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The Unsuspected Role of the Renin-Angiotensin System (RAS): Could its Dysregulation be at the Root of All Non-Genetic Human Diseases? 肾素-血管紧张素系统(RAS)未被察觉的作用:肾素-血管紧张素系统(RAS)未被察觉的作用:肾素-血管紧张素系统失调可能是人类所有非遗传性疾病的根源吗?
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-01-01 DOI: 10.2174/1871526524666230914114524
Ziad Fajloun, Jean-Marc Sabatier
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引用次数: 0
Apis mellifera syriaca Venom Modulates Splenic Cytokines Levels in BALB/c Mice. 蜂毒调节 BALB/c 小鼠脾细胞因子水平
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-01-01 DOI: 10.2174/1871526523666230623152045
Christina Sahyoun, Miriam Khoury, Charbel Mouawad, Dalida Darazy, Rabih Roufayel, César Mattei, Ziad Fajloun, Christian Legros, Marc Karam

Bee venoms are well-known for their important biological activities. More specifically, the venom of Apis mellifera syriaca was shown to exhibit various biological effects, including antimicrobial effects. It is suggested that the anti-microbial effect of venom could be accompanied by an immunomodulatory response in the host favoring anti-inflammatory responses. Thus, in this work, we investigated, for the first time, the immunomodulatory effects of A. mellifera syriaca venom in mice. Firstly, it was found that this venom exhibited mild toxicity in BALB/c mice after intraperitoneal injection with an LD50 of 3.8 mg/kg. We then investigated its immunomodulatory effects by evaluating the splenic levels of both pro- and anti-inflammatory cytokines in mice by ELISA. Interestingly, at 1 mg/kg, A. mellifera syriaca venom induced a decrease in IFN-γ, TNF-α, IL-4, and IL-10 at 24h postinjection. At a higher dose (3 mg/kg), an increase in IFN-γ and IL-4 levels was observed, while the levels of TNF-α and IL-10 remained low compared to the control. Altogether, these preliminary data suggest that A. mellifera syriaca venom exhibits anti-inflammatory effects at a sublethal dose (1 mg/kg), while at a higher dose (3 mg/kg), it induces inflammatory effects.

众所周知,蜂毒具有重要的生物活性。更具体地说,Apis mellifera syriaca 的毒液被证明具有多种生物效应,包括抗微生物效应。有人认为,毒液的抗微生物作用可能伴随着宿主的免疫调节反应,有利于抗炎反应。因此,在这项工作中,我们首次研究了 A. mellifera syriaca 毒液对小鼠的免疫调节作用。首先,我们发现这种毒液在 BALB/c 小鼠腹腔注射后具有轻微毒性,半数致死剂量为 3.8 毫克/千克。然后,我们通过酶联免疫吸附法(ELISA)评估了小鼠脾脏中促炎症和抗炎症细胞因子的水平,以研究其免疫调节作用。有趣的是,注射 1 毫克/千克的 A. mellifera syriaca 毒液后 24 小时,IFN-γ、TNF-α、IL-4 和 IL-10 的含量均有所下降。在较高剂量(3 毫克/千克)下,观察到 IFN-γ 和 IL-4 水平升高,而 TNF-α 和 IL-10 水平与对照组相比仍然较低。总之,这些初步数据表明,A. mellifera syriaca 毒液在亚致死剂量(1 毫克/千克)下具有抗炎作用,而在较高剂量(3 毫克/千克)下则会诱发炎症反应。
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引用次数: 0
Uncommon Location for a Common Disease, Simulating Cervical Cancer: A Rare Case Report. 常见疾病的不常见部位,模拟宫颈癌:罕见病例报告
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-01-01 DOI: 10.2174/1871526523666230822155148
Naina Kumar, Kanikaram Poojitha Kalyani, Abhimanyu Sharma, Sumitra Sivakoti, Mishu Mangla

Background: Genital tuberculosis (GTB) is a common form of extra-pulmonary TB with cervical TB being a rare entity accounting for 0.1-0.65% of all TB cases globally. It is usually asymptomatic but may present with infertility, menstrual irregularities, dyspareunia, dysmenorrhoea, or vaginal discharge.

Case presentation: The present case report briefs about a 39 years old nulliparous infertile woman who presented with complaints of irregular menstrual cycles and amenorrhea with an erosive papillary growth over the cervix simulating invasive cervical carcinoma. Her Pap smear report revealed the presence of granulomas. On cervical punch biopsy also a large number of granulomas were seen and on Ziehl Nielsen staining the diagnosis of TB was further confirmed by the presence of acid-fast rodlike bacilli. The patient responded well to anti-tubercular drugs.

Discussion: GTB in most of the cases remains asymptomatic with infertility being the most common presenting complaint. Other symptoms include menstrual irregularities, amenorrhoea, dysmenorrhoea, dyspareunia, chronic pelvic pain, and occasionally abnormal vaginal discharge. Tuberculous cervicitis is difficult to diagnose clinically and many times mimics cervical malignancy.

Result and conclusion: Hence, cervical tuberculosis should be kept in the differential diagnosis of cervical cancer especially in an infertile woman from a developing country.

背景:生殖器结核(GTB)是肺外结核病的一种常见形式,而宫颈结核是一种罕见病,占全球结核病例的 0.1-0.65%。它通常没有症状,但可能表现为不孕、月经不调、痛经、痛经或阴道分泌物:本病例报告简要介绍了一位 39 岁的无子宫不孕妇女,她主诉月经周期不规律和闭经,宫颈上有类似浸润性宫颈癌的糜烂性乳头状增生。她的巴氏涂片报告显示存在肉芽肿。宫颈穿刺活检时也发现了大量肉芽肿,经齐氏尼尔森染色,发现了耐酸棒状杆菌,进一步证实了结核病的诊断。患者对抗结核药物反应良好:讨论:大多数 GTB 病例没有症状,不孕是最常见的主诉。其他症状包括月经不调、闭经、痛经、排尿困难、慢性盆腔疼痛,偶尔还会出现阴道分泌物异常。结核性宫颈炎在临床上很难诊断,很多时候会模仿宫颈恶性肿瘤:因此,在宫颈癌的鉴别诊断中应保留宫颈结核,尤其是发展中国家的不孕妇女。
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引用次数: 0
Burdening Perspectives and Treatment Modalities of Monkeypox: A Central Dogma. 猴痘的致病观点和治疗模式:中心教条
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-01-01 DOI: 10.2174/1871526523666230825164222
Shivang Dhoundiyal, Md Aftab Alam, Awaneet Kaur, Sandesh Varshney

The monkeypox virus (MPXV), belonging to the genus Orthopoxvirus, is responsible for causing the zoonotic illness known as Monkeypox. The virus was initially identified during an outbreak at a Danish Zoo in 1958 and has since been found to infect various mammal species worldwide. While African squirrels and other rodents are believed to be the primary hosts, determining the natural host has proven challenging. While MPXV can be studied using different animal models in laboratory settings, understanding its natural transmission routes remains complex and species-dependent. Recent developments have elevated the global health concern surrounding Monkeypox, leading to its designation as a Global Health Emergency of International Concern on 23 July 2022. Enhancing surveillance and case detection is crucial in navigating the unpredictable epidemiology of this re-emerging disease. Human infections with the monkeypox virus are becoming less frequent due to population growth and economic improvements. Monkeypox, similar to smallpox, can potentially be controlled and eradicated in the future through vaccines, appropriate treatment, and personal protective equipment.

猴痘病毒(MPXV)属于正痘病毒属,是引起猴痘这种人畜共患疾病的罪魁祸首。这种病毒最初是在 1958 年丹麦动物园爆发的一次疫情中被发现的,此后又在全球范围内被发现感染各种哺乳动物。虽然非洲松鼠和其他啮齿类动物被认为是主要宿主,但事实证明确定自然宿主具有挑战性。虽然可以在实验室环境中使用不同的动物模型对 MPXV 进行研究,但对其自然传播途径的了解仍然十分复杂,而且取决于不同的物种。最近的事态发展提高了全球对猴痘的健康关注,导致该病毒于 2022 年 7 月 23 日被指定为国际关注的全球紧急卫生事件。加强监测和病例检测对于应对这种重新出现的疾病不可预测的流行病学至关重要。由于人口增长和经济发展,人类感染猴痘病毒的频率越来越低。猴痘与天花类似,未来有可能通过疫苗、适当的治疗和个人防护设备得到控制和根除。
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引用次数: 0
A Review on the Antibiotic Resistance of Shigella Strains in Iran. 伊朗志贺氏杆菌菌株的抗生素耐药性综述。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-01-01 DOI: 10.2174/1871526523666230811093114
Mahdi Shooraj, Marziye Taheri, Mohammadmahdi Karimi-Yazdi

Shigella infection is commonly related to diarrhea and has been a noteworthy source of morbidity and mortality worldwide. There is a wide range of symptoms associated with these contagious microorganisms, from watery diarrhea to fulminant dysentery manifesting with recurrent bloody stools, fever, and prostration. While the mortality rate from Shigellosis has decreased significantly during the past three decades, it remains a principal cause of death in the world. The use of antibiotics in Shigella treatment remarkably lowers the mortality rates and even the prevalence of the infection. However, strains are becoming increasingly resistant, while antibiotics are becoming increasingly ineffective. Shigella species, which were previously susceptible to common antibiotics such as nalidixic acid, co-trimoxazole, chloramphenicol, and ampicillin, have become resistant to cephalosporins, fluoroquinolones and macrolides like azithromycin. These strains have caused many Shigellosis outbreaks. Men who have had sex with men (MSM) and travelers have contributed to the spreading of multiresistant Shigella strains across continents, which has prompted new antibiotic recommendations. People should be informed about the threat of antimicrobial-resistant bacteria, so a periodic report of antibiotic susceptibility after analysis is essential for antibiotic treatment guidance. The present study provides a brief overview of the pathogenicity of Shigella spp., and the antibiotic resistance patterns of two common Shigella species during the last seven years in Iran were evaluated.

志贺氏菌感染通常与腹泻有关,在全球范围内一直是一个值得注意的发病率和死亡率来源。与这些传染性微生物相关的症状多种多样,从水样腹泻到表现为反复血便、发热和虚脱的暴发性痢疾。虽然志贺氏菌病的死亡率在过去 30 年中大幅下降,但它仍然是世界上的主要死亡原因。使用抗生素治疗志贺氏菌病可显著降低死亡率,甚至降低感染率。然而,菌株的抗药性越来越强,而抗生素的效果却越来越差。以前对纳利昔酸、联合曲唑、氯霉素和氨苄西林等常见抗生素敏感的志贺氏杆菌,现在已对头孢菌素类、氟喹诺酮类和大环内酯类(如阿奇霉素)产生耐药性。这些菌株导致了许多志贺氏杆菌病的爆发。男男性行为者(MSM)和旅行者造成了多重耐药志贺氏杆菌菌株在各大洲的传播,这促使人们提出了新的抗生素建议。人们应该了解抗菌药耐药菌的威胁,因此定期报告分析后的抗生素敏感性对于抗生素治疗指导至关重要。本研究简要概述了志贺氏杆菌的致病性,并评估了过去七年伊朗两种常见志贺氏杆菌的抗生素耐药性模式。
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引用次数: 0
Advancement of Computational Design Drug Delivery System in COVID-19: Current Updates and Future Crosstalk- A Critical update. COVID-19 中计算设计给药系统的进展:当前更新与未来交叉--关键更新。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-16 DOI: 10.2174/1871526523666230816151614
Abu Mohiuddin, Sumanta Mondal

Positive strides have been achieved in developing vaccines to combat the coronavirus-2019 infection (COVID-19) pandemic. Still, the outline of variations, particularly the most current delta divergent, has posed significant health encounters for people. Therefore, developing strong treatment strategies, such as an anti-COVID-19 medicine plan, may help deal with the pandemic more effectively. During the COVID-19 pandemic, some drug design techniques were effectively used to develop and substantiate relevant critical medications. Extensive research, both experimental and computational, has been dedicated to comprehending and characterizing the devastating COVID-19 disease. The urgency of the situation has led to the publication of over 130,000 COVID-19-related research papers in peer-reviewed journals and preprint servers. A significant focus of these efforts has been the identification of novel drug candidates and the repurposing of existing drugs to combat the virus. Many projects have utilized computational or computer-aided approaches to facilitate their studies. In this overview, we will explore the key computational methods and their applications in the discovery of small-molecule therapeutics for COVID-19, as reported in the research literature. We believe that the true effectiveness of computational tools lies in their ability to provide actionable and experimentally testable hypotheses, which in turn facilitate the discovery of new drugs and combinations thereof. Additionally, we recognize that open science and the rapid sharing of research findings are vital in expediting the development of much-needed therapeutics for COVID-19.

在开发疫苗以抗击冠状病毒-2019 感染(COVID-19)大流行方面取得了积极进展。尽管如此,变异概述,尤其是最新的三角洲分化,仍给人们的健康带来了重大挑战。因此,制定强有力的治疗策略,如抗COVID-19药物计划,可能有助于更有效地应对大流行。在 COVID-19 大流行期间,一些药物设计技术被有效地用于开发和证实相关的关键药物。大量的实验和计算研究致力于理解和描述 COVID-19 这一毁灭性疾病。由于形势紧迫,在同行评审期刊和预印本服务器上发表了 130,000 多篇与 COVID-19 相关的研究论文。这些工作的一个重要重点是确定新型候选药物,并对现有药物进行再利用,以抗击该病毒。许多项目利用计算或计算机辅助方法来促进研究。在本综述中,我们将探讨研究文献中报道的主要计算方法及其在发现 COVID-19 小分子疗法中的应用。我们相信,计算工具的真正功效在于它们能够提供可操作、可实验检验的假设,进而促进新药及其组合的发现。此外,我们认识到开放科学和快速共享研究成果对于加快 COVID-19 急需疗法的开发至关重要。
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引用次数: 0
Possible association between Toxoplasma gondii infection and sleep disorders: A systematic review. 刚地弓形虫感染与睡眠障碍之间可能存在的关联:一项系统综述。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-07-27 DOI: 10.2174/1871526523666230727093926
Tooran Nayeri, Shahabeddin Sarvi, Ahmad Daryani

Background: Few studies investigated the relationship between toxoplasmosis and sleep disorders. Sleep disorders can lead to suicidal behavior and traffic accidents. Therefore, the purpose of this study is to collect information and investigate the possible relationship between Toxoplasma gondii (T. gondii) and sleep disorders.

Methods: To achieve the goal of the present study, five English databases (PubMed, ScienceDirect, Web of Science, Scopus, and ProQuest) were systematically searched for related studies from their inception until October 18, 2022. The obtained articles were screened based on the title, abstract and full text. Then, the quality of the papers investigating the relationship between toxoplasmosis and sleep disorders was evaluated, and finally, the data from the relevant studies were extracted in a Microsoft Excel data sheet.

Results: Eight articles (4 case-control and 4 cross-sectional studies) were entered in this systematic review containing 926 patients with sleep disorders and 1877 people without sleep disorders in casecontrol studies, out of which 212 (22.89%) and 392 (20.88%) individuals were positive for anti-T. gondii IgG antibody using different serological methods. Also, 2885 people with sleep disorders were investigated for anti-T. gondii IgG antibody in cross-sectional studies, out of which 1559 (54.03%) cases were positive.

Conclusion: The results of this study suggest that T. gondii infection may be a risk factor for sleep disorders. However, the number of related studies is small, and there are contradictions in the findings of these articles. Therefore, further studies are necessary to clarify the possible association between T. gondii infections and sleep disorders.

背景:很少有研究调查弓形虫病与睡眠障碍的关系。睡眠障碍会导致自杀行为和交通事故。因此,本研究的目的是收集资料,探讨弓形虫(弓形虫)与睡眠障碍的可能关系。方法:为了实现本研究的目标,系统地检索了5个英文数据库(PubMed、ScienceDirect、Web of Science、Scopus和ProQuest)从建立到2022年10月18日的相关研究。根据标题、摘要和全文对获得的文章进行筛选。然后对研究弓形虫病与睡眠障碍关系的论文质量进行评价,最后将相关研究的数据提取到Microsoft Excel数据表中。结果:本系统综述纳入8篇文献(4篇病例对照研究和4篇横断面研究),共纳入926例睡眠障碍患者和1877例非睡眠障碍病例对照研究,其中抗t抗体阳性212例(22.89%)和392例(20.88%)。不同血清学方法检测弓形虫IgG抗体。此外,对2885名睡眠障碍患者的抗t抗体进行了调查。横断面研究中弓形虫IgG抗体阳性1559例(54.03%)。结论:本研究提示弓形虫感染可能是睡眠障碍的危险因素。然而,相关研究的数量较少,并且这些文章的研究结果存在矛盾。因此,有必要进一步研究弓形虫感染与睡眠障碍之间的可能联系。
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引用次数: 0
Current Leads and Marketed Formulations for an Effective Treatment of Fungal Infections. 目前有效治疗真菌感染的线索和已上市的配方。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-07-26 DOI: 10.2174/1871526523666230726114855
Trambak Basak, Amit K Goyal

Severe antifungal infections, especially opportunistic fungal infections, are increasing tremendously in immunocompromised patients. This is basically because more patients enduring neoplastic diseases lead to the wide use of chemotherapy, thus causing immunosuppression. Patients with HIV infection, burns, pancreatitis and neutropenia are also amenable to fungal infections. Out of a plethora of antifungal drugs applied, Amphotericin B, being a broad-spectrum antimicrobial drug, has been the gold standard treatment for a diverse variety of fungal infections since the 1950s and visceral leishmaniasis since the 1960s. However, Amphotericin B has major constraints of poor bioavailability and kidney toxicity, due to which newer antifungal compounds are being used. This article discusses fungal and parasitic diseases and formulations for treating these ailments.

严重的抗真菌感染,特别是机会性真菌感染,在免疫功能低下的患者中急剧增加。这主要是因为越来越多的患者患有肿瘤疾病,导致化疗的广泛使用,从而导致免疫抑制。HIV感染、烧伤、胰腺炎和中性粒细胞减少症患者也容易发生真菌感染。在大量使用的抗真菌药物中,两性霉素B作为一种广谱抗菌药物,自20世纪50年代以来一直是治疗各种真菌感染的金标准,自60年代以来一直是治疗内脏利什曼病的金标准。然而,两性霉素B具有生物利用度差和肾毒性的主要限制,因此正在使用较新的抗真菌化合物。本文讨论了真菌和寄生虫病以及治疗这些疾病的配方。
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引用次数: 0
Covid-19 and Parkinson's Disease: the Link also Established! Covid-19和帕金森病:联系也建立了!
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-19 DOI: 10.2174/1871526523666230619104142
Ziad Fajloun, Yingliang Wu, Zhijian Cao, Hervé Kovacic, Jean-Marc Sabatier
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引用次数: 0
Time-to-survival from COVID-19 disease and its associated factors in Osun State, Nigeria. 尼日利亚奥松州COVID-19疾病的生存时间及其相关因素。
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-13 DOI: 10.2174/1871526523666230613122108
O A Olowe, O Adeagbo, P B Olaitan, R A Olowe, T Opakunle, O D Eniade, A T Olarinmoye, J Atolagbe

Introduction This study focused on estimating the probability of survival and the specific time to survival from COVID-19 among patients who had COVID-19 in Osun state, Nigeria. Also, we examined some factors associated with the time to survival among COVID-19 patients in Osun state, Nigeria. Methods The retrospective data of 2596 records of COVID-19 patients in Osun state were analysed in this study. The outcome variable was the "COVID-19 treatment outcome (survived=1, dead=0)". The time date used in the survival analysis was treatment duration (in days). The explanatory variables were demographic characteristics, type of health facility, vaccination status, symptoms, and mode of admission. The descriptive statistics was computed and presented. Kaplan Meier was used to estimate the median time to survival. Bivariate analysis and multivariate analysis were done using the Log-Rank test and Cox regression, respectively. P values were set at P<0.05. Results The mean age was observed to be 40 (SD=17.51) years, ranging from mostly, 2 months to 98 years old. More (56.1%) of the participants were males. Most (99.5%) of them were Nigerians. Only 1.4% were vaccinated. The survival rate from COVID-19 was 98.1% in Osun State. The median time for survival was 14 (IQR= 14- 16) days. COVID-19 reduces as the number of days for being on treatment increases. Unvaccinated (HR=0.93, 95%CI: 0.43-2.03) and those whose vaccination status was unknown (HR=0.52, 95%CI: 0.37-0.74) were less likely to survive COVID-19 diseases. Conclusion The Survival rate was high, the observed median time to survival was 14 days, and the probability of survival reduces as the number of days of being on treatment for COVID-19 increases. Also, gender, vaccination, type of care, and ethnicity were associated with survival time. Similarly, unvaccinated and inpatients were less likely to rapidly survive COVID-19. This study recommends that the COVID-19 vaccine should be encouraged among patients who have the COVID-19 virus. Also, home care may be further explored to assess its effectiveness in caring for COVID-19 patients. In the same vein, COVID-19 data capturing, and databases need strengthening in Nigeria.

本研究的重点是估计尼日利亚奥松州COVID-19患者的生存概率和具体生存时间。此外,我们还研究了与尼日利亚奥松州COVID-19患者生存时间相关的一些因素。方法对奥松州2596例新冠肺炎患者的回顾性资料进行分析。结果变量为“COVID-19治疗结果(存活=1,死亡=0)”。生存分析中使用的时间日期是治疗持续时间(以天为单位)。解释变量包括人口统计学特征、卫生设施类型、疫苗接种状况、症状和入院方式。计算并给出了描述性统计。Kaplan Meier用于估计中位生存时间。双因素分析和多因素分析分别采用Log-Rank检验和Cox回归。P值设为P
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引用次数: 0
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