound care techniques to patients, and legislators should invest in enhancing medical education quality.
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Infecção da Ferida Cirúrgica , Ferida Cirúrgica , Adulto , Humanos , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Arábia Saudita , Ferida Cirúrgica/terapia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/terapia , CicatrizaçãoRESUMO
Repurposing existing drugs appears to be a potential solution for addressing the challenges in the treatment of non-small cell lung cancer (NSCLC). ß-adrenoceptor antagonist drugs (ß-blockers) have tumor-inhibiting effects, making them promising candidates for potential NSCLC treatment. This study investigates the anticancer potential of a subset of ß-blockers in NSCLC cell lines; A549 and H1299. Additionally, it investigates the underlying mechanism behind ß-blockers' anticancer effect by influencing a potential novel target named aldehyde dehydrogenase (ALDH). The MTT assay assessed ß-blockers' cytotoxicity on both cell lines, while Western blot and NADH fluorescence assays evaluated their influence on ALDH protein expression and activity. Carvedilol (CAR) was the most effective blocker in reducing cell survival of A549 and H1299 with IC50 of 18 µM and 13.7 µM, respectively. Significantly, CAR led to a 50% reduction in ALDH expression and 80% decrease in ALDH activity in A549 cells, especially when combined with ß-agonists, in comparison to the control. This effect might be attributed to ß-agonist blockade or an alternative pathway. This novel finding adds to our understanding of CAR's multifaceted anticancer properties, implying that combining CAR with ß-agonists could be a useful strategy for lung cancer treatment.
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Background: This study aimed to develop remineralizing calcium-phosphate (CaP) etchant pastes for enamel conditioning before bracket bonding and evaluate the bonding performance, failure pattern, and enamel surface integrity post bracket debonding in comparison with the conventional phosphoric acid (PA) etchant gel. Material and Methods: Micro-sized monocalcium phosphate monohydrate and hydroxyapatite (micro- and nano-sized) powders were mixed with various phosphoric and nitric acid concentrations to develop eight acidic CaP pastes. Ninety extracted human premolars were randomly assigned into eight experimental and one control group (n=10). The developed pastes and control (commercial 37% PA-gel) were applied onto the enamel using the etch-and-rinse protocol before bonding metal brackets. Shear bond strength and adhesive remnant index (ARI) scores were evaluated after 24 hours water storage (24 h) and post 5000 thermocycling (TC). Field emission scanning electron microscopy (FE-SEM) was used to evaluate enamel damage after bracket debonding. Results: The developed CaP pastes, excepting MNA1 and MPA1, resulted in significantly lower SBS values and ARI scores than 37% PA gel. Etching with 37% PA yielded roughened, cracked enamel surfaces with excessive retention of adhesive residue. In contrast, enamel treatment with the experimental pastes exhibited smooth, unblemished surfaces, with obvious CaP re-precipitation induced by mHPA2 and nHPA2 pastes and to a lesser extent by MPA2 paste. Conclusions: Three newly developed CaP etchant pastes (MPA2, mHPA2, and nHPA2) can be promising alternative enamel conditioners that outperform conventional PA by generating adequate bracket bond strengths besides precipitating CaP crystals on the enamel. Moreover, these pastes maintained unblemished enamel surfaces with no or minimal adhesive residue after bracket removal. Key words:Enamel Conditioning, Calcium Phosphate, Bracket Bond Strength, Orthodontic Bonding, enamel damage.
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Aldehyde dehydrogenase (ALDH) enzymes are involved in the growth and development of several tissues, including cancer cells. It has been reported that targeting the ALDH family, including the ALDH1A subfamily, enhances cancer treatment outcomes. Therefore, we aimed to investigate the cytotoxicity of ALDH1A3-affinic compounds that have been recently discovered by our group, on breast (MCF7 and MDA-MB-231) and prostate (PC-3) cancer cell lines. These compounds were investigated on the selected cell lines as single treatments and in combination with doxorubicin (DOX). Results showed that the combination treatment experiments of the selective ALDH1A3 inhibitors (compounds 15 and 16) at variable concentrations with DOX resulted in significant increases in the cytotoxic effect on the MCF7 cell line for compound 15, and to a lesser extent for compound 16 on the PC-3 cell line, compared to DOX alone. The activity of compounds 15 and 16 as single treatments on all cell lines was found to be non-cytotoxic. Therefore, our findings showed that the investigated compounds have a promising potential to target cancer cells, possibly via an ALDH-related pathway, and sensitize them to DOX treatment.
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OBJECTIVES: This study aimed to incorporate hydroxyapatite nanoparticles (nHA) or amorphous calcium phosphate nanoparticles (nACP) into a self-etch primer (SEP) to develop a simplified orthodontic bonding system with remineralizing and enamel preserving properties. MATERIALS AND METHODS: nHA and nACP were incorporated into a commercial SEP (Transbond™ plus) in 7% weight ratio and compared with the plain SEP as a control. Shear bond strengths (SBS), enamel damage, and adhesive remnant index (ARI) scores were evaluated at 24 h and post 5000 thermocycling. Field-emission scanning electron microscope (FESEM) was used to inspect the distribution of the nanoparticles in the experimental SEPs and evaluate the enamel surface integrity both before bracket bonding and post bracket debonding. Phase determination and remineralizing capability of the modified SEP were characterized by X-ray diffraction and Raman spectroscopy, respectively. RESULTS: The addition of nHA or nACP to the SEP significantly reduced the SBS, ARI, and enamel damage (p < 0.05) as compared to the control SEP; however, only nHA-SEP survived the thermocycling protocol and yielded acceptable SBS (13.38 MPa). Enamel remineralizing ability of the developed nHA-SEP was confirmed by both FESEM images and Raman phosphate map. CONCLUSIONS: Incorporating nHA into SEP resulted in clinically acceptable bond strengths with remineralizing ability. CLINICAL RELEVANCE: The newly developed nHA-SEP has unprecedented ability to simultaneously etch, prime, and remineralize the enamel in a single step leaving immaculate enamel surface with the potential of saving cost and time at the post-debonding step.
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Colagem Dentária , Nanopartículas , Braquetes Ortodônticos , Cimentos de Resina/química , Colagem Dentária/métodos , Fosfatos de Cálcio , Resistência ao Cisalhamento , Teste de Materiais , Propriedades de Superfície , Análise do Estresse DentárioRESUMO
Levofloxacin is a widely used fluoroquinolone in several infectious diseases. The structure-activity relationship of levofloxacin has been studied. However, the effect of changing the carbonyl into thiocarbonyl of levofloxacin has not been investigated up to the date of this report. In this work, levofloxacin structure was slightly modified by making a thionated form (compound 3), which was investigated for its antibacterial activity, biocompatibility, and cytotoxicity, as well as spectroscopic properties. The antibacterial susceptibility testing against five different bacteria showed promising minimum inhibitory concentrations (MICs), particularly against B. spizizenii and E. coli, with an MIC value of 1.9 µM against both bacteria, and 7.8 µM against P. mirabilis. The molecular docking experiment showed similar binding interactions of both levofloxacin and compound 3 with the active site residues of topoisomerase IV. The biocompatibility and cytotoxicity results revealed that compound 3 was more biocompatible with normal cells and more cytotoxic against cancer cells, compared to levofloxacin. Interestingly, compound 3 also showed an excitation profile with a distinctive absorption peak at λmax 404 nm. Overall, our results suggest that the thionation of quinolones may provide a successful approach toward a new generation with enhanced pharmacokinetic and safety profiles and overall activity as potential antibacterial agents.
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KP167 is a novel hypoxia-activated prodrug (HAP), targeting cancer cells via DNA intercalating and alkylating properties. The single agent and radiosensitizing efficacy of KP167 and its parental comparator, AQ4N, were evaluated in 2D and 3D cultures of luminal and triple negative breast cancer (TNBC) cell lines and compared against DNA damage repair inhibitors. 2D normoxic treatment with the DNA repair inhibitors, Olaparib or KU-55933 caused, as expected, substantial radiosensitization (sensitiser enhancement ratio, SER0.01 of 1.60-3.42). KP167 induced greater radiosensitization in TNBC (SER0.01 2.53 in MDAMB-231, 2.28 in MDAMB-468, 4.55 in MDAMB-436) and luminal spheroids (SER0.01 1.46 in MCF-7 and 1.76 in T47D cells) compared with AQ4N. Significant radiosensitization was also obtained using KP167 and AQ4N in 2D normoxia. Although hypoxia induced radioresistance, radiosensitization by KP167 was still greater under 2D hypoxia, yielding SER0.01 of 1.56-2.37 compared with AQ4N SER0.01 of 1.13-1.94. Such data show KP167 as a promising single agent and potent radiosensitiser of both normoxic and hypoxic breast cancer cells, with greater efficacy in TNBCs.
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Pró-Fármacos , Neoplasias de Mama Triplo Negativas , Antraquinonas/farmacologia , Hipóxia Celular , Linhagem Celular Tumoral , Humanos , Hipóxia/tratamento farmacológico , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/radioterapiaRESUMO
Aldehyde dehydrogenases (ALDHs) are overexpressed in various tumor types including prostate cancer and considered a potential target for therapeutic intervention. 4-(Diethylamino)benzaldehyde (DEAB) has been extensively reported as a pan-inhibitor of ALDH isoforms, and here, we report on the synthesis, ALDH isoform selectivity, and cellular potencies in prostate cancer cells of 40 DEAB analogues; three analogues (14, 15, and 16) showed potent inhibitory activity against ALDH1A3, and two analogues (18 and 19) showed potent inhibitory activity against ALDH3A1. Significantly, 16 analogues displayed increased cytotoxicity (IC50 = 10-200 µM) compared with DEAB (>200 µM) against three different prostate cancer cell lines. Analogues 14 and 18 were more potent than DEAB against patient-derived primary prostate tumor epithelial cells, as single agents or in combination treatment with docetaxel. In conclusion, our study supports the use of DEAB as an ALDH inhibitor but also reveals closely related analogues with increased selectivity and potency.
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Aldeído Desidrogenase , Neoplasias da Próstata , Benzaldeídos , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológicoRESUMO
Objective: This study aimed to evaluate the orthodontic bond strength and enamel-preserving ability of a hydroxyapatite nanoparticles-containingself-etch system following exposure to various ageing methods. Materials and Methods: Hydroxyapatite nanoparticles (nHAp) were incorporated into an orthodontic self-etch primer (SEP, Transbond™ plus) in three different concentrations (5%, 7%, and 9% wt) and tested versus the plain SEP (control) for shear bond strength (SBS), adhesive remnant index (ARI) scores, and enamel damage in range-finding experiments using premolar teeth. The best-performing formulation was further exposed to the following four artificial ageing methods: initial debonding, 24 h water storage, one-month water storage, and one-month acid challenge. A field-emission scanning electron microscope (FE-SEM) was used to examine the integrity of debonded enamel surfaces and calcium-phosphates (CaPs) reprecipitation. Results: The best-performing formulation (7% nHAp-SEP) resulted in significantly lower SBS (p < 0.001) than the control SEP following the four artificial ageing methods. Nevertheless, it survived the ageing protocols and yielded clinically acceptable SBS with the advantages of leaving minimal adhesive residue, preserving enamel integrity and smoothness, and inducing CaP reprecipitation as confirmed by FE-SEM images. Conclusions: A newly developed SEP produced adequate orthodontic bond strengths and left unblemished debonded enamel surfaces with minimal remnant adhesive and remineralisation potential, thereby suggesting simpler and safer bonding/debonding procedures.
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Aldehyde dehydrogenase 1A3 (ALDH1A3) has recently gained attention from researchers in the cancer field. Several studies have reported ALDH1A3 overexpression in different cancer types, which has been found to correlate with poor treatment recovery. Therefore, finding selective inhibitors against ALDH1A3 could result in new treatment options for cancer treatment. In this study, ALDH1A3-selective candidates were designed based on the physiological substrate resemblance, synthesized and investigated for ALDH1A1, ALDH1A3 and ALDH3A1 selectivity and cytotoxicity using ALDH-positive A549 and ALDH-negative H1299 cells. Two compounds (ABMM-15 and ABMM-16), with a benzyloxybenzaldehyde scaffold, were found to be the most potent and selective inhibitors for ALDH1A3, with IC50 values of 0.23 and 1.29 µM, respectively. The results also show no significant cytotoxicity for ABMM-15 and ABMM-16 on either cell line. However, a few other candidates (ABMM-6, ABMM-24, ABMM-32) showed considerable cytotoxicity on H1299 cells, when compared to A549 cells, with IC50 values of 14.0, 13.7 and 13.0 µM, respectively. The computational study supported the experimental results and suggested a good binding for ABMM-15 and ABMM-16 to the ALDH1A3 isoform. From the obtained results, it can be concluded that benzyloxybenzaldehyde might be considered a promising scaffold for further drug discovery aimed at exploiting ALDH1A3 for therapeutic intervention.
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Aldeído Oxirredutases/antagonistas & inibidores , Benzaldeídos/síntese química , Inibidores Enzimáticos/síntese química , Neoplasias/enzimologia , Células A549 , Benzaldeídos/química , Benzaldeídos/farmacologia , Linhagem Celular Tumoral , Simulação por Computador , Descoberta de Drogas , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Estrutura Molecular , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: This in vitro study compares a novel calcium-phosphate etchant paste to conventional 37% phosphoric acid gel for bonding metal and ceramic brackets by evaluating the shear bond strength, remnant adhesive and enamel damage following water storage, acid challenge and fatigue loading. MATERIAL AND METHODS: Metal and ceramic brackets were bonded to 240 extracted human premolars using two enamel conditioning protocols: conventional 37% phosphoric acid (PA) gel (control), and an acidic calcium-phosphate (CaP) paste. The CaP paste was prepared from ß-tricalcium phosphate and monocalcium phosphate monohydrate powders mixed with 37% phosphoric acid solution, and the resulting phase was confirmed using FTIR. The bonded premolars were exposed to four artificial ageing models to examine the shear bond strength (SBS), adhesive remnant index (ARI score), with stereomicroscopic evaluation of enamel damage. RESULTS: Metal and ceramic control subgroups yielded significantly higher (p < 0.05) SBS (17.1-31.8 MPa) than the CaP subgroups (11.4-23.8 MPa) post all artificial ageing protocols, coupled with higher ARI scores and evidence of enamel damage. In contrast, the CaP subgroups survived all artificial ageing tests by maintaining adequate SBS for clinical performance, with the advantages of leaving unblemished enamel surface and bracket failures at the enamel-adhesive interface. CONCLUSIONS: Enamel conditioning with acidic CaP pastes attained adequate bond strengths with no or minimal adhesive residue and enamel damage, suggesting a suitable alternative to the conventional PA gel for orthodontic bonding. Key words:Enamel etching, calcium phosphate, bracket bond strength, adhesive residue, enamel damage.
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BACKGROUND: This in vitro study compares a self-etch primer (SEP) to an etch-and-rinse (EaR) for bonding sapphire brackets by evaluation of the enamel etch-pattern, shear bond strength, amount of remnant adhesive and enamel surface damage following thermal and fatigue cyclic loading. MATERIAL AND METHODS: Ceramic (sapphire) brackets were bonded to 80 extracted human premolars using two enamel etching protocols: conventional EaR using 37% phosphoric acid (PA) gel (control), and a SEP (Transbond Plus). Each group was subdivided into two subgroups (n=20 teeth) according to the time of bracket debonding: after 24 h water storage or following 5000 thermo-cycles plus 5000 cycles fatigue loading, to determine the shear bond strength (SBS), adhesive remnant index (ARI score), with scanning electron microscopy (SEM) evaluation of enamel condition. RESULTS: The control subgroups consistently exhibited significantly higher (p<0.05) SBS mean values (23.4-29.8 MPa) than the SEP subgroups (15.1-22.4 MPa) at both bracket debonding time points. However, the SEP subgroups yielded milder etch-patterns and attained SBS values above the minimum requirement range for clinical performance. In addition, the higher SBS of control subgroups was accompanied with higher ARI scores and enamel damage grades than SEP subgroups as confirmed by SEM. Thermocycling and fatigue significantly reduced the SBS of all subgroups, with a non-significant drop in the amount of adhesive residue or enamel damage. CONCLUSIONS: The use of SEP can be a suitable alternative to the conventional PA gel for sapphire bracket bonding as it maintains suitable bond strength and has the potential to produce both less remnant adhesive and enamel damage. Key words:Enamel etching, ceramic brackets, orthodontic bonding, adhesive remnants, enamel damage.
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Tetrahydroisoquinoline (THIQ) is a key structural component in many biologically active molecules including natural products and synthetic pharmaceuticals. Here, we report on the use of transition-metal mediated [2 + 2 + 2] cyclotrimerisation of alkynes to generate tricyclic THIQs with potential to selectively inhibit AKR1C3.
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HSV-1 DNA was detected in 32 (30%) of 106 cerebrospinal fluid samples from patients with encephalitis. Cytomegalovirus, varicella-zoster virus, and human herpesvirus 6 (HHV-6) DNAs were each detected in three patients (3%); herpes simplex virus type 2 (HSV-2) and HHV-7 PCRs were negative. HSV detection was associated with seizure (P = 0.02), especially focal seizure (P = 0.0002), and pathological computed tomography (P = 0.02) with focal lesions (P = 0.0004).
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DNA Viral/líquido cefalorraquidiano , Encefalite Viral/virologia , Herpesviridae/isolamento & purificação , Adolescente , Adulto , Criança , Pré-Escolar , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Encefalite Viral/líquido cefalorraquidiano , Feminino , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/isolamento & purificação , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/isolamento & purificação , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/isolamento & purificação , Herpesvirus Humano 7/genética , Herpesvirus Humano 7/isolamento & purificação , Humanos , Lactente , MasculinoRESUMO
BACKGROUND: Herpes virus infections are suspected to be involved in the pathogenesis of atherosclerosis. OBJECTIVE AND METHOD: Viral DNA of herpes simplex virus (HSV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was analyzed by real-time PCR on 48 biopsies from atherosclerotic plaques extracted by end-arterectomy (46 coronary arteries, 2 carotid arteries), and in tissue from non-atherosclerosis vessels from the same patient as controls (23 internal mammary arteries, 43 saphenous veins). RESULTS: HSV-1 DNA was detected significantly more frequently in plaques (35%) than in control veins (9%, P = 0.006). However, the frequency of HSV-1 DNA detection in the internal mammary artery grafts was as high as in plaques (22%, P = 0.28). CMV and EBV DNA were exclusively found in plaques but not in controls, with 10% for CMV (P = 0.06 versus veins, P = 0.17 versus graft arteries) and 2% for EBV (P = 1.0), respectively. HSV-2 was neither detected in plaques nor in controls. Herpes viral DNA was significantly associated only with arterial hypertension but not with other classical risk factors (P = 0.02), in accordance with the hypothesis that herpes viral infection may alter the vessel wall. CONCLUSION: We conclude that herpes viral infections may have a role in atherosclerosis and that the presence of herpes viral DNA in the grafts used for bypass surgery might constitute a potential risk for atherosclerosis or restenosis.