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1.
RSC Adv ; 14(31): 22676-22689, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39027042

RESUMO

Twenty-eight compounds, viz., 1,8-naphthyridine-3-carbonitrile (ANC and ANA) derivatives, were designed and synthesized through a molecular hybridization approach. The structures of these compounds were analyzed and confirmed using 1H NMR, 13C NMR, LCMS, and elemental analyses. The synthesized compounds were evaluated by in vitro testing for their effectiveness against tuberculosis using the MABA assay, targeting the Mycobacterium tuberculosis H37Rv strain. Their minimum inhibitory concentration (MIC) was determined, showing that the tested compounds' MIC values ranged from 6.25 to ≤50 µg mL-1. Among the derivatives studied, ANA-12 demonstrated prominent anti-tuberculosis activity with a MIC of 6.25 µg mL-1. Compounds ANC-2, ANA-1, ANA 6-8, and ANA-10 displayed moderate to good anti-tuberculosis activity with MIC values of 12.5 µg mL-1. Compounds with MIC ≤ 12.5 µg mL-1 were screened against human embryonic kidney cells to assess their potential cytotoxicity. Interestingly, these compounds showed less toxicity towards normal cells, with a selectivity index value ≥ 11. To further evaluate the binding pattern in the active site of enoyl-ACP reductase (InhA) from Mtb (PDB-4TZK), a molecular docking analysis of compound ANA-12 was performed using the glide module of Schrodinger software. The stability, confirmation, and intermolecular interactions of the cocrystal ligand and the highly active compound ANA-12 on the chosen target protein were investigated through molecular dynamics simulations lasting 100 ns. In silico predictions were utilized to assess the ADMET properties of the final compounds. A suitable single crystal was developed and analyzed for compound ANA-5 to gain a deeper understanding of the compounds' structures.

2.
Entropy (Basel) ; 26(6)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38920442

RESUMO

Link prediction plays a crucial role in identifying future connections within complex networks, facilitating the analysis of network evolution across various domains such as biological networks, social networks, recommender systems, and more. Researchers have proposed various centrality measures, such as degree, clustering coefficient, betweenness, and closeness centralities, to compute similarity scores for predicting links in these networks. These centrality measures leverage both the local and global information of nodes within the network. In this study, we present a novel approach to link prediction using similarity score by utilizing average centrality measures based on local and global centralities, namely Similarity based on Average Degree (SACD), Similarity based on Average Betweenness (SACB), Similarity based on Average Closeness (SACC), and Similarity based on Average Clustering Coefficient (SACCC). Our approach involved determining centrality scores for each node, calculating the average centrality for the entire graph, and deriving similarity scores through common neighbors. We then applied centrality scores to these common neighbors and identified nodes with above average centrality. To evaluate our approach, we compared proposed measures with existing local similarity-based link prediction measures, including common neighbors, the Jaccard coefficient, Adamic-Adar, resource allocation, preferential attachment, as well as recent measures like common neighbor and the Centrality-based Parameterized Algorithm (CCPA), and keyword network link prediction (KNLP). We conducted experiments on four real-world datasets. The proposed similarity scores based on average centralities demonstrate significant improvements. We observed an average enhancement of 24% in terms of Area Under the Receiver Operating Characteristic (AUROC) compared to existing local similarity measures, and a 31% improvement over recent measures. Furthermore, we witnessed an average improvement of 49% and 51% in the Area Under Precision-Recall (AUPR) compared to existing and recent measures. Our comprehensive experiments highlight the superior performance of the proposed method.

3.
J Clin Pharmacol ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38831713

RESUMO

Diabetic nephropathy (DN), a severe complication of type 2 diabetes mellitus (T2DM), is marked by heightened endoplasmic reticulum stress (ERS) and oxidative stress (OS) due to protein misfolding and free radical generation. We investigated the sodium-glucose co-transporter-2 inhibitor (SGLT2i), canagliflozin (Cana), in alleviating ERS and OS in DN patients and THP-1 cells under hyperglycemic condition. A total of 120 subjects were divided into four groups, with 30 subjects in each group: healthy controls, T2DM individuals, DN patients receiving standard treatment, and those treated with Cana. The control group had no history of diabetes, cardiovascular or renal diseases, or other comorbidities. Cana was administered at doses of either 100 or 300 mg per day based on the estimated glomerular filtration rate (eGFR) value of DN individuals, with a mean follow-up of 6 months. Additionally, THP-1 monocytes were exposed to HGM (33.3 mM glucose with a cytokine cocktail of TNF-α and IFN-γ at 50 ng/mL each) to evaluate the relative levels of ERS, OS markers, and nuclear factor erythroid 2-related factor 2 (Nrf2), the transcription factor regulating cellular redox, which is downregulated in diabetes. Our results revealed that ERS markers GRP78 and PERK, as well as OS markers TXNIP and p22phox, were elevated in both DN patients and HGM-treated THP-1 monocytes and were reduced by Cana intervention. Furthermore, Cana regulated the phosphorylation of Nrf2, Akt, and EIF2α in HGM-treated monocytes. In conclusion, our findings highlight the role of Cana in activating Nrf2, thereby attenuating ERS and OS to mitigate DN progression.

4.
RSC Med Chem ; 15(5): 1709-1721, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38784465

RESUMO

A series of Meldrum's acid, 7-azaindole and 1,2,3-triazole hybrids were synthesized and evaluated for their in vitro anticancer activity against five different cancer cell lines viz. MCF-7 (breast cancer), HeLa (cervical cancer), DU-145 (prostate cancer), HepG2 (liver cancer) and K562 (myelogenous leukemia cell). Among the series, compound 6b containing a 4-methyl substitution showed potent activity against HeLa cell line. Cell cycle analysis revealed that compound 6b induced cell cycle arrest at the G2/M phase and induced apoptosis. Apoptotic activity was further confirmed by Hoechst staining and Annexin V-FITC assay. Compound 6b has been found to exhibit higher activity in all four cell lines, with IC50 values of 6.67 ± 0.39 µM, 4.44 ± 0.32 µM, 12.38 ± 0.51 µM and 9.97 ± 0.25 µM against MCF-7, HeLa, DU-145 and HepG2 cell lines respectively. Compounds 6m (9.68 ± 0.10 µM) and 6n (9.52 ± 0.38 µM), which have dimethoxy and trimethoxy substitutions, respectively, have demonstrated significant anticancer activity against HeLa cells compared to the other cells. The molecular docking study of ligand 6b against the crystal structure of EGFR and Mcl-1 scored notable binding energy values and displayed important interactions like H-bond, π-cation and other hydrophobic interactions.

5.
Med Biol Eng Comput ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38797762

RESUMO

Predicting a patient's future health state through the analysis of their clinical records is an emerging area in the field of intelligent medicine. It has the potential to assist healthcare professionals in prescribing treatments safely, making more accurate diagnoses, and improving patient care. However, clinical notes have been underutilized due to their complexity, high dimensionality, and sparsity. Nevertheless, these clinical records hold significant promise for enhancing clinical decision. To tackle these problems, a novel feedback attention-based bidirectional long short-term memory (FABiLSTM) model has been proposed for more effective diagnosis using clinical records. This model incorporates PubMedBERT for filtering irrelevant information, enhances global vector word embeddings for numerical representations and K-means clustering, and performs to explore term frequency and inverse document frequency intricacies. The proposed approach excels in capturing information, aiding accurate disease prediction. The predictive capability is further enhanced with the help of a billiards-inspired optimization algorithm. The effectiveness of the FABiLSTM method has been assessed with the MIMIC-III dataset, yielding impressive results in accuracy, precision, F1 score, and recall score of 98.52%, 98%, 98.2%, and 98.2% individually. These results reveal ways in which the proposed technique excels in comparison with current practices.

6.
Viruses ; 16(5)2024 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-38793612

RESUMO

As dengue expands globally and many vaccines are under trials, there is a growing recognition of the need for assessing T cell immunity in addition to assessing the functions of neutralizing antibodies during these endeavors. While several dengue-specific experimentally validated T cell epitopes are known, less is understood about which of these epitopes are conserved among circulating dengue viruses and also shared by potential vaccine candidates. As India emerges as the epicenter of the dengue disease burden and vaccine trials commence in this region, we have here aligned known dengue specific T cell epitopes, reported from other parts of the world with published polyprotein sequences of 107 dengue virus isolates available from India. Of the 1305 CD4 and 584 CD8 epitopes, we found that 24% and 41%, respectively, were conserved universally, whereas 27% and 13% were absent in any viral isolates. With these data, we catalogued epitopes conserved in circulating dengue viruses from India and matched them with each of the six vaccine candidates under consideration (TV003, TDEN, DPIV, CYD-TDV, DENVax and TVDV). Similar analyses with viruses from Thailand, Brazil and Mexico revealed regional overlaps and variations in these patterns. Thus, our study provides detailed and nuanced insights into regional variation that should be considered for itemization of T cell responses during dengue natural infection and vaccine design, testing and evaluation.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Vacinas contra Dengue , Vírus da Dengue , Dengue , Epitopos de Linfócito T , Epitopos de Linfócito T/imunologia , Vírus da Dengue/imunologia , Vírus da Dengue/genética , Vírus da Dengue/classificação , Humanos , Dengue/imunologia , Dengue/prevenção & controle , Dengue/virologia , Vacinas contra Dengue/imunologia , Linfócitos T CD8-Positivos/imunologia , Índia , Linfócitos T CD4-Positivos/imunologia , Brasil , Tailândia , México , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue
7.
Cureus ; 16(4): e59004, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38803746

RESUMO

BACKGROUND: Thyroid hormones play a pivotal role in regulating metabolic processes, including liver metabolism. The interplay between thyroid function and liver enzymes is complex, with thyroid dysfunction potentially impacting liver function. The relationship between thyroid-stimulating hormone (TSH) levels and liver function parameters is particularly noteworthy, especially in areas like North Karnataka, India, where dietary and environmental factors may impact thyroid disorders. AIM AND OBJECTIVES: The principal objective of this research is to explore the association between TSH levels and liver function parameters in individuals from North Karnataka. Secondary objectives include examining the relationship between TSH levels, blood pressure, and the prevalence of comorbidities in the study population. MATERIALS AND METHODS: This retrospective observational study included 75 patients admitted to a tertiary care hospital in North Karnataka. Patients who had undergone both thyroid function tests and liver function tests were included in the study. Data on blood pressure and comorbidities (like hypothyroidism, hyperthyroidism, hypertension, gastritis, alcohol-related liver disease, anemia, chronic obstructive pulmonary disease (COPD), arthritis, diabetes mellitus, migraine, and uterine disorder) were also collected and analyzed. RESULTS: The study population comprised 48 females (64%) and 27 males (36%), with a mean age of 46.52 years. Thyroid irregularities were observed in 16 patients (21.4%), with hypothyroidism being the predominant thyroid disorder, accounting for 14 cases (18.7%). The distribution of comorbidities included diabetes mellitus (14 patients; 18.7%), anemia (19 patients; 25.3%), migraine (18 patients; 24%), hypertension (17 patients; 22.7%), gastritis (10 patients; 13.3%), COPD (nine patients; 12%), alcohol-related disorders (four patients; 5.3%), arthritis (three patients; 4%), and uterine disorders (eight patients; 10.6%). It is important to note that some patients presented with more than one comorbidity, which may result in an overlap in the total count of specific conditions reported. DISCUSSION: The absence of a significant correlation between TSH levels and liver function tests in this study contrasts with some previous research, suggesting that regional factors and dietary habits may play a role in these associations. The high prevalence of thyroid disorders, particularly hypothyroidism, underscores the importance of monitoring thyroid function in this population. The presence of comorbidities such as diabetes mellitus and anemia further complicates the clinical picture and highlights the need for comprehensive healthcare approaches. CONCLUSION: This study did not find a significant correlation between TSH levels and liver function parameters in patients from North Karnataka. The findings emphasize the need for continued research into the complex interactions between thyroid function and liver metabolism, particularly in regions with unique environmental and dietary influences. Public health initiatives should focus on addressing the high prevalence of thyroid disorders and related comorbidities in this population.

8.
Heliyon ; 10(9): e30183, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726129

RESUMO

The present work describes the optimization of reinforcement parameters for hardness, thermal conductivity, and coefficient of thermal expansion while developing LM6 alloy/soda-lime glass particulate composite through Taguchi-based Grey Relational Analysis (GRA). Soda-lime glass particle weight % (1.5, 3.0 and 4.5 %), particle size (100, 150 and 300 µm) and pre-heat temperature (260, 380 and 500oC) are varied accordingly to explore the effect of reinforcement parameters on LM6 alloy/soda-lime glass composite properties. Composites are developed through stir casting based on the L9 Taguchi orthogonal array approach. The properties such as hardness, thermal conductivity and coefficient of thermal expansion of developed composites are assessed. Signal to Noise Ratios (S/N ratios) are calculated and used for the optimization of parameters. GRA is employed for multi-response optimization to find the levels of parameters that affect the desirable properties of the composite. Thus, the reinforcement parameters are optimized for attaining the combined objectives of higher hardness, higher thermal conductivity and lower coefficient of thermal expansion values considered in this investigation. The analysis shows that 4.5 wt %, particle size of 200 µm and pre-heat temperature of 380oC are optimal parameter levels. A confirmation test is carried out with the optimal parameter levels and the GRG value of 0.7778 is obtained. The GRG with the initial parameter settings is 0.4711, and the improvement of GRG is found to be 65.1 %. ANOVA is performed on GRG to find out significant parameters and the contribution of each parameter is identified. The wt.% of soda-lime glass is the most significant parameter and its contribution is 92.6 %.

10.
Inflammopharmacology ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683276

RESUMO

Piperine is an amide alkaloid responsible for producing the pungent smell that comes from black pepper. Piperine has been explained to exhibit significant properties such as anti-rheumatic, anti-inflammatory, and antihypertensive effects. The aim of the study was to synthesize pyrrole ester from piperine and evaluate its anti-arthritis effects in adjuvant-induced arthritis female Wistar rats. In this study, pyrrole ester (AU-5) was designed, synthesized and evaluated for ant-arthritic activity in adjuvant-induced arthritis Wistar rats. The synthesized pyrrole ester (AU-5) was administered in three selected doses (20, 10 and 5 mg/kg) to the arthritic-induced model. The administered ester significantly inhibited the increase in arthritis index, paw and ankle joint swelling compared to the arthritic control group. Similarly, the treated rats exhibited a remarkable increase in body weight increase, improved haematological, biochemical, histopathological and radiological parameters. Moreover, the excess production of rheumatoid factor (RF), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was noticeably attenuated in all AU-5-treated rats. However, the spleen index, tumour necrosis factor (TNF-α) and interleukin-6 (IL-6) were distinctly lowered compared to arthritic control rats. Moreover, AU-5 showed promising liver protection by lowering the level of liver function markers Serum glutamic pyruvic transaminase (SGPT), Serum glutamic-oxaloacetic transaminase (SGOT) and alkaline phosphatase (ALP) in serum. Henceforth, it might be concluded that AU-5 has an anti-arthritic effect which can be credited to the down regulation of inflammatory markers and the pro-inflammatory cytokines.

11.
Biomed Phys Eng Express ; 10(3)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437724

RESUMO

Motion artifacts are a pervasive challenge in EEG ambulatory monitoring, often obscuring critical neurological signals and impeding accurate seizure detection. In this study, we propose a new approach of outlier based grouping of two level Singular Spectrum Analysis (SSA) decomposition combined with Relative Total Variation (RTV) filter for the effective removal of motion-induced noise from ambulatory EEG data. A two-stage SSA method was employed to decompose single-channel EEG signal, which had been interfered with, into various fre quency bands. The affected sub-band signal was then subjected to an RTV filter to estimate the artifact signal. Subtracting this estimated artifact signal from the contaminated sub-band signal yielded the filtered sub-band signal. Subse quently, the filtered sub-band signal was reintegrated with the other decomposed components from noise-free bands, culminating in the generation of the ultimate denoised EEG signal. Based on the comprehensive set of simulation results, it can be deduced that the algorithm described in the paper outperforms existing methods. It demonstrates superior metrics evaluation in terms of ΔSNR,η,MAE, andPSNRwhen compared to these alternatives. Our framework sig- nificantly enhances the quality of EEG data by successfully eliminating motion artifacts while preserving crucial brainwave information. To evaluate the prac tical impact of this noise reduction technique, we assess its performance in the context of seizure detection. The results reveal a substantial improvement in the accuracy and reliability of seizure detection algorithms when applied to EEG data preprocessed with proposed method.


Assuntos
Artefatos , Eletroencefalografia , Humanos , Reprodutibilidade dos Testes , Movimento (Física) , Eletroencefalografia/métodos , Convulsões/diagnóstico
12.
Int J Biol Macromol ; 261(Pt 2): 129860, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309406

RESUMO

Marine bacteria can adapt to various extreme environments by the production of extracellular polymeric substances (EPS). Throughout this investigation, impact of variable pCO2 levels on the metabolic activity and physiochemical modulation in EPS matrix of marine bacterium Pseudomonas sihuiensis - BFB-6S was evaluated using a fluorescence microscope, excitation-emission matrix (EEM), 2D-Fourier transform infrared correlation spectroscopy (2D-ATR-FTIR-COS), FT-NMR and TGA-DSC. From the results at higher pCO2 levels, there was a substantial reduction in EPS production by 58-62.8 % (DW). In addition to the biochemical composition of EPS, reduction in carbohydrates (8.7-47.6 %), protein (7.1-91.5 %), and lipids (16.9-68.6 %) content were observed at higher pCO2 levels. Functional discrepancies of fluorophores (tyrosine and tryptophan-like) in EPS, speckled differently in response to variable pCO2. The 2D-ATR-FTIR-COS analysis revealed functional amides (CN, CC, CO bending, -NH bending in amines) of EPS were preferentially altered, which led to the domination of polysaccharides relevant functional groups at higher pCO2. 1H NMR analysis of EPS confirmed the absence of chemical signals from H-C-COOH of proteins, α, ß anomeric protons, and acetyl group relevant region at higher pCO2 levels. These findings can contribute new insights into the influence of pCO2 on the adaptation of marine microbes in future ocean acidification scenarios.


Assuntos
Matriz Extracelular de Substâncias Poliméricas , Água do Mar , Concentração de Íons de Hidrogênio , Pseudomonas , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Nat Med ; 30(3): 670-674, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38321219

RESUMO

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.


Assuntos
Coinfecção , Vírus da Dengue , Dengue , Dengue Grave , Humanos , Criança , Dengue/epidemiologia , Dengue Grave/epidemiologia , Anticorpos Antivirais , Coinfecção/epidemiologia , Febre
14.
Heliyon ; 10(1): e23712, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192868

RESUMO

A compact high bandwidth ratio (BDR) super wide band flower slotted micro strip patch antenna (SWB-FSMPA) for super wide band (SWB) applications is presented. The SWB-FSMPA is constructed on a FR-4 substrate having a size of 16 × 22 mm2. The SWB-FSMPA incorporates a 50 Ω tapered micro strip line and a rectangular beveled defected ground structure (RB-DGS). This design enables a simulation bandwidth from 3.78 to 109.86 GHz, allowing for coverage of various wireless applications such as WiMAX (3.3-3.6 GHz), 5G (3.3-3.7 GHz), WLAN (5.15-5.825 GHz), UWB (3.1-10.6 GHz), Ku- (12-18 GHz), K- (18-27 GHz), Ka- (27-40 GHz), V- (40-75 GHz), and W- (75-110 GHz) millimeter wave bands. The SWB-FSMPA antenna exhibits a gain that varies within the range of 3.22-7.23 dBi and a peak efficiency of 93.3 %. The SWB-FSMPA possesses a bandwidth ratio (BR) of 29.1:1, a BDR of 5284 in the frequency domain, a minimal group delay (GD) fluctuation of <0.48 ns, and a linear phase in the time domain, making it well-suited for SWB applications.

15.
J Biomol Struct Dyn ; 42(2): 734-746, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37315995

RESUMO

Hyperandrogenism, insulin resistance, and estrogen dominance are the prime defining traits of women with polycystic ovarian syndrome which disrupts hormonal, adrenal, or ovarian functions resulting in impaired folliculogenesis and excess androgen production. The purpose of this study is to identify an appropriate bioactive antagonistic ligand from isoquinoline alkaloids [palmatine (PAL), jatrorrhizine (JAT), magnoflorine (MAG) and berberine (BBR)] from stems of Tinospora cordifolia. Phytocomponents inhibit/prevent androgenic, estrogenic, and steroidogenic receptors, insulin binding, and resultant hyperandrogenism. Intending to develop new inhibitors for human androgen receptor (1E3G), insulin receptor (3EKK), estrogen receptor beta (1U3S), and human steroidogenic cytochromeP450 17A1 (6WR0), here we report the docking studies by employing a flexible ligand docking approach using AutodockVina 4.2.6. ADMET screened swissADME and toxicological predictions to identify novel and potent inhibitors against PCOS. Binding affinity was obtained using Schrodinger. Two ligands, mainly BER (-8.23) and PAL (-6.71) showed the best docking score against androgen receptors. A molecular docking study reveals that compounds BBR and PAL were found to be tight binder at the active site of IE3G. Molecular dynamics results suggest that BBR and PAL showed good binding stability of active site residues. The present study corroborates the molecular dynamics of the compound BBR and PAL, potent Inhibitors of IE3G, having therapeutic potential for PCOS. We project that this study's findings will be helpful in drug development efforts targeting PCOS. Hence isoquinoline alkaloids (BER& PAL) have potential roles against androgen receptors, and in specific PCOS, scientific evaluation has been put forth based on virtual screening.Communicated by Ramaswamy H. Sarma.


Assuntos
Alcaloides , Hiperandrogenismo , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/diagnóstico , Receptores Androgênicos , Simulação de Acoplamento Molecular , Ligantes , Alcaloides/farmacologia
16.
Clin Neuropathol ; 43(2): 48-52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38085093

RESUMO

OBJECTIVE: Rhabdomyosarcoma is a common soft tissue tumor, but isolated involvement of anterior portion of petrous bone is exceedingly rare. Here, we present a case of embryonal rhabdomyosarcoma involving the anterior petrous without involvement of the mastoid and middle ear. PATIENT: A 6-year-old boy presented with a progressive right side lower motor neuron facial paresis for 1-month duration along with headache and recurrent vomiting episodes. Radiology showed a contrast-enhancing lesion involving the right petrous apex. He underwent craniotomy and excision of the lesion. Based on the frozen section, a diagnosis of rhabdomyosarcoma was rendered, and gross total resection could be achieved. Postoperative course was uneventful. CONCLUSION: Isolated petrous bone involvement of embryonal rhabdomyosarcoma is a rare presentation. Intra-operative frozen section plays a key role in decision making regarding the extent of excision. Hence, a prompt and accurate diagnosis is essential in managing these cases.


Assuntos
Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Masculino , Criança , Humanos , Osso Petroso/patologia , Rabdomiossarcoma Embrionário/diagnóstico , Rabdomiossarcoma Embrionário/cirurgia , Rabdomiossarcoma Embrionário/patologia , Rabdomiossarcoma/diagnóstico , Orelha Média/patologia , Diagnóstico Diferencial
17.
Small Methods ; 8(3): e2300942, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37840387

RESUMO

The capacity to precisely pipette femtoliter volumes of liquid enables many applications, for example, to functionalize a nanoscale surface and manipulate fluids inside a single-cell. A pressure-controlled pipetting method is the most preferred, since it enables the widest range of working liquids. However, precisely controlling femtoliter volumes by pressure is challenging. In this work, a new concept is proposed that makes use of axisymmetrical phaseguides inside a microfluidic channel to pipette liquid in discrete steps of known volume. An analytical model for the design of the femtopipettes is developed and verified experimentally. Femtopipettes are fabricated using a multi-scale 3D printing strategy integrating a digital light processing printed part and a two-photon-polymerization printed part. Three different variants are designed and fabricated with pipetting resolutions of 10 picoliters, 180 femtoliters and 50 femtoliters. As a demonstration, controlled amounts of a water-glycerol mixture were first aspirated and then dispensed into a mineral oil droplet.

18.
Nat Prod Res ; : 1-9, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37929690

RESUMO

In recent years, clerodane diterpenes, a class of bioactive compounds, have come into the spotlight due to their amazing bioactivities. Three novel clerodane diterpene analogues were obtained by synthesising 16-hydroxycleroda-3,13(14)-Z-diene-15,16-olide (Lactone) with primary amines. Anti-tubercular activity was determined using Microplate Alamar Blue Assay. Among all the synthesised compounds from methanolic extract of seeds, results clearly showed that compounds 3 and 5 have significant anti TB activity with an MIC of 1.56 µg/ml against the Mycobacterium tuberculosis MTB H37Rv bacilli strain than the gold standard drugs pyrazinamide (3.13 µg/ml), ciprofloxacin (3.13 µg/ml), streptomycin (6.25 µg/ml) and rifampicin (6.25 µg/ml). Compound 5 exhibited significant antibacterial activity with zone of inhibition of 10.8 mm with Gram + ve and 7.95 mm with Gram -ve bacteria at a conc of 50 µg/ml respectively. In the current investigation, three novel heterocycles (compounds 3-5) of the diterpenoid were prepared, in high yield, using one-pot, efficient approach.

19.
Neurooncol Adv ; 5(1): vdad143, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38024238

RESUMO

Background: Mutant isocitrate dehydrogenase (IDHmut) catalyzes 2-hydroxyglutarate (2HG) production and is considered a therapeutic target for IDHmut tumors. However, response is mostly associated with inhibition of tumor growth. Response assessment via anatomic imaging is therefore challenging. Our goal was to directly detect IDHmut inhibition using a new hyperpolarized (HP) 13C magnetic resonance spectroscopy-based approach to noninvasively assess α-ketoglutarate (αKG) metabolism to 2HG and glutamate. Methods: We studied IDHmut-expressing normal human astrocyte (NHAIDH1mut) cells and rats with BT257 tumors, and assessed response to the IDHmut inhibitor BAY-1436032 (n ≥ 4). We developed a new 13C Echo Planar Spectroscopic Imaging sequence with an optimized RF pulse to monitor the fate of HP [1-13C]αKG and [5-12C,1-13C]αKG with a 2.5 × 2.5 × 8 mm3 spatial resolution. Results: Cell studies confirmed that BAY-1436032-treatment leads to a drop in HP 2HG and an increase in HP glutamate detectable with both HP substrates. Data using HP [5-12C,1-13C]αKG also demonstrated that its conversion to 2HG is detectable without the proximal 1.1% natural abundance [5-13C]αKG signal. In vivo studies showed that glutamate is produced in normal brains but no 2HG is detectable. In tumor-bearing rats, we detected the production of both 2HG and glutamate, and BAY-1436032-treatment led to a drop in 2HG and an increase in glutamate. Using HP [5-12C,1-13C]αKG we detected metabolism with an signal-to-noise ratio of 23 for 2HG and 17 for glutamate. Conclusions: Our findings point to the clinical potential of HP αKG, which recently received FDA investigational new drug approval for research, for noninvasive localized imaging of IDHmut status.

20.
iScience ; 26(11): 108268, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38026160

RESUMO

Bacteria that are resistant to antibiotics present an increasing burden on healthcare. To address this emerging crisis, novel rapid antibiotic susceptibility testing (AST) methods are eagerly needed. Here, we present an optical AST technique that can determine the bacterial viability within 1 h down to a resolution of single bacteria. The method is based on measuring intensity fluctuations of a reflected laser focused on a bacterium in reflective microwells. Using numerical simulations, we show that both refraction and absorption of light by the bacterium contribute to the observed signal. By administering antibiotics that kill the bacteria, we show that the variance of the detected fluctuations vanishes within 1 h, indicating the potential of this technique for rapid sensing of bacterial antibiotic susceptibility. We envisage the use of this method for massively parallelizable AST tests and fast detection of drug-resistant pathogens.

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