Niloofar Ghanizade, Maral Hemati, Habib Jaafarinejad, Mehrnoosh Pashaei, P. Kokhaei
Background: The incidence of B-chronic lymphocytic leukemia (B-CLL) resulting from the clonal accumulation of apoptosis-resistant malignant B lymphocytes is growing in the adult population of Iran. Inhibitors of apoptosis proteins (IAPs) are considered as factors that can delay the onset of CLL cell apoptosis. Berberine is an isoquinoline alkaloid isolated from Cotridis rhizoma that exhibits anti-tumor activities through various mechanisms. Objectives: In this study, we investigated the impact of berberine on the level of Apollon expression in peripheral blood mononuclear cells (PBMCs) of 12 cases newly diagnosed with CLL and 6 healthy donors. Methods: At first, the level of Apollon expression was assessed in PBMCs of CLL patients compared to the healthy donors. Peripheral blood mononuclear cells were cultured in RPMI-1640 medium with 5% fetal bovine serum (FBS) and 1% penicillin/streptomycin for 48 hours, and the effect of berberine (25 µM) on the level of Apollon expression in CLL patients was assessed and compared to that of healthy donors. Results: We found that the expression level of Apollon was not significantly different between CLL patients and healthy donors (P = 0.640). Moreover, berberine induced no significant differences in Apollon expression as compared to the untreated (control) group (P = 0.545 and P = 0.267 in CLL patients and healthy donors, respectively). Conclusions: Overall, our results suggest that berberine has no direct effect on the expression of Apollon gene in CLL patients, and pro-apoptotic impacts of berberine may be exerted through other mechanisms.
{"title":"Impact of Berberine on the Expression of Apollon Gene in Chronic Lymphocytic Leukemia","authors":"Niloofar Ghanizade, Maral Hemati, Habib Jaafarinejad, Mehrnoosh Pashaei, P. Kokhaei","doi":"10.5812/tms.115983","DOIUrl":"https://doi.org/10.5812/tms.115983","url":null,"abstract":"Background: The incidence of B-chronic lymphocytic leukemia (B-CLL) resulting from the clonal accumulation of apoptosis-resistant malignant B lymphocytes is growing in the adult population of Iran. Inhibitors of apoptosis proteins (IAPs) are considered as factors that can delay the onset of CLL cell apoptosis. Berberine is an isoquinoline alkaloid isolated from Cotridis rhizoma that exhibits anti-tumor activities through various mechanisms. Objectives: In this study, we investigated the impact of berberine on the level of Apollon expression in peripheral blood mononuclear cells (PBMCs) of 12 cases newly diagnosed with CLL and 6 healthy donors. Methods: At first, the level of Apollon expression was assessed in PBMCs of CLL patients compared to the healthy donors. Peripheral blood mononuclear cells were cultured in RPMI-1640 medium with 5% fetal bovine serum (FBS) and 1% penicillin/streptomycin for 48 hours, and the effect of berberine (25 µM) on the level of Apollon expression in CLL patients was assessed and compared to that of healthy donors. Results: We found that the expression level of Apollon was not significantly different between CLL patients and healthy donors (P = 0.640). Moreover, berberine induced no significant differences in Apollon expression as compared to the untreated (control) group (P = 0.545 and P = 0.267 in CLL patients and healthy donors, respectively). Conclusions: Overall, our results suggest that berberine has no direct effect on the expression of Apollon gene in CLL patients, and pro-apoptotic impacts of berberine may be exerted through other mechanisms.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124961286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hamid Ali-Bahar, Maysam Mard-Soltani, Yousef Paridar, Zahra Nasirbaghban, Z. Hashemi, Alireza Zakeri, S. Khalili
Background: One of the major microvascular complications of diabetes mellitus (DM) is diabetic retinopathy (DR). Studies have shown that angiotensin-converting enzyme (ACE) gene polymorphisms are correlated with DR progression. Accordingly, the elucidation of the association between ACE gene polymorphism and the risk of DR development seems to be highly crucial. Methods: In this study, 195 individuals with type 2 diabetes mellitus (T2DM) were classified as the case group with retinopathy (99 people) and control group without retinopathy (96 people). Screening for DR was performed by ophthalmologists using clinical examination and fluorescein angiography. Different ACE genotypes (II, ID, and DD) were identified by the collection of blood samples, extraction of DNA, and PCR amplification using specific primers. Results: The frequency distribution of genotypes was significantly different between the case and control groups (P = 0.009). Interestingly, possessing a DD genotype made diabetic patients approximately 2.5 folds (95% CI = 1.271 - 4.840, P = 0.007) and 3.25 folds (95% CI = 1.312 - 8.051, P = 0.01) more susceptible to DR when compared to having DI and II genotypes, respectively. Moreover, having a D allele made diabetic individuals nearly 1.75 folds (95% CI = 1.167 - 2.623, P = 0.007) more susceptible to DR than possessing an I allele. Conclusions: Our results potentiate the hypothesis that the DD genotype and D allele of the ACE gene might play a role in the pathogenesis of DR.
背景:糖尿病视网膜病变(DR)是糖尿病(DM)的主要微血管并发症之一。研究表明,血管紧张素转换酶(ACE)基因多态性与DR进展相关。因此,阐明ACE基因多态性与DR发生风险之间的关系似乎非常重要。方法:将195例2型糖尿病(T2DM)患者分为有视网膜病变的病例组(99人)和无视网膜病变的对照组(96人)。眼科医生通过临床检查和荧光素血管造影筛查DR。不同的ACE基因型(II型、ID型和DD型)通过采集血样、提取DNA和使用特定引物进行PCR扩增进行鉴定。结果:病例组与对照组基因型频率分布差异有统计学意义(P = 0.009)。有趣的是,与DI和II基因型相比,拥有DD基因型的糖尿病患者患DR的可能性分别增加了约2.5倍(95% CI = 1.271 - 4.840, P = 0.007)和3.25倍(95% CI = 1.312 - 8.051, P = 0.01)。此外,拥有D等位基因的糖尿病人比拥有I等位基因的糖尿病人患DR的几率高1.75倍(95% CI = 1.167 - 2.623, P = 0.007)。结论:我们的研究结果支持了ACE基因DD基因型和D等位基因可能在DR发病机制中起作用的假设。
{"title":"Distribution of DD Genotype of Angiotensin-Converting Enzyme Gene and Its Correlation with Diabetic Retinopathy","authors":"Hamid Ali-Bahar, Maysam Mard-Soltani, Yousef Paridar, Zahra Nasirbaghban, Z. Hashemi, Alireza Zakeri, S. Khalili","doi":"10.5812/tms.115489","DOIUrl":"https://doi.org/10.5812/tms.115489","url":null,"abstract":"Background: One of the major microvascular complications of diabetes mellitus (DM) is diabetic retinopathy (DR). Studies have shown that angiotensin-converting enzyme (ACE) gene polymorphisms are correlated with DR progression. Accordingly, the elucidation of the association between ACE gene polymorphism and the risk of DR development seems to be highly crucial. Methods: In this study, 195 individuals with type 2 diabetes mellitus (T2DM) were classified as the case group with retinopathy (99 people) and control group without retinopathy (96 people). Screening for DR was performed by ophthalmologists using clinical examination and fluorescein angiography. Different ACE genotypes (II, ID, and DD) were identified by the collection of blood samples, extraction of DNA, and PCR amplification using specific primers. Results: The frequency distribution of genotypes was significantly different between the case and control groups (P = 0.009). Interestingly, possessing a DD genotype made diabetic patients approximately 2.5 folds (95% CI = 1.271 - 4.840, P = 0.007) and 3.25 folds (95% CI = 1.312 - 8.051, P = 0.01) more susceptible to DR when compared to having DI and II genotypes, respectively. Moreover, having a D allele made diabetic individuals nearly 1.75 folds (95% CI = 1.167 - 2.623, P = 0.007) more susceptible to DR than possessing an I allele. Conclusions: Our results potentiate the hypothesis that the DD genotype and D allele of the ACE gene might play a role in the pathogenesis of DR.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122168590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Mehri, F. Saeedi, Roghaye Porbagher, Amrollah Mastafazadeh
Background: Immunometabolism targeting therapy of auto-inflammatory diseases is an emerging strategy compared to immune system global suppression. However, our knowledge in this field needs promotion. Objectives: We examined the effects of serum starvation stress on metabolic activity in human peripheral blood mononuclear cells (PBMCs). Methods: Fresh immune cells were isolated from four healthy adult volunteers and cultivated with or without fetal bovine serum (FBS) at various time points under standard conditions. Glucose and intra- and extracellular lactate levels were assessed using routine techniques, and 3-(4, 5 -dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) reduction assay was used to determine mitochondrial function. Results: Spindle shape macrophage-like cells, which appeared early, were replaced at 96 h by large round monocytes/macrophage-like cells, with more frequency in the non-starved group. Interestingly, serum starvation dictated a status, especially in monocyte/macrophage-like cells, that led to prolong decrement in mitochondrial dehydrogenase-mediated reduction of MTT. This difference was confirmed with the MTT assay quantitatively (P < 0.05). Moreover, the intra- and extracellular lactate concentrations were lower in starved cells than in non-starved controls (P < 0.05), and glucose levels were higher in 72 h starved cell culture supernatants than in non-starved control cells (P < 0.05). Conclusions: This study showed that under serum starvation-induced metabolic stress, lactate production is altered in immune cells, and total oxidative mitochondrial activity is reduced in macrophage-like cells. These findings open a new window to target immune cell metabolism for the treatment of autoinflammatory and autoimmune diseases.
{"title":"Alteration in Lactate Production and Decrease in MTT Dye Reduction in Serum-starved Human Peripheral Blood Mononuclear Cells (PBMCs)","authors":"M. Mehri, F. Saeedi, Roghaye Porbagher, Amrollah Mastafazadeh","doi":"10.5812/tms.115363","DOIUrl":"https://doi.org/10.5812/tms.115363","url":null,"abstract":"Background: Immunometabolism targeting therapy of auto-inflammatory diseases is an emerging strategy compared to immune system global suppression. However, our knowledge in this field needs promotion. Objectives: We examined the effects of serum starvation stress on metabolic activity in human peripheral blood mononuclear cells (PBMCs). Methods: Fresh immune cells were isolated from four healthy adult volunteers and cultivated with or without fetal bovine serum (FBS) at various time points under standard conditions. Glucose and intra- and extracellular lactate levels were assessed using routine techniques, and 3-(4, 5 -dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) reduction assay was used to determine mitochondrial function. Results: Spindle shape macrophage-like cells, which appeared early, were replaced at 96 h by large round monocytes/macrophage-like cells, with more frequency in the non-starved group. Interestingly, serum starvation dictated a status, especially in monocyte/macrophage-like cells, that led to prolong decrement in mitochondrial dehydrogenase-mediated reduction of MTT. This difference was confirmed with the MTT assay quantitatively (P < 0.05). Moreover, the intra- and extracellular lactate concentrations were lower in starved cells than in non-starved controls (P < 0.05), and glucose levels were higher in 72 h starved cell culture supernatants than in non-starved control cells (P < 0.05). Conclusions: This study showed that under serum starvation-induced metabolic stress, lactate production is altered in immune cells, and total oxidative mitochondrial activity is reduced in macrophage-like cells. These findings open a new window to target immune cell metabolism for the treatment of autoinflammatory and autoimmune diseases.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126467102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Chimeric antigen receptor (CAR) T cell therapy is rapidly being established as a new cancer treatment modality especially for the treatment of hematologic malignancies. Alongside being capable of inducing durable responses in such malignancies, CAR T cell therapy has always been accompanied by exclusive toxicities such as cytokine release syndrome (CRS), that can range from mild to life-threatening. These toxicities require intensive monitoring and fast and executive management procedures to reduce the level of damages or the rate of mortality in CAR T cell therapy recipients. In this review, we tend to introduced some of the most common CAR T cell therapy-related toxicities and their clinical demonstrations. Furthermore, we also introduce some of the management procedures commonly considered in this regard.
{"title":"Adverse Events and Side Effects of Chimeric Antigen Receptor (CAR) T Cell Therapy in Patients with Hematologic Malignancies","authors":"Pooria Safarzadeh Kozani, Shima Shabani","doi":"10.5812/tms.116301","DOIUrl":"https://doi.org/10.5812/tms.116301","url":null,"abstract":": Chimeric antigen receptor (CAR) T cell therapy is rapidly being established as a new cancer treatment modality especially for the treatment of hematologic malignancies. Alongside being capable of inducing durable responses in such malignancies, CAR T cell therapy has always been accompanied by exclusive toxicities such as cytokine release syndrome (CRS), that can range from mild to life-threatening. These toxicities require intensive monitoring and fast and executive management procedures to reduce the level of damages or the rate of mortality in CAR T cell therapy recipients. In this review, we tend to introduced some of the most common CAR T cell therapy-related toxicities and their clinical demonstrations. Furthermore, we also introduce some of the management procedures commonly considered in this regard.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"316 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132155858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Dolatshahi, S. Mahmoudi, Mansour Torabi nia, Vahid Kheirandish
Objectives: The etiology of Alzheimer’s disease is supposed to involve environmental exposure and genetic vulnerability. The present study aimed to assess the association between Alzheimer’s disease and its risk factors. Methods: We conducted a case-control study of 95 Alzheimer’s disease patients and 98 matched controls. All participants (case and control groups) were examined by mini-mental state examination. This information was collected by a risk factor questionnaire from January to June 2019. Data were analyzed using logistic regression analysis via SPSS-22 software. Results: The findings revealed the effect of risk factors' odds ratios on the occurrence of Alzheimer’s disease by logistic regression analysis. Sex (female), chronic disease, loneliness or being single, and family history showed positive associations with AD, whereas daily physical exercise, religious beliefs, high level of social communication, and male sex had negative associations with AD development (P < 0.05). Conclusions: The study highlighted the difficulty of etiology and recommended that the effective interventions for social support of older people, psychological condition, chronic disease, and lifestyle may be promising preventive policies.
{"title":"Alzheimer’s Disease and its Risk Factors: A Case-control Study","authors":"M. Dolatshahi, S. Mahmoudi, Mansour Torabi nia, Vahid Kheirandish","doi":"10.5812/tms.113857","DOIUrl":"https://doi.org/10.5812/tms.113857","url":null,"abstract":"Objectives: The etiology of Alzheimer’s disease is supposed to involve environmental exposure and genetic vulnerability. The present study aimed to assess the association between Alzheimer’s disease and its risk factors. Methods: We conducted a case-control study of 95 Alzheimer’s disease patients and 98 matched controls. All participants (case and control groups) were examined by mini-mental state examination. This information was collected by a risk factor questionnaire from January to June 2019. Data were analyzed using logistic regression analysis via SPSS-22 software. Results: The findings revealed the effect of risk factors' odds ratios on the occurrence of Alzheimer’s disease by logistic regression analysis. Sex (female), chronic disease, loneliness or being single, and family history showed positive associations with AD, whereas daily physical exercise, religious beliefs, high level of social communication, and male sex had negative associations with AD development (P < 0.05). Conclusions: The study highlighted the difficulty of etiology and recommended that the effective interventions for social support of older people, psychological condition, chronic disease, and lifestyle may be promising preventive policies.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"174 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124282893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}