Antibody Therapy for COVID-19: Categories, Pros, and Cons.

COVID-19 is a life-threatening respiratory disease triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has been considered a pandemic viral infection since December 2019. The investigation of the effective prophylaxis or therapeutic strategies for emergency management of the current condition has become a priority for medical research centers and pharmaceutical companies. This article provides a comprehensive review of antibody therapy and its different categories with their advantages and disadvantages for COVID-19 over the last few years of the current pandemic. Antibodies can be generated by active immunization, including natural infection with a pathogen and vaccination, or by the passive immunization method such as convalescent plasma therapy (CPT) and antibody synthesis in laboratories. Each of these ways has its characteristics. Arming the immune system with antibodies is the main aim of antiviral therapeutic procedures toward SARS-CoV-2. Collecting and discussing various aspects of available data in this field can give researchers a better perspective for the production of antibody-based products or selection of the most appropriate approach of antibody therapies to improve different cases of COVID-19. Moreover, it can help them control similar viral pandemics that may happen in the future appropriately.

Case Report: Mutation in AIMP2/P38, the Scaffold for the Multi-Trna Synthetase Complex, and Association With Progressive Neurodevelopmental Disorders.

Background: Leukodystrophies constitute a heterogeneous group of inherited disorders primarily affecting the white matter of the central nervous system. Aminoacyl-tRNA synthetases (ARSs) catalyze the attachment of an amino acids to their cognate transfer RNAs (tRNAs). Pathogenic variants in both cytosolic and mitochondrial ARSs have been linked to a broad range of neurological disorders, including hypomyelinating leukodystrophies and pontocerebellar hypoplasias (PCH). Aminoacyl tRNA synthetase-interacting multifunctional protein 2 (AIMP2), one of the three non-catalytic components of multi ARS complex, harbors anti-proliferative activity and functions as a proapoptotic factor thus promoting cell death. We report a case of a 7-month-old infant with a complex clinical presentation, including weight loss, severe anemia, skeletal abnormalities, microcephaly and MR imaging features of leukodystrophy with a novel mutation in AIMP2. Methods: Whole-exome sequencing (WES) was performed on the proband. Parental samples were analyzed by PCR amplification and Sanger sequencing. Results: Whole-exome sequencing revealed a novel variant c.A463T in the homozygous state in exon 3 (NM_001,326,607) of AIMP2 [p.(K155X)] in the proband. Parental carrier status was confirmed by target sequencing. Conclusion: Here, we present an Iranian case with leukodystrophy with a novel AIMP2 mutation. This finding broadens the mutational and phenotypic spectra of AIMP2-related leukodystrophy and offers guidance for proper genetic counselling for pre- and post-natal screenings as well as for disease management.

Association of a genetic variant in Interleukin-10 gene with increased risk and inflammation associated with cervical cancer.

BACKGROUND: Cervical-cancer is among the most commonly diagnosed cancers in women, and infection with human papillomavirus (HPV) is associated with an increased risk of cervical cancer and altered serum concentrations of inflammatory cytokines. We have explored the association between a genetic variation in the Interleukin-10 (IL-10) gene (rs1800896) and cervical cancer risk and its relationship with tissue Interferon gamma (IFN-γ), Transforming growth factor beta (TGF-ß), Tumor necrosis factor alpha (TNF-α) concentrations in women with cervical cancer. METHODS: A total of 315 women with, or without cervical cancer, were recruited into the study. DNA was extracted from cervical cells, and genotyping was undertaken using Taq-man real-time PCR. The genotype frequency and allele distribution were analyzed together with their association with pathological data. The association of the rs1800896 gene variation with tissue levels of the inflammatory cytokines was also investigated. RESULTS: Our data showed a significant association between the A allele of the rs1800896 gene variant and the presence of cervical cancer. In particular, patients with AG/AA genotypes had an increased risk of cervical cancer with an odds ratio of 1.929 (95% confidence interval [CI]: 0.879-4.23, P < 0.001) in a recessive model, compared with the GG genotype. Also, the tissue concentrations of IFN-γ, TGF-ß, and TNF-α in cervical tissues were significantly higher in women with cervical cancer (P < 0.001) and were associated with the AA genotype. CONCLUSION: We have found an association between the polymorphism rs1800896 in the IL-10 gene and an increased risk of cervical cancer as well as a higher level of tissue inflammatory cytokines. Further investigations are necessary on the value of emerging biomarkers for the risk stratification for the management of cervical cancer patients.

Significant association between Taq1 gene polymorphism in vitamin D receptor and chronic spontaneous urticaria in the Northeast of Iran.

OBJECTIVE: Chronic spontaneous urticaria (CSU) is defined as urticaria with an unknown etiology which persists for more than 6 weeks. CSU is an uncomfortable cutaneous condition that occurs due to an immune-mediated inflammatory reaction. Many studies have demonstrated that vitamin D deficiency and single-nucleotide polymorphisms in the vitamin D receptor (VDR) impact the immune response. In the current study, the frequency of the Taq1 polymorphism in the VDR gene were compared between patients with CSU and individuals without CSU. METHODS: In a case-control study, a group of CSU patients (n = 100) was compared with a group of healthy age- and gender-matched individuals as a control group (n =100) who visited our center between 2015 and 2017. After DNA extraction from EDTA-containing blood, polymerase chain reaction (PCR-RFLP) was used to determine the presence of the Taq1 polymorphism. Serum vitamin D levels were measured using ELISA method (Abcam, Cambridge, USA). RESULTS: Genotyping for Taq1 polymorphism showed that TT, Tt and tt genes frequency in the CSU group were 36%, 54%, and 10% respectively. The TT, Tt and tt genotypes had a distribution of 50%, 47% and 3% respectively in the control group. The mean serum vitamin D level in the CSU group was 19.88 ± 8.14 ng/ml, which was not significantly correlated with the Taq1 polymorphism (P = 0.841). There was a significant relationship between Taq1 gene polymorphism (tt genotype) and CSU (P = 0.038). Tt genotype increased the risk of CSU (odds ratio = 1.596), and inheritance of tt genotype increased the risk even further (odds ratio = 4.630). CONCLUSION: The frequency of Taq1 genotype polymorphism in the VDR gene was significantly higher in patients with CSU compared to the control group. The tt genotype polymorphism may be a risk factor for CSU.

Hypericin Induces Apoptosis in AGS Cell Line with No Significant Effect on Normal Cells.

It is of great importance to find an effective approach that not only eliminates gastric cancer cells but also do exhibits significant side effect to normal cells. Some studies have shown the effectiveness of hypericin against cancer cells. In this study, we evaluated the anti-cancer effect of Hypericin in the treatment of gastric cancer. In this study, the AGS cell line was exposed to different concentrations of hypericin for 24 and 48 h. Evaluation of cell death was done by MTT assay. The rate of apoptosis was measured by flow cytometry assay using Annexin V/ Propidium Iodide. The expression rate of Bcl2, p53 and Bax genes was evaluated by Real-time PCR test, and immunocytochemistry (ICC) analysis and western blotting was used for further evaluation of p53. MTT assay test showed that hyepricin induces 50% cell death in the concentration of 1 (µg/mL) and 0.5 (µg/mL) at 24 h and 48 h post-treatment, respectively, however no similar effect seen on fibroblast cells. Annexin/PI test revealed that cell apoptosis after exposure to hypericin for 24 h was 74%. Real-time PCR showed that expression level of Bax, p53 and Bax genes increases and Bcl2 gene decreases in AGS cell lines after treatment by hypericin. ICC analysis and western blotting for p53 confirmed these data. The results of this study indicated that hypericin has the potential to be introduced as an effective treatment for gastric cancer. Therefore, it seems that this substance has potential to be utilized as anti-cancer drug.

Hypericin Exerts Detrimental Effect on Huh-7 As a Delegacy of Hepatocellular Carcinoma: A P53 Dependent Pathway.

BACKGROUND: Hepatocellular carcinoma is the most common type of liver cancer which arises from the main cells in the liver. We address many studies investigating anti-cancer role of hypericin, however the proposing corresponding molecular pathway seems to be still a debate. Therefore, the present study aimed to evaluate the apoptotic effect of hypericin on the Huh7 as the liver cancer cell line and its relation with the gate keeper gene P53. MATERIALS AND METHODS: In this study, the Huh7 cell line and fibroblast cells (as control group) were treated with different concentrations of hypericin for 24 and 48 hours. Detection of cell death was performed by MTT assay and flow cytometry. The expression of bax, bcl2 and p53 mRNAs was evaluated by Real-time PCR. Also, Immunocytochemistry (ICC) analysis was used for further evaluation of P53expression. RESULTS: The results showed that hypericin has a dose-dependent cytotoxic effect on the Huh7 cell line, with no or marginal effect on fibroblastic cells. According to flow cytometry results, about 53%cells underwent apoptosis after exposure to LD50 of hypericin for 24 hours. Real-time PCR data demonstrated that the pro-apoptotic genes Bax and P53 expression level increased. Expectedly ICC results confirmed the up-regulation of P53 proteins in treated samples. CONCLUSION: Our results indicate the cytotoxicity of hypericin on Huh7 cells by affecting the expression of the gate keeper gene P53; furthermore it is suggested that this herb can be utilized simultaneously with modalities targeting P53 up-regulation or related molecular pathways.

CD14 as A Serum Immune Biomarker and Genetic Predisposition Factor for Allergic Rhinitis.

INTRODUCTION: Allergic Rhinitis (AR) is a common inflammatory disease of the nasal mucosa. The CD14 is a receptor for lipopolysaccharide and inhaled endotoxin which can stimulate the production of interleukins by antigen presenting cells. Accordingly, CD14 plays an important role in allergic and atopic diseases, which can be one of the etiological factors for allergic diseases. The present study investigated the association between the CD14 gene polymorphism C-159T and AR and aimed to detect the correlation between serum levels of CD14 and AR. MATERIALS AND METHODS: This study was conducted on two groups of participants. The experimental group consisted of 125 patients with AR referring to Ghaem Hospital, Mashhad University of Medical Sciences in Mashhad, Iran, and the control group included 125 healthy subjects from Mashhad National Blood Center, Iran. Serum CD14 levels were measured by enzyme-linked immunosorbent assay. Polymerase chain reaction-restriction fragment length polymorphism was employed to detect C-159T gene polymorphism in the CD14 promoter region. RESULTS: There was a significant association between CD14 C-159T gene polymorphism and AR (P<0.001). The results of the statistical analysis showed that the TT genotype could significantly increase the risk of AR (P<0.001). Additionally, a significant association was observed between C-159T gene polymorphism and the serum level of CD14 (P<0.001). Regardless of the genotypes, the serum CD14 levels were significantly higher in AR patients than in those of the participants in the controls (P=0.007). CONCLUSIONS: According to the obtained results of this study, CD14 in serum might be a potential marker for the diagnosis of AR, and in genetic levels it might be a predictive factor for the disease.

Hypericin Induces Apoptosis in MDA-MB-175-VII Cells in Lower Dose Compared to MDA-MB-231.

BACKGROUND: Breast cancer is the major cause of death from cancer among women around the world. Given the drug resistance in the treatment of this disease, it is very important to identify new therapies and anticancer drugs. Many studies demonstrated that hypericin could induce apoptosis in different cancer cell lines; however, the underlying mechanism is not well understood yet. Therefore, this study aimed to evaluate the anticancer effect of hypericin in two breast cancer cell lines, one with wild type P53 and the other with mutant P53. METHODS: In this study, the MDA-MB-231 and MDA-MB-175-VII cell lines were treated with different concentrations of hypericin for 24 and 48 hours. The measurement of cell death was performed by MTT assay. The cell apoptosis rate was measured using annexin V/propidium iodide assay through flow cytometry. The level of expression in P21 and P53 genes was evaluated by real time PCR. Immunocytochemistry (ICC) analysis was performed for P21 (direct target for P53 protein) to confirm the results. RESULTS: The results showed that hypericin could have dose-dependent cytotoxic effects on the MDA-MB-231 and MDA-MB-175-VII cell lines, and its cytotoxicity is much higher in the latter cells. According to flow cytometry results, 86% of MDA-MB-175-VII cells underwent apoptosis with IC50 dose of hypericin for MDA-MB-231 cells after 24 hours. Moreover, after 24 hours of exposure to hypericin with MDA- MB-231 IC50 concentration, the expression of P53 and P21 genes upregulated in MDA-MB-175-VII much more than MDA-MB-231 when both cell lines were treated with 24 hours IC50 dose of MDA-MB-231. The ICC analysis on P21 confirmed that by treating both cell lines with MDA-MB-231 IC50 dose of hypericin for 24 hours, this protein is overexpressed much more in MDA-MB-175-VII cells. CONCLUSION: The results of this study demonstrated that hypericin's apoptotic and cytotoxic effects on cancer cells may be mediated via P53 overexpression, cell cycle arrest and the subsequent apoptosis. Therefore, it is of great importance to consider that hypericin would have better impact on cells or tumors with wild type P53.

Cytotoxic Effects of Coated Gold Nanoparticles on PC12 Cancer Cell.

BACKGROUND: The use of gold nanoparticles in medicine and especially in cancer treatment has been of interest to researchers. The effectiveness of this nanoparticle on cells significantly depends on the amount of its entry into the cells. This study was performed to compare the rate and mechanism of effect of gold nanoparticles coated with different amino acid on PC12 cancer cell line. MATERIALS AND METHODS: The PC12 cells line were exposed to various concentrations of amino acid coated and uncoated gold nanoparticles (0.5, 2.5 and 5 µM). Cell death rate was determined according to level of Lactate dehydrogenase (LDH) release from cells and MTT assay. In addition cell morphology and the amount of Cellular Reactive oxygen species (ROS) were studied. RESULTS: The uncoated gold nanoparticles have shown minor effects on cellular life. Gold nanoparticles coated by tryptophan at high concentrations (2.5, 5 and 25µM) increase in cancer cells metabolic activity. Gold nanoparticles coated by Aspartate also produce the largest amount of LDH and ROS in cancer cells and therefore caused of highest rate of apoptosis. CONCLUSION: The results showed that the nanoparticles coated with amino acids are affected on cellular metabolism and apoptosis more than uncoated nanoparticles. Also the smallest coated nanoparticles (coated by aspartate) have the most influence and by increasing the size, this effect was reduced.

Diagnostic Value of Hepatic Vein Ultrasound in Early Detection of Liver Cirrhosis.

BACKGROUND: Cirrhosis is a common disease that destroys liver cells, and it has various etiologies. The early diagnosis of cirrhosis can be effective in improving prognosis. Considering the availability and affordability of ultrasound devices throughout the world, in this study we evaluated the diagnostic value of hepatic vein ultrasound examination in the early detection of liver cirrhosis. MATERIALS AND METHODS: In this study, 45 patients referred to the radiology department of Ghaem Hospital for liver biopsy were evaluated for changes in the hepatic veins under ultrasound with a transducer of 5-7MHz. One piece of the hepatic vein was selected for ultrasound, and the wall of hepatic veins was examined for straightness and uniformity of echogenicity. Subsequently, patients underwent biopsy by ultrasound guide. Of all the study subjects, eight patients presented mild chronic hepatitis without fibrosis, four patients were diagnosed with fatty liver, and 33 patients had severe cirrhosis or chronic hepatitis with fibrosis. RESULTS: Our results showed that hepatitis patients with or without fibrosis had irregular and wavy hepatic vein wall (impairment in straightness) with non-uniform echo (impairment in uniformity of echogenicity). While patients without hepatitis and cirrhosis, but diagnosed with fatty liver, had a smooth and regular hepatic vein wall with a uniform echo. CONCLUSION: The present study showed that hepatic vein examination in terms of echogenicity and straightness could be used to diagnose hepatitis, its severity as well as its course towards fibrosis and cirrhosis.

Effective Medicinal Plant in Cancer Treatment, Part 2: Review Study.

Cancer is the second cause of death after cardiovascular diseases. With due attention to rapid progress in the phytochemical study of plants, they are becoming popular because of their anticancer effects. The aim of this study was to investigate the effective medicinal plants in the treatment of cancer and study their mechanism of action. In order to gather information the keywords "traditional medicine," "plant compounds," "medicinal plant," "medicinal herb," "toxicity," "anticancer effect," "cell line," and "treatment" were searched in international databases such as ScienceDirect, PubMed, and Scopus and national databases such as Magiran, Sid, and Iranmedex, and a total of 228 articles were collected. In this phase, 49 nonrelevant articles were excluded. Enhancement P53 protein expression, reducing the expression of proteins P27, P21, NFκB expression and induction of apoptosis, inhibition of the PI3K/Akt pathway, and reduction of the level of acid phosphatase and lipid peroxidation are the most effective mechanisms of herbal plants that can inhibit cell cycle and proliferation. Common treatments such as radiotherapy and chemotherapy can cause some complications. According to results of this study, herbal extracts have antioxidant compounds that can induce apoptosis and inhibit cell proliferation by the investigated mechanisms.

Comparison of the Analgesic Effect of Paracetamol and Magnesium Sulfate during Surgeries.

BACKGROUND: New drugs are increasingly used to induce analgesia during surgeries. This study compared the analgesic effects of paracetamol and magnesium sulfate. METHODS: Sixty patients with American Society of Anesthesiologists (ASA) class I or II patients who were candidates for surgery of the lower limbs were randomly divided into three equal groups who were age and gender matched. Group 1 received paracetamol, and group 2, the magnesium sulfate during surgery and group 3 as the control. Pain intensities were measured and recorded using the Visual Analog Scale before surgery, in the recovery room, and 6, 12, and 18 hours after surgery. RESULTS: Pain intensities (7.10, 5.80, and 4.10) were higher in the control group; 6, 12, and 18 hours after surgery compared to the paracetamol (6.45, 4.15, 2.50) and the magnesium groups (7.25, 4.55, and 2.05), but the difference was not statistically significant. CONCLUSION: Paracetamol and magnesium sulfate were shown to have postoperative analgesic effects and reduce the quantity of narcotic use after surgery.

Prevalence of Urinary Tract Infection Among Pregnant Women and its Complications in Their Newborns During the Birth in the Hospitals of Dezful City, Iran, 2012 - 2013.

BACKGROUND: Urinary tract infection (UTI) is the most common disorder caused by bacterial agents in pregnancy, which can lead to important complications in newborn of such mothers in case of inappropriate diagnosis and treatment. OBJECTIVES: The purpose of this study was to study the prevalence of UTI among pregnant women and its complications in their newborns during the birth in the hospitals of Dezful City, Iran, during 2012 - 2013. PATIENTS AND METHODS: In this cross-sectional retrospective study, 1132 women admitted to Dr. Ganjavian and Ayatollah Nabavi Hospitals in Dezful City, Iran, during 2012 - 2013 were randomly allocated into the case and control groups and were matched based on their age, numbers of pregnancy, sex and diseases of their children. UTI was the only difference between the two groups. RESULTS: Twenty-two thousand six hundred deliveries occurred within the course of this study. Due to UTI, 5% of deliveries led to hospitalization of mothers (1132 patients).Weight and height of newborn infants of mothers afflicted with UTI (P < 0.001) were significantly lower compared to newborns of healthy women (P < 0.001). There was a significant association between the two groups of pregnant women with UTI in terms of type of delivery (normal and caesarean section) (P < 0.008). CONCLUSIONS: The lower incidence of UTI in pregnant women compared to other areas of Iran represents the role of climate and weather in the prevalence of UTI. In addition, the increased number of low-birth-weight infants had a remarkable correlation with UTI, which can influence the health of the next generation.

Women's Awareness and Attitude Toward Breast Self-Examination in Dezful City, Iran, 2013.

BACKGROUND: Over one million new cases of breast cancer (BC) are diagnosed each year with a mortality rate of more than 600 thousand women per year. Breast self-examination (BSE) is a patient-centered, inexpensive, and noninvasive diagnostic test. We focused on the role of screening in BC in early diagnosis. OBJECTIVES: The purpose of this study was to evaluate awareness and attitude of women toward BSE in Dezful City, Iran, in 2013. PATIENTS AND METHODS: This descriptive cross-sectional study included 1020 women over 15 years of age in Dezful City, in 2013. Simple random clustering was used to enroll accessible women. We have applied the available pieces of software for statistical analysis. RESULTS: The mean age of recruited women was 37.1 ± 1.3 and 23.6% of participants had a history of BC in themselves or in their relatives (mother, sister, aunt, and grandmother). In addition, 70.1% of participants benefited from early diagnosis of BC, 83.3% of participants considered BSE necessary and useful for early diagnosis of BC, and 51% of them performed BSE. There was a statistically significant correlation between being married and doing BSE (P = 0.034) and between women's level of education and awareness to perform BSE (P = 0.009). CONCLUSIONS: With regard to high prevalence of BC in Iran, this study showed a positive attitude of women in Dezful City toward BSE. Health policymakers in Dezful City can establish training programs to increase women's awareness of BSE and to instruct them to perform it properly.