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Involvement of protein kinases associated signal transduction mechanisms in cardiac diseases 蛋白激酶相关信号转导机制对心脏疾病的参与
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-08 DOI: 10.37349/emed.2023.00185
Jaykrishan Prasad, A. Shah, N. Dhalla
Protein kinases, a family of enzymes responsible for regulating various cellular processes, have been implicated in the development and progression of various heart diseases, making them attractive therapeutic targets. This review focuses on the role of protein kinases induced phosphorylation and protein phosphatase-induced dephosphorylation in cardiovascular disorders, including heart failure, ischemic heart disease, arrhythmias, hypertension, and diabetic cardiomyopathy. This paper explores the potential of novel kinase-targeted therapies and emerging technologies for the prevention and treatment of these conditions. It also discusses the involvement of protein kinase A (PKA), protein kinase C (PKC), phosphoinositide 3-kinases (PI3Ks), mitogen-activated protein kinases (MAPKs), and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in heart dysfunction and alterations in their function that contribute to their respective cardiac disorders. Furthermore, this article presents a comprehensive overview of protein kinases in cardiac disorders and the potential of innovative kinase-targeted therapies, advanced technologies, and multidisciplinary approaches for the effective prevention and treatment of cardiovascular diseases, ultimately aiming to improve patient outcomes and quality of life.
蛋白激酶是一个负责调节各种细胞过程的酶家族,与各种心脏病的发生和发展有关,使其成为有吸引力的治疗靶点。本文综述了蛋白激酶诱导的磷酸化和蛋白磷酸酶诱导的去磷酸化在心血管疾病中的作用,包括心力衰竭、缺血性心脏病、心律失常、高血压和糖尿病性心肌病。本文探讨了预防和治疗这些疾病的新型激酶靶向治疗和新兴技术的潜力。它还讨论了蛋白激酶A (PKA)、蛋白激酶C (PKC)、磷酸肌苷3激酶(PI3Ks)、丝裂原活化蛋白激酶(MAPKs)和Ca2+/钙调素依赖性蛋白激酶II (CaMKII)在心功能障碍中的参与,以及它们各自心脏疾病的功能改变。此外,本文还全面概述了蛋白激酶在心脏疾病中的作用,以及创新激酶靶向治疗、先进技术和多学科方法在有效预防和治疗心血管疾病方面的潜力,最终旨在改善患者的预后和生活质量。
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引用次数: 0
Impact of the type of breast cancer on the biodiversity of the vaginal Candida represented by estrogen receptor and its levels 乳腺癌类型对以雌激素受体及其水平为代表的阴道念珠菌生物多样性的影响
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-06 DOI: 10.37349/emed.2023.00183
A. A. H. S. AL-Janabi, Ruaa Kadhim Mohammed Jawad, Abdul Razzak Kalaf Hassan
Aim: Estrogen has an important role in the colonization of Candida through the presence of estrogen receptors (ERs). These ERs are usually used to categorize breast cancer into two types, positive and negative ER breast cancers. The effect of variation in the type of ER and estrogen levels on the biodiversity of Candida in the vagina was investigated.Methods: A case-control study, consisting of three groups of 30 patients with ER-positive, 29 with ER-negative breast cancer, and 30 healthy individuals, was carried out. The diversity and counting of Candida spp. in the vagina and estrogen levels were identified in all subjects.Results: The growth of Candida spp. was high in the vagina of patients with ER-positive breast cancer when estrogen was at normal levels. Otherwise, its growth was enhanced by high levels of estrogen in patients with ER-negative breast cancer.Conclusions: Estrogen levels have no effect on the vaginal content of Candida spp. in patients with ER-positive breast cancer, unlike those with ER-negative breast cancer. The principal recommendation from this study is that vaginal candidiasis and estrogen levels should be checked in patients with ER-negative breast cancer.
目的:雌激素通过雌激素受体(er)的存在在念珠菌的定植中起重要作用。这些ER通常用于将乳腺癌分为两种类型,阳性ER乳腺癌和阴性ER乳腺癌。研究了雌激素受体类型和雌激素水平变化对阴道内念珠菌生物多样性的影响。方法:采用病例对照研究,将雌激素受体阳性乳腺癌患者30例、雌激素受体阴性乳腺癌患者29例和健康人群30例分为3组。对所有受试者阴道内念珠菌的多样性、计数及雌激素水平进行了检测。结果:雌激素水平正常时,er阳性乳腺癌患者阴道内念珠菌生长旺盛。否则,雌激素受体阴性乳腺癌患者体内高水平的雌激素会促进其生长。结论:雌激素水平对er阳性乳腺癌患者阴道念珠菌含量无影响,与er阴性乳腺癌患者不同。本研究的主要建议是对er阴性乳腺癌患者应检查阴道念珠菌病和雌激素水平。
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引用次数: 0
Treatment of malignant diseases with phytocannabinoids: promising observations in animal models and patients 用植物大麻素治疗恶性疾病:在动物模型和患者身上观察到的有希望的结果
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-06 DOI: 10.37349/emed.2023.00182
Gerhard Nahler
Amazingly, almost 50 years after the first demonstration of anticancer effects of cannabinoids in vitro and in vivo, well-designed clinical trials that definitively prove tumour-inhibiting effects in man are still missing. Whereas a large number of preclinical studies exist that describe tumour-inhibiting effects of cannabinoids, alone or in combination, but also in the form of medical cannabis or natural extracts in vitro, the number of in vivo studies is still limited. Even more limited are well-documented experiences in man. Most animal studies and experience with cannabinoids in man concern brain tumours. This review summarises the effects of phytocannabinoids in brain, breast, colorectal, head and neck, haematological, liver, lung, pancreatic, ovarian, prostate, and skin cancers in animal models and, if available, in patients. The large majority of animal studies demonstrate tumour-inhibiting effects of cannabinoids, thus confirming in vitro data. Experiences in cancer patients are almost exclusively limited to individual case reports and case series without a control group. Many questions are currently unanswered such as the role of pure cannabinoids compared to combinations, cannabinoids as the eventual sole cancer therapy, optimal dosages, or duration of treatment. Pure cannabidiol (CBD) seems to be superior to pure delta-9-tetrahydrocannabinol (THC) in experimental settings. The role of medical cannabis or extracts is less clear as they vary in their phytochemical composition. In conclusion, cannabis/cannabinoids may slow the progression of tumours. However, the hope that cannabinoids could eventually cure cancer as often spread in social media, is, at present, wishful thinking. Above all, well-designed clinical trials paired with long-term follow-up of cancer patients are needed.
令人惊讶的是,在大麻素首次在体外和体内证明其抗癌作用近50年后,仍然没有经过精心设计的临床试验来明确证明其对人体的肿瘤抑制作用。尽管存在大量临床前研究,描述了大麻素单独或组合的肿瘤抑制作用,但也以医用大麻或天然提取物的形式在体外进行,但体内研究的数量仍然有限。更有限的是在人类身上有充分记录的经验。大多数动物研究和大麻素对人类的影响都与脑肿瘤有关。本文综述了植物大麻素在脑癌、乳腺癌、结直肠癌、头颈癌、血流变癌、肝癌、肺癌、胰腺癌、卵巢癌、前列腺癌和皮肤癌的动物模型和(如果有的话)患者中的作用。绝大多数动物研究表明大麻素具有肿瘤抑制作用,从而证实了体外数据。癌症患者的经验几乎完全局限于个别病例报告和病例系列,没有对照组。许多问题目前没有答案,例如纯大麻素与组合相比的作用,大麻素作为最终唯一的癌症治疗方法,最佳剂量或治疗持续时间。在实验环境中,纯大麻二酚(CBD)似乎优于纯δ -9-四氢大麻酚(THC)。药用大麻或提取物的作用不太清楚,因为它们的植物化学成分各不相同。总之,大麻/大麻素可以减缓肿瘤的进展。然而,希望大麻素最终能治愈癌症,就像社交媒体上经常传播的那样,目前还只是一厢情愿的想法。最重要的是,需要精心设计的临床试验,并对癌症患者进行长期随访。
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引用次数: 0
Roles of poly(ADP-ribose) polymerase 1 and mitophagy in progeroid syndromes as well as physiological ageing 聚(adp核糖)聚合酶1和线粒体自噬在类早衰综合征和生理性衰老中的作用
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-31 DOI: 10.37349/emed.2023.00180
Naoko Suga, Yuka Ikeda, Sayuri Yoshikawa, Satoru Matsuda
Progeroid syndromes are characterized by clinical signs of premature ageing, which may contain several diseases such as Werner syndrome, Bloom syndrome, Rothmund-Thomson syndrome, Hutchinson-Gilford progeria syndrome, and Cockayne syndrome. These disorders may also exhibit some pathological involvements reminiscent of primary mitochondrial diseases. Emerging evidence has linked mitochondria even to physiological ageing. In addition, alterations in the maintenance pathway of mitochondria have been also deliberated as relevant in age-related diseases. In particular, mitophagy and its regulatory pathway might be key process for the homeostasis of mitochondria. Therefore, chronic DNA damage and/or the activation of poly[adenosine diphosphate (ADP)-ribose] polymerase 1 (PARP1) could be a threat to the mitochondrial alterations. The PARP1 is an enzyme responding to the DNA damage, which might be also involved in the mitophagy. Interestingly, the PARP1 has been reported to play an important role in the longevity of lifespan, which has attracted growing attention with the social development. This review may provide a rationalized overview of the involvement of mitochondrial oxidative stresses in genetically defined accelerated ageing, progeroid syndromes, physiological ageing, and/or age-related diseases for the innovative therapeutic approaches.
类早衰综合征以早衰的临床体征为特征,可包含Werner综合征、Bloom综合征、rothmond - thomson综合征、Hutchinson-Gilford早衰综合征、Cockayne综合征等几种疾病。这些疾病也可能表现出一些病理参与,使人想起原发性线粒体疾病。新出现的证据甚至将线粒体与生理衰老联系起来。此外,线粒体维持途径的改变也被认为与年龄相关疾病有关。特别是,线粒体自噬及其调控途径可能是线粒体稳态的关键过程。因此,慢性DNA损伤和/或聚二磷酸腺苷(ADP)-核糖)聚合酶1 (PARP1)的激活可能是线粒体改变的威胁。PARP1是一种对DNA损伤作出反应的酶,它可能也参与了线粒体自噬。有趣的是,PARP1被报道在寿命延长中起着重要作用,随着社会的发展,这一问题越来越受到人们的关注。这篇综述可能为线粒体氧化应激在基因定义的加速衰老、类早衰综合征、生理性衰老和/或年龄相关疾病中的参与提供一个合理的概述,为创新的治疗方法提供参考。
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引用次数: 0
A U.S. Food and Drug Administration perspective on cannabis research and drug development 美国食品和药物管理局对大麻研究和药物开发的看法
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-31 DOI: 10.37349/emed.2023.00179
Cassandra L. Taylor, Schuyler A. Pruyn
Since the early 1970s, the U.S. Food and Drug Administration (FDA) has received over 800 investigational new drug applications (INDs) for, and pre-INDs pertaining to, research of cannabis or cannabis-derived products. The current data show that applications for research of these products submitted by both academic researchers and commercial developers focus on four major clinical areas: addiction and pain medicine (53%), neurology (19%), immunology and inflammation (14%), and psychiatry (9%). The product types studied have expanded greatly in recent years and include a wide variety of topical, inhalable, injectable, and oral products. In this article, the authors present a breakdown of cannabis and cannabis-derived applications received by the FDA over the past 50 years. The authors also provide a summary of their experience and challenges in reviewing applications for research of cannabis and cannabis-derived products, as well as recommendations for those interested in studying cannabis and cannabis-derived products in human clinical trials. This perspective article includes a discussion on important IND criteria, the pre-IND consultation program, drug master files (DMFs), and various guidance documents and resources. Lastly, the authors provide their perspective for the future of cannabis drug development.
自20世纪70年代初以来,美国食品和药物管理局(FDA)已经收到了800多份关于大麻或大麻衍生产品研究的研究性新药申请(ind)和pre- ind。目前的数据显示,学术研究人员和商业开发商提交的这些产品的研究申请主要集中在四个主要的临床领域:成瘾和疼痛药物(53%)、神经病学(19%)、免疫学和炎症(14%)以及精神病学(9%)。近年来,研究的产品类型大大扩展,包括各种外用、可吸入、可注射和口服产品。在这篇文章中,作者提出了在过去的50年里,FDA收到的大麻和大麻衍生应用程序的分解。作者还总结了他们在审查大麻和大麻衍生产品研究应用方面的经验和挑战,并为那些有兴趣在人体临床试验中研究大麻和大麻衍生产品的人提供了建议。这篇前瞻性文章包括对IND重要标准、IND前咨询计划、药物主文件(dmf)以及各种指导文件和资源的讨论。最后,作者对大麻药物开发的未来提出了自己的看法。
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引用次数: 0
Figuring the characteristics of the Delta variant SARS-CoV-2 gene mutations in an Indonesian hospital: a descriptive study 确定印尼一家医院Delta型SARS-CoV-2基因突变特征:一项描述性研究
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-31 DOI: 10.37349/emed.2023.00181
Phey Liana, Muhammad Agung Maulana, Eny Rahmawati, Rouly Pola Pasaribu, Kemas Yakub Rahadiyanto, Nelda Aprilia Salim, Tungki Pratama Umar
Aim: Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 has undergone several mutations, and ultimately, Indonesia was designated the Asian epicenter of the pandemic in 2021 due to the emergence of Delta variant SARS-CoV-2. Therefore, this study aimed to determine the characteristics of the Delta variant SARS-CoV-2 gene mutations. Methods: This is a cross-sectional descriptive study to determine the mutation characteristics of the Delta variant SARS-CoV-2 with data collected from patients’ medical records and whole genome sequencing (WGS). Results: The forty-nine patients who contracted the Delta variant SARS-CoV-2 were mainly aged 31−45 years and female. Four sublineages were identified, namely AY.23 (69.39%), AY.24 (22.45%), B.1.617.2 (6.12%), and AY.62 (2.04%), with fever and malaise being the most common clinical manifestations (79.60%). Furthermore, the spike (S) protein was most frequently mutated (12 mutations), with mutations in the Delta variant SARS-CoV-2 membrane (M) protein, nucleocapsid (N) protein, open reading frame (ORF), and nonstructural protein (NSP) also identified. Conclusions: The most common Delta variant SARS-CoV-2 sublineage in the current study cohort was AY.23, with the S protein being most frequently mutated. Continuous genomic surveillance is required to contain future outbreaks or infection waves, especially during the COVID-19 pandemic.
目的:冠状病毒病2019 (COVID-19)是由严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)引起的呼吸道感染。SARS-CoV-2经历了多次突变,最终,由于Delta变体SARS-CoV-2的出现,印度尼西亚于2021年被指定为大流行的亚洲中心。因此,本研究旨在确定Delta变体SARS-CoV-2基因突变的特征。方法:本研究是一项横断面描述性研究,利用从患者病历和全基因组测序(WGS)中收集的数据来确定Delta变体SARS-CoV-2的突变特征。结果:49例δ型SARS-CoV-2感染病例以31 ~ 45岁女性为主。发现4个亚系,分别为AY.23(69.39%)、AY.24(22.45%)、B.1.617.2(6.12%)和AY.62(2.04%),以发热和不适为最常见的临床表现(79.60%)。此外,刺突(S)蛋白最常发生突变(12个突变),δ变异SARS-CoV-2膜(M)蛋白、核衣壳(N)蛋白、开放阅读框(ORF)和非结构蛋白(NSP)也发生突变。结论:在当前的研究队列中,最常见的Delta变体SARS-CoV-2亚谱系是AY.23,其中S蛋白最常发生突变。需要持续的基因组监测来控制未来的疫情或感染浪潮,特别是在2019冠状病毒病大流行期间。
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引用次数: 0
Recent advancements in skin cancer treatment: a critical review 皮肤癌治疗的最新进展:综述
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-31 DOI: 10.37349/emed.2023.00178
Rajat Goyal, Shaheen Husain, Kashish Wilson, Hitesh Chopra, Rakesh Pahwa, Mathumalar Loganathan, Rohit Sharma
The prevalence of skin cancer has increased hastily in the recent decade for both kinds of melanoma and non-melanoma skin cancer. Skin cancers mostly encompass keratinocyte cancers: cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma. This review discusses the recent advancements in the treatment of skin cancer. In addition to chemotherapy, immunotherapy, targeted therapy, and photodynamic therapy (PDT), there are several other therapies for skin cancer. Additionally, PDT use in combination with chemotherapy, radiation, immunotherapy, and surgery is being actively investigated. This review will specifically address the pathophysiology of skin cancer, diagnostic approaches, and current therapies used in the topical treatment of skin cancers and introduce emerging treatment using nanotechnology that may be beneficial for these indications.
近十年来,黑色素瘤和非黑色素瘤皮肤癌的患病率迅速上升。皮肤癌主要包括角化细胞癌:皮肤鳞状细胞癌、基底细胞癌和黑色素瘤。本文就皮肤癌治疗的最新进展作一综述。除了化疗、免疫治疗、靶向治疗和光动力治疗(PDT)外,还有其他几种治疗皮肤癌的方法。此外,PDT与化疗、放疗、免疫治疗和手术联合使用正在积极研究中。这篇综述将专门讨论皮肤癌的病理生理学、诊断方法和目前用于皮肤癌局部治疗的治疗方法,并介绍使用纳米技术的新兴治疗方法,这些方法可能对这些适应症有益。
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引用次数: 0
Determinants of human longevity: input of environment, nutrition, physical activity, eustress, heredity, health care, motivation, and mental state 人类长寿的决定因素:环境、营养、体力活动、压力、遗传、保健、动机和精神状态的投入
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-30 DOI: 10.37349/emed.2023.00176
Renad I. Zhdanov, Rustem N. Khayrullin, Rovshan I. Khalilov, Aziz Eftekhari, Alexey S. Sozinov
The paper aims to review the possibilities of a complex transdisciplinary approach to forming health and longevity. Determinants of productive longevity (DPL) and health culture are reviewed; definitions of health, stress, and eustress, and their roles in active and productive longevity are given. DPL making a decisive contribution to the phenomenon of active longevity are stated and analyzed from the point of view of evidence-based medicine. They are as follows: 1) environmental factors including geographical location, “Blue zones”, and mountain areas, as well as level of the environmental pollution; 2) dietary regimen to support active longevity, including vegetarianism, calorie restriction, fasting, the role of vitamins, biological antioxidants, geroprotectors, and micronutrients; 3) importance of activity and eustress phenomenon, by other words, lifestyle: physical activity, sexual relationship, Qigong and Yoga practices, cognitive activity, sense of humor, and acceptance of age in activities of daily living and survival; 4) genetic and epigenetic particularities as a condition for long-living; 5) level of health care and early diagnostics to prevent age-associated diseases; 6) the role of the state of mind and meditation as well, how it is used for forming health due to Qigong and Yoga natural systems, in religion, and medical practice; 7) motivation for active longevity that significantly increases chances to productive longevity.
本文旨在回顾一种复杂的跨学科方法形成健康和长寿的可能性。审查了生产寿命(DPL)和健康文化的决定因素;给出了健康、压力和压力的定义,以及它们在积极和富有成效的长寿中的作用。从循证医学的角度阐述和分析了DPL对积极长寿现象的决定性贡献。主要包括:1)地理位置、“蓝带”、山区等环境因素以及环境污染程度;2)支持积极长寿的饮食方案,包括素食、热量限制、禁食、维生素、生物抗氧化剂、老年保护剂和微量营养素的作用;3)活动和应激现象的重要性,即生活方式:日常生活和生存活动中的体育活动、性关系、气功和瑜伽练习、认知活动、幽默感和年龄接受度;4)作为长寿条件的遗传和表观遗传特性;5)保健和早期诊断水平,以预防与年龄有关的疾病;6)心态和冥想的作用,以及如何利用气功和瑜伽自然系统来形成健康,在宗教和医疗实践中;7)积极长寿的动机,大大增加了有效长寿的机会。
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引用次数: 0
Contemporary review: recognition, management, and screening for radiation-induced heart disease 当代综述:辐射诱发心脏病的识别、管理和筛查
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-30 DOI: 10.37349/emed.2023.00177
Chirag Mehta, Puneet Singh, Jess Brar
Radiation is a primary therapy in the treatment of thoracic malignancies with clear survival benefits. Consequently, patients with cancer are living longer but may be subject to a wide array of cardiotoxic effects from collateral radiation damage. Ensuing fibrosis can affect any portion of the cardiac parenchyma, increasing the risk for accelerated coronary artery disease, pericardial sequelae such as constrictive pericarditis, valvulopathy, restrictive cardiomyopathy, and a myriad of conduction system abnormalities. Unfortunately, the effects of cardiotoxicity can be subclinical or delayed and there remains an unmet need to standardize management strategies for these patients. Based on current data, it is prudent to consider percutaneous approaches first for coronary and valvular disease and traditional, supportive measures for the remaining sequelae. Every attempt should be made to undergo a complete operative haul due to the increased risks of re-operation if surgery is to be performed. Surrounding the patient with a multidisciplinary heart team is critical.
放射是治疗胸部恶性肿瘤的主要治疗方法,具有明显的生存益处。因此,癌症患者的寿命更长,但可能会受到附带辐射损伤的广泛心脏毒性影响。随后的纤维化可影响心脏实质的任何部分,增加冠状动脉加速病变、心包后遗症(如缩窄性心包炎、瓣膜病、限制性心肌病)和无数传导系统异常的风险。不幸的是,心脏毒性的影响可能是亚临床的或延迟的,对这些患者的标准化管理策略的需求仍然没有得到满足。根据目前的数据,对于冠状动脉和瓣膜疾病,首先考虑经皮入路是谨慎的,对于剩余的后遗症,应考虑传统的支持性措施。如果要进行手术,再手术的风险会增加,因此应尽量进行一次完整的手术。让病人周围有多学科的心脏小组是至关重要的。
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引用次数: 0
A successful case of maturogenesis by stepwise excavation using calcium-enriched mixture cement 富钙混合水泥分步开挖成熟发生的成功案例
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-27 DOI: 10.37349/emed.2023.00173
Saeed Asgary, Laleh Alim Marvasti
This case report demonstrates the successful induction of apexogenesis in an extensively carious lower right first molar with immature roots through the use of stepwise excavation and calcium-enriched mixture (CEM) cement as an indirect pulp capping material. The patient, an 8-year-old boy, presented with pain and carious pulp exposure. The initial treatment involved removing soft dentin and applying CEM cement as an indirect pulp cap. The patient experienced pain relief after 24 h, and subsequent follow-up appointments showed complete healing and maturation of the tooth. The case highlights the potential of indirect pulp treatment with CEM cement and emphasizes the importance of regenerative biomaterials in promoting healing and dentin bridge formation. Further clinical work and research are recommended to explore the efficacy of this treatment approach.
本病例报告展示了通过使用逐步挖掘和富钙混合物(CEM)水泥作为间接髓盖材料,成功诱导具有未成熟根的广泛龋病的右下第一磨牙的尖牙发生。患者为一名8岁男孩,表现为疼痛和牙髓暴露。最初的治疗包括去除软牙本质并应用CEM水泥作为间接牙髓盖。患者在24小时后疼痛缓解,随后的随访显示牙齿完全愈合和成熟。该病例强调了CEM骨水泥间接牙髓治疗的潜力,并强调了再生生物材料在促进牙本质愈合和牙本质桥形成方面的重要性。建议进一步的临床工作和研究来探索这种治疗方法的疗效。
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引用次数: 0
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