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The protective mechanism of Naja Naja atra venom on diabetic kidney disease. Naja Naja atra 毒液对糖尿病肾病的保护机制
IF 2.4 3区 医学 Q4 TOXICOLOGY Pub Date : 2023-12-08 eCollection Date: 2023-01-01 DOI: 10.1590/1678-9199-JVATITD-2023-0037
HongYu Lu, YaJuan Wu, Yan Xie, XiaoWei Li, Xian Ji, TianHui Jiang, XiaoXian Pei, ZhuYa Zhou

Background: Diabetic kidney disease (DKD) is a serious microvascular complication of diabetes that affects both type 1 and type 2 diabetes patients at a high incidence rate. Naja Naja atra venom (NNAV) has been shown to have protective effects and improved renal function in diabetic rats. However, its mechanism of action is still unclear. This study aims to unravel the effectiveness and mechanisms of NNAV on DKD.

Methods: We conducted in vitro experiments in which Human Kidney-2 (HK-2) cells were stimulated with high glucose, and exposed to varying concentrations of NNAV. Cell morphology, as well as α-SMA, TGF-β1, and E-cadherin levels, were analyzed using immunofluorescence and western blot. In vivo experiments involved a diabetic rat model, where varying concentrations of cobra α-neurotoxin (CTX) were administrated via gastric treatment. We observed and noted pathomorphological changes, measured biochemical and oxidative stress indices, and used western blot to assess podocin and nephrin levels.

Results: High glucose levels can induce a decrease in E-cadherin expression and an increase in α-SMA and transforming growth factor-β1 (TGF-β1) expression in HK-2 cells. NNAV can inhibit the transdifferentiation of HK-2 cells to myofibroblast (MyoF) in a high glucose environment and reduce the expression of TGF-β1. Cobra α-neurotoxin (CTX) can reduce urine protein in diabetes model rats at an early stage, which is dose-independent and has a time application range. CTX can regulate the expression of nephrin and podocin.

Conclusion: The present study indicates that CTX and NNAV attenuate STZ and high glucose-induced DKD. Its mechanisms of action are associated with inhibiting oxidative stress and TEMT. The study suggests that NNAV and CTX might be a potential therapeutic drug for treating DKD.

背景:糖尿病肾病(DKD)是糖尿病的一种严重微血管并发症,1 型和 2 型糖尿病患者的发病率都很高。Naja Naja atra 毒液(NNAV)已被证明对糖尿病大鼠具有保护作用,并能改善其肾功能。然而,其作用机制仍不清楚。本研究旨在揭示 NNAV 对 DKD 的疗效和作用机制:我们进行了体外实验,用高糖刺激人肾-2(HK-2)细胞,并将其暴露于不同浓度的 NNAV。使用免疫荧光和 Western 印迹分析了细胞形态以及 α-SMA、TGF-β1 和 E-cadherin 水平。体内实验采用糖尿病大鼠模型,通过胃部处理给大鼠注射不同浓度的眼镜蛇α-神经毒素(CTX)。我们观察并记录了病理形态学变化,测量了生化和氧化应激指数,并使用 Western 印迹技术评估了荚膜蛋白和肾素水平:结果:高血糖水平可诱导 HK-2 细胞中 E-cadherin 表达减少、α-SMA 和转化生长因子-β1(TGF-β1)表达增加。NNAV 可抑制 HK-2 细胞在高糖环境中向肌成纤维细胞(MyoF)的转分化,并降低 TGF-β1 的表达。眼镜蛇α-神经毒素(CTX)能在早期降低糖尿病模型大鼠的尿蛋白,且与剂量无关,有一定的应用时间范围。CTX能调节肾素和荚膜蛋白的表达:本研究表明,CTX 和 NNAV 可减轻 STZ 和高糖诱导的 DKD。其作用机制与抑制氧化应激和 TEMT 有关。本研究表明,NNAV 和 CTX 可能是治疗 DKD 的潜在药物。
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引用次数: 0
Echinometra lucunter molecules reduce Aβ42-induced neurotoxicity in SH-SY5Y neuron-like cells: effects on disaggregation and oxidative stress. Echinometra lucunter 分子可减少 Aβ42 在 SH-SY5Y 神经元样细胞中诱导的神经毒性:对分解和氧化应激的影响。
IF 2.4 3区 医学 Q4 TOXICOLOGY Pub Date : 2023-12-01 eCollection Date: 2023-01-01 DOI: 10.1590/1678-9199-JVATITD-2023-0031
Amanda Gomes da Silva, Mariana da Mata Alves, Admilson Aparecido da Cunha, Giovanna Arruda Caires, Irina Kerkis, Hugo Vigerelli, Juliana Mozer Sciani

Background: Echinometra lucunter is a sea urchin commonly found on America's rocky shores. Its coelomic fluid contains molecules used for defense and biological processes, which may have therapeutic potential for the treatment of amyloid-based neurodegenerative diseases, such as Alzheimer's, that currently have few drug options available.

Methods: In this study, we incubated E. lucunter coelomic fluid (ELCF) and fractions obtained by solid phase extraction in SH-SY5Y neuron-like cells to evaluate their effect on cell viability caused by the oligomerized amyloid peptide 42 (Aβ42o). Moreover, the Aβ42o was quantified after the incubation with ELCF fractions in the presence or not of cells, to evaluate if samples could cause amyloid peptide disaggregation. Antioxidant activity was determined in ELCF fractions, and cells were evaluated to check the oxidative stress after incubation with samples. The most relevant fraction was analyzed by mass spectrometry for identification of molecules.

Results: ELCF and certain fractions could prevent and treat the reduction of cell viability caused by Aβ42o in SH-SY5Y neuron-like cells. We found that one fraction (El50) reduced the oligomerized Aβ42 and the oxidative stress caused by the amyloid peptide through its antioxidant molecules, which in turn reduced cell death. Mass spectrometry analysis revealed that El50 comprises small molecules containing flavonoid antioxidants, such as phenylpyridazine and dihydroquercetin, and two peptides.

Conclusion: Our results suggest that sea urchin molecules may interact with Aβ42o and oxidative stress, preventing or treating neurotoxicity, which may be useful in treating dementia.

背景:Echinometra lucunter是一种常见于美国岩石海岸的海胆。它的体腔液含有用于防御和生物过程的分子,这可能对治疗淀粉样蛋白为基础的神经退行性疾病具有治疗潜力,如阿尔茨海默氏症,目前可用的药物选择很少。方法:本研究以鼠黄鼠体腔液(ELCF)和固相萃取得到的部分分别培养于SH-SY5Y神经元样细胞,观察其对低聚淀粉样肽42 (a - β42)对细胞活力的影响。此外,在细胞存在或不存在的情况下,用ELCF组分孵育后定量a β42,以评估样品是否会引起淀粉样肽分解。测定ELCF组分的抗氧化活性,并评估细胞与样品孵育后的氧化应激。最相关的部分用质谱法进行分子鉴定。结果:ELCF及一定组分对a β42致SH-SY5Y神经元样细胞活力降低有预防和治疗作用。我们发现其中一种组分(El50)通过其抗氧化分子减少了Aβ42的寡聚和淀粉样肽引起的氧化应激,从而减少了细胞死亡。质谱分析表明,El50由含有类黄酮抗氧化剂的小分子(如苯基吡啶嗪和二氢槲皮素)和两种肽组成。结论:海胆分子可能与a β42和氧化应激相互作用,预防或治疗神经毒性,可能具有治疗痴呆的作用。
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引用次数: 0
Proteomic analyses of venom from a Spider Hawk, Pepsis decorata. 蜘蛛鹰毒液的蛋白质组学分析。
IF 2.4 3区 医学 Q4 TOXICOLOGY Pub Date : 2023-11-10 eCollection Date: 2023-01-01 DOI: 10.1590/1678-9199-JVATITD-2022-0090
Matheus Nolasco, Douglas O C Mariano, Daniel C Pimenta, Ilka Biondi, Alexsandro Branco

Background: The composition of the venom from solitary wasps is poorly known, although these animals are considered sources of bioactive substances. Until the present moment, there is only one proteomic characterization of the venom of wasps of the family Pompilidae and this is the first proteomic characterization for the genus Pepsis.

Methods: To elucidate the components of Pepsis decorata venom, the present work sought to identify proteins using four different experimental conditions, namely: (A) crude venom; (B) reduced and alkylated venom; (C) trypsin-digested reduced and alkylated venom, and; (D) chymotrypsin-digested reduced and alkylated venom. Furthermore, three different mass spectrometers were used (Ion Trap-Time of Flight, Quadrupole-Time of Flight, and Linear Triple Quadruple).

Results: Proteomics analysis revealed the existence of different enzymes related to the insect's physiology in the venom composition. Besides toxins, angiotensin-converting enzyme (ACE), hyaluronidase, and Kunitz-type inhibitors were also identified.

Conclusion: The data showed that the venom of Pepsis decorata is mostly composed of proteins involved in the metabolism of arthropods, as occurs in parasitic wasps, although some classical toxins were recorded, and among them, for the first time, ACE was found in the venom of solitary wasps. This integrative approach expanded the range of compounds identified in protein analyses, proving to be efficient in the proteomic characterization of little-known species. It is our understanding that the current work will provide a solid base for future studies dealing with other Hymenoptera venoms.

背景:尽管这些动物被认为是生物活性物质的来源,但对独居黄蜂毒液的成分知之甚少。到目前为止,只有一个关于Pompilidae家族黄蜂毒液的蛋白质组学表征,这是Pepsis属的第一个蛋白质组学表征。方法:利用四种不同的实验条件,即:(A)粗毒液;(B)还原和烷基化毒液;(C)胰蛋白酶消化的还原和烷基化毒液;(D)凝乳胰蛋白酶消化的还原烷基化毒液。此外,使用了三种不同的质谱仪(离子捕获飞行时间、四极飞行时间和线性三重四极)。结果:蛋白质组学分析显示,该昆虫的毒液成分中存在多种与生理相关的酶。除毒素外,血管紧张素转换酶(ACE)、透明质酸酶和kunitz型抑制剂也被鉴定出来。结论:资料显示,尽管有一些经典的毒素被记录下来,但与寄生蜂一样,decorata Pepsis的毒液主要由参与节肢动物代谢的蛋白质组成,其中ACE首次在独居黄蜂的毒液中被发现。这种综合方法扩大了蛋白质分析中鉴定的化合物的范围,证明在鲜为人知的物种的蛋白质组学表征中是有效的。我们认为,本研究将为今后对其他膜翅目昆虫的研究奠定坚实的基础。
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引用次数: 0
Research advances in the degradation of aflatoxin by lactic acid bacteria. 乳酸菌降解黄曲霉毒素的研究进展。
IF 2.4 3区 医学 Q4 TOXICOLOGY Pub Date : 2023-10-23 eCollection Date: 2023-01-01 DOI: 10.1590/1678-9199-JVATITD-2023-0029
Yuxi Wang, Lishi Jiang, Ying Zhang, Ran Ran, Xiao Meng, Shukun Liu

Aflatoxins are toxic secondary metabolites that often contaminate food and animal feed, causing huge economic losses and serious health hazards. Aflatoxin contamination has become a major concern worldwide. Biological methods have been used to reduce aflatoxins in food and feed by inhibiting toxin production and detoxification. Among biological methods, lactic acid bacteria are of significant interest because of their safety, efficiency, and environmental friendliness. This study aimed to review the mechanisms by which lactic acid bacteria degrade aflatoxins and the factors that influence their degradation efficiency, including the action of the lactic acid bacteria themselves (cell wall adsorption) and the antifungal metabolites produced by the lactic acid bacteria. The current applications of lactic acid bacteria to food and feed were also reviewed. This comprehensive analysis provided insight into the binding mechanisms between lactic acid bacteria and aflatoxins, facilitating the practical applications of lactic acid bacteria to food and agriculture.

黄曲霉毒素是一种有毒的次级代谢产物,经常污染食品和动物饲料,造成巨大的经济损失和严重的健康危害。黄曲霉毒素污染已成为全世界关注的主要问题。生物方法已被用于通过抑制毒素产生和解毒来减少食品和饲料中的黄曲霉毒素。在生物方法中,乳酸菌因其安全、高效和环境友好而备受关注。本研究旨在综述乳酸菌降解黄曲霉毒素的机制以及影响其降解效率的因素,包括乳酸菌自身的作用(细胞壁吸附)和乳酸菌产生的抗真菌代谢产物。综述了乳酸菌在食品和饲料中的应用现状。这一综合分析深入了解了乳酸菌和黄曲霉毒素之间的结合机制,促进了乳酸菌在食品和农业中的实际应用。
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引用次数: 0
Pulmonary involvement from animal toxins: the cellular mechanisms. 动物毒素对肺部的影响:细胞机制。
IF 1.8 3区 医学 Q4 TOXICOLOGY Pub Date : 2023-09-18 eCollection Date: 2023-01-01 DOI: 10.1590/1678-9199-JVATITD-2023-0026
Suthimon Thumtecho, Suchai Suteparuk, Visith Sitprija

Venomous animals and their venom have always been of human interest because, despite species differences, coevolution has made them capable of targeting key physiological components of our bodies. Respiratory failure from lung injury is one of the serious consequences of envenomation, and the underlying mechanisms are rarely discussed. This review aims to demonstrate how toxins affect the pulmonary system through various biological pathways. Herein, we propose the common underlying cellular mechanisms of toxin-induced lung injury: interference with normal cell function and integrity, disruption of normal vascular function, and provocation of excessive inflammation. Viperid snakebites are the leading cause of envenomation-induced lung injury, followed by other terrestrial venomous animals such as scorpions, spiders, and centipedes. Marine species, particularly jellyfish, can also inflict such injury. Common pulmonary manifestations include pulmonary edema, pulmonary hemorrhage, and exudative infiltration. Severe envenomation can result in acute respiratory distress syndrome. Pulmonary involvement suggests severe envenomation, thus recognizing these mechanisms and manifestations can aid physicians in providing appropriate treatment.

毒液动物及其毒液一直引起人类的兴趣,因为尽管存在物种差异,但共同进化使它们能够针对我们身体的关键生理成分。肺损伤引起的呼吸衰竭是环境恶化的严重后果之一,其潜在机制很少被讨论。这篇综述旨在证明毒素如何通过各种生物途径影响肺部系统。在此,我们提出了毒素诱导的肺损伤的常见潜在细胞机制:干扰正常细胞功能和完整性、破坏正常血管功能和引发过度炎症。毒蛇咬伤是环境致肺损伤的主要原因,其次是其他陆生有毒动物,如蝎子、蜘蛛和蜈蚣。海洋物种,尤其是水母,也会造成这种伤害。常见的肺部表现包括肺水肿、肺出血和渗出性浸润。严重的环境污染可导致急性呼吸窘迫综合征。肺部受累意味着严重的环境恶化,因此认识到这些机制和表现可以帮助医生提供适当的治疗。
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引用次数: 0
Snake venom disintegrins update: insights about new findings. 蛇毒崩解剂更新:关于新发现的见解。
IF 2.4 3区 医学 Q4 TOXICOLOGY Pub Date : 2023-09-18 eCollection Date: 2023-01-01 DOI: 10.1590/1678-9199-JVATITD-2023-0039
Gabriela de Oliveira Almeida, Isadora Sousa de Oliveira, Eliane Candiani Arantes, Suely Vilela Sampaio

Snake venom disintegrins are low molecular weight, non-enzymatic proteins rich in cysteine, present in the venom of snakes from the families Viperidae, Crotalidae, Atractaspididae, Elapidae, and Colubridae. This family of proteins originated in venom through the proteolytic processing of metalloproteinases (SVMPs), which, in turn, evolved from a gene encoding an A Disintegrin And Metalloprotease (ADAM) molecule. Disintegrins have a recognition motif for integrins in their structure, allowing interaction with these transmembrane adhesion receptors and preventing their binding to proteins in the extracellular matrix and other cells. This interaction gives disintegrins their wide range of biological functions, including inhibition of platelet aggregation and antitumor activity. As a result, many studies have been conducted in an attempt to use these natural compounds as a basis for developing therapies for the treatment of various diseases. Furthermore, the FDA has approved Tirofiban and Eptifibatide as antiplatelet compounds, and they are synthesized from the structure of echistatin and barbourin, respectively. In this review, we discuss some of the main functional and structural characteristics of this class of proteins and their potential for therapeutic use.

蛇毒崩解蛋白是一种低分子量、富含半胱氨酸的非酶蛋白,存在于毒蛇科、克氏蛇科、白术蛇科、蛇科和蛇科的毒液中。这一蛋白质家族通过金属蛋白酶(SVMP)的蛋白水解过程起源于毒液,而金属蛋白酶又是由编码分解蛋白和金属蛋白酶(ADAM)分子的基因进化而来的。崩解蛋白在其结构中具有整合素的识别基序,允许与这些跨膜粘附受体相互作用,并阻止它们与细胞外基质和其他细胞中的蛋白质结合。这种相互作用赋予崩解剂广泛的生物学功能,包括抑制血小板聚集和抗肿瘤活性。因此,已经进行了许多研究,试图将这些天然化合物作为开发治疗各种疾病的疗法的基础。此外,美国食品药品监督管理局已批准替罗非班和依替非肽为抗血小板化合物,它们分别由埃奇他汀和巴博林的结构合成。在这篇综述中,我们讨论了这类蛋白质的一些主要功能和结构特征及其治疗应用的潜力。
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引用次数: 1
Taiwan cobra envenoming: serum venom concentration before and after specific treatment and relationship with debridement of necrotic wound tissue. 台湾眼镜蛇中毒:特定治疗前后血清毒液浓度及其与坏死伤口组织清创的关系。
IF 2.4 3区 医学 Q4 TOXICOLOGY Pub Date : 2023-01-01 DOI: 10.1590/1678-9199-JVATITD-2022-0027
Chia-Cheng Wang, Chun-Hsiang Ou Yang, Chih-Po Hsu, Chien-Chun Liu, Jau-Song Yu, Chih-Hong Lo, Wen-Chih Fann, Yen-Chia Chen, Chih Chuan Lin

Background: Bivalent freeze-dried neurotoxic (FN) antivenom has been the primary treatment since the 1980s for Taiwan cobra (Naja atra) envenomation in Taiwan. However, envenomation-related wound necrosis is a significant problem after cobra snakebites. In the present study, we analyzed the changes in serum venom concentration before and after antivenom administration to discover their clinical implications and the surgical treatment options for wound necrosis.

Methods: The patients were divided into limb swelling and wound necrosis groups. The clinical outcome was that swelling started to subside 12 hours after antivenom treatment in the first group. Serum venom concentrations before and after using antivenoms were measured to assess the antivenom's ability to neutralize the circulating cobra venom. The venom levels in wound wet dressing gauzes, blister fluids, and debrided tissues were also investigated to determine their clinical significance. We also observed the evolutional changes of wound necrosis and chose a better wound debridement timing.

Results: We prospectively enrolled 15 Taiwan cobra snakebite patients. Males accounted for most of this study population (n = 11, 73%). The wound necrosis group received more antivenom doses than the limb swelling group (4; IQR:2-6 vs 1; IQR:1-2, p = 0.05), and less records of serum venom concentrations changed before/after antivenom use (p = 0.0079). The necrotic wound site may release venom into circulation and cause more severe envenomation symptoms. Antivenom can efficiently diminish limb swelling in cobra bite patients. However, antivenom cannot reduce wound necrosis. Patients with early debridement of wound necrosis had a better limb outcome, while late or without debridement may have long-term hospital stay and distal limb morbidity.

Conclusions: Antivenom can efficiently eliminate the circulating cobra venom in limb swelling patients without wound necrosis. Early debridement of the bite site wound and wet dressing management are suggestions for preventing extended tissue necrosis and hospital stay.

背景:自1980年代以来,二价冻干神经毒抗蛇毒一直是台湾眼镜蛇(Naja atra)中毒的主要治疗方法。然而,在眼镜蛇咬伤后,与毒液相关的伤口坏死是一个重大问题。在本研究中,我们分析了抗蛇毒血清给药前后血清毒液浓度的变化,以发现其临床意义和伤口坏死的手术治疗选择。方法:将患者分为肢体肿胀组和创面坏死组。临床结果是第一组抗蛇毒血清治疗12小时后肿胀开始消退。在使用抗蛇毒血清前后测量血清毒液浓度,以评估抗蛇毒血清中和循环眼镜蛇毒液的能力。还研究了伤口湿敷料、水泡液和清创组织中的毒液水平,以确定其临床意义。观察创面坏死的进化变化,选择较好的创面清创时机。结果:前瞻性纳入15例台湾眼镜蛇咬伤患者。男性占本研究人群的大部分(n = 11,73%)。创面坏死组抗蛇毒血清剂量高于肢体肿胀组(4;IQR:2-6 vs 1;IQR:1-2, p = 0.05),使用抗蛇毒血清前后血清毒液浓度变化记录较少(p = 0.0079)。坏死的伤口部位可能释放毒液进入血液循环,引起更严重的中毒症状。抗蛇毒血清能有效地减轻眼镜蛇咬伤患者的肢体肿胀。然而,抗蛇毒血清不能减少伤口坏死。早期清创创面坏死患者的肢体预后较好,而晚清创或不清创可能导致长期住院和远端肢体并发症。结论:抗蛇毒血清能有效清除无伤口坏死的肢体肿胀患者循环中的眼镜蛇毒液。早期清创和湿敷料处理是防止组织坏死延长和住院时间的建议。
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引用次数: 0
Antimalarial potential of Moringa oleifera Lam. (Moringaceae): A review of the ethnomedicinal, pharmacological, toxicological, and phytochemical evidence. 辣木的抗疟潜力。(辣木科):民族医学,药理学,毒理学和植物化学证据的综述。
IF 2.4 3区 医学 Q4 TOXICOLOGY Pub Date : 2023-01-01 DOI: 10.1590/1678-9199-JVATITD-2022-0079
José Jailson Lima Bezerra, Anderson Angel Vieira Pinheiro, Douglas Dourado

Several regions of the world frequently use the species Moringa oleifera Lam. (Moringaceae) in traditional medicine. This situation is even more common in African countries. Many literature reports point to the antimalarial potential of this species, indicating the efficacy of its chemical compounds against malaria-causing parasites of the genus Plasmodium. From this perspective, the present study reviews the ethnobotanical, pharmacological, toxicological, and phytochemical (flavonoids) evidence of M. oleifera, focusing on the treatment of malaria. Scientific articles were retrieved from Google Scholar, PubMed®, ScienceDirect®, and SciELO databases. Only articles published between 2002 and 2022 were selected. After applying the inclusion and exclusion criteria, this review used a total of 72 articles. These documents mention a large use of M. oleifera for the treatment of malaria in African and Asian countries. The leaves (63%) of this plant are the main parts used in the preparation of herbal medicines. The in vivo antimalarial activity of M. oleifera was confirmed through several studies using polar and nonpolar extracts, fractions obtained from the extracts, infusion, pellets, and oils obtained from this plant and tested in rodents infected by the following parasites of the genus Plasmodium: P. berghei, P. falciparum, P. yoelii, and P. chabaudi. Extracts obtained from M. oleifera showed no toxicity in preclinical tests. A total of 46 flavonoids were identified in the leaves and seeds of M. oleifera by different chromatography and mass spectrometry methods. Despite the scarcity of research on the antimalarial potential of compounds isolated from M. oleifera, the positive effects against malaria-causing parasites in previous studies are likely to correlate with the flavonoids that occur in this species.

世界上一些地区经常使用辣木(Moringa oleifera Lam)。传统医学中的辣木科植物。这种情况在非洲国家更为普遍。许多文献报告指出了该物种的抗疟疾潜力,表明其化合物对疟原虫属引起疟疾的寄生虫有效。从这个角度来看,本研究综述了油棕的民族植物学、药理学、毒理学和植物化学(类黄酮)证据,重点是治疗疟疾。科学文章从Google Scholar、PubMed®、ScienceDirect®和SciELO数据库中检索。只选择2002年至2022年间发表的文章。应用纳入和排除标准后,本综述共纳入72篇文献。这些文件提到在非洲和亚洲国家大量使用油橄榄来治疗疟疾。这种植物的叶子(63%)是制备草药的主要部分。通过使用极性和非极性提取物、提取物提取的部分、浸渍、颗粒和从该植物获得的油进行的几项研究,证实了油棕的体内抗疟活性,并在感染了以下疟原虫属寄生虫的啮齿动物中进行了测试:伯氏疟原虫、恶性疟原虫、约氏疟原虫和沙巴蒂疟原虫。从油橄榄中提取的提取物在临床前试验中显示没有毒性。采用不同的色谱和质谱分析方法,从油松叶和种子中鉴定出46种黄酮类化合物。尽管对从油棕中分离的化合物的抗疟疾潜力的研究很少,但在以前的研究中,对引起疟疾的寄生虫的积极作用可能与该物种中所含的类黄酮有关。
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引用次数: 2
COVID-19 impacts on healthcare access in sub-Saharan Africa: an overview. 2019冠状病毒病对撒哈拉以南非洲获得医疗保健的影响:概述。
IF 2.4 3区 医学 Q4 TOXICOLOGY Pub Date : 2023-01-01 DOI: 10.1590/1678-9199-JVATITD-2023-0002
Jean-Philippe Chippaux

This overview aimed to describe the situation of healthcare access in sub-Saharan Africa, excluding South Africa, during the COVID-19 pandemic. A PubMed® search from March 31, 2020, to August 15, 2022, selected 116 articles. Healthcare access and consequences of COVID-19 were assessed based on comparisons with months before its onset or an identical season in previous years. A general reduction of healthcare delivery, associated with the decline of care quality, and closure of many specialty services were reported. The impact was heterogeneous in space and time, with an increase in urban areas at the beginning of the pandemic (March-June 2020). The return to normalcy was gradual from the 3rd quarter of 2020 until the end of 2021. The impact of COVID-19 on the health system and its use was attributed to (a) conjunctural factors resulting from government actions to mitigate the spread of the epidemic (containment, transportation restrictions, closures of businesses, and places of entertainment or worship); (b) structural factors related to the disruption of public and private facilities and institutions, in particular, the health system; and (c) individual factors linked to the increase in costs, impoverishment of the population, and fear of contamination or stigmatization, which discouraged patients from going to health centers. They have caused considerable socio-economic damage. Several studies emphasized some adaptability of the healthcare offer and resilience of the healthcare system, despite its unpreparedness, which explained a return to normal activities as early as 2022 while the COVID-19 epidemic persisted. There appears to be a strong disproportion between the moderate incidence and severity of COVID-19 in sub-Saharan Africa, and the dramatic impact on healthcare access. Several articles make recommendations for lowering the socioeconomic consequences of future epidemics to ensure better management of health issues.

本概述旨在描述2019冠状病毒病大流行期间撒哈拉以南非洲(不包括南非)的医疗保健获取情况。PubMed®检索从2020年3月31日到2022年8月15日,选择了116篇文章。根据与前几年发病前几个月或同一季节的比较,评估了COVID-19的医疗保健可及性和后果。据报道,与护理质量下降有关的保健服务普遍减少,许多专业服务机构关闭。影响在空间和时间上是不均匀的,在大流行开始时(2020年3月至6月),城市地区的影响有所增加。从2020年第三季度到2021年底,恢复正常是逐步的。COVID-19对卫生系统及其使用的影响归因于:(a)政府采取行动缓解疫情传播(控制、交通限制、关闭企业和娱乐或礼拜场所)所导致的时局因素;(b)与公共和私人设施和机构,特别是卫生系统中断有关的结构性因素;(c)与费用增加、人口贫困以及对污染或污名的恐惧有关的个人因素,这些因素使病人不愿去保健中心。它们造成了相当大的社会经济损害。几项研究强调了医疗保健服务的一些适应性和医疗保健系统的复原力,尽管它没有做好准备,这解释了早在2022年COVID-19疫情持续期间就恢复正常活动的原因。在撒哈拉以南非洲,COVID-19的中等发病率和严重程度与对获得医疗保健的巨大影响之间似乎存在严重的不相称。一些文章提出了降低未来流行病的社会经济后果的建议,以确保更好地管理卫生问题。
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引用次数: 1
Glutamine ameliorates Bungarus multicinctus venom-induced lung and heart injury through HSP70: NF-κB p65 and P53/PUMA signaling pathways involved. 谷氨酰胺通过参与HSP70: NF-κB p65和P53/PUMA信号通路改善多角沙鼠毒液诱导的肺和心脏损伤。
IF 2.4 3区 医学 Q4 TOXICOLOGY Pub Date : 2023-01-01 DOI: 10.1590/1678-9199-JVATITD-2022-0080
Yalan Li, Zhezhe Guan, Shaocong Hu, Zhi Huang, Dongling He, Xiaoyang Cheng, Tianlin Song, Caifeng Mo, Manqi Xiao, Yue Huang, Yuanmei Wei, Yi Zhou, Xuerong Zhang, Ming Liao

Background: Bungarus multicinctus is one of the most dangerous venomous snakes prone to cardiopulmonary damage with extremely high mortality. In our previous work, we found that glutamine (Gln) and glutamine synthetase (GS) in pig serum were significantly reduced after Bungarus multicinctus bite. In the present study, to explore whether there is a link between the pathogenesis of cardiopulmonary injury and Gln metabolic changes induced by Bungarus multicinctus venom. We investigated the effect of Gln supplementation on the lung and heart function after snakebite.

Methods: We supplemented different concentrations of Gln to mice that were envenomated by Bungarus multicinctus to observe the biological behavior, survival rate, hematological and pathological changes. Gln was supplemented immediately or one hour after the venom injection, and then changes in Gln metabolism were analyzed. Subsequently, to further explore the protective mechanism of glutamine on tissue damage, we measured the expression of heat-shock protein70 (HSP70), NF-κB P65, P53/PUMA by western blotting and real-time polymerase in the lung and heart.

Results: Gln supplementation delayed the envenoming symptoms, reduced mortality, and alleviated the histopathological changes in the heart and lung of mice bitten by Bungarus multicinctus. Additionally, Gln increased the activity of glutamine synthetase (GS), glutamate dehydrogenase (GDH) and glutaminase (GLS) in serum. It also balanced the transporter SLC7A11 expression in heart and lung tissues. Bungarus multicinctus venom induced the NF-κB nuclear translocation in the lung, while the HO-1 expression was suppressed. At the same time, venom activated the P53/PUMA signaling pathway and the BAX expression in the heart. Gln treatment reversed the above phenomenon and increased HSP70 expression.

Conclusion: Gln alleviated the glutamine metabolism disorder and cardiopulmonary damage caused by Bungarus multicinctus venom. It may protect lungs and heart against venom by promoting the expression of HSP70, inhibiting the activation of NF-κB and P53/PUMA, thereby delaying the process of snake venom and reducing mortality. The present results indicate that Gln could be a potential treatment for Bungarus multicinctus bite.

背景:多纹蛇是最危险的毒蛇之一,易造成心肺损伤,死亡率极高。在我们之前的工作中,我们发现在多刺兔咬伤后猪血清中的谷氨酰胺(Gln)和谷氨酰胺合成酶(GS)显著降低。在本研究中,我们将探讨多刺沙鼠毒液引起的Gln代谢变化与心肺损伤的发病机制是否存在联系。我们研究了补充谷氨酰胺对蛇咬伤后肺和心脏功能的影响。方法:以不同浓度的谷氨酰胺(Gln)给毒鼠,观察其生物学行为、存活率、血液学及病理变化。即刻或注射后1小时补充Gln,分析Gln代谢变化。随后,为了进一步探讨谷氨酰胺对组织损伤的保护机制,我们采用western blotting和实时聚合酶检测肺和心脏组织中热休克蛋白70 (HSP70)、NF-κB P65、P53/PUMA的表达。结果:补充谷氨酰胺可延缓多刺沙鼠咬伤小鼠的中毒症状,降低死亡率,减轻其心肺组织病理改变。谷氨酰胺可提高血清谷氨酰胺合成酶(GS)、谷氨酸脱氢酶(GDH)和谷氨酰胺酶(GLS)活性。它还平衡了转运体SLC7A11在心肺组织中的表达。蛇毒诱导肺组织NF-κB核易位,抑制HO-1的表达。同时,毒液激活了P53/PUMA信号通路和心脏中BAX的表达。Gln处理逆转了上述现象,增加了HSP70的表达。结论:谷氨酰胺可减轻毒鼠引起的谷氨酰胺代谢紊乱和心肺损伤。它可能通过促进HSP70的表达,抑制NF-κB和P53/PUMA的激活,从而延缓蛇毒的过程,降低死亡率,从而保护肺和心脏免受蛇毒的侵害。本研究结果表明,谷氨酰胺可能是一种潜在的治疗多爪沙鼠咬伤的药物。
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引用次数: 1
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Journal of Venomous Animals and Toxins Including Tropical Diseases
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