Antibody profiling for the prognosis and diagnosis of multiple sclerosis in patients, compared with healthy subjects

Background: Multiple sclerosis is considered as an autoimmune disease of the central nervous system that is the main cause of disability in young adults around the world. The purpose of this study was to determine changes in antibodies in the prognosis of multiple sclerosis, and the use of antibody against aquaporin 4 for the diagnosis of multiple sclerosis.Materials and Methods: In this case - control study, 21 patients with a definite diagnosis of multiple sclerosis and 21 healthy subjects were selected as the study population.  Blood and urine samples were collected, and nephelometry technique was used to assess the presence or absence of IgG, IgM and IgA in serum and urine samples. ELISA method for measuring of antibodies against aquaporin 4 was used.Results: There was no major difference in  the mean of the total IgM  in the case and control groups , but the mean IgA and IgG levels in the control group were  evidently higher than in the case group.  It was releaved that IgA, RBC and Hb mean differences between the two groups are statistically significant.  Parallel with an increase in IgG, the probability of disease exacerbation was increased by 0.22, whereas with increasing ages, the probability of disease exacerbation was 15.0. There was also a positive and significant relationship between the average level of antibodies, IgG and IgM with the degree of illness However, the relationship between the mean serum IgA level and the degree of illness was inverse. It also became clear that antibodies against AQP-4 in serum and urine of patients with different degrees of illness showed no significant difference.  The difference between the mean of antibodies against AQP in the serum of patients with mild and moderate MS was 54.1, but in mild and severe MS   it was 53.3.Conclusion: The findings of this research suggest that serum antibody levels are directly related to the disease levels and can be used as a prognostic factor. Accordingly, it appears that the use of antibodies against aquaporin-4 in serum and urine for the diagnosis of this disease   can be considered as a reliable approach

Evaluation of allergy and eosinophilia level in peripheral blood of patients with cardiovascular diseases

Background: Cardiovascular diseases are the most common cause of deaths in Iran and other developing countries. The risk factors for cardiovascular diseases are divided into two categories; the variable risk factors and the non-variable risk factors. Many recent studies evaluated the relationship between higher eosinophilia and allergy levels with the incidence, progress and severity of cardiovascular diseases, but the exact correlation between these two still remains  unknown. The current study was designed to assess the relationship between allergic responses and eosinophilia amongst patients with cardiovascular diseases in Ilam province, in comparison with healthy individuals.Materials and Methods: In this case-control study, we enrolled 59 cardiovascular patients and 55 healthy individuals without any history of allergy and parasitic infections. A questionnaire including questions about demographic data, family history of heart disease, history of diabetes, hyperlipidemia, physical activity, smoking, stress, dietary fat consumption, salt intake, allergies to certain substances, history of parasitic disease and history of hypertension was completed. The blood was taken from each participant and CBC and IgE titer were measured.Results: There was a significant relationship for the variables such as the family history of cardiovascular disease (P<0.001), diabetes (P<0.003), hyperlipidemia (P<0.0001), high blood pressure (P<0.0001) and physical activity (P<0.0001) between the case and the control groups. The mean IgE titer in case group was 95.3±71 and 62.44±49 in control group. The mean eosinophilia level in peripheral blood was 3.95±1.057 in case and 1.53±0.57 in control group. The difference between the IgE and eosinophilia levels in the case and the control groups was statistically significant (P<0.0001).Conclusion: Based on our results, it can be concluded the increase in levels of IgE and eosinophilia can be considered by cardiologists as a reliable diagnostic tool for predicting cardiovascular diseases

Survey of the association between polymorphisms of CTLA-4 exon 1 49 A/G genes with rheumatoid arthritis in Iran

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which suppresses T cell proliferation, is a promising candidate for the susceptibility genes to rheumatic arthritis diseases (RA). This study aims to examine the association between the polymorphisms of the CTLA-4 exon 1(+ 49) genes with RA in the Qazvin city of Iran population. The polymerase chain reaction of genomic DNArestriction fragment length polymorphism (PCR-RFLP) was applied to genotype the CTLA-4 exon 1(+ 49) polymorphisms in 105 RA patients and 90 control subjects. Laboratory diagnostic tests were also measured for RA and control groups. Our results did not demonstrate a significant difference in allele and genotype frequencies of the CTLA-4 exon 1(+ 49) between RA patients and the control group (p < .0001). There was no significant difference in age at onset, CRP, RF value in patients with RA according to the CTLA-4 polymorphisms; just anti-CCP showed a significant difference. Our data declared that polymorphisms of CTLA-4 exon 1(+ 49) genes are not correlated with RA susceptibility and its clinical and paraclinical manifestations

Assessment of gastric caused by Helicobacter pylori and pathologic elements correlation with -511 IL1-β and -308 TNF-α polymorphisms in gastritis patients

Helicobacter pylori (H.pylori) is the main reason for gastric disorders including gastric lymphoma, ulcer disease, gastric carcinoma (GC), and chronic atrophic gastritis. H.pylori has two more significant virulence factors named cagA and vacA. Some host cytokines polymorphisms (Interleukin (IL-1) and tumor necrosis factor (TNF-α)) may contribute to H. pylori-related diseases. In the present study, we investigated the association of H. pylori gastritis and its pathogenic genes as well as the association of IL-1β and TNF-α polymorphisms in patients with gastritis. We collected gastric biopsy samples from patients with gastritis. After extracting DNA from biopsy specimens infected with H. pylori, cagA + and vacA + were detected by the polymerase chain reaction (PCR). To genotyping TNF-α polymorphism at position − 308 and IL-1β polymorphism at position − 511, PCR-based restriction fragment length polymorphism analysis was performed. Our study indicated that IL-1β-511 polymorphism, unlike TNF-α-308 polymorphism (P = 0.030), did not show a significant relationship between patients infected with H. pylori (p = 0.219). Also, our results indicated that alleles C and T of polymorphism of IL-1β-511 and alleles G of TNFα-308 were not significantly correlated with cagA status among patients infected with H. pylori (p = 0.793, p = 0.674, p = 0.179, respectively) unlike allele A of TNFα − 308 (p = 0.016

Anti-apoptotic effects of minocycline on doxorubicin-induced cardiotoxicity in male Wistar rats

Background and Aim: Doxorubicin is an effective chemotherapeutic agent. However, use of this drug is limited due to its dose-dependent cardiotoxicity. Activation of apoptotic pathways in myocardial tissue plays an important role in doxorubicin- induced cardiotoxicity. Minocycline is an antibiotic that has anti-apoptotic effects. In this study, we investigated the protective effects of minocycline against doxorubicin-induced cardiac toxicity in male rats. Materials and Methods: Forty two adult male rats were divided into control (normal saline), doxorubicin (2.5 mg / kg), minocycline (45 and 90 mg / kg) and treatment (doxorubicin + minocycline 45 and 90 mg / kg) groups. Minocycline was injected intraperitoneally, once a day for 3 weeks. Ejection fraction (EF) and fractional shortening (FS) were measured using echocardiography. The activity of caspase 3/7 and the expression of Bax and Bcli were measured by biochemical methods. Bax and Bcl-2 genes expression levels were estimated by real-time PCR. Results: In the minocycline-treated groups (45 and 90 mg / kg) the activity of caspase 7/3 and the expression of Bax gene were significantly lower and the levels of EF, FS and Bcl-2 expression were significantly higher than those in the doxorubicin group. Conclusion: Minocycline reduces doxorubicin-induced cardiotoxicity. The anti-apoptotic effects of minocycline may play an important role in its protective effects

The Synergistic Glucose-lowering Effects of Metformin and Bavachinin on Type II Diabetic Rats

Background: Diabetes is one of the most prevalent endocrine disorders in humans, and its first-line medication is metformin. Peroxisome proliferator-activated receptor gamma (PPAR–γ) agonists are the adjuncts to metformin. Bavachinin is a PPAR pan-agonist with fewer side effects than metformin" into PPAR–γ agonists. In this study, the synergistic effects of metformin and Bavachinin were investigated on type II diabetic rats. Methods: After four weeks of a high fat and glucose diet, type II diabetes was induced in 28 male Wistar rats, using injection of streptozotocin and nicotinamide. The animals were distributed into five groups of seven each: 1) Normal control (N), 2) Diabetic control (D), 3) Diabetic rats receiving metformin (DM), 4) Bavachinin (DB), and 5) Metformin plus Bavachinin (DMB). Oral glucose tolerance test (OGTT), fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of β-cell function (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR), and insulin sensitivity index (ISI) were obtained. Results: The OGTT results in DM, DB, and DMB groups were significantly improved compared to that of D group. The FBG levels were significantly lower in DMB than in DB, DM, and D groups. The FINS levels of DMB were significantly less than those of DB, DM, and D groups. The HOMA-IR and HOMA-β were comparable between DMB and N groups. The ISI improved significantly in DMB compared to those in DM, DB, and D groups. Conclusion: Bavachinin may be used combined with metformin for the treatment of type II diabetes at lower doses of metformin, thus having fewer side effects

Gold nanoparticles: Multifaceted roles in the management of autoimmune disorders

Gold nanoparticles (GNPs) have been recently applied for various diagnostic and therapeutic purposes. The unique properties of these nanoparticles (NPs), such as relative ease of synthesis in various sizes, shapes and charges, stability, high drug-loading capacity and relative availability for modification accompanied by non-cytotoxicity and biocompatibility, make them an ideal field of research in bio-nanotechnology. Moreover, their potential to alleviate various inflammatory factors, nitrite species, and reactive oxygen production and the capacity to deliver therapeutic agents has attracted attention for further studies in inflammatory and autoimmune disorders. Furthermore, the characteristics of GNPs and surface modification can modulate their toxicity, biodistribution, biocompatibility, and effects. This review discusses in vitro and in vivo effects of GNPs and their functionalized forms in managing various autoimmune disorders (Ads) such as rheumatoid arthritis, type 1 diabetes, and multiple sclerosis

PLGA-Based Curcumin Delivery System: An Interesting Therapeutic Approach in the Treatment of Alzheimer’s Disease

Progressive degeneration and dysfunction of the nervous system because of oxidative stress, aggregations of misfolded proteins, and neuroinflammation are the key pathological features of neurodegenerative diseases. Alzheimer's disease is a chronic neurodegenerative disorder driven by uncontrolled extracellular deposition of β-amyloid (Aβ) in the amyloid plaques and intracellular accumulation of hyperphosphorylated tau protein. Curcumin is a hydrophobic polyphenol with noticeable neuroprotective and anti-inflammatory effects that can cross the blood-brain barrier. Therefore, it is widely studied for the alleviation of inflammatory and neurological disorders. However, the clinical application of curcumin is limited due to its low aqueous solubility and bioavailability. Recently, nano-based curcumin delivery systems are developed to overcome these limitations effectively. This review article discusses the effects and potential mechanisms of curcumin-loaded PLGA nanoparticles in Alzheimer’s disease

Dynamic variation of kidney injury molecule-1 mRNA and protein expression in blood and urine of renal transplant recipients: a cohort study

BACKGROUND: Acute renal dysfunction still constitutes a highly significant obstacle to renal transplantation outcome. Kidney injury molecule-1 is highly upregulated in proximal tubular cells and shed into the urine and blood circulation following kidney injury. The aim of current cohort study was to evaluate the urine KIM-1 (uKIM-1) mRNA expression level and its protein concentration in blood and urine samples to determine whether sequential monitoring of KIM-1 in renal allograft recipients is a reliable biomarker for predicting the clinical status and outcome. METHODS: Both uKIM-1 mRNA expression level and the level of serum and uKIM-1 protein concentration in the 52 renal transplant recipients were respectively quantified using real-time PCR and ELISA methods at 2, 90 and 180 days after transplantation. RESULT: KIM-1 mRNA and protein expression level in the blood and urine samples of patients with graft dysfunction was significantly higher than patients with well-functioning graft on days 2, 90 and 180 after transplantation. Receiver-operating characteristic curve analysis of mRNA and protein expression levels showed that urinary and blood KIM-1 at months 3 and 6 could predict acute renal dysfunction at 6 months and 1 year after transplantation. CONCLUSION: Sequential monitoring of uKIM-1 mRNA expression level and its protein concentration in the serum and urine samples of renal transplant patients suggests that KIM-1 could be a sensitive and specific biomarker for early diagnosis and prognosis of kidney allograft injury

E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy

The distinction of self from non-self is crucial to prevent autoreactivity and ensure protection from infectious agents and tumors. Maintaining the balance between immunity and tolerance of immune cells is strongly controlled by several sophisticated regulatory mechanisms of the immune system. Among these, the E3 ligase ubiquitin Casitas B cell lymphoma-b (Cbl-b) is a newly identified component in the ubiquitin-dependent protein degradation system, which is thought to be an important negative regulator of immune cells. An update on the current knowledge and new concepts of the relevant immune homeostasis program co-ordinated by Cbl-b in different cell populations could pave the way for future immunomodulatory therapies of various diseases, such as autoimmune and allergic diseases, infections, cancers and other immunopathological conditions. In the present review, the latest findings are comprehensively summarized on the molecular structural basis of Cbl-b and the suppressive signaling mechanisms of Cbl-b in physiological and pathological immune responses, as well as its emerging potential therapeutic implications for immunotherapy in animal models and human diseases. © 2020 British Society for Immunolog