Background: Several studies have indicated an association between cadmium (Cd) exposure and the induction of thyroid dysfunction in animal models. Objective and Aims: There are inconsistent findings on the effect of Cd on the thyroid gland. Therefore, this systematic study was designed to determine the association between changes in thyroid function markers and Cd exposure in animals.
Method: The search was performed on Scopus, PubMed, Web of Science and databases, and Google Scholar until May 2023. Studies on the relationship between Cd exposure and fish's thyroid function were conducted on rodents and fish.
Results: In total, 171 articles were obtained from the main databases using the search strategy mentioned in this study. Finally, 24 articles were selected according to our inclusion criteria for systematic studies. The findings indicated an increase/decrease or no change in triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels in rodents, fish, and animals exposed to Cd.
Conclusion: Our findings indicated an association between Cd exposure and thyroid dysfunction in rodents, fish, and other animals. However, the association between urinary and blood Cd levels and thyroid function remains unclear in humans because of controversial findings and a lack of strong mechanistic evidence. We perform large cohort human studies to the answer to this question.
背景:多项研究表明,在动物模型中,镉(Cd)暴露与甲状腺功能障碍的诱导存在关联。目的和宗旨:关于镉对甲状腺的影响,研究结果并不一致。因此,本系统研究旨在确定动物甲状腺功能指标的变化与镉暴露之间的关联:方法:在Scopus、PubMed、Web of Science和数据库以及Google Scholar上进行搜索,搜索时间截止到2023年5月。有关镉暴露与鱼类甲状腺功能之间关系的研究以啮齿动物和鱼类为对象:采用本研究中提到的检索策略,从主要数据库中共获得 171 篇文章。最后,根据系统研究的纳入标准选出了 24 篇文章。研究结果表明,啮齿动物、鱼类和接触过镉的动物体内的三碘甲状腺原氨酸(T3)、甲状腺素(T4)和促甲状腺激素(TSH)水平有升高/降低或无变化:我们的研究结果表明,啮齿动物、鱼类和其他动物体内的镉暴露与甲状腺功能障碍之间存在关联。然而,由于研究结果存在争议且缺乏有力的机理证据,尿液和血液中的镉水平与人类甲状腺功能之间的关系仍不明确。我们对人类进行了大规模的队列研究,以寻找这一问题的答案。
{"title":"The Association between Cadmium Exposure and Thyroid Function in Animals: A Systematic Review.","authors":"Maryam Nazarian, Pouria Mohammadparast Tabas, Mohammad Sadra Harifi-Mood, Hamed Aramjoo, Ahmad Bavali-Gazik, Amirhossein Saberi, Yasaman Peyghambari, Peyman Mohammadparast-Tabas, Amirhosein Anghoshtary, Saeed Samarghandian, Tahereh Farkhondeh","doi":"10.2174/0115665240288797240704134652","DOIUrl":"https://doi.org/10.2174/0115665240288797240704134652","url":null,"abstract":"<p><strong>Background: </strong>Several studies have indicated an association between cadmium (Cd) exposure and the induction of thyroid dysfunction in animal models. Objective and Aims: There are inconsistent findings on the effect of Cd on the thyroid gland. Therefore, this systematic study was designed to determine the association between changes in thyroid function markers and Cd exposure in animals.</p><p><strong>Method: </strong>The search was performed on Scopus, PubMed, Web of Science and databases, and Google Scholar until May 2023. Studies on the relationship between Cd exposure and fish's thyroid function were conducted on rodents and fish.</p><p><strong>Results: </strong>In total, 171 articles were obtained from the main databases using the search strategy mentioned in this study. Finally, 24 articles were selected according to our inclusion criteria for systematic studies. The findings indicated an increase/decrease or no change in triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels in rodents, fish, and animals exposed to Cd.</p><p><strong>Conclusion: </strong>Our findings indicated an association between Cd exposure and thyroid dysfunction in rodents, fish, and other animals. However, the association between urinary and blood Cd levels and thyroid function remains unclear in humans because of controversial findings and a lack of strong mechanistic evidence. We perform large cohort human studies to the answer to this question.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.2174/0115665240303070240626075757
Saba Kamil, Shaheen Kouser, Nadia Naeem, Waqas Farroqui, Shaheen Sharafat, Farrukh Ali Khan, Ghulam Haider, Noor Kamil, Raahim Ali, Farah Fatima Abbass, Nehad Khan, Ramsha Khan
Background: Increased expression of MRP 1 in AML patients results in the efflux of drugs from the cells, preventing the patient from achieving remission or potentially leading to relapse. Several studies have demonstrated that early identification of ABC transporter may yield favorable outcomes.
Aims and objectives: The objectives of the study were to investigate the correlation between MRP 1 gene expression and MRP 1 protein levels and the response to remission induction in AML patients.
Method: A total of 40 AML patients were recruited from March 2021 to June 2022. Peripheral blood was collected in two tubes (yellow and purple top) to assess the MRP 1 gene and protein. For MRP 1 gene assessment, RNA was isolated from blood samples, cDNA was prepared, and qRT-PCR was performed to analyze gene expression. The relationship between the gene and complete remission was determined. Identification of MRP 1 protein was conducted using ELISA, and the relationship between protein levels and complete remission (CR) was explored.
Results: Most of the patients were aged between 25 and 39 years, encompassing both males and females. This study observed a clinical correlation between MRP 1 gene expression and complete remission. The findings revealed that 69.2 percent of patients with high gene expression failed to achieve complete remission, whereas the analysis of MRP 1 protein in relation to complete remission showed no statistical significance. The MRP1 gene showed high expression (66.7%) in patients with FLT3 mutation, whereas low expression of MRP1 was associated with a high occurrence (60%) of NMP1 mutation.
Conclusion: Further comprehensive multicenter studies with larger sample sizes are required to validate the findings of this study. It is recommended to pinpoint the mechanism and regulation of MRP 1 and its interaction with other molecular pathways.
{"title":"Unveiling the Significance of MRP 1 in Achieving Complete Remission Following Induction Therapy in Acute Myeloid Leukemia.","authors":"Saba Kamil, Shaheen Kouser, Nadia Naeem, Waqas Farroqui, Shaheen Sharafat, Farrukh Ali Khan, Ghulam Haider, Noor Kamil, Raahim Ali, Farah Fatima Abbass, Nehad Khan, Ramsha Khan","doi":"10.2174/0115665240303070240626075757","DOIUrl":"https://doi.org/10.2174/0115665240303070240626075757","url":null,"abstract":"<p><strong>Background: </strong>Increased expression of MRP 1 in AML patients results in the efflux of drugs from the cells, preventing the patient from achieving remission or potentially leading to relapse. Several studies have demonstrated that early identification of ABC transporter may yield favorable outcomes.</p><p><strong>Aims and objectives: </strong>The objectives of the study were to investigate the correlation between MRP 1 gene expression and MRP 1 protein levels and the response to remission induction in AML patients.</p><p><strong>Method: </strong>A total of 40 AML patients were recruited from March 2021 to June 2022. Peripheral blood was collected in two tubes (yellow and purple top) to assess the MRP 1 gene and protein. For MRP 1 gene assessment, RNA was isolated from blood samples, cDNA was prepared, and qRT-PCR was performed to analyze gene expression. The relationship between the gene and complete remission was determined. Identification of MRP 1 protein was conducted using ELISA, and the relationship between protein levels and complete remission (CR) was explored.</p><p><strong>Results: </strong>Most of the patients were aged between 25 and 39 years, encompassing both males and females. This study observed a clinical correlation between MRP 1 gene expression and complete remission. The findings revealed that 69.2 percent of patients with high gene expression failed to achieve complete remission, whereas the analysis of MRP 1 protein in relation to complete remission showed no statistical significance. The MRP1 gene showed high expression (66.7%) in patients with FLT3 mutation, whereas low expression of MRP1 was associated with a high occurrence (60%) of NMP1 mutation.</p><p><strong>Conclusion: </strong>Further comprehensive multicenter studies with larger sample sizes are required to validate the findings of this study. It is recommended to pinpoint the mechanism and regulation of MRP 1 and its interaction with other molecular pathways.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24DOI: 10.2174/0115665240307495240605101526
Vladimir Sobolev, Madina Muminova, Olga Zhukova, Elena Denisova, Anna Soboleva, Nikolay Potekaev, Irina Korsunskaya, Alexandre Mezentsev
Background: Restructuring of dermal microcapillaries is one of the hallmarks of plaque psoriasis. To control the proliferation of vascular endothelial cells, vascular endothelial growth factor (VEGF) promotes the remodeling of the existing blood vessels and angiogenesis.
Objective: This study aimed to explain the lowering protein and mRNA levels of VEGF in lesional skin of patients with severe psoriasis (the Psoriasis Area and Severity Index, PASI > 25).
Methods: Using the method of qPCR, we assessed the expression of VEGF mRNA in lesional and nonlesional psoriatic skin. Using ELISA, we also compared the levels of VEGF in skin homogenates of psoriasis patients and healthy volunteers.
Results: We found that the exacerbation of psoriasis induced VEGF on mRNA and protein levels 12 and 20 times, respectively. We also confirmed a strong correlation between VEGF and PASI score in patients with PASI < 25. In addition, we showed that several factors, namely HGF, HNRPD, and sFLT1 interfere with the biosynthesis of VEGF in skin lesions of patients with PASI > 25%.
Conclusion: Thus, using VEGF as a biomarker to monitor the disease shall be done cautiously in patients with severe psoriasis.
背景:真皮微毛细血管的重组是斑块状银屑病的特征之一。为了控制血管内皮细胞的增殖,血管内皮生长因子(VEGF)可促进现有血管的重塑和血管生成:本研究旨在解释重度银屑病患者(银屑病面积和严重程度指数 PASI > 25)皮损皮肤中血管内皮生长因子蛋白和 mRNA 水平降低的原因:方法:我们使用 qPCR 方法评估了病变和非病变银屑病皮肤中 VEGF mRNA 的表达。我们还使用 ELISA 方法比较了银屑病患者和健康志愿者皮肤匀浆中 VEGF 的水平:结果:我们发现,银屑病加重会诱导血管内皮生长因子的 mRNA 和蛋白质水平分别增加 12 倍和 20 倍。我们还证实,在 PASI 小于 25 的患者中,VEGF 与 PASI 评分之间存在很强的相关性。此外,我们还发现几个因素,即 HGF、HNRPD 和 sFLT1 会干扰 PASI > 25% 患者皮损中 VEGF 的生物合成:因此,将血管内皮生长因子作为监测重症银屑病患者病情的生物标志物应慎重使用。
{"title":"HGF, HNRPD, and sFLT1 Interfere with the Induction of VEGF in Patients with Severe Psoriasis.","authors":"Vladimir Sobolev, Madina Muminova, Olga Zhukova, Elena Denisova, Anna Soboleva, Nikolay Potekaev, Irina Korsunskaya, Alexandre Mezentsev","doi":"10.2174/0115665240307495240605101526","DOIUrl":"https://doi.org/10.2174/0115665240307495240605101526","url":null,"abstract":"<p><strong>Background: </strong>Restructuring of dermal microcapillaries is one of the hallmarks of plaque psoriasis. To control the proliferation of vascular endothelial cells, vascular endothelial growth factor (VEGF) promotes the remodeling of the existing blood vessels and angiogenesis.</p><p><strong>Objective: </strong>This study aimed to explain the lowering protein and mRNA levels of VEGF in lesional skin of patients with severe psoriasis (the Psoriasis Area and Severity Index, PASI > 25).</p><p><strong>Methods: </strong>Using the method of qPCR, we assessed the expression of VEGF mRNA in lesional and nonlesional psoriatic skin. Using ELISA, we also compared the levels of VEGF in skin homogenates of psoriasis patients and healthy volunteers.</p><p><strong>Results: </strong>We found that the exacerbation of psoriasis induced VEGF on mRNA and protein levels 12 and 20 times, respectively. We also confirmed a strong correlation between VEGF and PASI score in patients with PASI < 25. In addition, we showed that several factors, namely HGF, HNRPD, and sFLT1 interfere with the biosynthesis of VEGF in skin lesions of patients with PASI > 25%.</p><p><strong>Conclusion: </strong>Thus, using VEGF as a biomarker to monitor the disease shall be done cautiously in patients with severe psoriasis.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24DOI: 10.2174/0115665240307413240531111140
Mohammad Shabib Akhtar, Nehal Mohsin, Ahmad Zahak, Khalid Altigani Awad Alkarem Ahmed, Yasir Alhazmi, Mohamad Taleuzzaman
Targeting genes using siRNA shows promise as an approach to alleviate symptoms of diabetic neuropathy. It focuses on neuropathies and distal symmetric polyneuropathy (DSPN) to explore the potential use of small interfering RNA (siRNA) as a treatment for diabetic neuropathy. Timely identification and management of neuropathy play a critical role in mitigating potential complications. RNAi success depends on understanding factors affecting small interfering RNA (siRNA) functionality and specificity. These include sequence space restrictions, structural and sequence features, mechanisms for nonspecific gene modulation, and chemical modifications. Addressing these factors enhances siRNA performance for efficient gene silencing and confidence in RNAi-mediated genomic studies. Diabetic retinopathy, particularly in South Asian, African, Latin American, and indigenous populations, is a significant concern due to its association with diabetes. Ethnicity plays a crucial role in its development and progression. Despite declining rates in the US, global trends remain concerning, and further research is needed to understand regional differences and reinforce ethnicity-based screening and treatment protocols. In this regard, siRNA emerges as a valuable instrument for early intervention strategies. While presenting promising therapeutic applications, siRNA utilization encounters challenges within insect pest control contexts, thereby providing insights into enhancing its delivery mechanisms for neuropathy treatment purposes. Recent advancements in delivery modalities, such as nanoparticles, allow for the controlled release of siRNA. More investigation is necessary to grasp the safety and efficacy of siRNA technology fully. It holds promise in transforming the treatment of diabetic neuropathy by honing in on particular genes and tackling issues such as inflammation and oxidative stress. Continuous advancements in delivery techniques have the potential to enhance patient results significantly. SiRNA targets genes in diabetic neuropathy, curbing nerve damage and pain and potentially preventing or delaying the condition. Customized treatments based on genetic variations hold promise for symptom management and enhancing quality of life.
{"title":"siRNA Treatments for Diabetic Neuropathy: Obstacles and Delivery Techniques.","authors":"Mohammad Shabib Akhtar, Nehal Mohsin, Ahmad Zahak, Khalid Altigani Awad Alkarem Ahmed, Yasir Alhazmi, Mohamad Taleuzzaman","doi":"10.2174/0115665240307413240531111140","DOIUrl":"https://doi.org/10.2174/0115665240307413240531111140","url":null,"abstract":"<p><p>Targeting genes using siRNA shows promise as an approach to alleviate symptoms of diabetic neuropathy. It focuses on neuropathies and distal symmetric polyneuropathy (DSPN) to explore the potential use of small interfering RNA (siRNA) as a treatment for diabetic neuropathy. Timely identification and management of neuropathy play a critical role in mitigating potential complications. RNAi success depends on understanding factors affecting small interfering RNA (siRNA) functionality and specificity. These include sequence space restrictions, structural and sequence features, mechanisms for nonspecific gene modulation, and chemical modifications. Addressing these factors enhances siRNA performance for efficient gene silencing and confidence in RNAi-mediated genomic studies. Diabetic retinopathy, particularly in South Asian, African, Latin American, and indigenous populations, is a significant concern due to its association with diabetes. Ethnicity plays a crucial role in its development and progression. Despite declining rates in the US, global trends remain concerning, and further research is needed to understand regional differences and reinforce ethnicity-based screening and treatment protocols. In this regard, siRNA emerges as a valuable instrument for early intervention strategies. While presenting promising therapeutic applications, siRNA utilization encounters challenges within insect pest control contexts, thereby providing insights into enhancing its delivery mechanisms for neuropathy treatment purposes. Recent advancements in delivery modalities, such as nanoparticles, allow for the controlled release of siRNA. More investigation is necessary to grasp the safety and efficacy of siRNA technology fully. It holds promise in transforming the treatment of diabetic neuropathy by honing in on particular genes and tackling issues such as inflammation and oxidative stress. Continuous advancements in delivery techniques have the potential to enhance patient results significantly. SiRNA targets genes in diabetic neuropathy, curbing nerve damage and pain and potentially preventing or delaying the condition. Customized treatments based on genetic variations hold promise for symptom management and enhancing quality of life.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: T helper interplay and cytokines monitoring in auto-immune skin disorders such as Pemphigus Foliaceus [PF] may play a central role in predicting the clinical stratification of the pathology.
Objectives: In order to assess the CD4+ T cell imbalance, [i] this study aims to assess the related immune cells [Th1, Th2, Th17, and Treg cells] as well as the related cytokines [IL-1β, IFNγ, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL- 22, TNF-β, and TNFα] in peripheral blood, and [ii] their respective transcription factors in the lesioned skin of PF endemic patients during the clinical course.
Methods: Peripheral blood of 22 PF patients was analyzed by flow cytometry to assess the functional associations of Th cell subpopulations and their characteristic cytokines by multiplex bead assay of 14-plex cytokines. Skin mRNA expression of their associated transcription factors was analyzed using the TaqMan detection system.
Results: Our findings revealed that the CD4+ T cell subtypes in PF patients compared to Healthy Controls [HC] were characterized by [i] a similar Th1/Th2 ratio and increased Th17/Treg ratio and [ii] significantly higher plasma levels of Th-17 specific cytokines; IL- 6, IL-8, IL-17A. Higher percentages in Th17 and Treg subtypes and a significant increase in plasma IL-17F levels were maintained in relapsing PF patients, arguing the pivotal role of Th17 cells in PF pathogenesis. Furthermore, our findings pointed out the major contribution of the pro-inflammatory cytokine IL-6. Indeed, in addition to being involved in the initial stages of disease development, IL-6 seems to also be involved in the maintenance of the pathophysiological process, probably through its effect on Th17 differentiation. The skin-relative mRNA expression levels of FOXP3 and TBET were significantly higher in relapsing PF patients compared to de novo PF patients.
Conclusion: Our results highlight the central role played by Th17 lymphocytes and their related pro-inflammatory cytokines during the clinical course of the disease, reversing the Th1/Th2 dichotomy in PF.
{"title":"CD4+ T-cell Subsets and Cytokine Signature in Pemphigus Foliaceus Clinical Stratification beyond the th1/Th2 Paradigm.","authors":"Fakhfakh Raouia, Ben Jmaa Mariem, Elloumi Nesrine, Mseddi Meriam, Mohamed Mohany, Bahloul Emna, Khadija Sellami, Feki Sawsan, Marija Milošević, Turki Hamida, Masmoudi Hatem, Abida Olfa","doi":"10.2174/0115665240305096240611064617","DOIUrl":"https://doi.org/10.2174/0115665240305096240611064617","url":null,"abstract":"<p><strong>Background: </strong>T helper interplay and cytokines monitoring in auto-immune skin disorders such as Pemphigus Foliaceus [PF] may play a central role in predicting the clinical stratification of the pathology.</p><p><strong>Objectives: </strong>In order to assess the CD4+ T cell imbalance, [i] this study aims to assess the related immune cells [Th1, Th2, Th17, and Treg cells] as well as the related cytokines [IL-1β, IFNγ, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL- 22, TNF-β, and TNFα] in peripheral blood, and [ii] their respective transcription factors in the lesioned skin of PF endemic patients during the clinical course.</p><p><strong>Methods: </strong>Peripheral blood of 22 PF patients was analyzed by flow cytometry to assess the functional associations of Th cell subpopulations and their characteristic cytokines by multiplex bead assay of 14-plex cytokines. Skin mRNA expression of their associated transcription factors was analyzed using the TaqMan detection system.</p><p><strong>Results: </strong>Our findings revealed that the CD4+ T cell subtypes in PF patients compared to Healthy Controls [HC] were characterized by [i] a similar Th1/Th2 ratio and increased Th17/Treg ratio and [ii] significantly higher plasma levels of Th-17 specific cytokines; IL- 6, IL-8, IL-17A. Higher percentages in Th17 and Treg subtypes and a significant increase in plasma IL-17F levels were maintained in relapsing PF patients, arguing the pivotal role of Th17 cells in PF pathogenesis. Furthermore, our findings pointed out the major contribution of the pro-inflammatory cytokine IL-6. Indeed, in addition to being involved in the initial stages of disease development, IL-6 seems to also be involved in the maintenance of the pathophysiological process, probably through its effect on Th17 differentiation. The skin-relative mRNA expression levels of FOXP3 and TBET were significantly higher in relapsing PF patients compared to de novo PF patients.</p><p><strong>Conclusion: </strong>Our results highlight the central role played by Th17 lymphocytes and their related pro-inflammatory cytokines during the clinical course of the disease, reversing the Th1/Th2 dichotomy in PF.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-11DOI: 10.2174/0115665240310818240531080353
Yuan Yuan, Yufan Wu, Minhui He, Xue Jiang
Background: Podocyte injury is the most important pathological hallmark of kidney diseases. Autophagy is a critical factor that involves podocyte injury. Here, we sought to determine whether Astragaloside IV (AS-IV) was able to improve renal function and reverse podocyte injury through the regulation of autophagy.
Methods: Using the Adriamycin (ADR) mice model, cultured immortalized mouse podocytes were exposed to AS-IV. Western blotting, immunofluorescence, and histochemistry were used to analyze markers of autophagy, mitochondrial dysfunction, podocyte apoptosis, and glomerulopathy in the progression of focal segmental glomerular sclerosis.
Results: We observed that AS-IV can inhibit podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation, and dysfunction by inducing the Mfn2/Pink1/Parkin mitophagy pathway both in vivo and in vitro. Overexpression of Mfn2 reduced puromycin aminonucleoside (PAN)-induced podocyte injury, while downregulation of Mfn2 expression limited the renal protective effect of AS-IV by regulating mitophagy.
Conclusion: AS-IV ameliorates renal function and renal pathological changes in ADR mice and inhibits PAN-induced podocyte injury by directly enhancing Mfn2/Pink1/Parkin-associated autophagy.
{"title":"Astragaloside IV Protects Against Podocyte Injury by Upregulating Mitophagy via the Mfn2/Pink1/Parkin Axis.","authors":"Yuan Yuan, Yufan Wu, Minhui He, Xue Jiang","doi":"10.2174/0115665240310818240531080353","DOIUrl":"https://doi.org/10.2174/0115665240310818240531080353","url":null,"abstract":"<p><strong>Background: </strong>Podocyte injury is the most important pathological hallmark of kidney diseases. Autophagy is a critical factor that involves podocyte injury. Here, we sought to determine whether Astragaloside IV (AS-IV) was able to improve renal function and reverse podocyte injury through the regulation of autophagy.</p><p><strong>Methods: </strong>Using the Adriamycin (ADR) mice model, cultured immortalized mouse podocytes were exposed to AS-IV. Western blotting, immunofluorescence, and histochemistry were used to analyze markers of autophagy, mitochondrial dysfunction, podocyte apoptosis, and glomerulopathy in the progression of focal segmental glomerular sclerosis.</p><p><strong>Results: </strong>We observed that AS-IV can inhibit podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation, and dysfunction by inducing the Mfn2/Pink1/Parkin mitophagy pathway both in vivo and in vitro. Overexpression of Mfn2 reduced puromycin aminonucleoside (PAN)-induced podocyte injury, while downregulation of Mfn2 expression limited the renal protective effect of AS-IV by regulating mitophagy.</p><p><strong>Conclusion: </strong>AS-IV ameliorates renal function and renal pathological changes in ADR mice and inhibits PAN-induced podocyte injury by directly enhancing Mfn2/Pink1/Parkin-associated autophagy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-07DOI: 10.2174/0115665240304247240529074123
Mahrokh Abouali Gale Dari, Vahid Vahedian, Bartosz Kempisty, Olanrewaju B Morenikeji, Maryam Farzaneh, Amir Anbiyaiee
MicroRNAs (miRNAs) have emerged as crucial regulators of gene expression, playing pivotal roles in various biological processes, including cancer development and progression. Among them, miR-125b has garnered significant attention due to its multifaceted functional roles in human hepatocellular carcinoma (HCC). Extensive research has revealed that miR-125b plays a dual role in HCC, acting as both a tumor suppressor and an oncogene depending on the context. As a tumor suppressor, miR-125b exerts its inhibitory effects on HCC by targeting key oncogenic pathways and genes involved in cell proliferation, migration, invasion, and angiogenesis. Its downregulation in HCC is frequently observed and correlates with aggressive tumor characteristics and poor prognosis. Conversely, miR-125b can also function as an oncogene in specific HCC subtypes or under certain conditions. It has been shown to promote HCC growth, metastasis, and therapeutic resistance by targeting tumor suppressor genes, modulating the epithelial-mesenchymal transition (EMT) process, and enhancing cancer stem cell-like properties. The upregulation of miR-125b in HCC has been associated with advanced disease stages and unfavorable clinical outcomes. Furthermore, the dysregulation of miR-125b expression in HCC is influenced by a complex network of regulatory mechanisms. Understanding these regulatory mechanisms is crucial for deciphering the precise functional roles of miR-125b in HCC and exploring its potential as a diagnostic biomarker or therapeutic target. In the current review study, we comprehensively elucidated the diverse functional roles of miR-125b in HCC, providing a comprehensive overview of its regulatory mechanisms and impact on key cellular processes involved in HCC progression.
{"title":"The Protective Role of miR-125b in Hepatocellular Carcinoma: Unraveling Tumor-Suppressive Mechanisms.","authors":"Mahrokh Abouali Gale Dari, Vahid Vahedian, Bartosz Kempisty, Olanrewaju B Morenikeji, Maryam Farzaneh, Amir Anbiyaiee","doi":"10.2174/0115665240304247240529074123","DOIUrl":"https://doi.org/10.2174/0115665240304247240529074123","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have emerged as crucial regulators of gene expression, playing pivotal roles in various biological processes, including cancer development and progression. Among them, miR-125b has garnered significant attention due to its multifaceted functional roles in human hepatocellular carcinoma (HCC). Extensive research has revealed that miR-125b plays a dual role in HCC, acting as both a tumor suppressor and an oncogene depending on the context. As a tumor suppressor, miR-125b exerts its inhibitory effects on HCC by targeting key oncogenic pathways and genes involved in cell proliferation, migration, invasion, and angiogenesis. Its downregulation in HCC is frequently observed and correlates with aggressive tumor characteristics and poor prognosis. Conversely, miR-125b can also function as an oncogene in specific HCC subtypes or under certain conditions. It has been shown to promote HCC growth, metastasis, and therapeutic resistance by targeting tumor suppressor genes, modulating the epithelial-mesenchymal transition (EMT) process, and enhancing cancer stem cell-like properties. The upregulation of miR-125b in HCC has been associated with advanced disease stages and unfavorable clinical outcomes. Furthermore, the dysregulation of miR-125b expression in HCC is influenced by a complex network of regulatory mechanisms. Understanding these regulatory mechanisms is crucial for deciphering the precise functional roles of miR-125b in HCC and exploring its potential as a diagnostic biomarker or therapeutic target. In the current review study, we comprehensively elucidated the diverse functional roles of miR-125b in HCC, providing a comprehensive overview of its regulatory mechanisms and impact on key cellular processes involved in HCC progression.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-07DOI: 10.2174/0115665240309075240603062703
Barsa Sahebnazar, Javad Saberynejad, Mohammad Reza Atashzar
Interferon epsilon (IFN-ε) belongs to the type I IFN group and exhibits various biological properties. IFN-ε exhibits different regulation mechanisms and expression via other type I IFNs. Its hormonal regulation suggests that this INF can have different functions and pathways from other type I IFNs. Although IFN-ε exhibits lower antiproliferative, anti-tumor, and antiviral activities compared to IFN-α, it has been identified to contribute to mucosal immunity, combat bacterial infections, and aid in the prevention of specific sexually transmitted diseases, such as HIV, Zika virus, etc. IFN-α and IFN-β with their well-established properties have been a research hotspot for many years; nevertheless, IFN-ε, whose unique roles are only now beginning to emerge, may be an intriguing subject for future study. This review focuses on the known activity of IFN-ε in certain cancers, pregnancy, autoimmune diseases, bacterial infections, and viruses. The aim of this paper is to enhance the understanding of the potential efficacy of IFN-ε treatment in the future.
干扰素ε(IFN-ε)属于 I 型 IFN,具有多种生物学特性。IFN-ε 与其他 I 型 IFN 的调节机制和表达方式不同。它的激素调节表明,这种 INF 可能具有与其他 I 型 IFN 不同的功能和途径。虽然与 IFN-α 相比,IFN-ε 的抗增殖、抗肿瘤和抗病毒活性较低,但已发现它有助于粘膜免疫、抗细菌感染,并有助于预防特定的性传播疾病,如艾滋病、寨卡病毒等。多年来,IFN-α 和 IFN-β 以其公认的特性一直是研究热点;然而,IFN-ε 的独特作用现在才刚刚开始显现,它可能是未来研究的一个引人入胜的主题。本综述重点介绍 IFN-ε 在某些癌症、妊娠、自身免疫性疾病、细菌感染和病毒中的已知活性。本文旨在加深人们对未来 IFN-ε 治疗潜在疗效的理解。
{"title":"Interferon Epsilon: Properties and Functions.","authors":"Barsa Sahebnazar, Javad Saberynejad, Mohammad Reza Atashzar","doi":"10.2174/0115665240309075240603062703","DOIUrl":"https://doi.org/10.2174/0115665240309075240603062703","url":null,"abstract":"<p><p>Interferon epsilon (IFN-ε) belongs to the type I IFN group and exhibits various biological properties. IFN-ε exhibits different regulation mechanisms and expression via other type I IFNs. Its hormonal regulation suggests that this INF can have different functions and pathways from other type I IFNs. Although IFN-ε exhibits lower antiproliferative, anti-tumor, and antiviral activities compared to IFN-α, it has been identified to contribute to mucosal immunity, combat bacterial infections, and aid in the prevention of specific sexually transmitted diseases, such as HIV, Zika virus, etc. IFN-α and IFN-β with their well-established properties have been a research hotspot for many years; nevertheless, IFN-ε, whose unique roles are only now beginning to emerge, may be an intriguing subject for future study. This review focuses on the known activity of IFN-ε in certain cancers, pregnancy, autoimmune diseases, bacterial infections, and viruses. The aim of this paper is to enhance the understanding of the potential efficacy of IFN-ε treatment in the future.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gene silencing through RNA interference (RNAi) technology has provided forceful therapeutic modalities to specific knockdown of the genes' expression related to diseases. Small interfering RNAs (siRNAs) can start a process that specifically degrades and silences the expression of cognate mRNAs. These RNA interference processes could effectively adjust many biological processes, including immune responses. Dendritic cells (DCs) are specialist antigen-presenting cells with potent functions in regulating innate and adaptive immunity. SiRNAs performed vital roles in coordinating immune processes mediated by DCs. This review describes the findings that shed light on the significance of siRNAs in DC immune regulation and highlight their potential applications for improving DC-based immunotherapies.
通过 RNA 干扰(RNAi)技术进行基因沉默为特异性敲除与疾病相关的基因表达提供了有力的治疗方法。小干扰 RNA(siRNA)可以启动一个特异性降解和沉默同源 mRNA 表达的过程。这些 RNA 干扰过程可以有效调整许多生物过程,包括免疫反应。树突状细胞(DC)是专门的抗原递呈细胞,在调节先天性免疫和适应性免疫方面具有强大的功能。SiRNA 在协调由 DCs 介导的免疫过程中发挥着重要作用。本综述介绍了 siRNAs 在 DC 免疫调节中的重要作用,并强调了其在改善基于 DC 的免疫疗法中的潜在应用。
{"title":"Recent Advances in Immune Regulation by Targeting Dendritic Cells using Small Interfering RNAs.","authors":"Mahshid Shahverdi, Vahab Alamdari-Palangi, Shiva Alipour, Amir Ghaffari Jolfayi, Javad Masoumi, Leili Aghebati-Maleki, Arman Rostamlou, Behzad Baradaran","doi":"10.2174/0115665240303370240530120450","DOIUrl":"https://doi.org/10.2174/0115665240303370240530120450","url":null,"abstract":"<p><p>Gene silencing through RNA interference (RNAi) technology has provided forceful therapeutic modalities to specific knockdown of the genes' expression related to diseases. Small interfering RNAs (siRNAs) can start a process that specifically degrades and silences the expression of cognate mRNAs. These RNA interference processes could effectively adjust many biological processes, including immune responses. Dendritic cells (DCs) are specialist antigen-presenting cells with potent functions in regulating innate and adaptive immunity. SiRNAs performed vital roles in coordinating immune processes mediated by DCs. This review describes the findings that shed light on the significance of siRNAs in DC immune regulation and highlight their potential applications for improving DC-based immunotherapies.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.2174/0115665240306767240603091329
Wenlong Hu, Weiyi Huang, Wei Ji, Jun Sun
Subarachnoid hemorrhage is a serious subtype of stroke with high mortality and disability. The rupture of intracranial aneurysms is the main cause. However, in recent years, with the popularization of CT, MRI, and cerebral angiography, the detection rate of unruptured aneurysms has increased, and the incidence of aneurysm rupture and hemorrhage has gradually decreased. However, there are still some patients who fail to detect aneurysms in time and receive treatment, resulting in the occurrence of aneurysm rupture and bleeding, and these patients usually have a poor prognosis and leave a lasting disability. Therefore, exploring the causes of aneurysm formation and the mechanism of brain injury caused by aneurysm rupture is of great significance for preventing aneurysm formation and improving the prognosis of patients. MicroRNAs (miRNAs) are highly conserved non-coding RNAs that can bind to the 3'UTR of target mRNAs to regulate gene expression. Studies have shown that miRNAs can affect the formation and rupture of intracranial aneurysms by participating in apoptosis, inflammation, phagocyte migration, and vascular smooth muscle cells (VSMCs) regulation, and regulate the damage of brain tissue after aneurysm rupture. They play a role in multiple pathophysiological processes of aneurysmal subarachnoid hemorrhage. This article reviews the role of miRNAs in different pathophysiological stages of aneurysmal subarachnoid hemorrhage (aSAH). We further described the research progress of miRNAs as biomarkers for the diagnosis and prognosis of aSAH and discussed their application prospects in the prevention and treatment of aSAH.
{"title":"The Role of miRNAs in Aneurysmal Subarachnoid Hemorrhage.","authors":"Wenlong Hu, Weiyi Huang, Wei Ji, Jun Sun","doi":"10.2174/0115665240306767240603091329","DOIUrl":"https://doi.org/10.2174/0115665240306767240603091329","url":null,"abstract":"<p><p>Subarachnoid hemorrhage is a serious subtype of stroke with high mortality and disability. The rupture of intracranial aneurysms is the main cause. However, in recent years, with the popularization of CT, MRI, and cerebral angiography, the detection rate of unruptured aneurysms has increased, and the incidence of aneurysm rupture and hemorrhage has gradually decreased. However, there are still some patients who fail to detect aneurysms in time and receive treatment, resulting in the occurrence of aneurysm rupture and bleeding, and these patients usually have a poor prognosis and leave a lasting disability. Therefore, exploring the causes of aneurysm formation and the mechanism of brain injury caused by aneurysm rupture is of great significance for preventing aneurysm formation and improving the prognosis of patients. MicroRNAs (miRNAs) are highly conserved non-coding RNAs that can bind to the 3'UTR of target mRNAs to regulate gene expression. Studies have shown that miRNAs can affect the formation and rupture of intracranial aneurysms by participating in apoptosis, inflammation, phagocyte migration, and vascular smooth muscle cells (VSMCs) regulation, and regulate the damage of brain tissue after aneurysm rupture. They play a role in multiple pathophysiological processes of aneurysmal subarachnoid hemorrhage. This article reviews the role of miRNAs in different pathophysiological stages of aneurysmal subarachnoid hemorrhage (aSAH). We further described the research progress of miRNAs as biomarkers for the diagnosis and prognosis of aSAH and discussed their application prospects in the prevention and treatment of aSAH.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}