Pub Date : 2021-08-30eCollection Date: 2021-01-01DOI: 10.3906/biy-2105-45
Şebnem Garip Ustaoğlu, Hakan Kaygusuz, Mehmet Dinçer Bilgin, Feride Severcan
Since COVID-19 pandemic has been continuously rising and spreading, several original contributions and review articles on COVID-19 started to appear in the literature. The review articles are mainly focus on the current status of the pandemic along with current status of the corona diagnosis and treatment process. Due to some disadvantages of the currently used methods, the improvement on the novel promising diagnosis and treatment methods of corona virus is very important issue. In this review, after briefly discussing the status of current diagnosis and treatment methods, we present to the scientific community, novel promising methods in the diagnosis and treatment of COVID-19. As with other novel approaches, first, the diagnosis potential of mass spectroscopy and optical spectroscopic methods such as UV/visible, infrared, and Raman spectroscopy coupled with chemometrics will be discussed for the corona virus infected samples based on the relevant literature. In vibrational spectroscopy studies, due to complexity of the data, multivariate analysis methods are also applied to data. The application of multivariate analysis tools that can be used to extract useful information from the data for diagnostic and characterisation purposes is also included in this review. The reviewed methods include hierarchical cluster analysis, principal component analysis, linear and quadratic discriminant analysis, support vector machine algorithm, and one form of neural networks namely deep learning method. Second, novel treatment methods such as photodynamic therapy and the use of nanoparticles in the in-corona virus therapy will be discussed. Finally, the advantages of novel promising diagnosis and treatment methods in COVID-19, over standard methods will be discussed. One of the main aims of this paper is to encourage the scientific community to explore the potential of this novel tools for their use in corona virus characterization, diagnosis, and treatment.
{"title":"Novel approaches for COVID-19 diagnosis and treatment: a nonsystematic review.","authors":"Şebnem Garip Ustaoğlu, Hakan Kaygusuz, Mehmet Dinçer Bilgin, Feride Severcan","doi":"10.3906/biy-2105-45","DOIUrl":"10.3906/biy-2105-45","url":null,"abstract":"<p><p>Since COVID-19 pandemic has been continuously rising and spreading, several original contributions and review articles on COVID-19 started to appear in the literature. The review articles are mainly focus on the current status of the pandemic along with current status of the corona diagnosis and treatment process. Due to some disadvantages of the currently used methods, the improvement on the novel promising diagnosis and treatment methods of corona virus is very important issue. In this review, after briefly discussing the status of current diagnosis and treatment methods, we present to the scientific community, novel promising methods in the diagnosis and treatment of COVID-19. As with other novel approaches, first, the diagnosis potential of mass spectroscopy and optical spectroscopic methods such as UV/visible, infrared, and Raman spectroscopy coupled with chemometrics will be discussed for the corona virus infected samples based on the relevant literature. In vibrational spectroscopy studies, due to complexity of the data, multivariate analysis methods are also applied to data. The application of multivariate analysis tools that can be used to extract useful information from the data for diagnostic and characterisation purposes is also included in this review. The reviewed methods include hierarchical cluster analysis, principal component analysis, linear and quadratic discriminant analysis, support vector machine algorithm, and one form of neural networks namely deep learning method. Second, novel treatment methods such as photodynamic therapy and the use of nanoparticles in the in-corona virus therapy will be discussed. Finally, the advantages of novel promising diagnosis and treatment methods in COVID-19, over standard methods will be discussed. One of the main aims of this paper is to encourage the scientific community to explore the potential of this novel tools for their use in corona virus characterization, diagnosis, and treatment.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"358-371"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39642930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
With the emergence of the new SARS-CoV-2 virus, drug repurposing studies have gained substantial importance. Combined with the efficacy of recent improvements in ligand- and target-based virtual screening approaches, virtual screening has become faster and more productive than ever. In the current study, an FDA library of approved drugs and compounds under clinical investigation were screened for their antiviral activity using the antiviral therapeutic activity binary QSAR model of the MetaCore/MetaDrug platform. Among 6733-compound collection, we found 370 compounds with a normalized therapeutic activity value greater than a cutoff of 0.75. Only these selected compounds were used for molecular docking studies against the SARS-CoV-2 main protease (Mpro). After initial short (10 ns) molecular dynamics (MD) simulations with the top-50 docking scored compounds and following molecular mechanics generalized born surface area (MM/GBSA) calculations, top-10 compounds were subjected to longer (100 ns) MD simulations and end-point MM/GBSA estimations. Our virtual screening protocol yielded Cefuroxime pivoxetil, an ester prodrug of second-generation cephalosporin antibiotic Cefuroxime, as being a considerable molecule for drug repurposing against the SARS-CoV-2 Mpro.
{"title":"Binary-QSAR guided virtual screening of FDA approved drugs and compounds in clinical investigation against SARS-CoV-2 main protease.","authors":"Lalehan Oktay, Ece Erdemoğlu, İlayda Tolu, Yeşim Yumak, Ayşenur Özcan, Elif Acar, Şehriban Büyükkiliç, Alpsu Olkan, Serdar Durdaği","doi":"10.3906/biy-2106-61","DOIUrl":"https://doi.org/10.3906/biy-2106-61","url":null,"abstract":"<p><p>With the emergence of the new SARS-CoV-2 virus, drug repurposing studies have gained substantial importance. Combined with the efficacy of recent improvements in ligand- and target-based virtual screening approaches, virtual screening has become faster and more productive than ever. In the current study, an FDA library of approved drugs and compounds under clinical investigation were screened for their antiviral activity using the antiviral therapeutic activity binary QSAR model of the MetaCore/MetaDrug platform. Among 6733-compound collection, we found 370 compounds with a normalized therapeutic activity value greater than a cutoff of 0.75. Only these selected compounds were used for molecular docking studies against the SARS-CoV-2 main protease (M<sup>pro</sup>). After initial short (10 ns) molecular dynamics (MD) simulations with the top-50 docking scored compounds and following molecular mechanics generalized born surface area (MM/GBSA) calculations, top-10 compounds were subjected to longer (100 ns) MD simulations and end-point MM/GBSA estimations. Our virtual screening protocol yielded Cefuroxime pivoxetil, an ester prodrug of second-generation cephalosporin antibiotic Cefuroxime, as being a considerable molecule for drug repurposing against the SARS-CoV-2 M<sup>pro</sup>.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"459-468"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39643397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-08-30eCollection Date: 2021-01-01DOI: 10.3906/biy-2104-16
Hasan Önal, Bengü Arslan, Nurcan Üçüncü Ergun, Şeyma Topuz, Seda Yilmaz Semerci, Mehmet Eren Kurnaz, Yulet Miray Molu, Mehmet Abdussamet Bozkurt, Nurettin Süner, Ali Kocataş
Scientific research continues on new preventive and therapeutic strategies against severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). So far, there is no proven curative treatment, and a valid alternative therapeutic approach needs to be developed. This study is designed to evaluate the effect of quercetin in COVID-19 treatment. This was a single-centre, prospective randomized controlled cohort study. Routine care versus QCB (quercetin, vitamin C, bromelain) supplementation was compared between 429 patients with at least one chronic disease and moderate-to-severe respiratory symptoms. Demographic features, signs, laboratory results and drug administration data of patients were recorded. The endpoint was that QCB supplementation was continued throughout the follow-up period from study baseline to discharge, intubation, or death. The most common complaints at the time of hospital admission were fatigue (62.4%), cough (61.1%), anorexia (57%), thirst (53.7%), respiratory distress (51%) and chills (48.3%). The decrease in CRP and ferritin levels was higher in the QCB group (all Ps were < 0.05). In the QCB group, the increase in platelet and lymphocyte counts was higher (all Ps were < 0.05). QCB did not reduce the risk of events during follow-up. Adjustments for statistically significant parameters, including the lung stage, use of favipiravir and presence of comorbidity did not change the results. While there was no difference between the groups in terms of event frequency, the QCB group had more advanced pulmonary findings. QCB supplement is shown to have a positive effect on laboratory recovery. While there was no difference between the groups in terms of event frequency, QCB supplement group had more advanced pulmonar findings, and QCB supplement is shown to have a positive effect on laboratory recovery/results. Therefore, we conclude that further studies involving different doses and plasma level measurements are required to reveal the dose/response relationship and bioavailability of QCB for a better understanding of the role of QCB in the treatment of SARS CoV-2.
{"title":"Treatment of COVID-19 patients with quercetin: a prospective, single center, randomized, controlled trial.","authors":"Hasan Önal, Bengü Arslan, Nurcan Üçüncü Ergun, Şeyma Topuz, Seda Yilmaz Semerci, Mehmet Eren Kurnaz, Yulet Miray Molu, Mehmet Abdussamet Bozkurt, Nurettin Süner, Ali Kocataş","doi":"10.3906/biy-2104-16","DOIUrl":"https://doi.org/10.3906/biy-2104-16","url":null,"abstract":"<p><p>Scientific research continues on new preventive and therapeutic strategies against severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). So far, there is no proven curative treatment, and a valid alternative therapeutic approach needs to be developed. This study is designed to evaluate the effect of quercetin in COVID-19 treatment. This was a single-centre, prospective randomized controlled cohort study. Routine care versus QCB (quercetin, vitamin C, bromelain) supplementation was compared between 429 patients with at least one chronic disease and moderate-to-severe respiratory symptoms. Demographic features, signs, laboratory results and drug administration data of patients were recorded. The endpoint was that QCB supplementation was continued throughout the follow-up period from study baseline to discharge, intubation, or death. The most common complaints at the time of hospital admission were fatigue (62.4%), cough (61.1%), anorexia (57%), thirst (53.7%), respiratory distress (51%) and chills (48.3%). The decrease in CRP and ferritin levels was higher in the QCB group (all Ps were < 0.05). In the QCB group, the increase in platelet and lymphocyte counts was higher (all Ps were < 0.05). QCB did not reduce the risk of events during follow-up. Adjustments for statistically significant parameters, including the lung stage, use of favipiravir and presence of comorbidity did not change the results. While there was no difference between the groups in terms of event frequency, the QCB group had more advanced pulmonary findings. QCB supplement is shown to have a positive effect on laboratory recovery. While there was no difference between the groups in terms of event frequency, QCB supplement group had more advanced pulmonar findings, and QCB supplement is shown to have a positive effect on laboratory recovery/results. Therefore, we conclude that further studies involving different doses and plasma level measurements are required to reveal the dose/response relationship and bioavailability of QCB for a better understanding of the role of QCB in the treatment of SARS CoV-2.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"518-529"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39896510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-08-30eCollection Date: 2021-01-01DOI: 10.3906/biy-2105-73
Ahmet Onay, Abdulselam Ertaş, Veysel Süzerer, İsmail Yener, Mustafa Abdullah Yilmaz, Emine Ayaz-Tilkat, Remzi Ekinci, Nesrin Bozhan, Sevgi Irtegün-Kandemir
To combat the coronaviruses and their novel variants, therapeutic drugs and the development of vaccines that are to be effective throughout human life are urgently needed. The endocannabinoid system (ECS) acts as a modulator in the activation of the microcirculation, immune system, and autonomic nervous system, along with controlling pharmacological functions such as emotional responses, homeostasis, motor functions, cognition, and motivation. The ECS contains endogenous cannabinoids, cannabinoid receptor (CBRs), and enzymes that regulate their biosynthesis, transport, and degradation. Moreover, phytocannabinoids and synthetic cannabinoids that mimic the action of endocannabinoids also play an essential role in the modulation of the ECS. Cannabinoids, the main constituents of cannabis (Cannabis sativa L.), are therapeutic compounds that have received international attention in the health field due to their therapeutic properties. Recently, they have been tested for the treatment of COVID-19 due to their antiviral properties. Indeed, cannabinoid-type compounds, and in particular cannabidiol (CBD), isolated from glandular trichomes found in the calyx of cannabis flowers with reported antiviral properties is hypothesized to be a therapeutic option in the ministration of SARS-CoV-2 consorted with COVID-19 disease. The relevant articles were determined from the database search published mainly in Web of Science, Google scholar, PubMed, Crossref, and ClinicalTrials.gov database during the pandemic period. The articles were evaluated for the therapeutic potentials, mechanisms of action of cannabinoids, the roles of the ECS in the immune system, impact of cannabinoids in SARS-CoV-2 septic, especially if they address the application of cannabinoids as drugs for the curability and management of SARS-CoV-2 and its novel variants. Although the evidence needed to be considered using cannabinoids in the control and treatment of viral diseases is currently in its infancy, they already offer an opportunity for clinicians due to their effects in relieving pain, improving appetite, and improving childhood epilepsy, especially in cancer and human immunodeficiency virus (HIV/AIDS) patients. In addition to these, the most recent scientific evidence emphasizes their use in the treatment of the coronavirus infected patients. In brief, all preclinic and clinic studies that have been reported show that, through the cannabinoid system, cannabinoids, particularly CBD, have many mechanisms that are effective in the treatment of patients infected by SARS-CoV-2. Thus, more extensive studies are necessary in this area to fully identify the effects of cannabinoids on SARS-CoV-2.
为了对抗冠状病毒及其新变种,迫切需要治疗药物和开发在人类一生中有效的疫苗。内源性大麻素系统(ECS)在微循环、免疫系统和自主神经系统的激活中发挥调节剂的作用,同时控制情绪反应、稳态、运动功能、认知和动机等药理功能。ECS含有内源性大麻素、大麻素受体(CBRs)和调节其生物合成、运输和降解的酶。此外,植物大麻素和模拟内源性大麻素作用的合成大麻素在ECS的调节中也发挥着重要作用。大麻素是大麻(cannabis sativa L.)的主要成分,由于其治疗特性,在健康领域受到了国际关注。最近,由于其抗病毒特性,它们已被测试用于治疗新冠肺炎。事实上,大麻素型化合物,特别是大麻素二醇(CBD),从大麻花的花瓣中发现的腺毛中分离,具有报道的抗病毒特性,被假设是与新冠肺炎疾病合并的SARS-CoV-2的治疗选择。相关文章是根据疫情期间主要发表在Web of Science、Google scholar、PubMed、Crossref和ClinicalTrials.gov数据库中的数据库搜索确定的。这些文章评估了大麻素的治疗潜力、作用机制、ECS在免疫系统中的作用、大麻素在严重急性呼吸系统综合征冠状病毒2型败血症中的影响,特别是如果它们涉及大麻素作为治疗和管理严重急性呼吸系统冠状病毒2型及其新变种的药物的应用。尽管需要考虑使用大麻素控制和治疗病毒性疾病的证据目前尚处于起步阶段,但由于它们在缓解疼痛、改善食欲和改善儿童癫痫方面的作用,特别是在癌症和人类免疫缺陷病毒(艾滋病毒/艾滋病)患者中,它们已经为临床医生提供了机会。除此之外,最新的科学证据强调了它们在治疗冠状病毒感染患者中的用途。简言之,所有已报道的临床前和临床研究都表明,通过大麻素系统,大麻素,特别是CBD,具有许多有效治疗严重急性呼吸系统综合征冠状病毒2型感染患者的机制。因此,有必要在这一领域进行更广泛的研究,以充分确定大麻素对严重急性呼吸系统综合征冠状病毒2型的影响。
{"title":"Cannabinoids for SARS-CoV-2 and is there evidence of their therapeutic efficacy?","authors":"Ahmet Onay, Abdulselam Ertaş, Veysel Süzerer, İsmail Yener, Mustafa Abdullah Yilmaz, Emine Ayaz-Tilkat, Remzi Ekinci, Nesrin Bozhan, Sevgi Irtegün-Kandemir","doi":"10.3906/biy-2105-73","DOIUrl":"10.3906/biy-2105-73","url":null,"abstract":"<p><p>To combat the coronaviruses and their novel variants, therapeutic drugs and the development of vaccines that are to be effective throughout human life are urgently needed. The endocannabinoid system (ECS) acts as a modulator in the activation of the microcirculation, immune system, and autonomic nervous system, along with controlling pharmacological functions such as emotional responses, homeostasis, motor functions, cognition, and motivation. The ECS contains endogenous cannabinoids, cannabinoid receptor (CBRs), and enzymes that regulate their biosynthesis, transport, and degradation. Moreover, phytocannabinoids and synthetic cannabinoids that mimic the action of endocannabinoids also play an essential role in the modulation of the ECS. Cannabinoids, the main constituents of cannabis (<i>Cannabis sativa</i> L.), are therapeutic compounds that have received international attention in the health field due to their therapeutic properties. Recently, they have been tested for the treatment of COVID-19 due to their antiviral properties. Indeed, cannabinoid-type compounds, and in particular cannabidiol (CBD), isolated from glandular trichomes found in the calyx of cannabis flowers with reported antiviral properties is hypothesized to be a therapeutic option in the ministration of SARS-CoV-2 consorted with COVID-19 disease. The relevant articles were determined from the database search published mainly in Web of Science, Google scholar, PubMed, Crossref, and ClinicalTrials.gov database during the pandemic period. The articles were evaluated for the therapeutic potentials, mechanisms of action of cannabinoids, the roles of the ECS in the immune system, impact of cannabinoids in SARS-CoV-2 septic, especially if they address the application of cannabinoids as drugs for the curability and management of SARS-CoV-2 and its novel variants. Although the evidence needed to be considered using cannabinoids in the control and treatment of viral diseases is currently in its infancy, they already offer an opportunity for clinicians due to their effects in relieving pain, improving appetite, and improving childhood epilepsy, especially in cancer and human immunodeficiency virus (HIV/AIDS) patients. In addition to these, the most recent scientific evidence emphasizes their use in the treatment of the coronavirus infected patients. In brief, all preclinic and clinic studies that have been reported show that, through the cannabinoid system, cannabinoids, particularly CBD, have many mechanisms that are effective in the treatment of patients infected by SARS-CoV-2. Thus, more extensive studies are necessary in this area to fully identify the effects of cannabinoids on SARS-CoV-2.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 4","pages":"570-587"},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39896514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-23eCollection Date: 2021-01-01DOI: 10.3906/biy-2101-56
Dharaniyambigai Kuberapandian, Victor Arokia Doss
Cardiac hypertrophy (CH), leading to cardiac failure is due to chronic metabolic alterations occurring during cellular stress. Besides the already known relationship between oxidative stress and CH, there are implications of reductive stress leading to CH. This study attempted to develop reductive stress-based CH rat model using n-acetyl-L-cysteine (NAC), a glutathione agonist that was compared with typical isoproterenol (ISO) induced CH model. The main objective was to identify serum metabolites that can serve as potent predictors for seven routine clinical and diagnostic parameters in CH: 3-hydroxybutyrate (3-HB), lactic acid (LA), urea, and ECG-CH parameters (QRS complex, R-amplitude, R-R interval, heart rate) that were hypothesized to underlie metabolic remodelling in this study. CH was assessed using electrocardiography, hypertrophic index and histopathological analysis (H&E stain) in both ventricles after 2 weeks. Gas chromatography mass spectroscopy analysis (GC-MS) identified unique metabolite finger-prints. Correlation and pattern analysis revealed strong relationships between specific metabolites and parameters (Pearson's score > 0.7) of this study. Multiple regression analysis (MRA) for the strongly related metabolites (independent variables) with each of the seven parameters (dependent variables) identified significant predictors for the latter namely fructose, valine, butanoic acid in NAC and cholesterol, erythrose, isoleucine in ISO models, with proline and succinic acid as common for both models. Metabolite set enrichment analysis (MSEA) of those significant predictors (p < 0.05) mapped butyrate metabolism as highly influential pathway in NAC, with arginine-proline metabolism and branched chain amino acid (BCAA) degradation as common pathways in both models, thus providing new insights towards initial metabolic remodeling in the pathogenesis of CH.
{"title":"Identification of serum predictors of n-acetyl-l-cysteine and isoproterenol induced remodelling in cardiac hypertrophy.","authors":"Dharaniyambigai Kuberapandian, Victor Arokia Doss","doi":"10.3906/biy-2101-56","DOIUrl":"10.3906/biy-2101-56","url":null,"abstract":"<p><p>Cardiac hypertrophy (CH), leading to cardiac failure is due to chronic metabolic alterations occurring during cellular stress. Besides the already known relationship between oxidative stress and CH, there are implications of reductive stress leading to CH. This study attempted to develop reductive stress-based CH rat model using n-acetyl-L-cysteine (NAC), a glutathione agonist that was compared with typical isoproterenol (ISO) induced CH model. The main objective was to identify serum metabolites that can serve as potent predictors for seven routine clinical and diagnostic parameters in CH: 3-hydroxybutyrate (3-HB), lactic acid (LA), urea, and ECG-CH parameters (QRS complex, R-amplitude, R-R interval, heart rate) that were hypothesized to underlie metabolic remodelling in this study. CH was assessed using electrocardiography, hypertrophic index and histopathological analysis (H&E stain) in both ventricles after 2 weeks. Gas chromatography mass spectroscopy analysis (GC-MS) identified unique metabolite finger-prints. Correlation and pattern analysis revealed strong relationships between specific metabolites and parameters (Pearson's score > 0.7) of this study. Multiple regression analysis (MRA) for the strongly related metabolites (independent variables) with each of the seven parameters (dependent variables) identified significant predictors for the latter namely fructose, valine, butanoic acid in NAC and cholesterol, erythrose, isoleucine in ISO models, with proline and succinic acid as common for both models. Metabolite set enrichment analysis (MSEA) of those significant predictors (p < 0.05) mapped butyrate metabolism as highly influential pathway in NAC, with arginine-proline metabolism and branched chain amino acid (BCAA) degradation as common pathways in both models, thus providing new insights towards initial metabolic remodeling in the pathogenesis of CH.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 3","pages":"323-332"},"PeriodicalIF":0.0,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39299446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-23eCollection Date: 2021-01-01DOI: 10.3906/biy-2101-50
Ahmet Sinan Sari, Emre Demirçay, Ahmet Öztürk, Ayşen Terzi, Erdal Karaöz
Selective targeting of transfected mesenchymal stem cells (MSCs) carrying specific antioncogenes to the tumor was suggested as a treatment option. Bone morphogenetic protein-2 (BMP2) was shown to inhibit the proliferation and aggressiveness of osteosarcoma (OS) cells. Here, we aimed to assess the homing efficiency of intraperitoneally administered hMSCs transfected with BMP2 to the tumoral site and their effects on OS using an orthotopic xenograft murine model. Orthotopic xenograft murine model of OS in six-week-old female NOD/SCID mice using 143B cells was established. hMSCs transfected with BMP2 (BMP2+hMSC) were used. In vivo experiments performed on four groups of mice that received no treatment, or intraperitoneally administered BMP2, hMSCs, and BMP2+hMSCs. Histopathological and immunohistochemical studies were used to evaluate the pathological identification and to assess the dimensions and necrotic foci of the tumor, the features of lung metastases, and immunostaining against p27, Ki-67, and caspase-3 antibodies. The osteogenic differentiation markers BMP2, BMP4, COL1A1, OPN, OCN and PF4 evaluated using RT-PCR. The tumor dimensions in the hMSCs group were significantly higher than those of the remaining groups (p < 0.01). The number of metastatic foci in the BMP2+hMSCs group was significantly lower than those of the other groups (p < 0.01). The current results showed that the intraperitoneal route could be efficiently used for targeting hMSCs to the tumoral tissues for effective BMP2 delivery. In this study, the effects of BMP2 transfected hMSCs on human OS and metastasis were promising for achieving osteogenic differentiation and reduced metastatic process.
{"title":"The promising effects of BMP2 transfected mesenchymal stem cells on human osteosarcoma.","authors":"Ahmet Sinan Sari, Emre Demirçay, Ahmet Öztürk, Ayşen Terzi, Erdal Karaöz","doi":"10.3906/biy-2101-50","DOIUrl":"https://doi.org/10.3906/biy-2101-50","url":null,"abstract":"<p><p>Selective targeting of transfected mesenchymal stem cells (MSCs) carrying specific antioncogenes to the tumor was suggested as a treatment option. Bone morphogenetic protein-2 (BMP2) was shown to inhibit the proliferation and aggressiveness of osteosarcoma (OS) cells. Here, we aimed to assess the homing efficiency of intraperitoneally administered hMSCs transfected with <i>BMP2</i> to the tumoral site and their effects on OS using an orthotopic xenograft murine model. Orthotopic xenograft murine model of OS in six-week-old female NOD/SCID mice using 143B cells was established. hMSCs transfected with <i>BMP2</i> (BMP2<sup>+</sup>hMSC) were used. In vivo experiments performed on four groups of mice that received no treatment, or intraperitoneally administered BMP2, hMSCs, and BMP2<sup>+</sup>hMSCs. Histopathological and immunohistochemical studies were used to evaluate the pathological identification and to assess the dimensions and necrotic foci of the tumor, the features of lung metastases, and immunostaining against p27, Ki-67, and caspase-3 antibodies. The osteogenic differentiation markers BMP2, BMP4, COL1A1, OPN, OCN and PF4 evaluated using RT-PCR. The tumor dimensions in the hMSCs group were significantly higher than those of the remaining groups (p < 0.01). The number of metastatic foci in the BMP2<sup>+</sup>hMSCs group was significantly lower than those of the other groups (p < 0.01). The current results showed that the intraperitoneal route could be efficiently used for targeting hMSCs to the tumoral tissues for effective BMP2 delivery. In this study, the effects of BMP2 transfected hMSCs on human OS and metastasis were promising for achieving osteogenic differentiation and reduced metastatic process.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 3","pages":"301-313"},"PeriodicalIF":0.0,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39308902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular knowledge regarding the primary esophageal achalasia is essential for the early diagnosis and treatment of this neurodegenerative motility disorder. Therefore, there is a need to find the main microRNAs (miRNAs) contributing to the mechanisms of achalasia. This study was conducted to determine some patterns of deregulated miRNAs in achalasia. This case-control study was performed on 52 patients with achalasia and 50 nonachalasia controls. The miRNA expression profiling was conducted on the esophageal tissue samples using the next-generation sequencing (NGS). Differential expression of miRNAs was analyzed by the edgeR software. The selected dysregulated miRNAs were additionally confirmed using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fifteen miRNAs were identified that were significantly altered in the tissues of the patients with achalasia. Among them, three miRNAs including miR-133a-5p, miR-143-3p, and miR-6507-5p were upregulated. Also, six miRNAs including miR-215-5p, miR-216a-5p, miR-216b-5p, miR-217, miR-7641 and miR-194-5p were downregulated significantly. The predicted targets for the dysregulated miRNAs showed significant disease-associated pathways like neuronal cell apoptosis, neuromuscular balance, nerve growth factor signaling, and immune response regulation. Further analysis using qRT-PCR showed significant down-regulation of hsa-miR-217 (p-value = 0.004) in achalasia tissue. Our results may serve as a basis for more future functional studies to investigate the role of candidate miRNAs in the etiology of achalasia and their application in the diagnosis and probably treatment of the disease.
{"title":"Identification of differentially expressed microRNAs in primary esophageal achalasia by next-generation sequencing.","authors":"Mahin Gholipour, Javad Mikaeli, Seyed Javad Mowla, Mohammad Reza Bakhtiarizadeh, Marie Saghaeian Jazi, Naeme Javid, Narges Fazlollahi, Masoud Khoshnia, Naser Behnampour, Abdolvahab Moradi","doi":"10.3906/biy-2101-61","DOIUrl":"10.3906/biy-2101-61","url":null,"abstract":"<p><p>Molecular knowledge regarding the primary esophageal achalasia is essential for the early diagnosis and treatment of this neurodegenerative motility disorder. Therefore, there is a need to find the main microRNAs (miRNAs) contributing to the mechanisms of achalasia. This study was conducted to determine some patterns of deregulated miRNAs in achalasia. This case-control study was performed on 52 patients with achalasia and 50 nonachalasia controls. The miRNA expression profiling was conducted on the esophageal tissue samples using the next-generation sequencing (NGS). Differential expression of miRNAs was analyzed by the edgeR software. The selected dysregulated miRNAs were additionally confirmed using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fifteen miRNAs were identified that were significantly altered in the tissues of the patients with achalasia. Among them, three miRNAs including miR-133a-5p, miR-143-3p, and miR-6507-5p were upregulated. Also, six miRNAs including miR-215-5p, miR-216a-5p, miR-216b-5p, miR-217, miR-7641 and miR-194-5p were downregulated significantly. The predicted targets for the dysregulated miRNAs showed significant disease-associated pathways like neuronal cell apoptosis, neuromuscular balance, nerve growth factor signaling, and immune response regulation. Further analysis using qRT-PCR showed significant down-regulation of hsa-miR-217 (p-value = 0.004) in achalasia tissue. Our results may serve as a basis for more future functional studies to investigate the role of candidate miRNAs in the etiology of achalasia and their application in the diagnosis and probably treatment of the disease.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 3","pages":"262-274"},"PeriodicalIF":0.0,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39308899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-23eCollection Date: 2021-01-01DOI: 10.3906/biy-2011-16
Zeynep Demir Öksüz, Tuğrul Doruk, Nevin Yağci, Sedef Tunca Gedik
Polyhydroxyalkanoate (PHA) is stored as an important carbon and energy source in bacterial cells. For biomedical applications, gram-positive bacteria can be better sources of PHAs, since they lack outer membrane lipopolysaccharide. Although gram-positive Streptomyces coelicolor A3(2) has been indicated as a high potential PHA producer, pha C gene that encodes the key enzyme PHA synthase in the metabolic pathway is not determined in its genome. BLAST search results of the GenBank database argued that SCO7613 could specify a putative polyhydroxyalkanoate synthase (PhaC) responsible for PHA biosynthesis. Deduced amino acid sequence of SCO7613 showed the presence of conserved lipase box like sequence, 555GASAG559, in which serine residue was present as the active nucleophile. Present study describes deletion of putative S. coelicolor pha C gene via PCR dependent method. We showed that SCO7613 is not an essential gene in S. coelicolor and its deletion affected PHA accumulation negatively although it is not ceased. Transcomplementation abolished the mutant phenotype, demonstrating that the decrease in PHA resulted from the deletion of SCO7613.
{"title":"Polyhydroxyalkanoate accumulation in Streptomyces coelicolor affected by SCO7613 gene region.","authors":"Zeynep Demir Öksüz, Tuğrul Doruk, Nevin Yağci, Sedef Tunca Gedik","doi":"10.3906/biy-2011-16","DOIUrl":"https://doi.org/10.3906/biy-2011-16","url":null,"abstract":"<p><p>Polyhydroxyalkanoate (PHA) is stored as an important carbon and energy source in bacterial cells. For biomedical applications, gram-positive bacteria can be better sources of PHAs, since they lack outer membrane lipopolysaccharide. Although gram-positive <i>Streptomyces coelicolor</i> A3(2) has been indicated as a high potential PHA producer, <i>pha</i> C gene that encodes the key enzyme PHA synthase in the metabolic pathway is not determined in its genome. BLAST search results of the GenBank database argued that SCO7613 could specify a putative polyhydroxyalkanoate synthase (PhaC) responsible for PHA biosynthesis. Deduced amino acid sequence of SCO7613 showed the presence of conserved lipase box like sequence, <sup>555</sup>GASAG<sup>559</sup>, in which serine residue was present as the active nucleophile. Present study describes deletion of putative <i>S. coelicolor pha</i> C gene via PCR dependent method. We showed that SCO7613 is not an essential gene in <i>S. coelicolor</i> and its deletion affected PHA accumulation negatively although it is not ceased. Transcomplementation abolished the mutant phenotype, demonstrating that the decrease in PHA resulted from the deletion of SCO7613.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 3","pages":"275-286"},"PeriodicalIF":0.0,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39308900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, 341 Bacillus sp. strains were isolated from agricultural soils of Turkey. The potent extracellular lipase producer was selected. It was identified by 16S rRNA, named as Bacillus cereus ATA179. Optimal nutritional and physical parameters for lipase production were determined. Sucrose as the carbon source, (NH4)2HPO4 as the nitrogen source, CaCl2 as the metal ion were obtained. The best results of physical parameters were stated at 45°C, pH 7.0, shaking rate 50 rpm, inoculation amount 7% and inoculum age 24 h. ATA179 strain showed a 51% increase in enzyme production in the modified medium created by optimizing nutritional and physical conditions. Optimum pH value and temperature were found as 6.0 and 55 °C, respectively. CaCl2, Tween 20, Triton X-100 had an activating effect on enzyme activity. Vmax and Km kinetic values were found as 18.28 U/mL and 0.11 mM, respectively. The molecular weight was determined as 47 kDa. Lipase was found to be stable up to 75 days at -20 ºC. The potential of the enzyme in detergent industry was also investigated. It was not affected by detergent additives, but was found to be effective in removing oils from contaminated fabrics. This new lipase may have potential to be used in detergent industry.
{"title":"Lipase from new isolate Bacillus cereus ATA179: optimization of production conditions, partial purification, characterization and its potential in the detergent industry.","authors":"Elif Demirkan, Aynur Aybey Çetinkaya, Maoulida Abdou","doi":"10.3906/biy-2101-22","DOIUrl":"https://doi.org/10.3906/biy-2101-22","url":null,"abstract":"<p><p>In this study, 341 <i>Bacillus</i> sp. strains were isolated from agricultural soils of Turkey. The potent extracellular lipase producer was selected. It was identified by 16S rRNA, named as <i>Bacillus cereus</i> ATA179. Optimal nutritional and physical parameters for lipase production were determined. Sucrose as the carbon source, (NH<sub>4</sub>)<sub>2</sub>HPO<sub>4</sub> as the nitrogen source, CaCl<sub>2</sub> as the metal ion were obtained. The best results of physical parameters were stated at 45°C, pH 7.0, shaking rate 50 rpm, inoculation amount 7% and inoculum age 24 h. ATA179 strain showed a 51% increase in enzyme production in the modified medium created by optimizing nutritional and physical conditions. Optimum pH value and temperature were found as 6.0 and 55 °C, respectively. CaCl<sub>2</sub>, Tween 20, Triton X-100 had an activating effect on enzyme activity. V<sub>max</sub> and K<sub>m</sub> kinetic values were found as 18.28 U/mL and 0.11 mM, respectively. The molecular weight was determined as 47 kDa. Lipase was found to be stable up to 75 days at -20 ºC. The potential of the enzyme in detergent industry was also investigated. It was not affected by detergent additives, but was found to be effective in removing oils from contaminated fabrics. This new lipase may have potential to be used in detergent industry.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 3","pages":"287-300"},"PeriodicalIF":0.0,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39308901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-23eCollection Date: 2021-01-01DOI: 10.3906/biy-2103-3
Nurul Hidayah Samsulrizal, Khairul Shahyidi Khadzran, Tamil Chelvan Meenakshi Sundram, Zarina Zainuddin, Siti Hajar Nor Shaarani, Nur Sabrina Ahmad Azmi, Sarahani Harun
Stevia rebaudiana is a medicinal plant recommended to diabetic or obese patients as an alternative sweetener owing to its low-calorie property. Previous studies have found that the stevioside level is highest at the time of flower bud formation and lowest at the time of preceding and following flower bud formation. Hence, this study aims to identify the genes involved in the flowering of local S. rebaudiana accession MS007 by investigating the transcriptomic data of two stages of growth, before flowering (BF) and after flowering (AF) that were deposited under accession number SRX6362785 and SRX6362784 at the NCBI SRA database. The transcriptomic study managed to annotate 108299 unigenes of S. rebaudiana with 8871 and 9832 genes that were differentially expressed in BF and AF samples, respectively. These genes involved in various metabolic pathways related to flower development, response to stimulus as well as photosynthesis. Pheophorbide A oxygenase ( PAO ), eukaryotic translation initiation factor 3 subunit E ( TIF3E1 ), and jasmonate ZIM domain-containing protein 1 ( JAZ1 ) were found to be involved in the flower development. The outcome of this study will help further research in the manipulation of the flowering process, especially in the breeding programme to develop photo-insensitive Stevia plant.
{"title":"Transcriptome profiling of Stevia rebaudiana MS007 revealed genes involved in flower development.","authors":"Nurul Hidayah Samsulrizal, Khairul Shahyidi Khadzran, Tamil Chelvan Meenakshi Sundram, Zarina Zainuddin, Siti Hajar Nor Shaarani, Nur Sabrina Ahmad Azmi, Sarahani Harun","doi":"10.3906/biy-2103-3","DOIUrl":"https://doi.org/10.3906/biy-2103-3","url":null,"abstract":"<p><p><i>Stevia rebaudiana</i> is a medicinal plant recommended to diabetic or obese patients as an alternative sweetener owing to its low-calorie property. Previous studies have found that the stevioside level is highest at the time of flower bud formation and lowest at the time of preceding and following flower bud formation. Hence, this study aims to identify the genes involved in the flowering of local <i>S. rebaudiana</i> accession MS007 by investigating the transcriptomic data of two stages of growth, before flowering (BF) and after flowering (AF) that were deposited under accession number SRX6362785 and SRX6362784 at the NCBI SRA database. The transcriptomic study managed to annotate 108299 unigenes of <i>S. rebaudiana</i> with 8871 and 9832 genes that were differentially expressed in BF and AF samples, respectively. These genes involved in various metabolic pathways related to flower development, response to stimulus as well as photosynthesis. Pheophorbide A oxygenase ( <i>PAO</i> ), eukaryotic translation initiation factor 3 subunit E ( <i>TIF3E1</i> ), and jasmonate ZIM domain-containing protein 1 ( <i>JAZ1</i> ) were found to be involved in the flower development. The outcome of this study will help further research in the manipulation of the flowering process, especially in the breeding programme to develop photo-insensitive <i>Stevia</i> plant.</p>","PeriodicalId":23375,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"45 3","pages":"314-322"},"PeriodicalIF":0.0,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39308903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}