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Escape from apoptosis is one of the main demeanor characteristics of cancer cells. Mitochondria are key players in initiating and regulating the intrinsic apoptosis pathway. Hexokinase2 (HK2) is ubiquitously expressed in several cancer cells and is essential for cell survival and death. The binding of HK2 to mitochondria promotes cell proliferation, while AKT-1 mediated pathway is crucial in this process. Peimine, a steroidal alkaloid derived from plant steroids, is screened for docking properties, ADMET properties, and drug-likeness. Apoptosis targets are predicted by network pharmacology using 47 genes associated with apoptosis. According to in silico study, peimine has the potential for dual Targeting on HK2 and AKT1. For further confirmation, peimine was subjected to Cell culture studies using MRMT-1 rat breast cancer cells. The elevated levels of cytochrome c and Caspase 9 activity indicate that the intrinsic apoptosis pathway causes cell death. The decreased glucose uptake by the MRMT-1 cells indicates that pimine inhibits glucose transport by inhibiting the membrane HK2.
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Apoptose , Neoplasias , Humanos , Ratos , Animais , Morte Celular , Transdução de Sinais , Células MCF-7 , Proliferação de Células , Mitocôndrias/metabolismo , Linhagem Celular Tumoral , Neoplasias/metabolismoRESUMO
Abstract: The global market for fuel pellets (FPs) has been steadily growing because of a shift to coal substitutes. However, sustainability and the availability of biomass are the main issues. Various kinds of bio-wastes can be valorized through cutting-edge technologies. In the coffee industry, a valuable organic waste called spent coffee grounds (SCGs) is generated in bulk. SCG can be divided into two components, namely spent coffee ground oil and defatted spent coffee grounds (DSCG). SCG and DSCG can be used to produce FPs with excellent higher heating values. This review highlights that burning FPs composed of 100% SCG is not feasible due to the high emission of NOx. Moreover, the combustion is accompanied by a rapid temperature drop due to incomplete combustion which leads to lower boiler combustion efficiencies and increased carbon monoxide emissions. This was because of the low pellet strength and bulk density of the FP. Mixing SCG with other biomass offers improved boiler efficiency and emissions. Some of the reported optimized FPs include 75% SCG + 20% coffee silverskin, 30% SCG + 70% pine sawdust, 90% SCG + 10% crude glycerol, 32% SCG + 23% coal fines + 11% sawdust + 18% mielie husks + 10% waste paper + 6% paper pulp, and 50% SCG + 50% pine sawdust. This review noted the absence of combustion and emissions analyses of DSCG and the need for their future assessment. Valorization of DSCG offers a good pathway to improve the economics of an SCG-based biorefinery where the extracted SCGO can be valorized in other applications. The combustion and emissions of DSCG were not previously reported in detail. Therefore, future investigation of DSCG in boilers is essential to assess the potential of this industry and improve its economics. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-022-02361-z.
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Sleep deprivation (SD) is commonly associated with decreased attention, reduced responsiveness to external stimuli, and impaired locomotor and cognitive performances. Strong evidence indicates that SD disrupts neuro-immuno-endocrine system which is also linked to cognitive function. Recently Zebrafish have emerged as a powerful model sharing organizational and functional characteristics with other vertebrates, providing great translational relevance with rapid and reliable screening results. In the current study, we examined the effects of acetylsalicylic acid (aspirin) on cognitive and locomotor activity in sleep deprived Zebrafish model. Learning and memory were assessed by T-maze and locomotor activity was assessed by partition preference and swimming time in spinning tasks. Furthermore, brain bioavailability of aspirin was determined by high performance liquid chromatography. Following drug exposure and tasks, histopathology of the brain was performed. It was observed that three-day SD significantly reduces learning and memory and locomotion in the Zebrafish. Aspirin was found to restore SD induced cognitive decline and improve the locomotor functions. Neuro-inflammation and impaired functional network connectivity is linked to cognitive defects, which implicate the possible benefits of immunotherapeutics. In the present study, aspirin decreased neutrophil infiltration, and increased spine density in dentate gyrus granular and shrinkage and basophil in the CA1 neurons of hippocampus. This hints the benefit of aspirin on neuroimmune functions in sleep deprived fish and warrants more studies to establish the clear molecular mechanism behind this protective effect.
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Aspirina/farmacologia , Cognição/efeitos dos fármacos , Privação do Sono , Animais , Aspirina/farmacocinética , Aspirina/toxicidade , Disponibilidade Biológica , Masculino , Natação , Testes de Toxicidade Aguda , Peixe-ZebraRESUMO
Understanding the genetic mechanism underlying seed size, shape, and weight is essential for enhancing soybean cultivars. High-density genetic maps of two recombinant inbred line (RIL) populations, LM6 and ZM6, were evaluated across multiple environments to identify and validate M-QTLs as well as identify candidate genes behind major and stable quantitative trait loci (QTLs). A total of 239 and 43 M-QTLs were mapped by composite interval mapping (CIM) and mixed-model-based composite interval mapping (MCIM) approaches, from which 180 and 18, respectively, are novel QTLs. Twenty-two QTLs including four novel major QTLs were validated in the two RIL populations across multiple environments. Moreover, 18 QTLs showed significant AE effects, and 40 pairwise of the identified QTLs exhibited digenic epistatic effects. Thirty-four QTLs associated with seed flatness index (FI) were identified and reported here for the first time. Seven QTL clusters comprising several QTLs for seed size, shape, and weight on genomic regions of chromosomes 3, 4, 5, 7, 9, 17, and 19 were identified. Gene annotations, gene ontology (GO) enrichment, and RNA-seq analyses of the genomic regions of those seven QTL clusters identified 47 candidate genes for seed-related traits. These genes are highly expressed in seed-related tissues and nodules, which might be deemed as potential candidate genes regulating the seed size, weight, and shape traits in soybean. This study provides detailed information on the genetic basis of the studied traits and candidate genes that could be efficiently implemented by soybean breeders for fine mapping and gene cloning, and for marker-assisted selection (MAS) targeted at improving these traits individually or concurrently.
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IMPORTANCE: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. OBJECTIVE: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. DESIGN, SETTING, AND PARTICIPANTS: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. INTERVENTIONS: Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). MAIN OUTCOMES AND MEASURES: The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. RESULTS: Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. CONCLUSIONS AND RELEVANCE: Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01421342.
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Antidepressivos/administração & dosagem , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Bupropiona/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Substituição de Medicamentos , Adulto , Antidepressivos/uso terapêutico , Resistência a Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estados Unidos , VeteranosRESUMO
BACKGROUND: Comorbid depression and anxiety may result in greater symptom severity and poorer treatment response than either condition alone. Selective serotonin reuptake inhibitors have been found to be effective in treating both depression and anxiety; however, pharmacodynamic and pharmacokinetic changes associated with aging warrant special attention in medication trials in older patients. OBJECTIVE: The objective of this study was to assess the efficacy and tolerability of short-term (12-week) administration of escitalopram oxalate 10 to 20 mg/d for moderate to marked comorbid depression and anxiety in elderly patients. METHODS: This open-label, flexible-dose (10-20 mg/d), pilot trial was conducted at the Psychiatry Service, Veterans Affairs Medical Center, Cincinnati, Ohio. Outpatients aged > or =65 years were included if they met the criteria for comorbid major depressive disorder (MDD) and generalized anxiety disorder (GAD), as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, for > or =4 weeks and had a baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of >22 and a Hamilton Rating Scale for Anxiety (HAM-A) score of > or =18. All patients received escitalopram 10 to 20 mg/d. The primary efficacy variables were the mean changes from baseline in total MADRS and HAM-A scores at 12 weeks (last observation carried forward). The secondary efficacy end point was the change from baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) 8 subscale scores. Adverse events were assessed at each visit (treatment weeks 1, 2, 3, 4, 6, 8, 10, and 12) with the use of open-ended questioning. RESULTS: Twenty patients were enrolled (mean [SD] age, 73.0 [4.8] years; 6 [30%] women; race: 17 [85%] white, 2 [10%] black, and 1 [5%] "other"). Seventeen (85%) of 20 patients completed the study; 3 (15%) withdrew: 1 (5%) due to lack of efficacy and 2 (10%) due to adverse events (dizziness and somnolence [1 (5%) patient each]). Statistically significant improvements from baseline to end point were found with escitalopram treatment (MADRS: t19 = 7.38, P < 0.001, effect size = 2.93; HAM-A: t19 = 4.19, P < 0.001, effect size = 1.83). Significant changes from baseline in scores on 4 (Social Functioning, Role Functioning-Emotional, Mental Health, and Energy/Fatigue) of the 8 subscales of the SF-36 were also found (all, P < 0.01). CONCLUSION: In this small study in elderly patients with comorbid MDD and GAD, treatment with escitalopram 10 to 20 mg/d for 12 weeks was associated with significant improvements in symptoms of depression and anxiety.
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Transtornos de Ansiedade/tratamento farmacológico , Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Idoso , Transtornos de Ansiedade/complicações , Citalopram/administração & dosagem , Citalopram/efeitos adversos , Transtorno Depressivo Maior/complicações , Feminino , Humanos , Masculino , Projetos Piloto , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversosRESUMO
Intravascular papillary endothelial hyperplasia is a benign intravascular process thought to arise from an organizing thrombus. The lesion may present clinically as an abnormal mass and, depending on the location, may be confused with benign or malignant neoplasms. It has been described in a variety of locations. Involvement of the renal vein by papillary endothelial hyperplasia is extremely rare, with only 4 cases reported in the literature. We describe 2 additional cases. In both cases, the radiologic examination revealed a well-circumscribed mass in the hilar region of the kidney, which was considered to be a renal neoplasm. Nephrectomy specimen in each case revealed characteristic features of intravascular papillary endothelial hyperplasia. It is suggested that intravascular papillary endothelial hyperplasia should be included in the differential diagnosis of a hilar renal mass.