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The indigenous halophilic arsenite-resistant bacterium Halomonas elongata strain SEK2 isolated from the high saline soil of Malek Mohammad hole, Lut Desert, Iran, could tolerate high concentrations of arsenate (As 5+ ) and arsenite (As 3+ ) up to 800 and 40 mM in the SW-10 agar medium, respectively. The isolated strain was able to tolerate considerable concentrations of other toxic heavy metals and oxyanions, including Cadmium (Cd 2+ ), Chromate (Cr 6+ ), lead (Pb 2+ ), and selenite (Se 4+ ), regarding the high salinity of the culture media (with a total salt concentration of 10% (w/v)), the tolerance potential of the isolate SEK2 was unprecedented. The bioremoval potential of the isolate SEK2 was examined through the Silver diethyldithiocarbamate (SDDC) method and demonstrated that the strain SEK2 could remove 60% of arsenite from arsenite-containing growth medium after 48 h of incubation without converting it to arsenate. The arsenite adsorption or uptake by the halophilic bacterium was investigated and substantiated through Fourier-transform infrared spectroscopy (FTIR), Scanning Electron Microscope (SEM), and Energy Dispersive X-ray (EDX) analyses. Furthermore, Transmission electron microscope (TEM) analysis revealed ultra-structural alterations in the presence of arsenite that could be attributed to intracellular accumulation of arsenite by the bacterial cell. Genome sequencing analysis revealed the presence of arsenite resistance as well as other heavy metals/oxyanion resistance genes in the genome of this bacterial strain. Therefore, Halomonas elongata strain SEK2 was identified as an arsenite-resistant halophilic bacterium for the first time that could be used for arsenite bioremediation in saline arsenite-polluted environments., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Toxic heavy metal/oxyanion contamination has increased severely through the last decades. In this study, 169 native haloarchaeal strains were isolated from different saline and hypersaline econiches of Iran. After providing pure culture and performing morphological, physiological, and biochemical tests, haloarchaea resistance toward arsenate, selenite, chromate, cadmium, zinc, lead, copper, and mercury were surveyed using an agar dilution method. On the basis of minimum inhibitory concentrations (MICs), the least toxicities were found with selenite and arsenate, while the haloarchaeal strains revealed the highest sensitivity for mercury. On the other hand, the majority of haloarchaeal strains exhibited similar responses to chromate and zinc, whereas the resistance level of the isolates to lead, cadmium, and copper was very heterogeneous. 16 S ribosomal RNA (rRNA) gene sequence analysis revealed that most haloarchaeal strains belong to the Halorubrum and Natrinema genera. The obtained results from this study showed that among the identified isolates, Halococcus morrhuae strain 498 had an exceptional resistance toward selenite and cadmium (64 and 16 mM, respectively). Also, Halovarius luteus strain DA5 exhibited a remarkable tolerance against copper (32 mM). Moreover, strain Salt5, identified as Haloarcula sp., was the only strain that could tolerate all eight tested heavy metals/oxyanions and had a significant tolerance of mercury (1.5 mM)., (© 2023 Wiley-VCH GmbH.)

Background: COVID-19 infection is a severe condition in pregnant women. Previous studies have suggested that anti-COVID-19 antibodies may be able to be transmitted from mother to fetus, which in itself is a protective factor in infants against the disease. However, few studies have been done in this area. In the present study, we aimed to investigate the presence of anti-COVID-19 antibodies in infants born to symptomatic and asymptomatic mothers with positive COVID-19 test., Methods: This is a cross-sectional study performed in 2021 in Abadan on neonates, born to symptomatic and asymptomatic mothers with positive COVID-19 test. All pregnant women over the age of 38 weeks with positive PCR tests for COVID-19 were included. We collected five cc of blood from the umbilical cord of neonates immediately after birth. The samples were sent to the laboratory in laboratory tubes to measure the anti-COVID-19 IgM and IgG levels., Results: We evaluated data of 20 neonates born to mothers with symptomatic COVID-19 and 10 neonates born to asymptomatic mothers with positive COVID-19 tests. In symptomatic groups, sixteen neonates (80%) had positive IgG antibodies and the mothers of all these neonates had positive antibodies. The mean IgG levels in infants was 73.26 ± 12.54 RU/ml and the mean IgM levels were 14.29 ± 3.71 RU/ml. Among neonates born to mothers with no symptoms, 7 neonates (70%) had positive IgG antibody. All mothers had positive antibodies. The mean IgG levels in infants were 74.50 ± 11.37 RU/ml and the mean IgM levels was 12.49 ± 2.88 RU/ml. There were no significant differences between two groups of neonates regarding positivity of IgG and antibody levels (P>0.05 for all)., Conclusion: 80% of infants born to mothers with COVID-19 pneumonia had positive IgG levels that were in line with the previous reports., Competing Interests: None., (IJPPP Copyright © 2022.)

Objectives: The complications of normal vaginal delivery (NVD) are one of the issues that researchers have been discussing today and various ways to reduce these outcomes have been presented. In this study, we aimed to compare the effect of Transcutaneous Electrical Nerve Stimulation (TENS), the aromatherapy of Lavandula and physiologic delivery without medication on NVD outcomes., Methods: This randomized clinical trial was conducted on 150 women that were candidates of NVD. The information related had been registered in the Iranian clinical trial registration system with the code IRCT20210501051151N1 (https://www.irct.ir/trial/56014). Patients were divided into three groups of Lavandula, TENS, and physiologic delivery. Postpartum pain, maternal and neonatal outcomes, and labor duration were compared in groups., Results: Labor pain was significantly less in TENS and Lavandula than in the physiologic group, respectively (P<0.001). There was no significant difference between the groups in terms of labor duration and maternal and fetal outcomes., Conclusion: The use of TENS and Lavandula aromatherapy are useful methods for reducing pain in patients undergoing NVD, but using TENS method is better than Lavandula method, and on the other hand, there are no differences between groups as maternal and neonatal complications., (IJPPP Copyright © 2022.)

Background: Multiple Sclerosis (MS) is an autoimmune, inflammatory disease of the central nervous system. Magnetic resonance imaging (MRI) findings are associated with disease clinical activity and response to treatment. This study aimed to evaluate the future value of plaque number and volume in MRI as radiological criteria in determining the treatment response to INF-B in patients with MS., Methods: This is a cross-sectional study performed in 2016-2021 in Iran on patients with the newly diagnosed (less than one year) relapsing-remitting MS. Brain MRI was taken for all patients. The number and volumes of the MS plaques were evaluated from FLAIR images by the two radiologists. Patients were treated with INF-B1a with a dosage of 12 million units equal to 44 micrograms subcutaneously, three times per week. Patients were visited monthly by neurologists to examine their clinical status. After one year, the brain MRI was conducted with the similar characteristics to the beginning of the study, and the number and volume of MS plaques were measured again., Results: The study population consisted of 33 males and 90 females with a mean age of 28.37 ± 6.29 years. The mean Expanded Disability Status Scale (EDSS) of the patients was 3.16 ± 0.23 at the beginning of the study. The specificity for a 50% reduction in the number and volume of plaques as two separate criteria was the same and equal to 100%. The sensitivity of the number and volume of plaques were 65.5% and 90.6%, respectively. In addition, considering 10% as the cut-off point of the number of plaques, the sensitivity of the number of plaques as a criterion was equal to the sensitivity of the plaque volume., Conclusion: The results of this study showed that imaging criteria provide a more objective tool for evaluating the effectiveness of treatment. These findings indicate that the number and volume of plaques could be two reliable MRI imaging criteria for assessing therapy response. The number of plaques was less accurate than the volume of plaques., Competing Interests: None., (AJND Copyright © 2022.)

Magnetic resonance imaging (MRI) is widely used in meningeal lesions due to rapid and accurate diagnosis and prevention of serious complications. The aim of the present study was to compare these two sequences after injection of a contrast agent into meningeal lesions. This is a descriptive-analytical study that was performed in 2018-2020 on patients referred to the radiology ward with detection of any meningeal involvements in the MRI images. In addition to T1-W, FLAIR sequence imaging was also performed. Images were initially evaluated by two expert radiologists and a neurologist. The diagnostic values of the sequences were compared. Overall, a total number of 147 patients with meningeal lesions in their brain MRI entered the study. 57.1% of cases (84 patients) had an infectious etiology and 42.9% (63 patients) had a tumoral etiology. T1-W images without contrast were able to diagnose 78 cases of meningitis (92.8% of them), and FLAIR sequences could diagnose 82 patients (97.6% of them). Without contrast injection on MRI, the diagnostic value of T1-W sequence was higher than FLAIR sequence for tumoral lesions (P < 0.01). The enhancement degree of T1-W was higher for tumoral findings (P < 0.01). In contrast, the enhancement degree of the FLAIR sequence was higher for infectious findings, which was also statistically significant (P = 0.015). FLAIR sequences had 92% sensitivity and 85% specificity for diagnosis of brain inflammatory diseases. Similar analysis showed that T1 sequence had 82% sensitivity and 73% specificity for diagnosis of brain inflammatory diseases., Competing Interests: None., (AJNMMI Copyright © 2022.)

Multiple Sclerosis (MS) is chronic, inflammatory, a neurologic disorder of the central nervous system (CNS). Although the exact mechanisms of MS have not been yet discovered some drugs are found helpful for its treatment. These drugs which are divided into the first line, second line and third-line therapies, have demonstrated to be helpful for MS patients based on immune basic of the disease. Previous studies have been indicated that deterioration of MS condition is associated with a stronger immune system. Most of these therapies impact on the immune system and immune cells including shifting immune cell populations toward a Th2 dominant population or suppression of the immune system so that auto-reactive immune cells cannot attack myelin sheath of neurons. Beside many beneficial effects of these drugs, some adverse effects (AE) have been reported in many experiments and clinical trials among patients suffering from MS. In this review, we conclude some AEs of beta interferon, mitoxantrone, natalizumab and fingolimod, reported in different papers and we continue the rest of the drugs in second part of our review article., Competing Interests: None.

Introduction: Fingolimod is the first oral drug approved by Food and Drug Administration (FDA) of United States for treating patients with relapsing-remitting multiple sclerosis (RRMS). Fingolimod acts by immunomodulation but there are still much remained about its different effects., Objectives: The aim of this study was to evaluate the changes in hematocrit (Hct), hemoglobin (Hb), and red blood cells (RBC) of patients with MS under treatments with fingolimod., Methods: A total number of 66 MS patients were included to our study based on certain exclusion criteria and eligibility for fingolimod oral treatment. Hct, Hb, and RBC were measured for each patient before drug administrations. Patients were treated with Fingolimod. 5 mg daily and after three months of treatments, measurements of Hct, Hb, and RBC were performed. Data were analyzed using SPSS software version 24., Results: Amounts of Hct, Hb, and RBC were significantly decreased in this patient cohort. Hematocrit was decreased in all patients. Hemoglobin levels were significantly decreased in the female cohorts. Such decreases for male patients were insignificant. Red blood cell counts were also significantly decreased in patients., Conclusion: Accumulating line of evidence had surveys on different side effects of fngolimod but here we indicated that fingolimod will also decrease amounts of Hct, Hb, and RBC which could result further problems in patients susceptible to other diseases., Competing Interests: None.

Multiple Sclerosis (MS) is an autoimmune, inflammatory disease of the central nervous system (CNS) mostly affecting young adults. The exact mechanism and pathogenesis of MS remain still undiscovered but there have been useful treatments with different efficacy rates. Most of these therapies are divided into the first line, second line and third line, impact on the immune system and immune cells. These drugs are approved to be useful in MS, but like any other therapies, adverse effects (AE) are associated with these drugs. In this review, we continue the survey over mechanisms of actions and AEs of MS drugs. Physicians must be aware of such AEs and complications to choose the best drug for each patient., Competing Interests: None.

Introduction: Fingolimod is an immunomodulating oral treatment used for treating relapsing-remitting multiple sclerosis (RRMS). The exact mechanism for its action in preventing relapses is unknown. Also, its affect on immune cell populations remains unestablished., Objectives: This study will measure the changes in cell populations of WBCs, lymphocytes, and neutrophils in MS patients after one month of treatment., Methods: 66 MS patients from Isfahan Province with RRMS were chosen based on certain exclusion criteria and eligibility for fingolimod oral treatment. Initial cell counts for WBC, lymphocyte, and neutrophil cell populations were achieved. Fingolimod .5 mg daily treatment was then initiated under the supervision of a physician. After one month of treatment, cell counts were repeated. Statistical analysis was performed using SPSS., Results: Both lymphocyte and WBC mean cell counts were significantly decreased in this patient cohort. Neutrophil average cell counts were significantly increased in this 66 patient cohort. Only the decrease of WBC populations was significant for both male and female cohorts individually. Only female sub-cohorts were significantly changed for neutrophils and lymphocytes, increased and decreased respectively. Male sub-cohorts maintained the same directionality but failed to produce statistical significance., Conclusion: While fingolimod has been effectively proven as reducing lymphocyte cells in most patient populations, its effects on neutrophils have not been studied in abundance. Also, there may be sex-related differences in responses to fingolimod treatment with regards to lymphocytes and neutrophils, suggesting a possible difference in RRMS pathogenesis between males and females., Competing Interests: None.

Curcumin is a polyphenolic phytonutrient that has antineurodegenerative properties. In this study, we investigated the anti-amyloidogenic properties of curcumin. Following incubation with curcumin, intrinsic tryptophan fluorescence emission of apolipoprotein (apo) A-I was strongly quenched. At the same time, curcumin fluorescence emission was enhanced. The fluorescence emission spectra of curcumin in the presence of amyloid-like aggregates formed by methionine-oxidized (ox) apoA-I varied, depending on whether curcumin was added before, or after, aggregate formation. The impact of curcumin on the structure of the aggregating material was revealed by the lower amount of β-structure in ox-apoA-I amyloid-like aggregates formed in the presence of curcumin, compared to aggregates formed without curcumin. However, the kinetics of ox-apoA-I amyloid-like aggregate formation was not altered by the presence of curcumin. Moreover, electron microscopy analysis detected no discernable differences in amyloid morphology when ox-apoA-I amyloid-like aggregates were formed in the presence or absence of curcumin. In conclusion, curcumin interacts with apoA-I and alters the structure of ox-apoA-I amyloid-like aggregates yet does not diminish the propensity of ox-apoA-I to form aggregates.

Seven proteins in the human blood clotting cascade bind, via their GLA (γ-carboxyglutamate-rich) domains, to membranes containing exposed phosphatidylserine (PS), although with membrane binding affinities that vary by 3 orders of magnitude. Here we employed nanodiscs of defined phospholipid composition to quantify the phospholipid binding specificities of these seven clotting proteins. All bound preferentially to nanobilayers in which PS headgroups contained l-serine versus d-serine. Surprisingly, however, nanobilayers containing phosphatidic acid (PA) bound substantially more of two of these proteins, factor VIIa and activated protein C, than did equivalent bilayers containing PS. Consistent with this finding, liposomes containing PA supported higher proteolytic activity by factor VIIa and activated protein C toward their natural substrates (factors X and Va, respectively) than did PS-containing liposomes. Moreover, treating activated human platelets with phospholipase D enhanced the rates of factor X activation by factor VIIa in the presence of soluble tissue factor. We hypothesize that factor VII and protein C bind preferentially to the monoester phosphate of PA because of its accessibility and higher negative charge compared with the diester phosphates of most other phospholipids. We further found that phosphatidylinositol 4-phosphate, which contains a monoester phosphate attached to its myo-inositol headgroup, also supported enhanced enzymatic activity of factor VIIa and activated protein C. We conclude that factor VII and protein C bind preferentially to monoester phosphates, which may have implications for the function of these proteases in vivo.

Many regulatory processes in biology involve reversible association of proteins with membranes. Clotting proteins bind to phosphatidylserine (PS) on cell surfaces, but a clear picture of this interaction has yet to emerge. We present a novel explanation for membrane binding by GLA domains of clotting proteins, supported by biochemical studies, solid-state NMR analyses, and molecular dynamics simulations. The model invokes a single "phospho-L-serine-specific" interaction and multiple "phosphate-specific" interactions. In the latter, the phosphates in phospholipids interact with tightly bound Ca(2+) in GLA domains. We show that phospholipids with any headgroup other than choline strongly synergize with PS to enhance factor X activation. We propose that phosphatidylcholine and sphingomyelin (the major external phospholipids of healthy cells) are anticoagulant primarily because their bulky choline headgroups sterically hinder access to their phosphates. Following cell damage or activation, exposed PS and phosphatidylethanolamine collaborate to bind GLA domains by providing phospho-L-serine-specific and phosphate-specific interactions, respectively.

Most steps of the blood clotting cascade require the assembly of a serine protease with its specific regulatory protein on a suitable phospholipid bilayer. Unfortunately, the molecular details of how blood clotting proteins bind to membrane surfaces remain poorly understood, owing to a dearth of techniques for studying protein-membrane interactions at high resolution. Our laboratories are tackling this question using a combination of approaches, including nanoscale membrane bilayers, solid-state NMR, and large-scale molecular dynamics simulations. These studies are now providing structural insights at atomic resolution into clotting protein-membrane interactions., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Receptor tyrosine kinases (RTKs) are a group of enzymes involved in a variety of physiological and pathological processes. The human Ror1 is a member of the RTK family with unknown ligand and biological function. Overexpression of Ror1 has recently been reported in B-cell chronic lymphocytic leukemia. The aim of this study was to explore the expression profile of Ror1 in acute lymphoblastic leukemia (ALL) cells. Therefore, leukemic cells were isolated from the bone marrow and/or peripheral blood (PB) of 57 ALL patients. Immunophenotyping was performed by flow cytometry and mRNA expression was detected by RT-PCR. Overexpression of Ror1 mRNA was detected in 23 of 57 (40%) ALL patients. A similar expression pattern was observed in ALL cell lines, with 4 of 12 (33%) being positive. Stimulation of normal PB mononuclear cells with pokeweed mitogen and phorbol myristate acetate induced substantially higher Ror1 mRNA expression compared to unstimulated cultured cells. There has been neither a significant association between Ror1 expression and the immunophenotypic profile of the leukemic cells, nor with other clinical or hematological features of the patients. In conclusion, our findings propose Ror1 as a new tumor-associated antigen and a potential tool for targeted immunotherapy and monitoring of minimal residual disease in ALL., ((c) 2008 S. Karger AG, Basel.)