Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, A. Sheikhi
{"title":"Promoting the Effector Function of Natural Killer (NK) Cells with a Focus on Bispecific Redirecting Antibodies","authors":"Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, A. Sheikhi","doi":"10.5812/tms.119095","DOIUrl":"https://doi.org/10.5812/tms.119095","url":null,"abstract":"<jats:p />","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"104 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124694397","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}
Hoda Memar, Peyman ERFAN TALAB EVİNİ, Golnar Seirafi, Mitra Rahimi
: In this study, we investigated the naphthalene poisoning cases using the archived medical records of patients who were referred to Loghman-Hakim Hospital in Tehran, Iran, from 2008 to 2018. In the 52 studied cases, the highest prevalence was observed in the age groups of below five years and 20 - 25 years. Eighteen (34%) patients had no symptoms, and in others, gastrointestinal problems were the most common complaints. None of the patients needed intubation, and no one was admitted to the intensive care unit. Hemolysis was observed only in one patient with a background of G6PD deficiency. The average length of hospital stay was one day, and all patients improved without any complications. In general, naphthalene poisoning is not highly prevalent in Iran and usually does not cause severe morbidity and mortality. However, it is an available substance and can cause serious complications, especially in children. Therefore, it is necessary to investigate the clinical characteristics of these patients to improve the quality of health care.
{"title":"Naphthalene Poisoning During a Decade: A Retrospective Clinical Study","authors":"Hoda Memar, Peyman ERFAN TALAB EVİNİ, Golnar Seirafi, Mitra Rahimi","doi":"10.5812/tms.118974","DOIUrl":"https://doi.org/10.5812/tms.118974","url":null,"abstract":": In this study, we investigated the naphthalene poisoning cases using the archived medical records of patients who were referred to Loghman-Hakim Hospital in Tehran, Iran, from 2008 to 2018. In the 52 studied cases, the highest prevalence was observed in the age groups of below five years and 20 - 25 years. Eighteen (34%) patients had no symptoms, and in others, gastrointestinal problems were the most common complaints. None of the patients needed intubation, and no one was admitted to the intensive care unit. Hemolysis was observed only in one patient with a background of G6PD deficiency. The average length of hospital stay was one day, and all patients improved without any complications. In general, naphthalene poisoning is not highly prevalent in Iran and usually does not cause severe morbidity and mortality. However, it is an available substance and can cause serious complications, especially in children. Therefore, it is necessary to investigate the clinical characteristics of these patients to improve the quality of health care.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"76 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124420586","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}
Background: Breast cancer (BC) is the most common malignant tumor in women around the world. Genetic factors do play a vital role in the development and progression of BC. Genetic alterations in the ESR1 (estrogen receptor 1) gene can lead to estrogen dysfunction and increased risk for BC. Nevertheless, due to genetic diversity, the information from different studies is contradictory and controversial. Objectives: This study aimed to investigate the potential relationship between the rs1801132 and rs2234693 single nucleotide polymorphism (SNPs) of the ESR1 gene with susceptibility to BC in the Iranian population. Methods: The genotyping of the rs2234693 and rs1801132 SNPs was assessed in 63 BC patients referred to Imam Hasan Mojtaba Center, which is a charity-based foundation for cancer care in Dezful, Iran, from March 2018 to November 2019. Also, 65 healthy women were selected as a control group. The genotyping of the SNPs was performed using the high-resolution melting (HRM) technique and confirmed by DNA sequencing. Results: The genotype distribution and allele frequency of the rs2234693 SNP were significantly different in BC patients compared to the control group (genotype frequency with P = 0.018 and allele frequency with P = 0.004, OR = 2.085, 95% CI = 1.253 -3.468). In genetic models, rs2234693 increased BC risk in recessive model (P = 0.005, OR = 2.813, 95% CI = 1.363 - 5.802). However, there was no significant difference regarding genotype distribution of the rs1801132 SNP between the BC patients and controls. Conclusions: Our results showed that the CC genotype of the rs2234693 SNP is significantly associated with BC. Accordingly, it can be suggested that the rs2234693 SNP be considered for susceptibility to BC.
背景:乳腺癌(Breast cancer, BC)是世界范围内女性最常见的恶性肿瘤。遗传因素在BC的发生和发展中起着至关重要的作用。ESR1(雌激素受体1)基因的遗传改变可导致雌激素功能障碍，增加患BC的风险。然而，由于遗传多样性，来自不同研究的信息是相互矛盾和有争议的。目的:本研究旨在探讨伊朗人群ESR1基因rs1801132和rs2234693单核苷酸多态性(snp)与BC易感性之间的潜在关系。方法:对2018年3月至2019年11月在伊朗Dezful的癌症慈善基金会Imam Hasan Mojtaba中心转诊的63例BC患者进行rs2234693和rs1801132 snp的基因分型评估。同时，选取65名健康女性作为对照组。snp的基因分型采用高分辨率熔融(HRM)技术进行，并通过DNA测序进行确认。结果:BC患者rs2234693 SNP基因型分布和等位基因频率与对照组比较差异有统计学意义(基因型频率P = 0.018，等位基因频率P = 0.004, OR = 2.085, 95% CI = 1.253 ~ 3.468)。在遗传模型中，rs2234693增加了隐性模型中的BC风险(P = 0.005, OR = 2.813, 95% CI = 1.363 ~ 5.802)。然而，rs1801132 SNP的基因型分布在BC患者和对照组之间没有显著差异。结论:我们的研究结果表明rs2234693 SNP的CC基因型与BC显著相关。因此，可以考虑rs2234693 SNP对BC的易感性。
{"title":"An Interdependence between Estrogen Receptor 1 Gene Polymorphisms and Susceptibility to Breast Cancer","authors":"Maryam Saneipour, A. Sheikhi, A. Moridnia","doi":"10.5812/tms.117221","DOIUrl":"https://doi.org/10.5812/tms.117221","url":null,"abstract":"Background: Breast cancer (BC) is the most common malignant tumor in women around the world. Genetic factors do play a vital role in the development and progression of BC. Genetic alterations in the ESR1 (estrogen receptor 1) gene can lead to estrogen dysfunction and increased risk for BC. Nevertheless, due to genetic diversity, the information from different studies is contradictory and controversial. Objectives: This study aimed to investigate the potential relationship between the rs1801132 and rs2234693 single nucleotide polymorphism (SNPs) of the ESR1 gene with susceptibility to BC in the Iranian population. Methods: The genotyping of the rs2234693 and rs1801132 SNPs was assessed in 63 BC patients referred to Imam Hasan Mojtaba Center, which is a charity-based foundation for cancer care in Dezful, Iran, from March 2018 to November 2019. Also, 65 healthy women were selected as a control group. The genotyping of the SNPs was performed using the high-resolution melting (HRM) technique and confirmed by DNA sequencing. Results: The genotype distribution and allele frequency of the rs2234693 SNP were significantly different in BC patients compared to the control group (genotype frequency with P = 0.018 and allele frequency with P = 0.004, OR = 2.085, 95% CI = 1.253 -3.468). In genetic models, rs2234693 increased BC risk in recessive model (P = 0.005, OR = 2.813, 95% CI = 1.363 - 5.802). However, there was no significant difference regarding genotype distribution of the rs1801132 SNP between the BC patients and controls. Conclusions: Our results showed that the CC genotype of the rs2234693 SNP is significantly associated with BC. Accordingly, it can be suggested that the rs2234693 SNP be considered for susceptibility to BC.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116563629","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}
Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, F. Rahbarizadeh
: Targeted cancer therapy is developing rapidly according to the fact that it has been demonstrated that this type of therapy can reduce various side effects and adverse events of the commonly available cancer treatment approaches such as chemotherapy and radiotherapy. This selective type of cancer therapy can mediate encouraging outcomes where the frontline cancer treatment methods have failed to do so. Aptamer-assisted delivery of various types of cargoes or the utilization of aptamer for the redirection of delivery vehicles is among various fields of targeted cancer therapy that have gained significant attention lately. Aptamers are single-stranded oligonucleotides or peptide molecules that harbor significant levels of specificity and affinity toward various types of targets such as cell surface antigens, ions, toxins, chemicals, etc. They have shown encouraging results in several types of targeted cancer therapy for the redirection of a variety of cargoes. In this review, we shed the light on the application of aptamers for the delivery of nucleotides such as MicroRNAs (miRNAs), short or small interfering RNAs (siRNAs), and short hairpin RNA or small hairpin RNAs (shRNAs) that harbor tumor suppression properties in various kinds of malignancies.
{"title":"Aptamer-Assisted Delivery of Nucleotides with Tumor-Suppressing Properties for Targeted Cancer Therapies","authors":"Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, F. Rahbarizadeh","doi":"10.5812/tms.114909","DOIUrl":"https://doi.org/10.5812/tms.114909","url":null,"abstract":": Targeted cancer therapy is developing rapidly according to the fact that it has been demonstrated that this type of therapy can reduce various side effects and adverse events of the commonly available cancer treatment approaches such as chemotherapy and radiotherapy. This selective type of cancer therapy can mediate encouraging outcomes where the frontline cancer treatment methods have failed to do so. Aptamer-assisted delivery of various types of cargoes or the utilization of aptamer for the redirection of delivery vehicles is among various fields of targeted cancer therapy that have gained significant attention lately. Aptamers are single-stranded oligonucleotides or peptide molecules that harbor significant levels of specificity and affinity toward various types of targets such as cell surface antigens, ions, toxins, chemicals, etc. They have shown encouraging results in several types of targeted cancer therapy for the redirection of a variety of cargoes. In this review, we shed the light on the application of aptamers for the delivery of nucleotides such as MicroRNAs (miRNAs), short or small interfering RNAs (siRNAs), and short hairpin RNA or small hairpin RNAs (shRNAs) that harbor tumor suppression properties in various kinds of malignancies.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131237038","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}
Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, F. Rahbarizadeh
: Cancer radiotherapy and phototherapy have been known as alternative approaches for the treatment of chemotherapy-resistant malignancies. Additionally, cancer immunotherapy has recently demonstrated to be a potential cancer treatment modality that has had its ups and downs despite the heart-warming outcomes it has achieved. However, researchers have proved that nanotechnology-facilitated approaches might bring the success of these modalities to an upper class. The nucleolin-targeting aptamer, AS1411, is among various aptamers utilized for the redirection of nanocarriers carrying radiosensitizers and photosensitizers. Recently, the potential applicability of this aptamer has been investigated in cancer immunotherapy. In this review, we discuss how aptamer-mediated nucleolin targeting nanoplatforms might ameliorate the side effects of cancer radiotherapy, phototherapy, and immunotherapy and improve the outcomes of these treatment approaches.
{"title":"Flexible Aptamer-Based Nucleolin-Targeting Cancer Treatment Modalities: A Focus on Immunotherapy, Radiotherapy, and Phototherapy","authors":"Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, F. Rahbarizadeh","doi":"10.5812/tms.113991","DOIUrl":"https://doi.org/10.5812/tms.113991","url":null,"abstract":": Cancer radiotherapy and phototherapy have been known as alternative approaches for the treatment of chemotherapy-resistant malignancies. Additionally, cancer immunotherapy has recently demonstrated to be a potential cancer treatment modality that has had its ups and downs despite the heart-warming outcomes it has achieved. However, researchers have proved that nanotechnology-facilitated approaches might bring the success of these modalities to an upper class. The nucleolin-targeting aptamer, AS1411, is among various aptamers utilized for the redirection of nanocarriers carrying radiosensitizers and photosensitizers. Recently, the potential applicability of this aptamer has been investigated in cancer immunotherapy. In this review, we discuss how aptamer-mediated nucleolin targeting nanoplatforms might ameliorate the side effects of cancer radiotherapy, phototherapy, and immunotherapy and improve the outcomes of these treatment approaches.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116299079","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}
Pouya Safarzadeh Kozani, A. Naseri, Pooria Safarzadeh Kozani, Sanaz Khatami, A. Sheikhi
: Monoclonal antibodies are one of the most eminent types of immunotherapeutics that have taken over the biopharmaceutical market because they are approved for a wide range of cancers, either blood-based malignancies or solid tumors, and also non-cancer indications, from migraine to viral infections. Due to their wide applicability as immunotherapeutics, countless biopharmaceutical companies try to be in the competition by developing monoclonal antibodies and advancing into clinical trials with them. Since the approval of the first monoclonal antibodies, the speed of their discovery and approval for medical use have been rather incremental, so that the progress of this market has been anticipated to increase in the current decade. Herein, we take a look at some of the monoclonal antibodies, which have been approved for clinical use in the current decade, so far. Moreover, we underline the encouraging results from the clinical trials that led to the approval of these immunotherapeutics.
{"title":"Monoclonal Antibodies (mAbs) Approved for Cancer Treatment in the 2020s","authors":"Pouya Safarzadeh Kozani, A. Naseri, Pooria Safarzadeh Kozani, Sanaz Khatami, A. Sheikhi","doi":"10.5812/tms.116686","DOIUrl":"https://doi.org/10.5812/tms.116686","url":null,"abstract":": Monoclonal antibodies are one of the most eminent types of immunotherapeutics that have taken over the biopharmaceutical market because they are approved for a wide range of cancers, either blood-based malignancies or solid tumors, and also non-cancer indications, from migraine to viral infections. Due to their wide applicability as immunotherapeutics, countless biopharmaceutical companies try to be in the competition by developing monoclonal antibodies and advancing into clinical trials with them. Since the approval of the first monoclonal antibodies, the speed of their discovery and approval for medical use have been rather incremental, so that the progress of this market has been anticipated to increase in the current decade. Herein, we take a look at some of the monoclonal antibodies, which have been approved for clinical use in the current decade, so far. Moreover, we underline the encouraging results from the clinical trials that led to the approval of these immunotherapeutics.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"24 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":"114843128","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}
Motahareh Musavi Ghahfarokhi, Elina Mehrafruz, Arman Radmehr, M. Kiarsi, Marzieh Beigom Bigdeli Shamloo
Background: Clinical competency is the ability of nurses to play a professional role in a clinical environment, in terms of the quality of the services provided. Objectives: The present study aimed to compare the clinical competence of emergency department nurses using self-assessments and evaluations by head nurses. Methods: A descriptive-analytical study was conducted from July to September 2019. The census method was used to select 70 nurses working in the emergency departments of three hospitals. Data was collected by using self-assessment questionnaires and evaluations by head nurses. The instrument was a clinical competency questionnaire with questions related to seven functional fields and 73 skills. Results: The viewpoints of nurses and head nurses on the clinical competencies of nurses were assessed at a moderate level in the majority of domains. Nurses defined their clinical competencies at a significantly higher level than the head nurses (P < 0.05). Conclusions: Based on the results, it is assumed that using more than one method and simultaneously applying multiple methods in an assessment will provide more accurate results about nurses’ clinical competence.
{"title":"Comparative Study of Evaluating the Clinical Competence of Emergency Nurses Using Self-assessments and Assessment by Head Nurses","authors":"Motahareh Musavi Ghahfarokhi, Elina Mehrafruz, Arman Radmehr, M. Kiarsi, Marzieh Beigom Bigdeli Shamloo","doi":"10.5812/tms.115391","DOIUrl":"https://doi.org/10.5812/tms.115391","url":null,"abstract":"Background: Clinical competency is the ability of nurses to play a professional role in a clinical environment, in terms of the quality of the services provided. Objectives: The present study aimed to compare the clinical competence of emergency department nurses using self-assessments and evaluations by head nurses. Methods: A descriptive-analytical study was conducted from July to September 2019. The census method was used to select 70 nurses working in the emergency departments of three hospitals. Data was collected by using self-assessment questionnaires and evaluations by head nurses. The instrument was a clinical competency questionnaire with questions related to seven functional fields and 73 skills. Results: The viewpoints of nurses and head nurses on the clinical competencies of nurses were assessed at a moderate level in the majority of domains. Nurses defined their clinical competencies at a significantly higher level than the head nurses (P < 0.05). Conclusions: Based on the results, it is assumed that using more than one method and simultaneously applying multiple methods in an assessment will provide more accurate results about nurses’ clinical competence.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"1 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":"129516406","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}
Context: The immunopathology of SARS-CoV-2 infection in COVID-19 is not well described yet, especially regarding dysregulation of the immune system. In this mini-review, current knowledge about the SARS-CoV-2 infection and immunopathogenesis of COVID-19 disease is described. We also discuss possible induced reactions against SARS-COV-2. Evidence Acquisition: Based on the authors' experience and knowledge, the current review aimed to, firstly, discuss and overview SRAS-CoV-2 infection and reactions in the body, and, secondly, to obtain related subjects from the PubMed database. Results and Conclusion: In most COVID-19 patients, uncontrollable cytokines secretion and mediators are major key points in the pathogenesis of the disease. Of all cytokines and mediators, serum levels of IL-6, IL-1β, TNF-α, IL-8, and soluble TNF-α receptor (sTNFR) have been reported. Lymphopenia and hypoxia, as well as the severity of the disease, can be considered as COVID-19 manifestations. High levels of intracellular NO inside of the red blood cells (RBCs) of patients drive the unexpected silent hypoxia phenotype induced ARDS importantly related to the patient's immune system dysfunction.
{"title":"Overview of SARS-CoV-2 Infection and Its Potential Reactions","authors":"E. Mortaz, Neda K. Dezfuli","doi":"10.5812/tms.115161","DOIUrl":"https://doi.org/10.5812/tms.115161","url":null,"abstract":"Context: The immunopathology of SARS-CoV-2 infection in COVID-19 is not well described yet, especially regarding dysregulation of the immune system. In this mini-review, current knowledge about the SARS-CoV-2 infection and immunopathogenesis of COVID-19 disease is described. We also discuss possible induced reactions against SARS-COV-2. Evidence Acquisition: Based on the authors' experience and knowledge, the current review aimed to, firstly, discuss and overview SRAS-CoV-2 infection and reactions in the body, and, secondly, to obtain related subjects from the PubMed database. Results and Conclusion: In most COVID-19 patients, uncontrollable cytokines secretion and mediators are major key points in the pathogenesis of the disease. Of all cytokines and mediators, serum levels of IL-6, IL-1β, TNF-α, IL-8, and soluble TNF-α receptor (sTNFR) have been reported. Lymphopenia and hypoxia, as well as the severity of the disease, can be considered as COVID-19 manifestations. High levels of intracellular NO inside of the red blood cells (RBCs) of patients drive the unexpected silent hypoxia phenotype induced ARDS importantly related to the patient's immune system dysfunction.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"375 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":"127585400","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}
Background: Immunotherapy can now be considered as game changer of cancer treatment. So far, numerous monoclonal antibodies (mAbs) and their derivatives, such as antibody-drug conjugates (ADCs), have been approved by regulatory agencies for medical use. This implies that the recombinant or chemical conjugation of mAbs to cytotoxic agents can be regarded as a potential cancer treatment modality. Objectives: This study aimed to design an antibody conjugate through the recombinant conjugation of a humanized CD19-specific single-chain variable fragment (scFv), named HuFMC63, to granzyme B (GrB) using precise in silico approaches. Methods: Four different linker peptides were used for the conjugation of HuFMC63 to GrB, and the 3D structure of these antibody conjugates were predicted using GalaxyWEB. The antibody conjugate whose linker peptide had the least impact on the structural conformation of HuFMC63 and GrB was subsequently selected. Additionally, the solubility and melting temperature of the selected conjugate was compared with those of HuFMC6 and GrB, and its physicochemical properties and flexibility were also assessed. Ultimately, the binding capacity and the dissociation constant (Kd) of the selected conjugate to CD19 were compared with those of HuFMC63 (concisely referred to as Hu63), and then the residues that contributed to antigen binding were identified using LigPlot+ software. Results: The Hu63-(G4S)3-GrB conjugate, which is constructed using the (G4S)3 linker, was selected as the best conjugate. The solubility of Hu63-(G4S)3-GrB was predicted to be higher than HuFMC63 and GrB (from 60% in the unconjugated to 98% in the conjugated format). Moreover, it was elucidated that Hu63-(G4S)3-GrB binds CD19 in the same orientation as that of HuFMC63 and with the same Kd of 17 and 33 nM at 25.0°C and 37.0°C, respectively. Conclusions: In silico techniques, such as those employed in this study, could be utilized for the early development of immune-based therapeutics. Moreover, Hu63-(G4S)3-GrB could be introduced as a potent therapeutic for the elimination of CD19-positive malignant cells after careful preclinical and clinical evaluations.
{"title":"In Silico Designing of a Novel Antibody Conjugate as a Potential Immunotherapeutic for the Treatment of CD19-Positive Hematologic Malignancies","authors":"Pooria Safarzadeh Kozani","doi":"10.5812/tms.117219","DOIUrl":"https://doi.org/10.5812/tms.117219","url":null,"abstract":"Background: Immunotherapy can now be considered as game changer of cancer treatment. So far, numerous monoclonal antibodies (mAbs) and their derivatives, such as antibody-drug conjugates (ADCs), have been approved by regulatory agencies for medical use. This implies that the recombinant or chemical conjugation of mAbs to cytotoxic agents can be regarded as a potential cancer treatment modality. Objectives: This study aimed to design an antibody conjugate through the recombinant conjugation of a humanized CD19-specific single-chain variable fragment (scFv), named HuFMC63, to granzyme B (GrB) using precise in silico approaches. Methods: Four different linker peptides were used for the conjugation of HuFMC63 to GrB, and the 3D structure of these antibody conjugates were predicted using GalaxyWEB. The antibody conjugate whose linker peptide had the least impact on the structural conformation of HuFMC63 and GrB was subsequently selected. Additionally, the solubility and melting temperature of the selected conjugate was compared with those of HuFMC6 and GrB, and its physicochemical properties and flexibility were also assessed. Ultimately, the binding capacity and the dissociation constant (Kd) of the selected conjugate to CD19 were compared with those of HuFMC63 (concisely referred to as Hu63), and then the residues that contributed to antigen binding were identified using LigPlot+ software. Results: The Hu63-(G4S)3-GrB conjugate, which is constructed using the (G4S)3 linker, was selected as the best conjugate. The solubility of Hu63-(G4S)3-GrB was predicted to be higher than HuFMC63 and GrB (from 60% in the unconjugated to 98% in the conjugated format). Moreover, it was elucidated that Hu63-(G4S)3-GrB binds CD19 in the same orientation as that of HuFMC63 and with the same Kd of 17 and 33 nM at 25.0°C and 37.0°C, respectively. Conclusions: In silico techniques, such as those employed in this study, could be utilized for the early development of immune-based therapeutics. Moreover, Hu63-(G4S)3-GrB could be introduced as a potent therapeutic for the elimination of CD19-positive malignant cells after careful preclinical and clinical evaluations.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"9 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":"127757598","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}
Background: Using different skill levels for patient care not only helps better and more fully meet patients' needs but also reduces the need for expert nurses. Objectives: This study was conducted to determine the perceptions of nurses and nursing assistants about the nursing assistant role. Methods: This study was conducted based on a conventional content analysis approach. The data was collected at the Ganjavian hospital in Dezful, Iran. Ten nurses and eleven nursing assistants were selected by purposeful sampling, and data were collected using unstructured interviews. The recorded interviews were eventually transcribed verbatim, and meaning units were then identified. Coding was then performed by compressing the meaning units and converting them into codes. The codes were summarized and classified to form categories. At last, the categories formed themes based on their similarities and differences. Results: Displeasure of the position was the main category of the study, which consisted of the two main subcategories of “having a small role in assisting nurses” and “reluctance to work”. Conclusions: The results of the study showed that nursing assistants have problems performing their roles, which need to be addressed by nursing managers.
{"title":"Perceptions About the Nursing Assistant Role in Ganjavian Hospital of Dezful: A Conventional Content Analysis","authors":"N. Sarabi","doi":"10.5812/tms.115791","DOIUrl":"https://doi.org/10.5812/tms.115791","url":null,"abstract":"Background: Using different skill levels for patient care not only helps better and more fully meet patients' needs but also reduces the need for expert nurses. Objectives: This study was conducted to determine the perceptions of nurses and nursing assistants about the nursing assistant role. Methods: This study was conducted based on a conventional content analysis approach. The data was collected at the Ganjavian hospital in Dezful, Iran. Ten nurses and eleven nursing assistants were selected by purposeful sampling, and data were collected using unstructured interviews. The recorded interviews were eventually transcribed verbatim, and meaning units were then identified. Coding was then performed by compressing the meaning units and converting them into codes. The codes were summarized and classified to form categories. At last, the categories formed themes based on their similarities and differences. Results: Displeasure of the position was the main category of the study, which consisted of the two main subcategories of “having a small role in assisting nurses” and “reluctance to work”. Conclusions: The results of the study showed that nursing assistants have problems performing their roles, which need to be addressed by nursing managers.","PeriodicalId":408913,"journal":{"name":"Trends in Medical Sciences","volume":"9 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":"126836429","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}
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