Successful use of Nicotiana tabacum hairy roots for the recombinant production of Cecropin A peptide.

Cecropin A, as an antimicrobial peptide (AMP), is possible to use in medical and agricultural fields as a new and safe biocontrol agent. Therefore, it is highly necessary to find a cost-effective and scalable approach to generate a large scale of it. In this research, the Agrobacterium rhizogenes strain ATCC 15834 was used to transfer the Cecropin A gene to the Nicotiana tabacum. After confirmation of transgenic hairy roots, the antibacterial activity of purified Cecropin A peptide was measured using the agar gel diffusion method. Successful transforming of Cecropin A was confirmed at the RNA and protein levels in hairy root cells using RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The highest Cecropin A amount was detected in line 4 of the transgenic lines using ELISA in comparison with the nontransgenic line. Subsequently, the antimicrobial activity of Cecropin A extracted from line 4 showed the highest inhibition activity against Aspergillus niger. Besides, this activity was stable against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans pathogens after 7 days. The recombinant production of Cecropin A AMP had a yield of 63.81 µg/g of fresh weight. According to a significant yield, this system can be used to produce the Cecropin A peptide for pharmacological and food science applications.

Polysomnography findings of patients with overlap syndrome according to severity of lower airway obstruction.

BACKGROUND: The concurrence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) is known as overlap syndrome (OS). The obstruction of the upper airway leads to OSA and the obstruction of the lower airway leads to COPD. The aim of this study was to compare polysomnographic findings of patients with OS according to severity of lower airway obstruction. MATERIALS AND METHODS: Seventy-two patients were included in this cross-sectional study. Patients with COPD referred to a sleep clinic with suspicion of OSA were evaluated by polysomnography (PSG). PSG findings were interpreted based on the American Academy of Sleep Association criteria (2012). COPD severity was categorized into four groups based on GOLD criteria using forced expiratory volume in the first second (FEV1). PSG findings also were compared between patients regarding severity of lower airway obstruction (FEV1 ≥50% and FEV1 <50%). RESULTS: Sixty-eight of the patients had OS. Twenty-nine (42.6%) were male. The mean age was 62.3 ± 6.88 years. Thirty-two (54.4%) of the patients were in GOLD 2. The mean apnea/hypopnea index was 57.41 ± 36.16. Seventy-two percent of patients had severe OSA. Severe OSA was more prevalent in patients of GOLD 2 and 3 groups compared to the other groups. Among PSG findings, only N2 sleep stage was significantly longer in patients with FEV1 < 50% than in patients with FEV1 ≥50% (61.5 ± 11.2, 55.3 ± 13.4, P = 0.039). CONCLUSION: Polysomnographic findings (except N2 stage) are not different in patients with OS with respect to severity of lower airway obstruction.

Acquired Bartter-like syndrome associated with colistin use in an adult patient: a case report.

Colistin is an effective antibiotic utilized for the treatment of Gram-negative bacterial infections with coverage against a broad spectrum of bacteria. Despite the broad antibacterial coverage, this antibiotic can have serious complications such as acute kidney injury. Colistin also can have a toxic effect on the loop of Henle, causing tubulopathy, electrolyte imbalances, and the occurrence of Bartter-like syndrome (BLS) which is characterized by magnesium and calcium disturbances, polyuria, and metabolic alkalosis. We here report a 32-year-old male with a history of multiple trauma due to an accident that received colistin therapy for Pseudomonas isolation from wound culture on the 5th day of hospitalization. Polyuria, hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalcemia were developed on the first week of colistin administration. The patient received colistin until the 21st day of hospitalization. Serum calcium and magnesium levels became normal 1 day after stopping colistin, while urine volume and metabolic alkalosis resolved 6 days after colistin discontinuing. Therefore, it is crucial to adjust the dose of colistin to minimize its toxicity.

Hydrogen nanobubbles: A novel approach toward radio-sensitization agents.

BACKGROUND: Ocular melanoma is a rare kind of eye malignancy that threatens the patient's eyesight. Radiotherapy and surgical removal are the most commonly used therapeutic modalities, and nanomedicine has lately entered this field. Brachytherapy using Ruthenium-106 (106 Ru) ophthalmic plaques has been used for decades to treat ocular melanoma, with the applicator placed on the patient's eyes until the prescribed dose reaches the tumor apex. PURPOSE: To investigate the efficiency of hydrogen nanobubbles (H2 -NBs) employment during intraocular melanoma brachytherapy using a 106 Ru electron emitter plaque. METHODS: The Monte Carlo (MC) simulation and experimental investigation using a 3D-designed phantom and thermoluminescence dosimetry (TLD) were employed. Various concentrations of H2 -NBs with a diameter of 100 nm were simulated inside tumor tissue. The results were presented as deposited energy and dose enhancement factor (DEF). An equivalent Resin phantom of the human eyeball was made using AutoCAD and 3D-Printer technologies. The glass-bead TLDs dosimeter were employed and placed inside the phantom. RESULTS: Using a 1% concentration of H2 -NBs, a DEF of 93% and 98% were achieved at the tumor apex of 10 mm from the experimental setup and MC simulation, respectively. For simulated concentrations of 0.1%, 0.3%, 0.5%, 1%, and 4% H2 -NBs, a maximum dose enhancement of 154%, 174%, 188%, 200%, and 300% were achieved, respectively, and a dose reduction was seen at about 3 mm from the plaque surface. CONCLUSION: H2 -NBs can be used as an absorbed dose enhancer in 106 Ru eye brachytherapy because of their unique physical characteristics. Reducing plaque implantation time on the patient's eye, reducing sclera absorbed dose, and decreasing the risk of patients' healthy organs irradiation are reported as some of the potential benefits of using H2-NBs.

Lower limb arterial thrombosis followed by sub-massive pulmonary thromboembolism after Sinopharm BBIBP-CorV COVID-19 vaccination.

The global COVID-19 vaccination had an undeniable influence on the pandemic management, despite of having reported rare but life-threatening side-effects of vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare autoimmune complication determined by thrombocytopenia and thrombosis propensity in the circulatory system. The activation of antibodies against platelet factor-4 (PF-4) which mimics the heparin-induced thrombocytopenia (HIT) characteristic is the main known pathogenicity of the disease. Herein, we reported a case of VITT in a middle-aged woman with no previous history of thrombophilia or other medical conditions who presented with thrombosis of the left superficial femoral artery 3-days after receiving the second dose of inactivated BBIBP-CorV (Sinopharm) vaccine. The patient underwent bypass vascular surgery and received none-heparin anticoagulation consistent with high-dose intravenous immunoglobin. Eight days after the discharge, she was subsequently referred to our center with the presentation of sub-massive pulmonary thromboembolism in spite of receiving the prophylactic anticoagulants during follow-up period. Details on side-effects of COVID-19 vaccines, specifically the inactivated ones are yet to be fully ascertained. Clinicians should consider the history of COVID-19 vaccines in thromboembolism patients who do not have well-acknowledged risk factors. Further studies about the necessity of prophylactic anticoagulants and clinical judgment for receiving other vaccines in such patients are required.

Dose characteristics of Au-198 eye brachytherapy applicator: A Monte Carlo study.

PURPOSE: The use of ocular plaques is a promising treatment option for eye melanoma brachytherapy. Although several studies have been done on various ocular plaques, little is known about the dose characterization of 198Au plaque. MATERIALS AND METHOD: The full mathematical model of the eye phantom, tumor, 106Ru/106Rh CCA, and 198Au plaque were simulated using the Monte Carlo MCNPX code. The dose distribution was measured in the plaque's central axis direction, and a dose profile was also measured at a distance of 2.5 mm from the plaque surface. RESULTS: The findings showed that 198Au plaque has superior dosimetric characteristics than CCA plaque for tumors with a thickness of greater than 3.5 mm, while CCA plaque is better for tumors with a thickness of less than 3.5 mm. The dose to the sclera and choroid is higher in the case of CCA plaque, while the dose to the organs at risk (lens and optic nerve) is greater in the case of 198Au applicator. In the case of 198Au plaque, however, the dose to sensitive organs was within their permissible dose range. CONCLUSION: In the treatment of medium and large tumors, 198Au plaque is more successful than CCA plaque. It can produce a much more homogeneous lateral dose profile in the target. In the treatment of dome-shaped tumors, 198Au plaque may be more successful than CCA plaque. As a result, the tumor's shape influences the plaque type selection.

Evaluation of Long-term Survival and Predictors of Mortality in Hemodialysis Patients by Using Time Dependent Variables, A Single Centre Cohort Analysis.

INTRODUCTION: Despite significant improvement in End Stage Kidney Disease (ESKD) patient's management, and better availability of dialysis for caregivers, mortality among these patients is unacceptably high. METHODS: We collected the data of 751 incident hemodialysis patients from March 2004 to November 2018. Survival curves was created by using the Kaplan-Meier method. Comorbidities, as well as time-dependent values of laboratory findings, were examined as independent factors by three models of Cox regression analysis. RESULTS: The median follow-up period was 31.7 months (1.08 to 169.28). Patient survival rates were 88%, 77%, 56%, 32%, 26% ,16% and 12%, at 1, 2, 4,6, 8, 10, 12 and 14 years of follow-up, respectively. The most common cause of mortality was cardiovascular disease. We observed lower survival rates in patients ≥ 65 years (HR = 2.684, 95% CI: 1.133 to 3.377; P < .001), diabetes mellitus (HR = 1.729, 95% CI: 1.484 to 2.014; P < .001) and walking disability (HR = 2.505; 95% CI: 2.104 to 2.983; P < .001). Low hemoglobin level (HR = 1.496; 95% CI: 1.257 to 1.779; P < .001), hyperphosphatemia (HR = 1.305, 95% CI: 1.104 to 1.542; P = 0.002) and high low-density lipoprotein cholesterol level (HR = 1.933; 95% CI: 1.431 to 2.611; P < .001) were predictors of mortality. A single pool Kt/V > 1.2 (HR = 0.743, 95% CI: 0.635 to 0.870; P < .001) and high serum creatinine level (HR = 0.842, 95% CI: 0.811 to 0.874; P < .001) showed protective effects. CONCLUSION: Our study showed a high survival rate in a single center cohort of hemodialysis patients in Iran. Traditional risk factors of mortality in general population, as well as indices of dialysis efficacy and general health status were the main predictors of mortality. Nationwide registries are necessary to investigate the dialysis survival rates and their predictors in our country. DOI: 10.52547/ijkd.6435.

An in silico study on the effect of host tissue at brachytherapy dose enhancement by gold nanoparticles.

PURPOSE: Iridium-192 brachytherapy dose enhancement by gold nanoparticles was investigated in five different tumor tissues to observe the tissue-related differences as an effective environmental factor in the applications of nanoparticles as radio-enhancer agents. METHODS AND MATERIALS: The brachytherapy high-dose-rate source of BEBIG Ir-192, a tumor volume with five different tissues including water, Plexiglas, soft tissue, adipose, and bone with and without a uniform distribution of gold nanoparticles were mimicked by MCNPX Monte Carlo simulation code using lattice feature. Dose enhancement factors in the tumor volume were measured separately regarding the types of tissue, and a previous study using GEometry ANd Tracking 4 simulation was used for result validation. RESULTS: The results demonstrated that various types of tissue, as the host of gold nanoparticles, lead to different dose enhancement level, so that the bone and adipose have the lowest and the highest amount of dose enhancement factor with values 20.8% and 39.75%, respectively. The maximum difference of 4.8% was achieved from data benchmarking. CONCLUSIONS: The results of this study indicate that the MCNPX code can be used as a valid tool for dose measurement in the presence of nanoparticles. Moreover, tissue types of tumor as an environmental feature, alongside with the nanoparticle's size and concentration as well as the conditions of radiotherapy, should be considered in the dose calculation.

A novel approach to classify urinary stones using dual-energy kidney, ureter and bladder (DEKUB) X-ray imaging.

OBJECTIVES: Detection of urinary stone composition before treatment can help in its management. The purpose of this work is to study the feasibility of classifying the kidney stone compositions in vivo by dual-energy kidney, ureter, and bladder (DEKUB) X-ray imaging. METHODS: Six urinary stone compositions with nine diameters were simulated in a water phantom, and two 70- and 120-kVp images were acquired by radiography tally of the Monte Carlo code. Six image features among 10 were selected for classification of the kidney stones. Four classification algorithms were applied to the dataset using MatLab software. Five-fold cross-validation was applied to the most accurate algorithm for 1000 times and the true and false detection rates were reported. RESULTS: The obtained accuracy of kidney stone classification was 96 ± 2% and this decreased with increasing noise level. The DEKUB was successful in distinguishing brushite, calcium oxalate monohydrate, cystine, and calcium phosphate stones from other types. CONCLUSIONS: Acceptable results achieved by the low-cost, low-dose DEKUB system in detection of kidney stone composition not only obviates a need for complicated imaging systems such as dual-energy computed tomography, but also provides an available and useful aid for physicians to choose between treatment approaches.

Discovery of direct inhibitor of KRAS oncogenic protein by natural products: a combination of pharmacophore search, molecular docking, and molecular dynamic studies.

BACKGROUND AND PURPOSE: Aberrant signaling by oncogenic RAS proteins occurs in almost all human tumors. One of the promising strategies to overcome such cancers is the inhibition of KRAS protein, a subtype of RAS family involved in cell growth, differentiation, and apoptosis, through preventing its effector, SOS1, from being attached to the protein. EXPERIMNTAL APPROACH: Herein, a virtual screening process was performed using pharmacophore search, molecular docking, and molecular dynamic simulations. A pharmacophore model was created to indicate essential features for a KRAS inhibitor and used for screening the National Cancer Institution (NCI) database to retrieve similar compounds to the pharmacophore model with more than 70% similarity. Chosen compounds were then docked into KRAS and four compounds were selected based on the highest binding scores. Next, a similarity search was done in the whole PubChem database to increase the number of potential inhibitors. The filtered compounds were docked again into KRAS and three of them were selected for molecular dynamic simulation. FINDINGS / RESULTS: Compounds 1a, 2d, and 3a can inhibit SOS-iKRASG12D interaction due to the higher number of interactions with the protein. Moreover, they achieved the equilibrium faster than the approved inhibitor. CONCLUSION AND IMPLICATIONS: Auriculasin, a polyphenol flavonoid, can be considered as a potential inhibitor of SOS1-KRAS interaction. This compound seems to be a stronger anticancer than 9LI, a known inhibitor of KRAS, due to its better docking scores. Moreover, this compound can be an appropriate candidate to be formulated as an oral drug.