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1.
Arch Pharm (Weinheim) ; : e2400418, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39086040

RESUMO

Green seaweed (Ulva sp.) is frequently used as a food component and nutraceutical agent because of its high polysaccharide and natural fiber content in Asian countries. This study investigates both metabolomic profiling of Ulva sp. and the neuroprotective efficacy of its ethanol extract and its underlying mechanisms in a rotenone-induced rat model of neurodegeneration, mimicking Parkinson's disease (PD) in humans. Metabolomic profiling of Ulva sp. extract was done using liquid chromatography high resolution electrospray ionization mass spectrometry and led to the identification of 22 compounds belonging to different chemical classes.Catenin Beta Additionally, this study demonstrated the neuroprotective properties against rotenone-induced PD, which was achieved through the suppression of elevated levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 together with the inhibition of reactive oxygen species (ROS) generation, apoptosis, inflammatory mediators, and the phosphoinositide 3-kinases/serine/threonine protein kinase (PI3K/AKT) pathway. Using a protein-protein interaction network, AKT1, GAPDH, TNF-α, IL-6, caspase 3, signal transducer and activator of transcription 3, Catenin Beta 1, epidermal growth factor receptor, B-cell lymphoma -2, and HSP90AA1 were identified as the top 10 most significant genes. Finally, molecular docking results showed that compounds 1, 3, and 7 might possess a promising anti-parkinsonism effect by binding to active sites of selected hub genes. Therefore, it is hypothesized that the Ulva sp. extract has the potential to be further developed as a potential therapeutic agent for the treatment of PD.

2.
J Thromb Thrombolysis ; 56(1): 164-174, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37097552

RESUMO

Anticoagulation during Impella® support is a challenge due to its complications and inconsistent practice across the globe. This observational, retrospective chart review included all patients with Impella® support at our advanced cardiac center at a quaternary care hospital in the Middle East gulf region. The study was conducted over six years (2016-2022), a time period during which manufacturer recommendations for purge solution, anticoagulation protocols as well as Impella® place in therapy and utilization were all evolving. We aimed to evaluate the efficacy of different anticoagulation practices and association with complications and outcomes. Forty-one patients underwent Impella® during the study period, including 25 patients with support for more than 12 h, and are the focus of our analysis. Cardiogenic shock (n = 25, 60.9%) was the primary indication for Impella®, followed by facilitating high-risk PCI (n = 15, 36.7%) and left ventricular afterload reduction in patients undergoing veno-arterial extracorporeal membrane oxygenation (n = 1, 2.4%). Our overall Impella® usage evolved over the years from a primary use to facilitate a high-risk PCI to the recent more common use of LV unloading in cardiogenic shock. No patients experienced device malfunction and the incidence of other complications including ischemic stroke and bleeding were comparable to those reported in the literature (12.2% and 24% respectively). The 30-day all-cause mortality of 41 patients was 53.6%. In line with the evolving recommendations and evidence, we observed an underutilization of non-heparin-based purge solutions and inconsistent management of anticoagulation in the setting of both Impella® and VA ECMO which necessitates more education and protocols.


Assuntos
Coração Auxiliar , Intervenção Coronária Percutânea , Humanos , Anticoagulantes/efeitos adversos , Coagulação Sanguínea , Coração Auxiliar/efeitos adversos , Estudos Retrospectivos , Choque Cardiogênico/terapia , Resultado do Tratamento
3.
Molecules ; 28(18)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37764362

RESUMO

A series of novel 3-cyanopyridone/pyrazoline hybrids (21-30) exhibiting dual inhibition against EGFR and BRAFV600E has been developed. The synthesized target compounds were tested in vitro against four cancer cell lines. Compounds 28 and 30 demonstrated remarkable antiproliferative activity, boasting GI50 values of 27 nM and 25 nM, respectively. These hybrids exhibited dual inhibitory effects on both EGFR and BRAFV600E pathways. Compounds 28 and 30, akin to Erlotinib, displayed promising anticancer potential. Compound 30 emerged as the most potent inhibitor against cancer cell proliferation and BRAFV600E. Notably, both compounds 28 and 30 induced apoptosis by elevating levels of caspase-3 and -8 and Bax, while downregulating the antiapoptotic Bcl2 protein. Molecular docking studies confirmed the potential of compounds 28 and 30 to act as dual EGFR/BRAFV600E inhibitors. Furthermore, in silico ADMET prediction indicated that most synthesized 3-cyanopyridone/pyrazoline hybrids exhibit low toxicity and minimal adverse effects.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Relação Estrutura-Atividade , Proteínas Proto-Oncogênicas B-raf , Simulação de Acoplamento Molecular , Antineoplásicos/farmacologia , Proliferação de Células , Receptores ErbB/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia
4.
Clin Rehabil ; 36(8): 1083-1096, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35369762

RESUMO

OBJECTIVE: To compare the effect of mechanical traction from different knee angles on pain, physical function, and range of motion in patients with knee osteoarthritis. DESIGN: A single-blinded, randomized controlled trial. SETTING: Outpatient public and governmental Hospital clinics. PARTICIPANTS: One hundred and twenty patients with knee osteoarthritis were randomly assigned into 4 equal groups with 30 patients in each group. INTERVENTIONS: Group (A) received conventional physiotherapy(CPT) treatment; group (B) received CPT with knee traction from full extension, group (C) received CPT with knee traction from 90° flexion, while group (D) received CPT with knee traction from 20° flexion. Interventions were applied 3 sessions a week for 4 weeks. OUTCOME MEASUREMENTS: Visual analog scale (VAS), knee passive range of motion and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were measured at baseline, immediately after 4 weeks of intervention, and after 4 weeks of no intervention as a follow-up. RESULTS: After eight weeks, the mean (SD) for VAS scores were 30.97 ± 8.68, 24.0 ± 8.8, 15.43 ± 6.31, and 16.17 ± 6.11 mm; for total WOMAC scores were 26.77 ± 9.19, 20.3 ± 8.52, 13.27 ± 6.25, and 13.43 ± 7.14 for groups A, B, C and D, respectively. The three traction groups showed statistically significant changes in pain scores, physical function, and total WOMAC, but not for knee passive range of motion, in favor of traction groups C and D than the conventional group (P < 0.05). CONCLUSIONS: Traction from 90°and 20° of knee flexion was found superior to full extension knee in improving pain and physical function, but not for knee passive range of motion, in patients with knee osteoarthritis.


Assuntos
Osteoartrite do Joelho , Humanos , Articulação do Joelho , Osteoartrite do Joelho/terapia , Dor , Amplitude de Movimento Articular , Tração , Resultado do Tratamento
5.
J Cell Mol Med ; 24(5): 2791-2801, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32030883

RESUMO

Pathogenic bacteria can enter into a viable but non-culturable (VBNC) state under unfavourable conditions. Proteus mirabilis is responsible for dire clinical consequences including septicaemia, urinary tract infections and pneumonia, but is not a species previously known to enter VBNC state. We suggested that stress-induced P. mirabilis can enter a VBNC state in which it retains virulence. P. mirabilis isolates were incubated in extreme osmotic pressure, starvation, low temperature and low pH to induce a VBNC state. Resuscitation was induced by temperature upshift and inoculation in tryptone soy broth with Tween 20 and brain heart infusion broth. Cellular ultrastructure and gene expression were examined using transmission electron microscopy (TEM) and quantitative real-time polymerase chain reaction (qPCR), respectively. High osmotic pressure and low acidity caused rapid entry into VBNC state. Temperature upshift caused the highest percentage of resuscitation (93%) under different induction conditions. In the VBNC state, cells showed aberrant and dwarf morphology, virulence genes and stress response genes (envZ and rpoS) were expressed (levels varied depending on strain and inducing factors). This is the first-time characterization of VBNC P. mirabilis. The ability of P. mirabilis pathogenic strains to enter a stress-induced VBNC state can be a serious public health threat.


Assuntos
Proteus mirabilis/fisiologia , Regulação Bacteriana da Expressão Gênica , Viabilidade Microbiana , Proteus mirabilis/genética , Proteus mirabilis/ultraestrutura , RNA Ribossômico 16S/genética , Transcrição Gênica
6.
Indian J Crit Care Med ; 23(10): 462-466, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31749555

RESUMO

Intensive care unit (ICU) healthcare professionals work under a stressful environment which can lead to burnout syndrome. We conducted this study to evaluate the prevalence of stress and burnout syndrome among doctors and other healthcare professionals in ICU. We also evaluated the individual contributing factors for stress and burnout syndrome among these ICU healthcare workers. The cross-sectional survey was conducted among the healthcare professionals (doctors, nurses, clinical pharmacists, respiratory therapists and physiotherapists) in the ICUs of multispecialty hospital in south India. The survey was conducted using well-accepted tools which included job satisfaction scale, perceived stress scale and Maslach burnout inventory-human service survey. Overall, 204 healthcare professionals completed the survey. The prevalence of high burnout in our study was 80% which included 6% (n = 12) of doctors and 69% (n = 140) of nurses. Our study showed statistically significant correlation between level of job satisfaction and the level of burnout. There was a significant correlation between the level of stress and the emotional exhaustion and depersonalization domains of Maslach burnout inventory. Critical care societies and institutional committees should step forward to draft policies and benchmarks to curb the causes of stress, reduce burnout and to increase the job satisfaction. HOW TO CITE THIS ARTICLE: Lakshmikanthcharan S, Sivakumar MN, Hisham M. Stress and Burnout among Intensive Care Unit Healthcare Professionals in an Indian Tertiary Care Hospital. Indian J Crit Care Med 2019;23(10):462-466.

7.
Indian J Crit Care Med ; 22(9): 680-682, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30294138

RESUMO

Almost one-third of the people suffering from epilepsy continue to have seizures in spite of using appropriate antiepileptics. Pharmacoresistance is defined as the failure to achieve seizure control with two or more anticonvulsant medications at appropriate daily dosage. Here, we discuss one such gentleman whose seizures had been intractable despite multiple antiepileptic drugs in maximum tolerable doses. Verapamil, a calcium channel blocker, was used for its P-glycoprotein inhibition properties to overcome the pharmacoresistance in this patient with satisfactory seizure control. There are a few studies with limited patients on the successful usage of verapamil in a patient with pharmacoresistant status epilepticus (SE). We intend to publish this case report to draw interest among the critical care physicians on pharmacoresistant SE, the different hypotheses that prevail, its causes and the available management strategies.

8.
Indian J Crit Care Med ; 21(3): 179-181, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28400693

RESUMO

A 52-year-old obese gentleman presented to the hospital with complaints of fever and shortness of breath for 10 days. He was admitted in the ward and treated for acute exacerbation of asthma. He was shifted to the Intensive Care Unit (ICU) for persistent fever, neck swelling, airway obstruction and desaturation. Ludwig's angina was suspected and computed tomography of neck confirmed it. A difficult airway was anticipated and preceded with surgical tracheostomy. The patient had hypersensitivity reactions to piperacillin/tazobactam; hence, he was treated with clindamycin and metronidazole. The patient improved and was discharged after five days of ICU stay and 12 days of hospitalization. This case summarizes the rare incidence of Ludwig's angina with antibiotic adverse reactions. If angioneurotic edema is coincidental with features of Ludwig's angina, it becomes more challenging. Early identification, securing the airway, and antibiotic administration are the keystone to better survival.

10.
Indian J Crit Care Med ; 20(2): 78-83, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27076707

RESUMO

BACKGROUND AND OBJECTIVES: A critically ill patient is treated and reviewed by physicians from different specialties; hence, polypharmacy is a very common. This study was conducted to assess the impact and effectiveness of having a clinical pharmacist in an Indian Intensive Care Unit (ICU). It also evaluates the clinical pharmacist interventions with a focus on optimizing the quality of pharmacotherapy and patient safety. MATERIALS AND METHODS: The prospective, observational study was carried out in medical and surgical/trauma ICU over a period of 1 year. All detected drug-related problems and interventions were categorized based on the Pharmaceutical Care Network Europe system. RESULTS: During the study period, average monthly census of 1032 patients got treated in the ICUs. A total of 986 pharmaceutical interventions due to drug-related problems were documented, whereof medication errors accounted for 42.6% (n = 420), drug of choice problem 15.4% (n = 152), drug-drug interactions were 15.1% (n = 149), Y-site drug incompatibility was 13.7% (n = 135), drug dosing problems were 4.8% (n = 47), drug duplications reported were 4.6% (n = 45), and adverse drug reactions documented were 3.8% (n = 38). Drug dosing adjustment done by the clinical pharmacist included 140 (11.9%) renal dose, 62 (5.2%) hepatic dose, 17 (1.4%) pediatric dose, and 104 (8.8%) insulin dosing modifications. A total of 577 drug and poison information queries were answered by the clinical pharmacist. CONCLUSION: Clinical pharmacist as a part of multidisciplinary team in our study was associated with a substantially lower rate of adverse drug event caused by medication errors, drug interactions, and drug incompatibilities.

11.
Arch Gynecol Obstet ; 290(5): 891-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24930117

RESUMO

PURPOSE: To estimate the incidence of emergency peripartum hysterectomy over 6 years in Ain-shams University Maternity Hospital. METHODS: Detailed chart review of all cases of emergency peripartum hysterectomy, 2003-2008, including previous obstetric history, details of the index pregnancy, indications for emergency peripartum hysterectomy, outcome of the hysterectomy and infant morbidity. RESULTS: The overall rate of emergency peripartum hysterectomy was 149 of 66,306 or 2.24 per 1,000 deliveries. The primary indications for hysterectomies were placenta accreta/increta 59 (39.6 %), uterine atony 37 (24.8 %), uterine rupture 35 (23.5 %) and placenta previa without accreta 18 (12.1 %). After hysterectomy, 115 (77 %) women were admitted to the intensive care unit. Women were discharged home after a mean 11.2 day length of stay. Using multifactorial logistic regression analysis, we found that woman's age, atonic uterus, placenta accreta/increta, previous cesarian section and ruptured uterus were independent predictors for peripartum hysterectomy CONCLUSION: Abnormal placentation was the main indication for peripartum hysterectomy. The risk factors for peripartum hysterectomy were morbid adherence of placentae in scared uteri, uterine atony and uterine rupture. The most important step in prevention of major postpartum hemorrhage is recognizing and assessing women's risk. The risk of peripartum hysterectomy seems to be significantly decreased by limiting the number of cesarean section deliveries, thus reducing the occurrence of abnormal placentation in the form of placenta accreta, increta or percreta.


Assuntos
Emergências/epidemiologia , Tratamento de Emergência/estatística & dados numéricos , Histerectomia/estatística & dados numéricos , Complicações do Trabalho de Parto/cirurgia , Período Periparto , Adulto , Cesárea/estatística & dados numéricos , Egito/epidemiologia , Feminino , Maternidades/estatística & dados numéricos , Hospitais Universitários , Humanos , Incidência , Tempo de Internação , Complicações do Trabalho de Parto/epidemiologia , Placenta Acreta/epidemiologia , Placenta Acreta/cirurgia , Placenta Prévia/epidemiologia , Placenta Prévia/cirurgia , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/cirurgia , Gravidez , Estudos Retrospectivos , Fatores de Risco , Inércia Uterina/epidemiologia , Inércia Uterina/cirurgia , Ruptura Uterina/cirurgia
12.
J Ethnopharmacol ; 327: 117970, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38428660

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Solenostemma argel is widely distributed in Africa & Asia with traditional usage in alleviating abdominal colic, aches, & cramps. This plant is rich in phytochemicals, which must be explored for its pharmacological effects. PURPOSE: Peptic Ulcer Disease (PUD) is the digestion of the digestive tube. PUD not only interferes with food digestion & nutrient absorption, damages one of the largest defensive barriers against pathogenic micro-organisms, but also impedes drug absorption & bioavailability, rendering the oral route, the most convenient way, ineffective. Omeprazole, one of the indispensable cost-effective proton-pump inhibitors (PPIs) extensively prescribed to control PUD, is showing growing apprehensions toward multiple drug interactions & side effects. Hence, finding a natural alternative with Omeprazole-like activity & limited side effects is a medical concern. STUDY DESIGN: Therefore, we present Stemmoside C as a new gastroprotective phytochemical agent isolated from Solenostemma argel to be tested in upgrading doses against ethanol-induced gastric ulcers in mice compared to negative, positive, & reference Omeprazole groups. METHODS: We carried out in-depth pharmacological & histopathological studies to determine the possible mechanistic pathway. RESULTS: Our results showed that Stemmoside C protected the stomach against ethanol-induced gastric ulcers parallel to Omeprazole. Furthermore, the mechanistic studies revealed that Stemmoside C produced its effect using an orchestrated array of different mechanisms. Stemmoside C stimulates stomach defense by increasing COX-2, PGE-2, NO, & TFF-1 healing factors, IL-10 anti-inflammatory cytokine, & Nrf-2 & HO-1 anti-oxidant pathways. It also suppresses stomach ulceration by inhibiting leucocyte recruitment, especially neutrophils, leading to subsequent inhibition of NF-κBp65, TNF-α, IL-1ß, & iNOS pro-inflammatory cytokines & JAK-1/STAT-3 inflammation-induced carcinogenicity cascade in addition to MMP-9 responsible for tissue degradation. CONCLUSION: These findings cast light on Stemmoside C's clinical application against gastric ulcer progression, recurrence, & tumorigenicity & concurrently with chemotherapy.


Assuntos
Antiulcerosos , Úlcera Gástrica , Camundongos , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/metabolismo , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Etanol/farmacologia , Citocinas/metabolismo , Mucosa Gástrica
13.
RSC Adv ; 14(26): 18296-18310, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38863821

RESUMO

Osteoarthritis (OA) is a degenerative joint disease, characterized by infiltration of monocytes into the synovial joint which promotes inflammation, stiffness, joint swelling, cartilage degradation and further bone destruction. The leaves of Ocimum forskolei have been used for inflammation-related disease management in traditional medicine. Additionally, the downregulation of NF-κB and the MMP/TIMP-1 ratio has been shown to protect against OA. The LC-HR-MS metabolic analysis of Ocimum yielded 19 putative compounds, among which ursolic acid (UA) was detected. Ursolic acid possesses significant anti-inflammatory effects and has been reported to downregulate oxidative stress and inflammatory biomarkers. It was tested on rats in a model of intra-articular carrageenan injection to investigate its efficacy on osteoarthritis progression. The UA emulgel exerted chondroprotective, analgesic and local anaesthetic efficacies confirmed via histopathological investigation and radiographical imaging. A network pharmacology followed by molecular docking highlighted TNF-α, TGF-ß and NF-κB as the top filtered genes. Quantitative real-time PCR analysis showed that UA significantly attenuated serum levels of TNF-α, IL-1ß, NF-κB, MMP-9/TIMP-1 and elevated levels of TGF-ß. Taken together, these results suggest that UA could serve as a functional food-derived phytochemical with a multi-targeted efficacy on progression of OA, regulating the immune and inflammatory responses, particularly, attenuating chondrocytes degeneration via suppression of NF-κB and MMP-9/TIMP-1. Accordingly, UA might be a promising alternative to conventional therapy for safe, easily applicable and effective management of OA.

14.
J Multidiscip Healthc ; 17: 1931-1941, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706507

RESUMO

Purpose: The main aim of the trial was to assess the effectiveness of inspiratory muscle training on respiratory muscle strength, functional capacity, fatigue, and stress in post-surgical breast cancer survivors. Methods: Forty-seven females who had undergone unilateral post-mastectomy were randomly assigned to an intervention group (IG; n = 24) and a control group (CG; n = 23). Both groups received aerobic exercise training. In addition, the intervention group received inspiratory muscle training 3 days a week for 8 weeks. Maximum inspiratory and expiratory pressure (Pimax) (Pemex), 6-minute walk test, Handgrip strength by hand-held dynamometer, Fatigue Assessment Scale (FAS), and Perceived Stress Scale pss 10 values were measured before the training and then at the eighth week for both groups. Results: No differences were detected between the groups in terms of sample and clinical characteristics 8 weeks post-intervention. In favor of the intervention group, a significant difference with medium to high effect size was found in terms of Pimax, Pemax, FAS, PS, and 6MWT (p < 0.05). However, there was no difference in terms of handgrip strength (p-value: 0.072), with a medium effect size (0.070). Regarding within-group comparisons, IG exhibited substantial differences in all outcome measures (p < 0.05) compared to CG, with the exception of PImax and 6MWT. Conclusion: In post-operative breast cancer survivors, respiratory muscle training combined with aerobic training increases respiratory muscle strength and functional ability while lowering stress and tiredness.

15.
Anticancer Agents Med Chem ; 23(17): 1932-1943, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497685

RESUMO

BACKGROUND: Quinazolinone scaffolds have drawn international attention due to their potent anticancer activity and therapeutic applications. Furthermore, Chalcone and Oxime are special chemical templates with a wide range of biological activities, including anti-cancer activity. As a result, the purpose of this research is to synthesize and develop a new series of 2-thioxo-3-substituted quinazolin-4-one/chalcone analogues and 2-thioxo-3-substituted quinazolin-4-one/oximes analogues in order to obtain a new cytotoxic agent that can target epidermal growth factor (EGFR) and/or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAFV600E) oncogene. OBJECTIVE: All synthesised compounds were tested for anticancer activity against four human cancer cell lines. The new hybrids' potential anti-cancer mechanism was evaluated using EGFR and BRAF enzymatic tests. The most active molecules within the target enzyme's active site were studied using molecular docking. Apoptosis and cell cycle analysis were also investigated. METHODS: The target compounds 7a-j (series I) are obtained in high yields by alkylation of 2-mercapto-3-ethyl-(3H)- quinazolin-4-one 3a with acylated chalcones 6a-j. Alkylation of compounds 3b-c with N-(4-acetylphenyl)-2- bromoacetamide 8, the corresponding ketones intermediates 9b-c was produced in high yields. Compounds 7a-j, 9b-c, and 10b-c were tested for their antiproliferative activity against four human cancer cell lines using the MTT assay and doxorubicin as a control drug. The EGFR and BRAF assay tests were used to assess the inhibitory potency against EGFR and BRAF. RESULTS: Compounds 7c, 7d, 7f and 10c exhibited high proliferative activity and inhibited EGFR, which could serve as a potential target for antiproliferative activity. The most active hybrid, 7c, primarily caused cell cycle arrest in G0/G1 phase and S phase as well as cell apoptosis. Finally, the most active hybrids were docked well to the EGFR active site. CONCLUSION: 2-thioxo-3-substituted quinazolin-4-one/chalcone derivatives have significant apoptotic and antiproliferative properties.


Assuntos
Antineoplásicos , Chalcona , Chalconas , Camundongos , Animais , Humanos , Chalcona/farmacologia , Relação Estrutura-Atividade , Fator de Crescimento Epidérmico/farmacologia , Proliferação de Células , Receptores ErbB , Chalconas/farmacologia , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas B-raf/metabolismo , Quinazolinonas , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Desenho de Fármacos
16.
Nat Prod Res ; 37(17): 2905-2910, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36305731

RESUMO

The main aim of our study is to investigate the anticancer potential of our cultivated entophytic fungal strains from Nigella sativa seeds. The strains were identified by sequencing of the partial 18S rRNA gene and the internal transcribed spacer (ITS) region as Aspergillus sp. (SA4), Penicillium sp. (SA5), and Fusarium sp. (SA6). We carried out metabolic profiling for three fungal strains to investigate their metabolites diversity. Profiling of the different extracts revealed their richness in diverse metabolites and consequently fourteen compounds (1-14) were annotated. In addition, the obtained extracts were examined against three cell lines HepG2, MCF-7 and Caco-2 showed activity with IC50 values in the range of 1.95-39.7 µg/mL. Finally, molecular docking study was performed showing questinol as the lowest glide binding score value (-5.925 kcal/mol) among all identified compounds. Our results showed Nigella sativa-associated endophytes as a promising source for further studies to look for anticancer secondary metabolites.

17.
Pharmaceuticals (Basel) ; 16(11)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-38004388

RESUMO

A novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAFV600E. These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds 8, 9, 18, and 19 inhibited cell proliferation significantly in the four cancer cells, with GI50 values ranging from 1.20 to 1.80 µM when compared to Doxorubicin (GI50 = 1.10 µM). Within this group of hybrids, compounds 18 and 19 exhibited substantial inhibition of EGFR and BRAFV600E. Molecular docking investigations provided confirmation that compounds 18 and 19 possess the capability to inhibit EGFR and BRAFV600E. Moreover, computational ADMET prediction indicated that most of the newly synthesized hybrids have low toxicity and minimal side effects.

18.
Nat Prod Res ; : 1-6, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37590004

RESUMO

Endophytic fungi are known to be a rich source for anti-infective drugs. In this study, Aptenia cordifolia associated endophytic fungi were explored for the first time. Seven isolates were identified morphologically followed by screening of these fungi by plug diffusion assay which revealed their potential activity against Staphylococcus aureus (ATCC 9144), Bacillus cereus (ATCC 14579), Serratia marcescens (ATCC 14756), Fusarium oxysporum (ATCC 48112), and Aspergillus flavus (ATCC 22546). Additionally, the crude ethyl acetate extract of the most potent three isolates in plug diffusion assay showed that Aspergillus sp. ACEFR2 was the most potent as anti-infective in disc diffusion assay; Accordingly, Aspergillus sp. ACEFR2 was investigated using phylogenetic analysis and LC-HR-ESI-MS. The phylogenetic analysis placed the strain into the Aspergillus section Niger close related to few species including A. niger. Whereas the metabolomic profiling revealed the presence of diverse pool of metabolites. Furthermore, in silico molecular docking study was carried out to predict which compounds most likely responsible for the anti-infective activity.

19.
Toxicol Ind Health ; 28(10): 901-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22080036

RESUMO

Noise exposure has been commonly regarded as the main hazard of occupational hearing loss. Recent studies indicate that several chemicals, including organic solvents have ototoxic effects. This study aimed at evaluating the hearing of workers exposed to both noise and a mixture of organic solvents at concentrations anticipated as safe. The study comprised three groups. The first one included 70 workers exposed to noise only, the second group consisted of 93 workers exposed to organic solvents and noise, and the control group included 59 individuals exposed to neither noise nor organic solvents. The three groups were matched for age, socioeconomic status, and smoking habit. The results of this study revealed that there was no statistically significant difference between the two exposed groups as regards the duration of exposure. There was a highly statistically significant difference between the two exposed groups as regards the different types of hearing loss (conductive deafness, sensory neural hearing loss, and mixed type) compared with the control one. Our study reported that sensory neural hearing loss occurred earlier in subjects with combined exposure to noise and solvents at a mean duration of exposure (16.38 ± 9.44 years) compared to (24.53 ± 9.59 years) the subjects with sole exposure to noise. The difference between the two groups was statistically significant regarding this type of hearing impairment (p < 0.05). There was a positive significant correlation between hearing impairment and duration of exposure in the two exposed groups. As regards the results of the environmental monitoring, both noise exposure levels (dB) and levels of different organic solvents measured (mg/m(3)) in different work departments were less than the levels recommended by Egyptian Environmental Law No. 4 for 1994. It is recommended that in the case of combined exposure, noise and solvent levels should be lowered than the permissible limits recommended for either alone.


Assuntos
Perda Auditiva/etiologia , Ruído Ocupacional/efeitos adversos , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Compostos Orgânicos/intoxicação , Adulto , Análise de Variância , Estudos de Casos e Controles , Perda Auditiva/induzido quimicamente , Humanos , Indústrias , Pessoa de Meia-Idade , Doenças Profissionais/induzido quimicamente , Estudos Retrospectivos , Solventes/intoxicação , Inquéritos e Questionários
20.
Obes Surg ; 32(8): 2753-2763, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35654929

RESUMO

In 2016, the Enhanced Recovery After Bariatric Surgery guidelines (G16) was published, and in 2022, an update to it was released (G22). Grading of recommendations, assessment, development, and evaluations (GRADE), emphasizing the level of evidence (LoE) of both the guidelines, was performed. An overview of methodology was also performed, considering the following questions: how can research be improved, what can be done in the future using data, and how to collaborate more? Both guidelines did not explain how the LoE conclusions were derived regarding the risk of bias. There is also potential for forming a global consortium that deals with bariatric research, which can serve as a repository for all relevant data. Ensuring that this data is FAIR (findability, accessibility, interoperability, reusability) compliant and using this data to formulate future guidelines will benefit clinicians and patients alike.


Assuntos
Cirurgia Bariátrica , Recuperação Pós-Cirúrgica Melhorada , Laparoscopia , Obesidade Mórbida , Cirurgia Bariátrica/métodos , Humanos , Laparoscopia/métodos , Tempo de Internação , Obesidade Mórbida/cirurgia
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