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1.
Artigo em Inglês | MEDLINE | ID: mdl-37816254

RESUMO

Objective: To assess the prevalence of psychiatric comorbidities in patients with neurofibromatosis.Methods: In this cross-sectional study, we used the 2010-2014 National Inpatient Sample database. Patients ≥ 18 years of age with a primary or secondary diagnosis of neurofibromatosis and psychiatric comorbidities were queried.Results: A total of 43,270 patients with a mean age of 48.7 years (female: 55.7%, White: 70.1%) were included in the study. Overall, psychiatric comorbidities were present in 46.5% of patients; mood disorders (22.1%) and anxiety disorders (12.2%) were the most prevalent comorbidities. Although previous studies report prevalence rates of attention-deficit/hyperactivity disorder in up to 50% of patients with neurofibromatosis, our study found that the rate was much lower at 1.10%. Female sex and non-White race were less associated with psychiatric comorbidities (odds ratio = 0.868 [P = .003] and 0.689 [P < .001], respectively). The moderate-to-extreme loss of function illness severity category was associated with 1.35-times higher odds of having psychiatric comorbidities compared to mild-to-moderate or no loss of function (P < .001). The total length of stay was similar in patients with and without psychiatric comorbidities (mean = 4.98 [95% CI, 4.72-5.24] vs mean = 4.83 [95% CI, 4.60-5.07], respectively; P = .34).Conclusions: In adult patients with neurofibromatosis, 46.5% were found to have at least one psychiatric comorbid diagnosis. The most frequent psychiatric comorbid disorders were mood disorders and anxiety disorders. Female sex and non-White race predicted a lower likelihood of having a psychiatric disorder.Prim Care Companion CNS Disord 2023;25(5):23m03514. Author affiliations are listed at the end of this article.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Neurofibromatoses , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Prevalência , Estudos Transversais , Comorbidade , Transtornos do Humor/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Neurofibromatoses/epidemiologia
2.
Cureus ; 15(9): e45907, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37885564

RESUMO

Graves' disease is a self-limiting autoimmune thyroid disorder caused by stimulating antibodies to the thyroid-stimulating hormone receptor. It usually affects middle-aged females in the fourth to sixth decade of life. It is distinguished by keratopathy, chemosis, proptosis, and eyelid swelling, in addition to ocular discomfort. A total of 3-5% of cases present with a severe form of Graves' orbitopathy, which manifests with diminution of vision, optic nerve compression, optic neuropathy, and exposure keratopathy. We describe a case of a 34-year-old female patient who presented with the chief complaint of rapid deterioration of vision over a period of three months in the right eye. Ocular examination revealed proptosis, widened palpebral aperture, elevation of intra-ocular pressure (IOP) in the upgaze, restricted eye movements, and signs of optic nerve compression. Findings were confirmed on a CT scan of the orbit. The unusual presentation in this case was that she had rapid, significant deterioration of vision in the right eye, with a progression of proptosis more marked in the contralateral eye. This underlies the importance of thoroughly examining for any possible orbital apex syndrome in both eyes, not just the eye with marked proptosis. The patient, being reluctant for orbital decompression, was prescribed IV methylprednisolone 1 g for three consecutive days, which reduced her proptosis and improved her vision. This acted as a temporary measure to increase the duration of the surgical window until the time the patient undergoes the surgery.

3.
Sci Rep ; 13(1): 15806, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37737272

RESUMO

Smoking has been associated with an increased risk of asthma, lung cancer, cardiovascular diseases, chronic bronchitis, and a massive amount of oxidative stress. The present study was undertaken to determine the modulatory effects of Holi Basil/Tulsi, (Ocimum sanctum) leaf extract on cigarette smoke-induced pulmonary damage in mice. Cigarette smoke (CS) inhalation increased the levels of pulmonary lipid peroxidation, and reactive oxygen species and decreased the levels of glutathione. Histoarchitectural alterations and enhanced tissue lactate dehydrogenase (LDH) activity in pulmonary tissue was distinctly indicative of damage. Enhanced mucin production was also observed through mucicarmine and Alcian Blue-Periodic Acid Schiff (PAS) staining. Increased expression of MUC5AC was also observed. Alterations in the lung were also evident through FTIR studies. Administration of Ocimum sanctum leaf extract (80 mg/kg b.w) to CS exposed mice ameliorated these alterations to a greater extent. These findings are suggestive of the fact that Ocimum sanctum leaf extract effectively modulated CS-induced deleterious effects on pulmonary tissue.


Assuntos
Fumar Cigarros , Lesão por Inalação de Fumaça , Animais , Camundongos , Roedores , Ocimum sanctum , Pulmão
4.
J Pharm Bioallied Sci ; 15(Suppl 2): S1097-S1100, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37693981

RESUMO

Aim: Metabolic syndrome (MS) itself has become a new entity being a constellation of physiological, biochemical, metabolic, and clinical factors that have been related to an increased risk of cardiovascular diseases, type 2 diabetes mellitus (T2DM), and morbidity and mortality. The burden of MS is increasing all over the world with the current prevalence being 30%. The QT interval and QT dispersion (QTd) have been long associated with ventricular arrhythmia and sudden cardiac deaths. The association between QT and diabetes and healthy subjects has been clearly studied, but the association between QT and uncomplicated MS has not been very well defined. Methods: A total of 400 patients visiting the medicine clinics were assessed for blood pressure, anthropometric measurements, fasting serum lipid profile, FBS, and electrocardiogram (ECG). The patients diagnosed with uncomplicated MS as per the International Diabetic Federation (IDF) criteria were included in the study. QT interval in the ECG was recorded, and the relationship between various parameters of an uncomplicated MetS and the QT interval was recorded. Results: Our study revealed more females with uncomplicated MS as compared to males and increasing burden as age progressed. Body mass index (BMI), waist circumference (WC), hip circumference (HC), WHP, systolic blood pressure (SBP), Diastolic blood pressure (DBP), Fasting blood sugar (FBS), serum cholesterol, triglyceride (TG), and low-density lipoprotein (LDL) levels were positively correlated with QT values. Conclusion: QT interval, a strong predictor of malignant ventricular arrhythmias and sudden cardiac deaths, is associated with uncomplicated MS.

5.
Br Ir Orthopt J ; 19(1): 26-34, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063611

RESUMO

Purpose: To conduct a costing study comparing orthoptist-led with consultant-led clinics screening for optic pathway gliomas (OPGs) in children with neurofibromatosis Type 1 (NF1) attending the Royal Children's Hospital (RCH), Melbourne. Methods: Patients with NF1 examined in the orthoptist-led NF1 screening clinic and/or consultant-led clinics during the study period were identified. The workflow management software Q-Flow 6® provided data documenting patient's time spent with the orthoptist, nurse, and ophthalmologist. Time points were converted into minutes and multiplied by the cost-per-minute for each profession. A bottom-up micro-costing approach was used to estimate appointment level costs. Bootstrap simulations with 1000 replications were used to estimate 95% confidence intervals (CIs) for the difference in mean appointment time and cost between clinics. Results: Data for 130 consultant-led clinic appointments and 234 orthoptist-led clinic appointments were extracted for analysis. The mean time per appointment for the consultant-led clinic was 45.11 minutes, and the mean time per appointment for the orthoptist-led clinic was 25.85 minutes. The mean cost per appointment for the consultant-led clinic was A $84.15 (GBP £39.60) compared to the orthoptist-led clinic at A $20.40 (GBP £9.60). This represents a mean reduction of 19.25 minutes per appointment (95% CI, -24.85 to -13.66) and a mean reduction of A $63.75 (GBP £30.00) per appointment (95% CI, (A $-75.40 to $-52.10 [GBP £ -35.48 to £ -24.52]). Conclusion: An orthoptist-led clinic screening for OPGs in patients with NF1 can be a more cost-efficient model of care for ophthalmic screening in this patient group.

6.
Curr Top Med Chem ; 23(5): 334-348, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36476430

RESUMO

BACKGROUND: Colebrookea oppositifolia Smith. is a valuable traditional therapeutic plant belonging to the family Lamiaceae. It is a dense and wool-like shrub that is mostly found in subtropical regions of some countries of Asia, such as China and India. It has been widely used for the mitigation of nervous system disorders like epilepsy. The active constituents of the plant have exhibited antioxidant, anti-microbial, and antifungal properties, which are considered due to the presence of polyphenols and flavonoids as chief chemical constituents. Flavonoids like quercetin, landenein, chrysin, and 5, 6, 7-trimethoxy flavones cause protein denaturation of the microbial cell wall. OBJECTIVES: To comprehend and assemble the fragmented pieces of evidence presented on the traditional uses, botany, phytochemistry, and pharmacology of the plant to reconnoiter its therapeutic perspective and forthcoming research opportunities. METHODS: The available information on Colebrookea oppositifolia has been established by electronically searching peer-reviewed literature from PubMed, Google Scholar, Springer, Scopus, Web of Science, and Science Direct over the earlier few years. RESULTS: The plant has been greatly used for the preparation of many herbal medicines which are used for treating traumatic injuries, fever, rheumatoid arthritis, headache, and gastric problems. From the aerial parts of the plant, a phenylethanoid glycoside named acteoside has been isolated and evaluated for its therapeutic potential viz. immunomodulatory, neuroprotective, hepatoprotective, analgesic, anti-tumour, antispasmodic, antioxidant, antibacterial, free radical scavenger, and improving sexual function. Acteoside showed neuroprotective activities against Aß-peptide, which is neurotoxic and causes apoptosis. The petroleum ether extract of the plant leaves offers many active compounds like sitosterol, n-triacontane, hydroxydotriacontyl ferulate, acetyl alcohol, and 3,7,4,2-tetramethoxyflavones which have shown hepatoprotective potential. CONCLUSION: The plant should be evaluated further for the estimation of some other health benefits. The consequences of restricted pharmacological screening and reported phytomolecules of Colebrookea oppositifolia Smith. advocate that there is still an exigent requisite for in-depth pharmacological studies of the plant.


Assuntos
Flavonas , Lamiaceae , Plantas Medicinais , Animais , Antioxidantes/farmacologia , Extratos Vegetais/química , Fenóis , Lamiaceae/química , Etnofarmacologia , Compostos Fitoquímicos/farmacologia , Fitoterapia
7.
Heliyon ; 8(11): e11636, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36419664

RESUMO

Banana is an important food crop responsible for ensuring food security, nutrition, and employment for a significant portion of the world population. It has fairly broad genetic diversity and is distributed widely across the globe. Due to its socio-economic importance, there has been growing demand for healthy and improved planting materials of banana. In recent years many companies and organizations are working hard to narrow down the gap between demand and supply of quality planting materials. The other challenges includes its susceptibility to adverse environmental conditions, attack of various pests/pathogens and improvement of nutritional quality of bananas. To address these issues, refinement of existing techniques and introduction of new experimental tools are required. However, the genetic improvement of bananas to a large extent is limited by using conventional methods due to polyploidy, heterozygosity, and sterility of this plant. For rapid multiplication and obtaining disease free and healthy plants, efficient in vitro propagation techniques and fine tuning of the existing protocols are being tried in many laboratories across the globe. Besides, for developing a successful protocol for propagation of different cultivars of bananas, a deeper understanding of the factors associated with various steps of its multiplication till transfer to the land is immensely critical. Similarly, developing biotic and abiotic stress tolerant banana and enhancing its commercial value through biotechnological interventions could be very useful. The key intent of this review is to highlight the research endeavor in this direction, associated challenges and future prospects.

8.
J Family Med Prim Care ; 11(6): 3304-3307, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36119190

RESUMO

Degenerative changes in lumbosacral spine or disc bulges impinging on the thecal sac are the usual causes of sciatica. However peripheral compression of sciatic nerve in pelvis or lower limb presenting as sciatica is an uncommon entity. The sciatic hernia is a rare type of hernia. Due to the deep location of this pathology, the clinical examination would add little and imaging plays a pivotal role in diagnosis. We present a case of sciatica diagnosed with giant gluteal lipoma presenting as sciatic notch hernia and compressing sciatic nerve in the greater sciatic notch. Less than 100 cases are reported in the literature so far. The possibility of this rare diagnosis should be kept in mind by family physicians while evaluating patients of sciatica with no significant imaging findings in lumbosacral spine.

9.
AAPS PharmSciTech ; 23(6): 209, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902454

RESUMO

The present study is focused on the use of solid dispersion technology to triumph over the solubility-related problems of bexarotene which is currently used for treating various types of cancer and has shown potential inhibitory action on COVID-19 main protease and human ACE2 receptors. It is based on comparison of green locust bean gum and synthetic poloxamer as polymers using extensive mechanistic methods to explore the mechanism behind solubility enhancement and to find suitable concentration of drug to polymer ratio to prepare porous 3rd generation solid dispersion. The prepared solid dispersions were characterized using different studies like X-ray diffraction (XRD), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), differential scanning calorimetry (DSC), and particle size analysis in order to determine the exact changes occurred in the product which are responsible for enhancing solubility profiles of an insoluble drug. The results showed different profiles for particle size, solubility, dissolution rate, porosity, BET, and Langmuir specific surface area of prepared solid dispersions by using different polymers. In addition to the comparison of polymers, the BET analysis deeply explored the changes occurred in all dispersions when the concentration of polymer was increased. The optimized solid dispersion prepared with MLBG using lyophilization technique showed reduced particle size of 745.7±4.4 nm, utmost solubility of 63.97%, pore size of 211.597 Å, BET and Langmuir specific surface area of 5.6413 m2/g and 8.2757 m2/g, respectively.


Assuntos
COVID-19 , Química Farmacêutica , Adsorção , Varredura Diferencial de Calorimetria , Química Farmacêutica/métodos , Humanos , Microscopia Eletrônica de Varredura , Polímeros/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
10.
South Asian J Cancer ; 11(1): 19-23, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35833045

RESUMO

Prathepa JagdishBackground Hand-foot syndrome (HFS) can result in significant deficits in health-related quality of life (HRQOL) and can lead to poor compliance, dose reduction, or interruption. This study was performed to assess the HRQOL with HFS on physical, psychological, social, and sexual aspects of patients receiving capecitabine-based chemotherapy with gastrointestinal cancer along with validating and assessing the reliability score of the questionnaire. Patients and Methods HFS-related QOL (HF-QOL) questionnaire was developed and validated in a sample of 30 patients randomly selected for this pilot study. The internal consistency of the tool was tested by calculating the Cronbach's α coefficient, while content and construct validity were assessed by Pearson's correlation. Statistical analyses were performed using SPSS version 25.0. Results Out of 30, 22 (73%) patients were males, mean age was 44 ± 13 years; 21 (70%) patients had grade 1 HFS, while 6 (20%) and 3 (10%) patients had grades 2 and 3 HFS, respectively. Cronbach's α coefficient was high for physical (0.79) and sexual scales (0.79), while it was moderately low for psychological (0.65) and social (0.53) domains. The average HF-QOL scores were 70.6 ± 13.2 in physical domain and 71.3 ± 23.7 in sexual domain indicating poor quality of life (QOL), while it was 50.9 ± 9.9 in social domain indicating moderately worse QOL. Grades 2 and 3 of HFS were found to have statistical significance on physical (0.0001), psychological (0.05), and social (0.02) domains, whereas sexual domain did not have any statistical significance (0.594). Conclusion This pilot study showed the feasibility of use and validity of a new patient-reported instrument, the HF-QOL, which measures the effect of HFS on daily activities (physical, psychological, social, and sexual domains) after capecitabine-based chemotherapy.

11.
Int J Mol Sci ; 23(4)2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35216106

RESUMO

Antimicrobial resistance (AMR) is a global health challenge with methicillin resistant Staphylococcus aureus (MRSA), a leading cause of nosocomial infection. In the search for novel antibiotics, marine sponges have become model organisms as they produce diverse bioactive compounds. We investigated and compared the antibacterial potential of 3 bis-indole alkaloids-bromodeoxytopsentin, bromotopsentin and spongotine A-isolated from the Northeastern Atlantic sponge Spongosorites calcicola. Antimicrobial activity was determined by MIC and time-kill assays. The mechanism of action of bis-indoles was assessed using bacterial cytological profiling via fluorescence microscopy. Finally, we investigated the ability of bis-indole alkaloids to decrease the cytotoxicity of pathogens upon co-incubation with HeLa cells through the measurement of mammalian cell lysis. The bis-indoles were bactericidal to clinically relevant Gram-positive pathogens including MRSA and to the Gram-negative gastroenteric pathogen Vibrio parahaemolyticus. Furthermore, the alkaloids were synergistic in combination with conventional antibiotics. Antimicrobial activity of the bis-indole alkaloids was due to rapid disruption and permeabilization of the bacterial cell membrane. Significantly, the bis-indoles reduced pathogen cytotoxicity toward mammalian cells, indicating their ability to prevent bacterial virulence. In conclusion, sponge bis-indole alkaloids are membrane-permeabilizing agents that represent good antibiotic candidates because of their potency against Gram-positive and Gram-negative bacterial pathogens.


Assuntos
Membrana Celular/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Poríferos/química , Animais , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Células HeLa , Humanos , Testes de Sensibilidade Microbiana/métodos
12.
J Vis Exp ; (173)2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34369924

RESUMO

Osteoarthritis (OA) is a chronic and degenerative joint disease most often affecting the knee. As there is currently no cure, total knee arthroplasty (TKA) is a common surgical intervention. Experiments using primary human OA tissues obtained from TKA provide the capability to investigate disease mechanisms ex vivo. While OA was previously thought to impact mainly the cartilage, it is now known to impact multiple tissues in the joint. This protocol describes patient selection, sample processing, tissue homogenization, RNA extraction, and quality control (based on RNA purity, integrity, and yield) from each of seven unique tissues to support disease mechanism investigation in the knee joint. With informed consent, samples were obtained from patients undergoing TKA for OA. Tissues were dissected, washed, and stored within 4 h of surgery by flash freezing for RNA or formalin fixation for histology. Collected tissues included articular cartilage, subchondral bone, meniscus, infrapatellar fat pad, anterior cruciate ligament, synovium, and vastus medialis oblique muscle. RNA extraction protocols were tested for each tissue type. The most significant modification involved the method of disintegration used for low-cell, high-matrix, hard tissues (considered as cartilage, bone, and meniscus) versus relatively high-cell, low-matrix, soft tissues (considered as fat pad, ligament, synovium, and muscle). It was found that pulverization was appropriate for hard tissues, and homogenization was appropriate for soft tissues. A proclivity for some subjects to yield higher RNA integrity number (RIN) values than other subjects consistently across multiple tissues was observed, suggesting that underlying factors such as disease severity may impact RNA quality. The ability to isolate high-quality RNA from primary human OA tissues provides a physiologically relevant model for sophisticated gene expression experiments, including sequencing, that can lead to clinical insights that are more readily translated to patients.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Osteoartrite , Ligamento Cruzado Anterior , Cartilagem Articular/cirurgia , Humanos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/cirurgia , RNA/genética
13.
Appl Biochem Biotechnol ; 193(11): 3570-3585, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34313919

RESUMO

The current study was conducted to evaluate the antiproliferative and oxidative damage protection potential of endophytic fungi Aspergillus fumigatus and Chaetomium globosum isolated from Moringa oleifera. The chloroformic extract (CE) of both the fungi showed dose dependent antiproliferative activity against human prostate adenocarcinoma (PC-3) cell line with (IC50) value of 0.055 mg/ml and 0.008 mg/ml, respectively. Further, CE of both the fungi was studied for their ability to induce apoptosis in PC-3 cell line. Various deformities in the cancerous cells treated with CE of both the fungi have been observed by confocal microscopy which indicates the cell death by apoptosis. Further apoptosis inducing ability of CE of both the fungi was observed using various flow cytometric studies. The chloroformic extract of both the fungi showed slight increase in the level of reactive oxygen species to induce apoptosis. It also showed arrest of cancerous cells at G0/G1 phase of cell cycle to induce apoptosis. The externalization of phosphatidylserine (PS) to induce apoptosis was also observed when analysed using Annexin V-FITC/PI double staining assay where the CE of A. fumigatus and C. globosum showed the total apoptosis of 94.2% and 90.3%, respectively, at the highest tested concentration of GI70. The CE of both the fungi further showed the protective behaviour for plasmid DNA pBR322, when tested for their effect against the oxidative stress caused by the Fenton's reagent. Thus, the studies demonstrated a good antiproliferative and oxidative damage protection potential of the endophytic fungi.


Assuntos
Antioxidantes , Aspergillus fumigatus/química , Proliferação de Células/efeitos dos fármacos , Chaetomium/química , Misturas Complexas , Endófitos/química , Moringa oleifera/microbiologia , Neoplasias da Próstata , Antioxidantes/química , Antioxidantes/farmacologia , Misturas Complexas/química , Misturas Complexas/farmacologia , Humanos , Masculino , Células PC-3 , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo
14.
Stem Cell Res Ther ; 12(1): 165, 2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676544

RESUMO

BACKGROUND: Growing evidence suggests that the pluripotent state of mesenchymal stem cells (MSCs) relies on specific local microenvironmental cues such as adhesion molecules and growth factors. Fibronectin (FN), fibroblast growth factor 2 (FGF2), and bone morphogenetic protein 4 (BMP4) are the key players in the regulation of stemness and lineage commitment of MSCs. Therefore, this study was designed to investigate the pluripotency and multilineage differentiation of bone marrow-derived MSCs (BMSCs) with the introduction of FN, FGF-2, and BMP4 and to identify the metabolic and proteomic cues involved in stemness maintenance. METHODS: To elucidate the stemness of BMSCs when treated with FN, FGF-2, and BMP4, the pluripotency markers of OCT4, SOX2, and c-MYC in BMSCs were monitored by real-time PCR and/or western blot. The nuclear translocation of OCT4, SOX2, and c-MYC was investigated by immunofluorescence staining. Multilineage differentiation of the treated BMSCs was determined by relevant differentiation markers. To identify the molecular signatures of BMSC stemness, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and bioinformatics analysis were utilized to determine the metabolite and protein profiles associated with stem cell maintenance. RESULTS: Our results demonstrated that the expression of stemness markers decreased with BMSC passaging, and the manipulation of the microenvironment with fibronectin and growth factors (FGF2 and BMP4) can significantly improve BMSC stemness. Of note, we revealed 7 differentially expressed metabolites, the target genes of these metabolites may have important implications in the maintenance of BMSCs through their effects on metabolic activity, energy production, and potentially protein production. We also identified 21 differentially abundant proteins, which involved in multiple pathways, including metabolic, autophagy-related, and signaling pathways regulating the pluripotency of stem cells. Additionally, bioinformatics analysis comfirned the correlation between metabolic and proteomic profiling, suggesting that the importance of metabolism and proteome networks and their reciprocal communication in the preservation of stemness. CONCLUSIONS: These results indicate that the culture environment supplemented with the culture cocktail (FN, FGF2, and BMP4) plays an essential role in shaping the pluripotent state of BMSCs. Both the metabolism and proteome networks are involved in this process and the modulation of cell-fate decision making. All these findings may contribute to the application of MSCs for regenerative medicine.


Assuntos
Fator 2 de Crescimento de Fibroblastos , Fibronectinas , Células da Medula Óssea , Proteína Morfogenética Óssea 4 , Diferenciação Celular , Células Cultivadas , Cromatografia Líquida , Sinais (Psicologia) , Fator 2 de Crescimento de Fibroblastos/genética , Fibronectinas/genética , Proteômica , Espectrometria de Massas em Tandem
15.
Eur J Med Chem ; 215: 113169, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33588178

RESUMO

The study focuses on the prudent design and synthesis of anilide type class I HDAC inhibitors employing a functionalized pyrrolo[2,3-d]pyrimidine skeleton as the surface recognition part. Utilization of the bicyclic aromatic ring to fabricate the target compounds was envisioned to confer rigidity to the chemical architecture of MS-275 and chidamide. In-vitro enzymatic and cellular assays led to the identification of compound 7 as a potent inhibitor of HDAC1 and 2 isoform that exerted substantial cell growth inhibitory effects against human breast MDA-MB-231, cervical HeLa, breast MDA-MB-468, colorectal DLD1, and colorectal HCT116 cell lines with an IC50 values of 0.05-0.47 µM, better than MS-275 and chidamide. In addition, the anilide 7 was also endowed with a superior antiproliferative profile than MS275 and chidamide towards the human cutaneous T cell lymphoma (HH and HuT78), leukemia (HL60 and KG-1), and HDACi sensitive/resistant gastric cell lines (YCC11 and YCC3/7). Exhaustive exploration of the construct 7 confirmed it to be a microtubule-targeting agent that could trigger the cell-cycle arrest in mitosis. In pursuit of extracting the benefits of evidenced microtubule-destabilizing activity of the anilide 7, it was further evaluated against non-small-cell lung cancer cell lines as well as the multiple-drug resistant uterine cancer cell line (MES-SA/Dx5) and overwhelmingly positive results in context of inhibitory effects were attained. Furthermore, molecular modelling studies were performed and some key interactions of the anilide 7 with the amino acid residues of the active site of HDAC1 isoform and tubulin were figured out.


Assuntos
Anilidas/farmacologia , Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Moduladores de Tubulina/farmacologia , Aminopiridinas/química , Anilidas/síntese química , Anilidas/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Benzamidas/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Histona Desacetilase 1/metabolismo , Histona Desacetilase 2/metabolismo , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/metabolismo , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Piridinas/química , Pirimidinas/síntese química , Pirimidinas/metabolismo , Pirróis/síntese química , Pirróis/metabolismo , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/metabolismo
16.
Anesth Essays Res ; 15(2): 233-238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35281356

RESUMO

Background: The incidence of postoperative recall under total intravenous anesthesia (TIVA) is not yet fully established. Avoidance of inhalational agent is a known risk factor for awareness. In addition, lack of reliable technique to monitor drug concentration needed for adequate depth of anesthesia makes TIVA challenging. Hence, we intend to evaluate our standard anesthesia practice for postoperative recall. Methodology: This questionnaire-based observational study was done over the period of 2 years. We enrolled 1080 adult (American Society of Anesthesiologists physical status Class I or II) patients undergoing TIVA for Endoscopic retrograde cholangiopancreatography (ERCP). All patients received fentanyl, midazolam and propofol-based anesthesia. Manual boluses of propofol were given to achieve adequate sedation. (Ramsay sedation scale of 5) in accordance with clinical signs as judged by the primary anesthesiologist. Postoperatively within 12-24 h, patients were assessed for recall using Brice questionnaire. Primary outcome was number of patients reporting postoperative recall in the Brice interview. Secondary outcome was the incidence of dreaming. Results: On postoperative interview, none of the patients reported awareness. 12.5% of patients had dreams which were pleasant. None of the dreams was unpleasant. The worst thing about surgery was pain. Conclusion: Our study suggests that if adequate doses of propofol are adhered to and necessary action is taken against responses indicating wakefulness, postoperative recall under TIVA is an uncommon occurrence.

17.
Nutr Cancer ; 73(7): 1168-1174, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32643413

RESUMO

Colon cancer risk appears to be lowered by consumption of a diet rich in fruits and vegetables. Chokeberries are rich in phytochemicals that may act as potent anticancer agents. Phytochemicals that are particularly abundant in chokeberries include anthocyanins and phenolic acids. In this study, we compared the growth inhibitory activity of three chokeberry extracts in HT-29 human colon cancer cells. The three extracts tested were derived from Aronia arbutifolia (red), Aronia prunifolia (purple), and Aronia melanocarpa (black). Cells were incubated with either red, purple, or black chokeberry extracts and cell viability was quantified using the thiazolyl blue tetrazolium bromide (MTT) assay. The black chokeberry extract had the greatest effect in reducing cell proliferation. The extracts were also characterized for total phenols (Folin-Ciocalteu assay), total antioxidant activity (oxygen radical absorbance capacity assay), and levels of bioactive phenolic acids (high-performance liquid chromatography). The growth inhibitory activities of the extracts correlated well with total phenolic content, antioxidant activity, and levels of caffeic and chlorogenic acids. The black chokeberry extract had the greatest level of total phenols, antioxidant activity, and individual phenolic acids. This research suggests that the phenolic profile of foods such as chokeberries can help determine their cancer cell growth inhibitory activity.


Assuntos
Antocianinas , Photinia , Antocianinas/farmacologia , Antioxidantes/farmacologia , Humanos , Fenóis/farmacologia , Extratos Vegetais/farmacologia
18.
Health Psychol Rev ; 15(3): 395-429, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32449477

RESUMO

Tens-of-millions of women every year test positive for human papillomavirus (HPV) at routine cervical screening. We performed a mixed-methods systematic review using a results-based convergent design to provide the first comprehensive overview of emotional response to testing positive for HPV (HPV+). We mapped our findings using the cognitive behavioural framework. Six electronic databases were searched from inception to 09-Nov-2019 and 33 papers were included. Random-effects meta-analyses revealed that HPV+ women with abnormal or normal cytology displayed higher short-term anxiety than those with normal results (MD on State-Trait Anxiety Inventory = 7.6, 95% CI: 4.59-10.60 and MD = 6.33, CI: 1.31-11.35, respectively); there were no long-term differences. Psychological distress (general/sexual/test-specific) was higher in HPV+ women with abnormal cytology in the short-term and long-term (SMD = 0.68, CI: 0.32-1.03 and SMD = 0.42, CI: 0.05-0.80, respectively). Testing HPV+ was also related to disgust/shame, surprise and fear about cancer. Broadly, adverse response related to eight cognitive constructs (low control, confusion, cancer-related concerns, relationship concerns, sexual concerns, uncertainty, stigma, low trust) and six behavioural constructs (relationship problems, social impact, non-disclosure of results, idiosyncratic prevention, indirect clinical interaction, changes to sexual practice). Almost exclusive use of observational and qualitative designs limited inferences of causality and conclusions regarding clinical significance.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Detecção Precoce de Câncer/psicologia , Emoções , Feminino , Humanos , Programas de Rastreamento/psicologia , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle
19.
Sci Rep ; 10(1): 18792, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139805

RESUMO

The recent exploration of various medicinal plants for bioactive potential has led to the growing interest to explore their endophytes for such bioactive potential which may turn out to be better option than the plants. In the present study, Chaetomium globosum, an endophytic fungus isolated from Moringa oleifera Lam has been explored for its various biological activities. The chloroformic extract of C. globosum showed good antimutagenicity against the reactive carcinogenic mutagen, 2-aminofluorene (2-AF) in Ames test. The antiproliferative activity against various cell lines such as HCT-15, HeLa and U87-MG was found to be dose dependent and the viability reduced to 9.26%, 15.7% and 16.3%, respectively. Further, the chloroformic fungal extract was investigated for free radical scavenging activity using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethyl-benzthiazolin-6-sulfonic acid) assay which showed the IC50 value of 45.16 µg/ml and 50.55 µg/ml, respectively. The fungal extract also showed good ferric reducing power. Total phenolic and flavonoid content was found to be in linear relationship with the antioxidant potential of the fungal extract. High performance liquid chromatography showed the presence of phenolics which may help to combat the free radicals. The presence of various bioactive compounds was analysed by GC-MS which endorsed Chaetomium globosum to be a promising candidate for drug development.


Assuntos
Antimutagênicos , Extratos Celulares/farmacologia , Chaetomium , Endófitos , Moringa oleifera/microbiologia , Antioxidantes , Extratos Celulares/análise , Extratos Celulares/isolamento & purificação , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Chaetomium/química , Relação Dose-Resposta a Droga , Desenvolvimento de Medicamentos , Flavonoides/análise , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Fenóis/análise , Fenóis/isolamento & purificação , Fenóis/farmacologia
20.
Mol Biol Rep ; 47(4): 2901-2911, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32239464

RESUMO

An endophytic fungus Aspergillus fumigatus isolated from Moringa oleifera has been evaluated for its various bioactivities. The chloroformic fungal extract exhibited a good antimicrobial as well as antibiofilm activity against various pathogenic microorganisms. It also demonstrated a good antimutagenicity against the reactive carcinogenic ester generating mutagen, 2-aminofluorene (2-AF) with IC50 values of 0.52 mg ml-1 and 0.36 mg ml-1 in case of co-incubation and pre-incubation, respectively. The antiprolifertive activity against different cancer cell lines; such as HCT-15, HeLa A549 and U87-MG showed the IC50 values of 0.061, 0.065 and 0.072 mg ml-1, respectively. The antioxidant activity of fungal extract has been assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethyl-benzthiazolin-6-sulfonicacid) (ABTS) methods with IC50 values of 40.07 µg and 54.28 µg, respectively. Total phenolics and flavonoid contents have been also determined. Ultra-high performance liquid chromatography (UPLC) of fungal extract revealed the presence of various phenolic compounds (caffeic acid, rutin, ellagic acid, quercetin and kaempferol). Further an attempt has been made to purify the bioactive compounds by column chromatography and GC-MS analysis. The above studies demonstrated a good bioactive potential of endophytic fungus Aspergillus fumigatus and shows the pharmacological importance of an endophytic fungus and justify the need to carry out further studies.


Assuntos
Aspergillus fumigatus/isolamento & purificação , Aspergillus fumigatus/metabolismo , Moringa oleifera/microbiologia , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Aspergillus fumigatus/fisiologia , Biofilmes/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/farmacologia , Fungos/efeitos dos fármacos , Moringa oleifera/metabolismo , Fenóis/farmacologia , Extratos Vegetais/farmacologia
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