Pediatric-Onset Chronic Inflammatory Demyelinating Polyneuropathy: A Multicenter Study.

BACKGROUND: To evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. METHODS: The clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. RESULTS: A total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 44.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). CONCLUSIONS: This multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.

Frequency of myelin oligodendrocyte glycoprotein antibodies in pediatric onset multiple sclerosis.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are associated with acute demyelinating syndromes and only rarely detected in multiple sclerosis (MS). As MOG-Ab associated disease is common in childhood, we speculated young patients might be more likely to produce MOG-Ab and investigated the frequency of MOG-Ab seropositivity in pediatric onset MS (POMS). MATERIAL AND METHODS: Patients who experienced their first acute demyelinating event before age 18 years and were diagnosed with MS during follow-up were included in this single-center study. Patient data were retrieved from clinical records. Serum samples obtained and frozen at clinical visits were analyzed for MOG-Ab by a live cell-based assay (CBA) measuring delta mean fluorescence intensity (MFI) and MFI ratio. The control group consisted of patients referred to pediatric neurology for headache or vertigo and who had no neurological disorder (n = 48). Another control group consisted of patients with systemic inflammatory disorders systemic lupus erythematosus (n = 17) and juvenile idiopathic arthritis (n = 13) diagnosed in the rheumatology clinic. RESULTS: The patient group (n = 122, F/M: 90/32, mean age 17.8 ± 2.6 years) were initially diagnosed as: MS, 62/122 (50.8%), clinically isolated syndrome, 43/122 (35.2%), radiologically isolated syndrome, 9/122 (7.3%), and acute disseminated encephalomyelitis 8/122 (6.5%). All received the final diagnosis of POMS. Serum was sampled 22.4 ± 29.2 (0-132) months after the first episode. None of the control groups had MOG-Ab positivity while 2/122 (1.6%) POMS cases had MOG-Abs, and a third patient had positive MFI and a MFI ratio slightly below the cut-off. These three patients' initial and final diagnoses were MS, their annualized relapsing rates (ARRs) were 0.4-0.6, and most recent Expanded Disability Status Scale was 0. CONCLUSION: Low titers of MOG-Ab can be detected in a small number of POMS patients at similar frequency with adult MS. Our POMS cases with MOG-Abs presented brainstem-cerebellar findings or seizures and had low ARR. Further series and longer follow-up will define whether these cases differ significantly from MOG-Ab negative POMS cases.

Myelin oligodendrocyte glycoprotein antibodies in genetic leukodystrophies.

Accumulation of intermediate metabolites due to enzyme deficiencies and demyelination can provoke inflammation in genetic leukodystrophies. Thirty patients with genetic leukodystrophy and 48 healthy control sera were tested for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies by fixed and/or live cell-based assays. MOG-IgG was detected in two late infantile metachromatic leukodystrophy (MLD) cases, both of which were also weakly positive for IgG1, and one with IgG3 as the dominant anti-MOG IgG subclass. MOG-IgG was borderline positive in a vanishing white matter (VWM) disease patient. These results suggest that inherited metabolic or degenerative processes can have an autoimmune component, possibly as an epiphenomenon.

A comparison between constitutive models for the municipal solid waste.

This paper compares the behavioural models of municipal solid waste (MSW) using the corresponding experimental data. To do so, the proposed models are first reviewed and, then, the algorithms and codes of different models are written. After obtaining each model's algorithm, the same experimental data are considered as input, and the strain-stress curve is plotted for each model. In the first method, the total strain in the waste is obtained based on the summation of the elastic, plastic, biological, and creep strains. Afterward, the equivalent stress is obtained. In this method, using biological changes over time, the age of the waste is calculated as an effective parameter in MSW behaviour. Moreover, the effect of creep on the waste is considered independently. In the second algorithm, MSW is considered as fibre and paste material, and the strain-stress curve is obtained. In this method, the waste is considered as a soil model, and the effect of different parameters are calculated. Due to the complexity of the MSW behaviour and considering various parameters, such as the age of the waste, E changes over time, creep, and biological changes, the Krase model has less error than the other models. Using the soil behaviour model for the waste has a significant error, indicating the difference between the results for the behaviours of the two substances.

Cytoprotective and cytofunctional effect of polyanionic polysaccharide alginate and gelatin microspheres on rat cardiac cells.

This study investigated the cyto-functional effect of Alginate-Gelatin microspheres on rat cardiomyoblasts after 7 days. Rat cardiomyoblasts were encapsulated inside Alginate-Gelatin microspheres via application of high voltage rate and dropping in a stirring CaCl2 solution. The swelling rate, biodegradation, and mechanical features were measured. Cell viability was assessed using MTT. Cell membrane integrity was monitored via calculation supernatant SGOT, SGPT, CPK, and LDH. We also measured SOD, GPx, and anti-oxidant capacity. Protein levels of Nrf-2 and PCCG-1α were detected via western blotting. The cyto-functional activity of encapsulated cells was monitored using real-time PCR assay targeting the expression of Connexin-43, α-actinin, and myosin light chain. Data showed suitable biodegradation and swelling rate in Alginate-gelatin microspheres by time. 7-day incubation of rat cells inside microspheres did not exert cytotoxicity compared to control cells (p > 0.05). The release of SGPT, SGOT, CPK, and LDH in encapsulated cells was significantly decreased compared to the control group (p < 0.05). We also found enhanced anti-oxidant capacity and SOD and GPx activity in cells after being-encapsulated inside Alginate-Gelatin microspheres (p < 0.05) coincided with increased Nrf-2 synthesis (p < 0.05) compared to control cells. The expression of Connexin-43, α-actinin, and myosin light chain was significantly up-regulated, showing cyto-functional effect of Alginate-Gelatin microspheres after 7-days.

Protective effect of bacterial lipase on lipopolysaccharide-induced toxicity in rat cardiomyocytes; H9C2 cell line.

Introduction: Cardiovascular system is highly sensitive to LPS-induced oxidative damage. This study aimed to show the inhibitory effect of bacterial Lipase on LPS-induced cardiomyoblasts toxicity. Methods: Rat cardiomyoblasts H9C2 were classified into Control, LPS (cells received 0.1, 1 and 10 µg/mL LPS) and LPS+ Lipase groups. In LPS+Lipase group, different concentrations of lipopolysaccharide were pre-incubated with 5 mg/mL bacterial lipase at 37˚C overnight prior to cell treatment. After 72 hours, cell viability was assessed by MTT assay. The expression of key genes related to toll-like receptor signaling pathways was assessed by real-time PCR assay. Percentage of fatty acids was evaluated in each group using gas chromatography assay. The levels of NO was also measured using the Griess reaction. Results: Data showed H9C2 cells viability was decreased after exposure to LPS in a dose-dependent manner (P < 0.05). Incubation of LPS with lipase increased cell survival rate and closed to near-to-control levels (P < 0.05). Lipase had the potential to blunt the increased expression of IRAK and NF-κB in cells after exposure to the LPS. Compared to the LPS group, lipase attenuated the increased level of NO-induced by LPS (P < 0.05). Gas chromatography analysis showed the reduction of saturated fatty acids in cells from LPS group while the activity of lipase prohibited impact of LPS on cell fatty acid composition. LPS decreased the ability of cardiomyoblasts to form colonies. Incubation of LPS with lipase enhanced clonogenic capacity. Conclusion: Reduction in lipopolysaccharide-induced cytotoxicity is possibly related to lipase activity and reduction of modified lipopolysaccharide with toll-like receptor.

Toll-like receptors in the functional orientation of cardiac progenitor cells.

Cardiac progenitor cells (CPCs) have the potential to differentiate into several cell lineages with the ability to restore in cardiac tissue. Multipotency and self-renewal activity are the crucial characteristics of CPCs. Also, CPCs have promising therapeutic roles in cardiac diseases such as valvular disease, thrombosis, atherosclerosis, congestive heart failure, and cardiac remodeling. Toll-like receptors (TLRs), as the main part of the innate immunity, have a key role in the development and differentiation of immune cells. Some reports are found regarding the effect of TLRs in the maturation of stem cells. This article tried to find the potential role of TLRs in the dynamics of CPCs. By showing possible crosstalk between the TLR signaling pathways and CPCs dynamics, we could achieve a better conception related to TLRs in the regeneration of cardiac tissue.

The effect of moderate endurance training on gastrocnemius retinol-binding protein 4 and insulin resistance in streptozotocin-induced diabetic rats.

BACKGROUND: Retinol-binding protein 4 (RBP4) is suggested to be involved in the occurrence of insulin resistance. There are contradictory studies about the effects of exercise training on RBP4 levels and insulin resistance. Hence, we designed this study to investigate the impact of moderate endurance training on gastrocnemius RBP4 and insulin resistance in streptozotocin (STZ)-induced diabetic rats. METHOD: Forty male albino Wistar rats were randomly divided into four groups: healthy control (HC), diabetic control (DC), healthy training (HT), and diabetic training (DT). Animals in HT and DT groups ran on a treadmill on the basis of overload principle for 6 weeks, three sessions per week. Rats in DC and DT groups are affected by diabetes using STZ (50 mg/kg of body weight). Gastrocnemius RBP4 content was measured using an enzyme-linked immunosorbent assay kit. Data were analyzed by one-way analysis of variance at P < 0.05 level. RESULTS: Serum blood glucose level (P = 0.001) and insulin resistance (P = 0.001) increased in DC compared with HC group, whereas serum insulin (P = 0.001) and gastrocnemius RBP4 (P = 0.001) reduced. However, there were no significant differences between serum blood glucose level (P = 0.384), insulin resistance (P = 0.999), and RBP4 (P = 0.999) content in DT compared with HT group. CONCLUSION: Moderate endurance training reduces blood glucose level and subsequently improves insulin sensitivity by decreasing gastrocnemius RBP4 content independent of insulin.

Soluble Expression of Humanized Anti-CD20 Single Chain Antibody in Escherichia coli by Cytoplasmic Chaperones Co-expression.

BACKGROUND: CD20 is an important cell surface receptor that is used for target therapy of B cell lymphoma and some related blood diseases due to vital function of CD20. In previous studies, a Rituximab based humanized single chain variable fragment (scFv) antibody showed good reactivity against B cell related cancer cells. But this recombinant protein produced Inclusion Bodies (IBs) in Escherichia coli (E. coli) cytoplasm. The aim of this study was to investigate the effect of coexpression with cytoplasmic chaperones on expression and solubility of humanized anti-CD20 scFv in E. coli. METHODS: For this purpose, the fragment coding for anti-CD20 huscFv subcloned into the pET22b (+) and transformed into the E. coli BL21 (DE3) was evaluated. In order to inhibit the production of IBs, the effects of co-expression with cytoplasmic chaperones GroEL, DnaK, GroES, Tig, DnaJ and GrpE were investigated. RESULT: Coexpression with cytoplasmic chaperones led to increased soluble expression of anti-CD20 recombinant protein. Among investigated chaperones, pKJE7 chaperone plasmid containing DnaJ, GrpE, DnaK chaperone genes had significant effects with an expression yield of 325 µg/ml soluble anti-CD20 scFv. CONCLUSION: The result of this study demonstrated remarkable effect of pKJE7 chaperone on enhancement of soluble expression of anti-CD20 huscFv antibody in E. coli.

An overview on molecular chaperones enhancing solubility of expressed recombinant proteins with correct folding.

The majority of research topics declared that most of the recombinant proteins have been expressed by Escherichia coli in basic investigations. But the majority of high expressed proteins formed as inactive recombinant proteins that are called inclusion body. To overcome this problem, several methods have been used including suitable promoter, environmental factors, ladder tag to secretion of proteins into the periplasm, gene protein optimization, chemical chaperones and molecular chaperones sets. Co-expression of the interest protein with molecular chaperones is one of the common methods The chaperones are a group of proteins, which are involved in making correct folding of recombinant proteins. Chaperones are divided two groups including; cytoplasmic and periplasmic chaperones. Moreover, periplasmic chaperones and proteases can be manipulated to increase the yields of secreted proteins. In this article, we attempted to review cytoplasmic chaperones such as Hsp families and periplasmic chaperones including; generic chaperones, specialized chaperones, PPIases, and proteins involved in disulfide bond formation.

Anti-bacterial activity of graphene oxide as a new weapon nanomaterial to combat multidrug-resistance bacteria.

Antibiotic resistance in microbial pathogens has become a serious health problem in the world. The increasing spread of hospital acquired infections especially in immunocompromised and cancer patients caused by multidrug-resistant (MDR) microbial pathogens is restricting the choices for impressive antibiotic therapy. So many efforts have been made to develop new compounds with antimicrobial activity. In recent years, nanoparticles, particularly graphene oxide (GO) nanoparticles have found many applications in various fields, including antibacterial action, pathogens bio detection, cancer therapy, and drug and gene delivery. The use of graphene oxide as an antibacterial agent for the treatment of infections with multidrug resistance is growing due to the unique physicochemical properties as wide surface area, excellent electrical and thermal conductivity, and biocompatibility. To reduce toxicity and increase the efficiency of graphene oxide as an antimicrobial agent, different surface modification and functionalization with inorganic nanostructures, biomolecules and polymers were developed. In this review article, we give our overview of the progress made on the graphene oxide nanocomposites as a new generation of antimicrobial agents.

Immunotoxins in cancer therapy: Review and update.

Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes. This article will also review different generations of immunotoxins with special focus on immunotoxins which are under clinical trials or approved for clinical use. Finally, current deimmunization strategies for development of new less-immunogenic recombinant immunotoxins will be discussed. ABBREVIATIONS: mAbs: Monoclonal antibodies; EF2: elongation factor 2; ITs: Immunotoxins; DT: Diphtheria toxin; PE: Pseudomonas exotoxin; dgA: de-glycosylated A-chain of ricin; rGel: recombinant de-glycosylated form of gelonin; NKC: natural killer cells; HTR: human transferrin receptor; EGF: epidermal growth factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; DAB389: truncated Diphtheria toxin; B-CCL: B-cell chronic lymphocytic leukemia; RCC: renal cell carcinoma; GVHD: Graft-versus-host disease; EGFR: epidermal growth factor receptor; AML: acute myeloid leukemia; Fab: fragment antigen-binding; dsFv: disulfide-stabilized fragment variable; scFv: single-chain fragment variable; B-ALL: B-lineage Acute Lymphoblastic Leukemia; Fv: fragment variable; HCL: hairy cell leukemia; IL-2R: Interleukin-2 receptor; CR: complete response; CLL: chronic lymphocytic leukemia; ATL: adult T-cell leukemia; DARPins: designed Ankyrin repeat proteins; pmol: picomolar; HAMA: human-anti mouse antibody.