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Screening and Druggability Analysis of Marine Active Metabolites against SARS-CoV-2: An Integrative Computational Approach 海洋活性代谢物抗SARS-CoV-2的筛选及药物活性分析:综合计算方法
Pub Date : 2022-12-28 DOI: 10.20944/preprints202212.0008.v1
Selvakumar Murugesan, C. Ragavendran, Amir Ali, Velusamy Arumugam, D. Lakshmanan, P. Palanichamy, M. Venkatesan, C. Kamaraj, J. Luna-Arias, Fernández-Luqueño Fabián, S. Khan, Z. Mashwani, M. Younas
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds are under clinical investigation for various diseases. In particular, marine natural compounds are gaining more attention in the new drug development process. The present study aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the 4 SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds, namely, chrysophaentin A (−6.6 kcal/mol), geodisterol sulfates (−6.6 kcal/mol), hymenidin (−6.4 kcal/mol), plinabulin (−6.4 kcal/mol), and tetrodotoxin (−6.3 kcal/mol) expressed minimized binding energy and molecular interactions, such as covalent and hydrophobic interactions, with the SARS CoV-2 main protease. Using molecular dynamic studies, the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (ROG), and hydrogen bond (H-Bond) values were calculated for the SARS-CoV-2 main protease with a hymenidin docked complex. Additionally, in silico drug-likeness and pharmacokinetic property assessments of the compounds demonstrated favorable druggability. These results suggest that marine natural compounds are capable of fighting SARS-CoV-2. Further in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.
严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)感染引发了最近的呼吸系统疾病大流行,并影响了世界上几乎所有国家。大量的天然生物活性化合物正处于各种疾病的临床研究中。特别是海洋天然化合物在新药开发过程中受到越来越多的关注。本研究旨在利用计算方法确定针对COVID-19靶蛋白的潜在海洋来源抑制剂。目前,选择了16种海洋临床级化合物对4种SARS-CoV-2主要蛋白酶进行计算筛选。基于结合亲和力评分和氨基酸相互作用,计算筛选出每个靶点的最佳候选药物。其中,五种海洋来源的化合物,即大黄嘌呤A (- 6.6 kcal/mol)、硫酸地二醇(- 6.6 kcal/mol)、膜苷(- 6.4 kcal/mol)、plinabulin (- 6.4 kcal/mol)和河豚毒素(- 6.3 kcal/mol)与SARS CoV-2主要蛋白酶的结合能和分子相互作用(如共价和疏水相互作用)最小。利用分子动力学研究方法,计算了膜酶对接复合物的SARS-CoV-2主蛋白酶的均方根偏差(RMSD)、均方根波动(RMSF)、旋转半径(ROG)和氢键(h -键)值。此外,该化合物的药物相似性和药代动力学性质评估显示出良好的药物性。这些结果表明,海洋天然化合物能够对抗SARS-CoV-2。进一步的体外和体内研究需要进行,以确认其抑制潜力。
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引用次数: 1
Association between Peer Victimization (PV) in Childhood/Adolescence and Personality Disorders among Adult Patients 儿童/青少年同伴受害与成人人格障碍的关系
Pub Date : 2022-12-26 DOI: 10.3390/ijtm3010002
R. Fernández-Martínez, C. Fernandez-Pereira, D. Pérez-Rodríguez, Á. Salgado-Barreira, Cesar Veiga García, Sara Teso-Cuesta, J. Prieto-González, J. M. Olivares Díez, R. Agís-Balboa
Peer Victimization (PV) or being bullied in childhood/adolescence has been associated with several negative outcomes in mental health conditions beyond the time of its occurrence. However, its possible association with personality disorders has been slightly explored. In the present study we have compared the frequency of DSM IV personality disorders among adult patients with (N = 28) or without (N = 418) a reported history of PV. For this purpose, axis II was evaluated with the Self-Report Checklist for Preliminary Items for Major Categories, whereas self-esteem and self-assessment of functioning were evaluated with single questions. Patients with PV history have met the diagnostic criteria of the avoidant (60.7% vs. 12.2%), depressive (28.5% vs. 5.2%) and paranoid (17.9% vs. 5%) personality disorders more frequently than patients without history of PV. Moreover, these patients with antecedents of being bullied have also reported lower self-esteem (2 vs. 3) and in the assessment of social functioning (4 vs. 5). Our study indicated that there is a clear association between PV and avoidant, depressive and paranoid personality patterns. These results suggest that the stress related with the experience of PV threatens a basic psychobiological need such as social acceptance with implications for the beginning of long-term dysfunctional personality trajectories.
同伴受害(PV)或在儿童/青少年时期被欺负与心理健康状况的一些负面结果相关,而这些负面结果在其发生后仍存在。然而,它与人格障碍的可能联系已经被稍微探讨了一下。在本研究中,我们比较了有PV病史(N = 28)和无PV病史(N = 418)的成人患者DSM IV人格障碍的频率。为此目的,第二轴用主要类别初步项目自我报告清单进行评估,而自尊和功能自我评估则用单题进行评估。有PV病史的患者比无PV病史的患者更符合逃避型(60.7%比12.2%)、抑郁症(28.5%比5.2%)和偏执型(17.9%比5%)人格障碍的诊断标准。此外,这些有欺凌经历的患者也报告了较低的自尊(2比3)和社会功能评估(4比5)。我们的研究表明,PV与回避型、抑郁型和偏执型人格模式之间存在明显的关联。这些结果表明,与PV经验相关的压力威胁到基本的心理生物学需求,如社会接受,并暗示长期功能失调人格轨迹的开始。
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引用次数: 0
Comparison of the Basic Reproduction Numbers for COVID-19 through Four Waves of the Pandemic in Vietnam 越南四波新冠肺炎基本复制数比较
Pub Date : 2022-12-21 DOI: 10.3390/ijtm3010001
N. T. Mai, G. Tran, A. H. Dang, Phuong Cao, T. Nguyen, H. Pham, Tra Thi Thu Vu, Hieu Van Dong, Le Thi My Huynh
Estimating the basic reproduction number (R0) of an infectious disease is a crucial step to describe the contagiousness and provides suggestions for interventions. To lift the effectiveness of preventive measures for the COVID-19 pandemic, we need to minimize the newly infected cases by reaching adequate herd immunity. This study thus aimed to compare the R0 through four waves of COVID-19 outbreaks in Vietnam and to calculate the minimal vaccination coverage in different populations. The data on the number of daily confirmed COVID-19 patients were collected from 21 January 2020 to 16 November 2021 from the daily reports through the four waves of the pandemic in Vietnam. The R0 values were estimated by exponential growth and the maximum likelihood methods to range from 1.04 to 3.31 from the first to the third wave. The fourth wave was the most severe, especially in the southern provinces, and the highest R0 was in Ho Chi Minh City. The herd immunity would range from 43.50% to 95.76% by various R0 values from different populations. Overall, the presence of new viral mutants increased the infectiousness and the vaccination coverage was higher to establish the required herd immunity in a high-density population. The results provide the basis for policy recommendations and resource allocation for vaccine management and distribution at a time when the COVID-19 pandemic is not yet over.
估计传染病的基本繁殖数(R0)是描述传染病传染性和提供干预建议的关键步骤。为了提高COVID-19大流行预防措施的有效性,我们需要通过达到足够的群体免疫来最大限度地减少新感染病例。因此,本研究旨在比较越南四波COVID-19疫情的R0,并计算不同人群的最低疫苗接种覆盖率。从2020年1月21日至2021年11月16日,从越南四波大流行期间的每日报告中收集了每日确诊COVID-19患者人数的数据。采用指数增长法和最大似然法估计第一波至第三波的R0值在1.04 ~ 3.31之间。第四波是最严重的,特别是在南部省份,最高的R0是在胡志明市。根据不同群体的R0值,群体免疫范围为43.50% ~ 95.76%。总的来说,新的病毒突变体的存在增加了传染性,并且在高密度人群中建立所需的群体免疫的疫苗接种覆盖率更高。在COVID-19大流行尚未结束之际,这些结果为疫苗管理和分发的政策建议和资源分配提供了依据。
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引用次数: 0
Efficacy and Safety of Brazilian Green Propolis in Biochemically Recurrent Prostate Cancer after Radical Prostatectomy: A Single-Arm Phase II Study 巴西绿蜂胶治疗根治性前列腺切除术后复发前列腺癌的疗效和安全性:一项单组II期研究
Pub Date : 2022-12-17 DOI: 10.3390/ijtm2040047
Takayuki Goto, H. Kimura, T. Yoshino, A. Sawada, S. Akamatsu, Takashi Kobayashi, Toshinari Yamasaki, Shigemi Tazawa, M. Fujimoto, Y. Hidaka, R. Uozumi, S. Morita, Osamu Ogawa, Takahiro Inoue
Background: Radiation or hormonal therapy is considered for prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, these therapies have their own complications. To delay the start of these therapies, we investigated the efficacy and safety of Brazilian green propolis for the treatment for BCR after RP. Materials and Methods: This single-center, single-arm open trial included 22 patients who experienced BCR after RP between 2016 and 2019. The patients received nine softgels of Brazilian green propolis (containing 40 mg propolis per capsule) daily for 6 months. The primary outcome was the prostate-specific antigen (PSA) response rate. The secondary outcomes included progression-free time, PSA slope (1/PSA doubling time) response rate, quality of life, and safety profile. Results: The PSA response rate was 0%. The mean PSA slopes before and after baseline were 0.12 month−1 and 0.08 month−1, respectively. Fifteen patients (68%) showed a decreased PSA slope after treatment. There were no negative effects on quality of life or serious adverse events leading to treatment discontinuation. Conclusion: There was no significant anticancer response in patients who received Brazilian green propolis. However, the PSA slope was decreased after propolis administration. Further, Brazilian green propolis may be safely consumed by patients.
背景:放疗或激素治疗是根治性前列腺切除术(RP)后生化复发(BCR)患者的首选治疗方法。然而,这些疗法有其自身的并发症。为了推迟这些治疗的开始,我们研究了巴西绿蜂胶治疗RP后BCR的有效性和安全性。材料和方法:这项单中心、单臂开放试验包括22例2016年至2019年期间RP术后BCR的患者。患者每天服用9粒巴西绿蜂胶软胶囊(每粒含40毫克蜂胶),持续6个月。主要终点是前列腺特异性抗原(PSA)应答率。次要结局包括无进展时间、PSA斜率(1/PSA加倍时间)反应率、生活质量和安全性。结果:PSA有效率为0%。基线前后的平均PSA斜率分别为0.12个月和0.08个月。15例(68%)患者治疗后PSA斜率下降。没有对生活质量的负面影响或导致治疗中断的严重不良事件。结论:接受巴西绿蜂胶治疗的患者无明显的抗癌反应。蜂胶处理后,PSA斜率降低。此外,巴西绿色蜂胶可被患者安全食用。
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引用次数: 0
Water-Soluble Carbon Nanotube Enhances Gossypol Production in Cotton Cell Suspension Culture 水溶性碳纳米管提高棉花细胞悬浮培养棉酚产量
Pub Date : 2022-12-05 DOI: 10.3390/ijtm2040046
S. Dixit, Akanchha Shukla, Santosh Kumar Upadhyay, P. Verma
Plant secondary metabolites are well-recognized medicinally important compounds. Gossypol is an important plant secondary metabolite with several medicinal properties. Carbon nanotubes (CNTs) are allotropes of carbon with diverse applicability in chemical, physical, and biological sciences due to their high surface area. The current study demonstrates the enhancement of gossypol production in cotton cell suspension culture in culture media supplemented with water-soluble carbon nanotubes. The fresh and dry weights of cotton cell suspension culture grown in MS media with 20 µg/mL CNTs were, respectively, 1.9 and 2.13 fold higher than in control MS media after one month. The net enhancement of gossypol production in MS media supplemented with 20 µg/mL CNTs was 2.47 fold higher than the control. Confocal and SEM imaging showed the presence CNTs on the cell surface, which mediated the formation of extra channels that resulted in high biomass production in cotton cell suspension culture. The gossypol produced by this cell suspension culture showed antiproliferative activity against the prostate cancer cell line. Thus, this study demonstrated a new method for enhanced gossypol production, which can prove beneficial for the production of other plant-based biological active compounds.
植物次生代谢物是公认的重要药用化合物。棉酚是一种重要的植物次生代谢产物,具有多种药用特性。碳纳米管(CNTs)是碳的同素异形体,由于其高表面积,在化学、物理和生物科学中具有广泛的适用性。本研究表明,在添加水溶性碳纳米管的培养基中,棉花细胞悬浮培养可以提高棉酚的产量。在添加20µg/mL CNTs的MS培养基中,棉花细胞悬浮培养1个月后的鲜重和干重分别比对照MS培养基高1.9倍和2.13倍。在添加20µg/mL CNTs的MS培养基中,棉酚产量的净增强量是对照组的2.47倍。共聚焦和扫描电镜成像显示,在棉花细胞悬浮培养中,细胞表面存在碳纳米管,碳纳米管介导了额外通道的形成,从而产生了高生物量。该细胞悬浮培养产生的棉酚对前列腺癌细胞具有抗增殖活性。因此,本研究证明了一种增强棉酚生产的新方法,可用于生产其他植物性生物活性化合物。
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引用次数: 1
Variations in Urinary Renin-Angiotensin-Aldosterone Component Concentrations in Paediatric IgA Vasculitis Nephritis 小儿IgA血管炎肾炎患者尿肾素-血管紧张素-醛固酮成分浓度的变化
Pub Date : 2022-12-02 DOI: 10.3390/ijtm2040045
Andrew J Chetwynd, Julien Marro, S. Northey, Daniel J. Hughes, L. Oni
IgA Vasculitis (IgAV) is the most common form of vasculitis in children, and 1–2% of patients develop chronic kidney disease. In other forms of glomerulonephritis, there is strong evidence to support the role of the renin-angiotensin-aldosterone system (RAAS); however, data are lacking in IgAV nephritis. This study evaluated urinary RAAS components in children with IgA vasculitis, both with nephritis (IgAVN) and without nephritis (IgAVwoN). Urinary concentrations of renin, angiotensinogen and aldosterone were quantified using ELISAs. In total, 40 patients were included: IgAVN n = 9, IgAVwoN n = 17, HC n = 14, with a mean age of 8.3 ± 3.3 years. Urinary renin demonstrated no trend with nephritis. Urinary angiotensinogen was statistically significantly elevated in IgAV (1.18 ± 1.16 ng/mmol) compared to HC (0.28 ± 0.27 ng/mmol, p = 0.0015), and IgAVN (2.00 ± 1.22 ng/mmol) was elevated compared to IgAVwoN (0.74 ± 0.89 ng/mmol, p = 0.0492) and HC (p = 0.0233). Urinary aldosterone levels were significantly elevated in IgAV (1236 ± 1438 pg/mmol) compared to HC (73.90 ± 65.22 pg/mmol, p < 0.0001); this was most increased in IgAVwoN patients (1793 ± 1507 pg/mmol; IgAVN 183.30 ± 111.30 pg/mmol, p = 0.0035, HC p < 0.0001). As expected, the RAAS system is activated in patients with IgAVN and, more surprisingly, even in those without active nephritis. Further studies are needed to fully understand the role of the RAAS system in IgA vasculitis.
IgA血管炎(IgAV)是儿童中最常见的血管炎形式,1-2%的患者发展为慢性肾脏疾病。在其他形式的肾小球肾炎中,有强有力的证据支持肾素-血管紧张素-醛固酮系统(RAAS)的作用;然而,缺乏IgAV肾炎的数据。本研究评估了患有IgA血管炎的儿童尿液RAAS成分,包括肾炎(IgAVN)和非肾炎(IgAVwoN)。采用elisa法测定尿肾素、血管紧张素原和醛固酮浓度。共纳入40例患者,IgAVN = 9, IgAVwoN = 17, HC = 14,平均年龄8.3±3.3岁。尿肾素与肾炎无相关性。IgAV组尿血管紧张素原(1.18±1.16 ng/mmol)高于HC组(0.28±0.27 ng/mmol, p = 0.0015), IgAVN组(2.00±1.22 ng/mmol)高于IgAVwoN组(0.74±0.89 ng/mmol, p = 0.0492)和HC组(p = 0.0233)。IgAV组尿醛固酮水平显著高于HC组(73.90±65.22 pg/mmol, p < 0.0001)(1236±1438 pg/mmol);这在IgAVwoN患者中增加最多(1793±1507 pg/mmol;IgAVN 183.30±111.30 pg/mmol, p = 0.0035, HC p < 0.0001)。正如预期的那样,RAAS系统在IgAVN患者中被激活,更令人惊讶的是,甚至在那些没有活动性肾炎的患者中也被激活。需要进一步的研究来充分了解RAAS系统在IgA血管炎中的作用。
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引用次数: 1
Effects of Phototherapy on Free Vitamin D Levels in Ten Patients with Atopic Dermatitis 光疗对10例特应性皮炎患者游离维生素D水平的影响
Pub Date : 2022-12-01 DOI: 10.3390/ijtm2040044
Andrea Elmelid, A. Osmancevic, M. Gillstedt, M. Alsterholm
The role of vitamin D in atopic dermatitis (AD) is controversial. Conflicting data could be due to the use of inadequate markers for assessing vitamin D status. So far, directly measured free 25(OH)D concentrations have not been reported in AD patients. Ten adults with AD were treated with narrow band ultraviolet light B (NB-UVB) for 10–12 weeks. SCORing atopic dermatitis (SCORAD) and the visual analogue scale (VAS) were used to assess disease severity before and after NB-UVB therapy. Total and free 25(OH)D and 1,25(OH)2D serum levels were analyzed before and after treatment. Free 25(OH)D concentrations were measured with a two-step immunosorbent assay (ELISA). The majority of patients had sufficient levels of 25(OH)D before treatment (mean 76.4 nmol/L). Mean free 25(OH)D was 11.9 pmol/L and mean 1,25(OH)2D was 108.9 pmol/L. Median SCORAD decreased from 37.1 to 19.8 and VAS improved significantly after phototherapy. Total and free 25(OH)D increased in all subjects. No correlations between disease severity and vitamin D levels were found. There was no correlation between total and free 25(OH)D levels. Larger studies are needed to test the applicability of the free hormone hypothesis in AD pathogenesis.
维生素D在特应性皮炎(AD)中的作用存在争议。相互矛盾的数据可能是由于使用了不适当的标记来评估维生素D水平。到目前为止,还没有在AD患者中直接测量游离25(OH)D浓度的报道。10例成人AD患者接受窄带紫外线B (NB-UVB)治疗10-12周。采用评分特应性皮炎(SCORAD)和视觉模拟量表(VAS)评估NB-UVB治疗前后疾病严重程度。分析治疗前后血清总25(OH)D、游离25(OH)D、1,25(OH)2D水平。用两步免疫吸附法(ELISA)测定游离25(OH)D浓度。大多数患者在治疗前25(OH)D水平足够(平均76.4 nmol/L)。平均游离25(OH)D为11.9 pmol/L,平均1.25 (OH)2D为108.9 pmol/L。光疗后中位SCORAD由37.1降至19.8,VAS明显改善。所有受试者的总25(OH)D和游离25(OH)D均增加。没有发现疾病严重程度与维生素D水平之间的相关性。总25(OH)D水平与游离25(OH)D水平无相关性。需要更大规模的研究来验证游离激素假说在AD发病机制中的适用性。
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引用次数: 1
Celosia trigyna Linn (Cucurbitaceae) Annihilate Human Breast, Colon, and Lung Cancer Cells: Combination of Cheap Template for Anticancer Screening 三叶草(葫芦科)消灭人乳腺癌、结肠癌和肺癌细胞:用于抗癌筛选的廉价模板组合
Pub Date : 2022-11-30 DOI: 10.3390/ijtm2040043
Adedokun Oluwasegun, E. Ntungwe, Ayinde Bunyamin, L. Saraíva, S. Princiotto, P. Rijo
Celosia trigyna is a well-known vegetable used in the preparation of many indigenous soups in Southwestern Nigeria. The aim of this study was to evaluate the anticancer property of C. trigyna of crude and solvent fractions using antioxidant, cytotoxic bench-top bioassays, and cancer cell line experiments. Cytotoxicity was carried out using Raniceps ranninus, Saccharomyces cerevisiae, and Sorghum bicolor models, as well as cytotoxicity studies against human breast (MCF), colon (HCT116), and lung (H460) cancer cell lines; radical scavenging potential against DPPH was likewise performed. A concentration of nondependent cytotoxicity against S. cerevisiae was observed in CTA, with the lowest inhibition of organism growth at 31.2 µg/mL (26.40 ± 1.92%) and highest activity at 250 µg/mL (56.00 ± 2.12%). Concentration-dependent inhibition was observed in CTA with 84.80 ± 1.97% at 250 µg/mL, which is significantly different from values observed in DMSO (negative control) at 33.84 ± 1.03% at p < 0.01. Moreover, 100% motility of R. ranninus (tadpoles) was recorded for all concentrations (20–40 µg/mL) in CT and CTA, with significantly different p < 0.05 from values obtained for the vehicle (distilled water). Concentration-dependent DPPH radical scavenging potential was likewise noted both in CT and CTA at 20–100 µg/mL. The lowest inhibition was observed at 20 µg/mL (41.35% and 32.31%), while the highest was noted at 100 µg/mL (63.26% and 41.73%) for CT and CTA, respectively. CT showed cytotoxic effects against all cancer cell lines examined, with CTA exhibiting improved activity compared to CT against human lung (H460), breast (MCF-7), and colon (HCT116) cancer cell lines, with IC50 51.69 ± 5.13, 39.16 ± 9.21, and 38.52 ± 7.65, respectively. Findings from this research experimentally justify the ethnomedicinal claim of usage of C. trigyna in the treatment of cancer in southwestern Nigeria.
在尼日利亚西南部,青菜是一种著名的蔬菜,用于制作许多当地的汤。本研究旨在通过抗氧化、细胞毒性实验和癌细胞系实验来评价甘油三酯粗馏分和溶剂馏分的抗癌特性。使用Raniceps rananninus、Saccharomyces cerevisiae和Sorghum双色模型进行细胞毒性研究,以及对人乳腺癌(MCF)、结肠癌(HCT116)和肺癌(H460)细胞系的细胞毒性研究;对DPPH的自由基清除潜力也进行了同样的测试。CTA对酿酒酵母具有非依赖性的细胞毒性,抑制菌体生长的最低浓度为31.2µg/mL(26.40±1.92%),最高活性为250µg/mL(56.00±2.12%)。在250µg/mL浓度下,CTA的抑制率为84.80±1.97%,显著高于阴性对照DMSO的33.84±1.03% (p < 0.01)。此外,所有浓度(20-40µg/mL)的CT和CTA均记录了ranninus(蝌蚪)100%的运动性,与载体(蒸馏水)的值有显著差异p < 0.05。在CT和CTA中同样注意到浓度依赖性DPPH自由基清除潜力,浓度为20-100µg/mL。CT和CTA在20µg/mL时的抑制率最低(41.35%和32.31%),而在100µg/mL时的抑制率最高(63.26%和41.73%)。CT显示出对所有肿瘤细胞系的细胞毒作用,与CT相比,CTA对人肺(H460)、乳腺癌(MCF-7)和结肠癌(HCT116)癌细胞的活性有所提高,IC50分别为51.69±5.13、39.16±9.21和38.52±7.65。这项研究的结果从实验上证明了在尼日利亚西南部使用甘油三籽治疗癌症的民族医学主张。
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引用次数: 0
Non-Clear Cell Renal Cell Carcinoma: Molecular Pathogenesis, Innovative Modeling, and Targeted Therapeutic Approaches 非透明细胞肾细胞癌:分子发病机制、创新模型和靶向治疗方法
Pub Date : 2022-11-23 DOI: 10.3390/ijtm2040042
Niloofar Khoshdel Rad, Maryam Vahidyeganeh, M. Mohammadi, A. Shpichka, P. Timashev, N. Hossein-khannazer, M. Vosough
Non-clear cell renal cell carcinomas (nccRCC) are a diverse group of kidney cancers with histopathologically and genetically heterogeneous features. About 25% of renal cell carcinomas (RCCs) are nccRCC types. The management and treatment of nccRCCs are rather limited, and the data are often estimated from studies in the more common clear cell renal cell carcinoma (ccRCC). Each subtype has its own distinctive biological and therapeutic profile. Our knowledge of the underlying biological features of nccRCC has directed and continues to shape the use of novel therapy targeting the main signaling pathways and leading to improved overall survival (OS) of the patients. This review discusses the characteristic molecular features of the major types of nccRCC and current cell-based and animal models for studying them. In the following, we highlighted major signaling pathways and therapeutic approaches for nccRCC patients.
非透明细胞肾细胞癌(nccRCC)是一种具有组织病理学和遗传异质性特征的多种肾癌。约25%的肾细胞癌(rcc)为ncccc型。nccrcc的管理和治疗相当有限,数据通常来自更常见的透明细胞肾细胞癌(ccRCC)的研究。每个亚型都有其独特的生物学和治疗概况。我们对nccRCC潜在生物学特征的了解已经指导并继续塑造针对主要信号通路的新疗法的使用,从而提高患者的总生存期(OS)。本文综述了nccRCC主要类型的分子特征以及目前用于研究它们的细胞模型和动物模型。在下面,我们重点介绍了nccRCC患者的主要信号通路和治疗方法。
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引用次数: 3
Trigeminal Neuralgia Treatment Outcomes Following Gamma Knife Stereotactic Radiosurgery 伽玛刀立体定向放射治疗三叉神经痛的疗效
Pub Date : 2022-11-22 DOI: 10.3390/ijtm2040041
Abbas Jarrahi, R. Cantrell, Cynthia Norris, K. Dhandapani, J. Barrett, J. Vender
Trigeminal neuralgia (TN) is a chronic pain condition causing lancinating pain in the distribution of one or more divisions of the trigeminal nerve. Gamma knife stereotactic radiosurgery (GKSRS) is a surgical option for TN refractory to medical therapy. To report our experience and to analyze the reasons for the variance in radiosurgery outcomes between patients in our diverse population, we conducted a retrospective analysis of a prospectively created database. The 178 patients completed a pain assessment questionnaire before surgery, and at 1 and 2 year follow-ups. We used the “Trigeminal Neuralgia Gamma Knife Outcome Scale” (TN GKOS) to report the response. At 1-year, 35.4% of patients had grade 1A outcome (pain-free and off all pain medications), 24.7% had grade 1B (pain-free on pain medications), 24.2% had grade 1C (some pain but improved with radiosurgery), 12.9% had grade 2 (same as before radiosurgery) and 2.8% had grade 3 (worse pain compared to before radiosurgery). At 2 years, 42.3% had grade 1A, 20.5% had grade 1B, 19.2% had grade 1C, 14.1% had grade 2 and 3.8% had grade 3 outcome. Remarkably, a statistically significant association was found between GKOS and age, racial background and obesity.
三叉神经痛(TN)是一种引起三叉神经一个或多个分支分布的刺痛的慢性疼痛状况。伽玛刀立体定向放射外科(GKSRS)是治疗顽固性脑炎的一种手术选择。为了报告我们的经验并分析不同人群患者放射手术结果差异的原因,我们对前瞻性创建的数据库进行了回顾性分析。178例患者在手术前及随访1年和2年时完成疼痛评估问卷。我们使用“三叉神经痛伽玛刀结局量表”(TN GKOS)来报告反应。1年后,35.4%的患者预后为1A级(无疼痛且停用所有止痛药),24.7%的患者预后为1B级(无疼痛且使用止痛药),24.2%的患者预后为1C级(有部分疼痛但放疗后有所改善),12.9%的患者预后为2级(与放疗前相同),2.8%的患者预后为3级(与放疗前相比疼痛加重)。2年后,42.3%为1A级,20.5%为1B级,19.2%为1C级,14.1%为2级,3.8%为3级。值得注意的是,GKOS与年龄、种族背景和肥胖之间存在统计学上显著的关联。
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引用次数: 0
期刊
Journal of International Translational Medicine
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