Journal of Trends in Medical Sciences
Volume:1 Issue: 2, Spring 2021

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.

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.

 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.

Monoclonal antibodies (mAbs) have demonstrated promising clinical efficacy in various therapeutic fields over the past decades. However, their size has emerged as the most restricting factor limiting their application in antibody-drug conjugate platforms or antibody-redirected delivery systems. This limitation was mainly due to the inability of these platforms to penetrate the tumor site and reach their intended destination. Single-domain antibodies, also known as VHHs or nanobodies®, are known as promising alternatives capable of addressing the drawbacks of conventional full-sized antibodies. Alongside a great level of affinity and selectivity towards their target, the small size of nanobodies, which is about 15 kDa, their capability for tissue penetrance, the significant level of stability, their simple and cost-friendly manufacturing process, and fleeting half-life in the circulation system, are all among the reasons that have made them suitable candidates for the development of various types of therapies. In this review, we briefly discuss the application of nanobodies in checkpoint blockade therapy and nanobody-drug conjugate platforms. We also discuss nanobody-assisted redirection of various types of delivery systems carrying different types of cargoes. In the last section, we underline the promising and effective application of nanobodies in the fight against infectious diseases.

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.

This study was conducted to determine the perceptions of nurses and nursing assistants about the nursing assistant role.

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.

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”.

The results of the study showed that nursing assistants have problems performing their roles, which need to be addressed by nursing managers.

Immunotherapy cannowbe considered asgamechanger 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.

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.

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.

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-GrBwaspredicted to be higher thanHuFMC63andGrB(from60% 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.

In silico techniques, such as those employed in this study, could be utilized for the early development of immunebased 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.

The incidence of B-chronic lymphocytic leukemia (B-CLL) resulting from the clonal accumulation of apoptosisresistant 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.

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.

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 M) on the level of Apollon expression in CLL patients was assessed and compared to that of healthy donors.

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).

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.

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.

The present study aimed to compare the clinical competence of emergency department nurses using self-assessments and evaluations by head nurses.

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.

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).

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.

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.

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.

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.

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.