Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 146
Filtrar
1.
J Mater Sci Mater Med ; 35(1): 24, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526738

RESUMO

Multi-walled Carbon Nanotubes (MWCNTs) are inert structures with high aspect ratios that are widely used as vehicles for targeted drug delivery in cancer and many other diseases. They are largely non-toxic in nature however, when cells are exposed to these nanotubes for prolonged durations or at high concentrations, they show certain adverse effects. These include cytotoxicity, inflammation, generation of oxidative stress, and genotoxicity among others. To combat such adverse effects, various moieties can be attached to the surface of these nanotubes. Curcumin is a known anti-inflammatory, antioxidant and cytoprotective compound derived from a medicinal plant called Curcuma longa. In this study, we have synthesized and characterized Curcumin coated-lysine functionalized MWCNTs and further evaluated the cytoprotective, anti-inflammatory, antioxidant and antiapoptotic effect of Curcumin coating on the surface of MWCNTs. The results show a significant decrease in the level of inflammatory molecules like IL-6, IL-8, IL-1ß, TNFα and NFκB in cells exposed to Curcumin-coated MWCNTs as compared to the uncoated ones at both transcript and protein levels. Further, compared to the uncoated samples, there is a reduction in ROS production and upregulation of antioxidant enzyme-Catalase in the cells treated with Curcumin-coated MWCNTs. Curcumin coating also helped in recovery of mitochondrial membrane potential in the cells exposed to MWCNTs. Lastly, cells exposed to Curcumin-coated MWCNTs showed reduced cell death as compared to the ones exposed to uncoated MWCNTs. Our findings suggest that coating of Curcumin on the surface of MWCNTs reduces its ability to cause inflammation, oxidative stress, and cell death.


Assuntos
Curcumina , Nanotubos de Carbono , Humanos , Curcumina/farmacologia , Nanotubos de Carbono/toxicidade , Nanotubos de Carbono/química , Antioxidantes/farmacologia , Inflamação , Anti-Inflamatórios/farmacologia
2.
JAMA Netw Open ; 7(3): e240728, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38446483

RESUMO

Importance: Diabetic retinopathy (DR) is a complication of diabetes that can lead to vision loss. Outcomes of continuous glucose monitoring (CGM) and insulin pump use in DR are not well understood. Objective: To assess the use of CGM, insulin pump, or both, and DR and proliferative diabetic retinopathy (PDR) in adults with type 1 diabetes (T1D). Design, Setting, and Participants: A retrospective cohort study of adults with T1D in a tertiary diabetes center and ophthalmology center was conducted from 2013 to 2021, with data analysis performed from June 2022 to April 2023. Exposure: Use of diabetes technologies, including insulin pump, CGM, and both CGM and insulin pump. Main Outcomes and Measures: The primary outcome was development of DR or PDR. A secondary outcome was the progression of DR for patients in the longitudinal cohort. Multivariable logistic regression models assessed for development of DR and PDR and association with CGM and insulin pump use. Results: A total of 550 adults with T1D were included (median age, 40 [IQR, 28-54] years; 54.4% female; 24.5% Black or African American; and 68.4% White), with a median duration of diabetes of 20 (IQR, 10-30) years, and median hemoglobin A1c (HbA1c) of 7.8% (IQR, 7.0%-8.9%). Overall, 62.7% patients used CGM, 58.2% used an insulin pump, and 47.5% used both; 44% (244 of 550) of the participants had DR at any point during the study. On univariate analysis, CGM use was associated with lower odds of DR and PDR, and CGM with pump was associated with lower odds of PDR (all P < .05), compared with no CGM use. Multivariable logistic regression adjusting for age, sex, race and ethnicity, diabetes duration, microvascular and macrovascular complications, insurance type, and mean HbA1c, showed that CGM was associated with lower odds of DR (odds ratio [OR], 0.52; 95% CI, 0.32-0.84; P = .008) and PDR (OR, 0.42; 95% CI, 0.23-0.75; P = .004), compared with no CGM use. In the longitudinal analysis of participants without baseline PDR, 79 of 363 patients (21.8%) had progression of DR during the study. Conclusions and Relevance: In this cohort study of adults with T1D, CGM use was associated with lower odds of developing DR and PDR, even after adjusting for HbA1c. These findings suggest that CGM may be useful for diabetes management to mitigate risk for DR and PDR.


Assuntos
Diabetes Mellitus Tipo 1 , Retinopatia Diabética , Insulinas , Doenças Retinianas , Adulto , Humanos , Feminino , Masculino , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Retinopatia Diabética/epidemiologia , Automonitorização da Glicemia , Estudos de Coortes , Hemoglobinas Glicadas , Estudos Retrospectivos , Glicemia
3.
Nat Commun ; 15(1): 1987, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443336

RESUMO

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase inhibitor stiripentol emerges as the top hit. Combined profiling and functional studies demonstrate that lactate dehydrogenase A (LDHA)-directed extracellular signal-regulated kinase (ERK) pathway activates yes-associated protein 1 (YAP1)/ signal transducer and activator of transcription 3 (STAT3) transcriptional co-activators in glioblastoma cells to upregulate C-C motif chemokine ligand 2 (CCL2) and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.


Assuntos
Glioblastoma , Animais , Humanos , Camundongos , Glioblastoma/genética , L-Lactato Desidrogenase/genética , Lactato Desidrogenase 5 , Ácido Láctico , Simbiose , Microambiente Tumoral
4.
Trends Mol Med ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38453529

RESUMO

Glioma is a type of aggressive and incurable brain tumor. Patients with glioma are highly resistant to all types of therapies, including immunotherapies. Epigenetic reprogramming is a key molecular hallmark in tumors across cancer types, including glioma. Mounting evidence highlights a pivotal role of epigenetic regulation in shaping tumor biology and therapeutic responses through mechanisms involving both glioma cells and immune cells, as well as their symbiotic interactions in the tumor microenvironment (TME). In this review, we discuss the molecular mechanisms of epigenetic regulation that impacts glioma cell biology and tumor immunity in both a cell-autonomous and non-cell-autonomous manner. Moreover, we provide an overview of potential therapeutic approaches that can disrupt epigenetic-regulated tumor-immune symbiosis in the glioma TME.

5.
Int J Surg Case Rep ; 116: 109400, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368668

RESUMO

INTRODUCTION: Multiple primary cancers (MPCs) have attracted attention in medical research due to their increasing incidence. The coexistence of invasive breast carcinoma and clear cell carcinoma of the kidney, alongside a family history of cancer, highlights the multifactorial origins of MPCs, particularly their potential association with genetic factors. CASE PRESENTATION: A 70-year-old female initially sought medical attention for a two-year history of a right breast lump as her primary concerns centered on the long-standing lump. Clinical evaluations and imaging studies revealed an invasive breast carcinoma diagnosis, and simultaneously, an incidental mass in her left kidney was identified as clear cell carcinoma. DISCUSSION: Emphasis and further researh should be on the potential role of genetic factors in MPC development, necessitating comprehensive genetic evaluations. CONCLUSION: This study highlights the significance of customized treatment approaches for each malignancy, facilitating early detection, improved patient outcomes, and an enhanced understanding of MPCs.

6.
ACS Appl Mater Interfaces ; 16(6): 6709-6742, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38315446

RESUMO

Information exchange is essential for the brain, where it communicates the physiological and pathological signals to the periphery and vice versa. Extracellular vesicles (EVs) are a heterogeneous group of membrane-bound cellular informants actively transferring informative calls to and from the brain via lipids, proteins, and nucleic acid cargos. In recent years, EVs have also been widely used to understand brain function, given their "cell-like" properties. On the one hand, the presence of neuron and astrocyte-derived EVs in biological fluids have been exploited as biomarkers to understand the mechanisms and progression of multiple neurological disorders; on the other, EVs have been used in designing targeted therapies due to their potential to cross the blood-brain-barrier (BBB). Despite the expanding literature on EVs in the context of central nervous system (CNS) physiology and related disorders, a comprehensive compilation of the existing knowledge still needs to be made available. In the current review, we provide a detailed insight into the multifaceted role of brain-derived extracellular vesicles (BDEVs) in the intricate regulation of brain physiology. Our focus extends to the significance of these EVs in a spectrum of disorders, including brain tumors, neurodegenerative conditions, neuropsychiatric diseases, autoimmune disorders, and others. Throughout the review, parallels are drawn for using EVs as biomarkers for various disorders, evaluating their utility in early detection and monitoring. Additionally, we discuss the promising prospects of utilizing EVs in targeted therapy while acknowledging the existing limitations and challenges associated with their applications in clinical scenarios. A foundational comprehension of the current state-of-the-art in EV research is essential for informing the design of future studies.


Assuntos
Encéfalo , Vesículas Extracelulares , Encéfalo/metabolismo , Vesículas Extracelulares/metabolismo , Barreira Hematoencefálica , Biomarcadores/metabolismo , Biologia
7.
Curr Probl Cardiol ; 49(3): 102388, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38184133

RESUMO

Heart failure (HF) is a clinical syndrome due to either functional or structural impairment of the ventricular pump or filling, representing a major cause of global morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF), characterized by a left ventricular ejection fraction (LVEF) of ≥50%, constitutes over half of the HF population, with a rising prevalence. Until recently, therapeutic options in treating HFpEF and reducing hospitalization and mortality remained limited. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown promising results in this patient population. This review article explores current literature and significant clinical trials investigating the impact of sodium- SGLT2 inhibitors in patients with HFpEF.


Assuntos
Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Insuficiência Cardíaca/terapia , Volume Sistólico , Função Ventricular Esquerda , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sódio/uso terapêutico
8.
bioRxiv ; 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38293232

RESUMO

Purpose: Uveal melanoma (UM) is a highly aggressive disease with very few treatment options. We previously demonstrated that mUM is characterized by high oxidative phosphorylation (OXPHOS). Here we tested the anti-tumor, signaling and metabolic effects of imipridones, CLPP activators which reduce OXPHOS indirectly and have demonstrated safety in patients. Experimental Design: We assessed CLPP expression in UM patient samples. We tested the effects of imipridones (ONC201, ONC212) on the growth, survival, signaling and metabolism of UM cell lines in vitro, and for therapeutic effects in vivo in UM liver metastasis models. Results: CLPP expression was confirmed in primary and mUM patient samples. ONC201/212 treatment of UM cell lines in vitro decreased OXPHOS effectors, inhibited cell growth and migration, and induced apoptosis. ONC212 increased metabolic stress and apoptotic pathways, inhibited amino acid metabolism, and induced cell death-related lipids. ONC212 also decreased tumor burden and increased survival in vivo in two UM liver metastasis models. Conclusion: Imipridones are a promising strategy for further testing and development in mUM.

9.
J Thromb Thrombolysis ; 57(2): 293-301, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37932590

RESUMO

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment are of interest in oncology due to ease of administration and lack of need for therapeutic monitoring compared to other anticoagulants. Data supporting their use in patients with hematologic malignancies post-hematopoietic stem cell transplant (HCT) are limited. The purpose of the study is to characterize DOAC use in HCT patients. This multicenter, retrospective cohort analysis included allogeneic and autologous HCT recipients. The primary outcome was major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB)/minor bleeding and VTE recurrence. Of 126 patients, 91 (72.2%) patients received an autologous HCT, and 35 (27.8%) patients received an allo-HCT. No major bleeding occurred in either transplant recipient groups. In autologous HCT recipients, CRNMB/minor bleeding occurred in four (4.4%) patients and VTE recurrence occurred in one (1.1%) patient. For allogeneic HCT recipients, CRNMB/minor bleeding occurred in five (14.3%) patients and VTE recurrence occurred in two (5.7%) patients. For patients that experienced a CRNMB, five (100%) of the allogeneic HCT and two (50%) of the autologous HCT recipients were thrombocytopenic at the time of bleeding. Only 38.5% of patients who experienced a drug-drug interaction requiring DOAC dose adjustment received the appropriate dose adjustment. DOACs were associated with low rates of recurrent VTE and no major bleeding events, similar to published data on DOAC use in the general cancer patient population. This suggests that DOACs may be safe therapeutic options with proactive management of drug interactions and careful monitoring for bleeding events, especially in the allogeneic HCT population where minor bleeding rates were slightly higher.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Tromboembolia Venosa , Adulto , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/induzido quimicamente , Estudos Retrospectivos , Transplantados , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Administração Oral , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
10.
Lasers Surg Med ; 56(1): 45-53, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37933762

RESUMO

OBJECTIVES: The treatment of recalcitrant keloids is challenging. Although intralesional bleomycin using conventional needle injectors (CNI) is effective, it has important drawbacks, such as the need for repetitive and painful injections. Therefore, we aimed to evaluate the effectiveness, tolerability and patient satisfaction of intralesional bleomycin with lidocaine administered with a needle-free electronically-controlled pneumatic jet-injector (EPI) in recalcitrant keloids. METHODS: This retrospective study included patients with recalcitrant keloids who had received three intralesional EPI-assisted treatments with bleomycin and lidocaine. Effectiveness was assessed using the Patient and Observer Scar Assessment Scale (POSAS) at baseline and four to six weeks after the third treatment. Additionally, treatment related pain scores numeric rating scale, adverse effects, patient satisfaction and Global Aesthetic Improvement Scale (GAIS) were assessed. RESULTS: Fifteen patients with a total of >148 recalcitrant keloids were included. The median total POSAS physician- and patient-scores were respectively 40 and 41 at baseline, and reduced with respectively 7 and 6-points at follow-up ( p < 0.001; p < 0.001). The median pain scores during EPI-assisted injections were significantly lower compared to CNI-assistant injections, (2.5 vs. 7.0, respectively ( p < 0.001)). Adverse effects were mild. Overall, patients were "satisfied" or "very satisfied" with the treatments (14/15, 93.3%). The GAIS was "very improved" in one patient, "improved" in nine patients and "unaltered" in four patients. CONCLUSIONS: EPI-assisted treatment with bleomycin and lidocaine is an effective, well tolerated, patient-friendly alternative for CNI in patients with recalcitrant keloid scars. Randomized controlled trials are warranted to confirm our findings and improve the clinical management of recalcitrant keloids.


Assuntos
Cicatriz Hipertrófica , Queloide , Humanos , Queloide/tratamento farmacológico , Queloide/induzido quimicamente , Bleomicina/uso terapêutico , Bleomicina/efeitos adversos , Cicatriz Hipertrófica/patologia , Lidocaína/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Injeções Intralesionais , Dor
11.
Crit Rev Food Sci Nutr ; : 1-24, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38032160

RESUMO

Linseed is an ancient crop used for diverse purposes since the beginning of civilization. In recent times, linseed has emerged as a superfood due to its high content of health-promoting omega-3 fatty acids and other bioactive compounds. Among primary health effects, it has potential to manage hypertension, diabetes, osteoporosis, atherosclerosis, cancer, arthritis, neurological, cardiovascular diseases including blood cholesterol levels, constipation, diarrhea, and autoimmune disorders etc. due to the presence of omega-3 fatty acid, lignans, high dietary fibers, and proteins, whereas, secondary health effects comprise of relieving from various skin disorders. Due to these health-beneficial properties, interest in linseed oil necessitates the intensification of research efforts on various aspects. These include cultivation technology, varietal and genetic improvement, post-harvest processing, profiling of nutrients and bioactive compounds, pre-clinical and clinical studies, etc. The present review discussed the advances in linseed research including pre- and post-harvest processing. However, focus on the bioactive compounds present in linseed oil and their health effects are also presented. Linseed cultivation, pre- and post-harvest processing aspects are covered including climatic, edaphic, agronomic factors, type of cultivar and storage conditions etc, which impact the overall oil yield and its nutritional quality. Various emerging applications of linseed oil in functional food, nutraceutical, pharmaceutical, and cosmeceutical preparations were also presented in detail. Further, recommendations were made on linseed oil research in the field of genetics, breeding germplasm resources and genome editing for exploring its full applications as a nutrition and health product.

12.
Cell Rep Med ; 4(11): 101238, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37858339

RESUMO

Glioblastoma (GBM) is a hypoxic and "immune-cold" tumor containing rich stromal signaling molecules and cell populations, such as proteases and immunosuppressive tumor-associated macrophages (TAMs). Here, we seek to profile and characterize the potential proteases that may contribute to GBM immunosuppression. Legumain (LGMN) emerges as the key protease that is highly enriched in TAMs and transcriptionally upregulated by hypoxia-inducible factor 1-alpha (HIF1α). Functionally, the increased LGMN promotes TAM immunosuppressive polarization via activating the GSK-3ß-STAT3 signaling pathway. Inhibition of macrophage HIF1α and LGMN reduces TAM immunosuppressive polarization, impairs tumor progression, enhances CD8+ T cell-mediated anti-tumor immunity, and synergizes with anti-PD1 therapy in GBM mouse models. Thus, LGMN is a key molecular switch connecting two GBM hallmarks of hypoxia and immunosuppression, providing an actionable therapeutic intervention for this deadly disease.


Assuntos
Glioblastoma , Camundongos , Animais , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Peptídeo Hidrolases , Glicogênio Sintase Quinase 3 beta , Terapia de Imunossupressão , Hipóxia
13.
Res Sq ; 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37886538

RESUMO

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase (LDH) inhibitor stiripentol (an FDA-approved anti-seizure drug for Dravet Syndrome) emerges as the top hit. Combined profiling and functional studies demonstrate that LDHA-directed ERK pathway activates YAP1/STAT3 transcriptional co-activators in glioblastoma cells to upregulate CCL2 and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.

14.
Hypertens Res ; 46(11): 2535-2542, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37673958

RESUMO

Adrenal vein sampling (AVS) is the standard procedure for distinguishing unilateral primary aldosteronism (PA) from bilateral PA. In cases where only one adrenal vein is successfully cannulated, it has been suggested that subtype classification can be determined based on the ratio of the concentration of aldosterone between the adrenal vein and the inferior vena cava (AV/IVC index). However, diagnostic performance of the ipsilateral versus contralateral AV/IVC index in predicting lateralization has not been directly compared. In a retrospective cohort of 133 patients with confirmed PA who underwent successful AVS, the performance of the AV/IVC index to predict laterality was evaluated and the area under the receiver operating characteristic (AUROC) curves was calculated. In detecting left unilateral PA (n = 47), the AUROC of the right AV/IVC index (RAV/IVC) was significantly higher than the AUROC of the left AV/IVC (LAV/IVC) index (0.967 vs. 0.871, p = 0.008). In detecting right unilateral PA (n = 30), the AUROC of the LAV/IVC index tended to be higher than that of the RAV/IVC index, but the difference did not reach statistical significance (0.966 vs. 0.906, p = 0.08). In detecting left unilateral PA, the sensitivities of the RAV/IVC and LAV/IVC indices were 83% and 46%, respectively, while the specificities of both were above 90%. In detecting right unilateral PA, the sensitivities of the LAV/IVC and RAV/IVC indices were 80% and 43%, respectively, while the specificities of both were above 90%. The AV/IVC index has superior diagnostic performance in detecting contralateral unilateral PA compared to ipsilateral unilateral PA.


Assuntos
Aldosterona , Hiperaldosteronismo , Humanos , Veia Cava Inferior/diagnóstico por imagem , Hiperaldosteronismo/diagnóstico , Estudos Retrospectivos , Glândulas Suprarrenais/irrigação sanguínea
15.
Nat Immunol ; 24(10): 1654-1670, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37667051

RESUMO

Glioblastoma (GBM) tumors consist of multiple cell populations, including self-renewing glioblastoma stem cells (GSCs) and immunosuppressive microglia. Here we identified Kunitz-type protease inhibitor TFPI2 as a critical factor connecting these cell populations and their associated GBM hallmarks of stemness and immunosuppression. TFPI2 promotes GSC self-renewal and tumor growth via activation of the c-Jun N-terminal kinase-signal transducer and activator of transcription (STAT)3 pathway. Secreted TFPI2 interacts with its functional receptor CD51 on microglia to trigger the infiltration and immunosuppressive polarization of microglia through activation of STAT6 signaling. Inhibition of the TFPI2-CD51-STAT6 signaling axis activates T cells and synergizes with anti-PD1 therapy in GBM mouse models. In human GBM, TFPI2 correlates positively with stemness, microglia abundance, immunosuppression and poor prognosis. Our study identifies a function for TFPI2 and supports therapeutic targeting of TFPI2 as an effective strategy for GBM.


Assuntos
Glioblastoma , Animais , Camundongos , Humanos , Glioblastoma/metabolismo , Inibidores de Proteases/metabolismo , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico , Microambiente Tumoral , Transdução de Sinais , Proteínas de Transporte/metabolismo , Imunossupressores/farmacologia , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/metabolismo
16.
Indian J Med Res ; 158(1): 47-54, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-37602586

RESUMO

Background & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George's Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (≥3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of "BRCAness" in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP-ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.


Assuntos
Proteína BRCA1 , Metilação de DNA , Regiões Promotoras Genéticas , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Proteína BRCA1/genética , Metilação de DNA/genética , Mastectomia
17.
J Biomol Struct Dyn ; : 1-11, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37449757

RESUMO

De novo generation of molecules with the necessary features offers a promising opportunity for artificial intelligence, such as deep generative approaches. However, creating novel compounds having biological activities toward two distinct targets continues to be a very challenging task. In this study, we develop a unique computational framework for the de novo synthesis of bioactive compounds directed at two predetermined therapeutic targets. This framework is referred to as the dual-target ligand generative network. Our approach uses a stochastic policy to explore chemical spaces called a sequence-based simple molecular input line entry system (SMILES) generator. The steps in the high-level workflow would be to gather and prepare the training data for both targets' molecules, build a neural network model and train it to make molecules, create new molecules using generative AI, and then virtually screen the newly validated molecules against the SARS-CoV-2 PLpro and 3CLpro drug targets. Results shows that novel molecules generated have higher binding affinity with both targets than the conventional drug i.e. Remdesivir being used for the treatment of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

19.
ACS Omega ; 8(22): 20042-20055, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37305313

RESUMO

This work reports an environmentally friendly and economically feasible green synthesis of monometallic oxides (SnO2 and WO3) and their corresponding mixed metal oxide (SnO2/WO3-x) nanostructures from the aqueous Psidium guajava leaf extract for light-driven catalytic degradation of a major industrial contaminant, methylene blue (MB). P. guajava is a rich source of polyphenols that acts as a bio-reductant as well as a capping agent in the synthesis of nanostructures. The chemical composition and redox behavior of the green extract were investigated by liquid chromatography-mass spectrometry and cyclic voltammetry, respectively. Results acquired by X-ray diffraction and Fourier transform infrared spectroscopy confirm the successful formation of crystalline monometallic oxides (SnO2 and WO3) and bimetallic SnO2/WO3-x hetero-nanostructures capped with polyphenols. The structural and morphological aspects of the synthesized nanostructures were analyzed by transmission electron microscopy and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. Photocatalytic activity of the synthesized monometallic and hetero-nanostructures was investigated for the degradation of MB dye under UV light irradiation. Results indicate a higher photocatalytic degradation efficiency for mixed metal oxide nanostructures (93.5%) as compared to pristine monometallic oxides SnO2 (35.7%) and WO3 (74.5%). The hetero-metal oxide nanostructures prove to be better photocatalysts with reusability up to 3 cycles without any loss in degradation efficiency or stability. The enhanced photocatalytic efficiency is attributed to a synergistic effect in the hetero-nanostructures, efficient charge transportation, extended light absorption, and increased adsorption of dye due to the enlarged specific surface area.

20.
Proc (Bayl Univ Med Cent) ; 36(4): 490-495, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37334074

RESUMO

Background: The COVID-19 global pandemic has raised many challenges in training family medicine residents. Family medicine is at the frontline for treating and managing patients with COVID-19. Attention is needed on the critical issue of the effect of the pandemic on resident training, the safety of those performing needed medical services, and the psychological well-being of trainees. Methods: We performed a cross-sectional, 25-question survey-based study to evaluate the perceived effect of the COVID-19 pandemic on family medicine residents' training and residents' well-being in the state of Texas. Results: A total of 250 Texas-based family medicine residents were surveyed with a response rate of 12.8% (n = 32). After the pandemic began, all residents worried about exposing their loved ones to COVID-19, and 65% felt like the COVID-19 pandemic negatively impacted their training overall. Respondents indicated that changes occurred in their respective residency curricula that altered training such as canceling of scheduled lectures (84.3%) and more telemedicine visits (56.25%). There was a significant difference for postgraduate year level and the effect on rotation assignments, with more disruption to the first- and third-year residents (P = 0.03). Conclusions: The COVID-19 pandemic has had a notable impact on the perception of quality of training and mental health within family medicine. Our findings may guide programs in how to proactively target pandemic-related training challenges.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...