Relationship Between Helicobacter pylori (H. pylori) Infection and Multiple Sclerosis (MS) in Southeast of Iran

Abstract: Helicobacter pylori (H. pylori) are one of the most common, well-known pathogenic agents in the development of peptic ulcers. Some investigators have shown a relationship between H. pylori and Multiple Sclerosis (MS). However, this relationship is controversial. The aim of this study was to determine the association between H. pylori infection and MS. In a prospective case-control study, we studied 78 patients with MS and 123 Healthy Blood Donors (HBDs) for bacterial DNA detection and antibody assay. DNA extracted from samples (serum and saliva) and Real-time PCR was employed to detection of H. pylori genome. The present of anti H. pylori CagA and VacA Immunoglobulin G (IgG) were measured in serum by Western blot technique. We found H. pylori DNA in both samples of the 32.05% (25/78) and 32.52% (40/123) of patients and HBDs respectively (p = NS). Furthermore, anti H. pylori IgG for both antigens were detected in 21.95% (27/123) of HBDs in contrast with 25.64% (20/78) of patients (p = NS). Moreover, genome copy number of H. pylori was not significantly change in patients (140 copies/mL) and HBDs (147copies/mL). We didn't see significant correlation between H. pylori infection in both groups, But H. pylori CagA/VacA-IgG was found in patient quite more than HBDs (p<0.05) and this patients showed more positively for serum H. pylori genome. Although, these results indicate a lack of connection between the Helicobacter pylori infection and multiple sclerosis, the role of immune response against H. pylori in the modulation of MS requires further study

Protective effects of hydrogen sulfide on chronic kidney disease by reducing oxidative stress, inflammation and apoptosis

The current study aimed to examine the renoprotective effects of long-term treatment with sodium hydrosulfide (NaHS), a prominent hydrogen sulfide donor, in 5/6 nephrectomy animal model. Twenty-four rats were randomly divided into 3 groups including sham-operated group (Sham), 5/6-nephrectomized group (5/6 Nx), and NaHStreated group (5/6Nx+NaHS). NaHS (30 micromol/l) was added twice daily into the drinking water and renal failure was induced by 5/6 nephrectomy. Twelve weeks after surgical procedure, blood pressure, creatinine clearance (CCr), urine concentration of neutrophil gelatinase associated lipocalin (NGAL) and tissue concentration of malondialdehyde (MDA), superoxide dismutase (SOD), as well as renal morphological changes, apoptosis (cleaved caspase-3) and inflammation (p-NF-κB) were measured. Five-sixth nephrectomy induced severe renal damage as indicated by renal dysfunction, hypertension and significant histopathological injury which were associated with increased NGAL and MDA levels, oxidant/antioxidant imbalance, decreased SOD activity and CCr and also overexpression of p-NF-κB and cleaved caspase-3 proteins. Instead, NaHS treatment attenuated renal dysfunction through reduction of NGAL concentration, hypertension, CCr, oxidant/antioxidant imbalance, inflammation and apoptosis. These findings suggest that long term NaHS treatment can be useful in preventing the progression of CKD by improving oxidant/antioxidant balance and reducing inflammation and apoptosis in the kidney

Metformin accelerates myelin recovery and ameliorates behavioral deficits in the animal model of multiple sclerosis via adjustment of AMPK/Nrf2/mTOR signaling and maintenance of endogenous oligodendrogenesis during brain self-repairing period

BACKGROUND: Multiple sclerosis (MS) is a devastating autoimmune disorder characterized by oligodendrocytes (OLGs) loss and demyelination. In this study, we have examined the effects of metformin (MET) on the oligodendrogenesis, redox signaling, apoptosis, and glial responses during a self-repairing period (1-week) in the animal model of MS. METHODS: For induction of demyelination, C57BL/6 J mice were fed a 0.2% cuprizone (CPZ) for 5 weeks. Thereafter, CPZ was removed for 1-week and molecular and behavioral changes were monitored in the presence or absence of MET (50 mg/kg body weight/day). RESULTS: MET remarkably increased the localization of precursor OLGs (NG2+/O4+ cells) and subsequently the renewal of mature OLGs (MOG+ cells) in the corpus callosum via AMPK/mammalian target of rapamycin (mTOR) pathway. Moreover, we observed a significant elevation in the antioxidant responses, especially in mature OLGs (MOG+/nuclear factor erythroid 2-related factor 2 (Nrf2+) cells) after MET intervention. MET also reduced brain apoptosis markers and lessened motor dysfunction in the open-field test. While MET was unable to decrease active astrogliosis (GFAP mRNA), it reduced microgliosis by down-regulation of Mac-3 mRNA a marker of pro-inflammatory microglia/macrophages. Molecular modeling studies, likewise, confirmed that MET exerts its effects via direct interaction with AMPK. CONCLUSIONS: Altogether, our study reveals that MET effectively induces lesion reduction and elevated molecular processes that support myelin recovery via direct activation of AMPK and indirect regulation of AMPK/Nrf2/mTOR pathway in OLGs. These findings facilitate the development of new therapeutic strategies based on AMPK activation for MS in the near future. KEYWORDS: AMPK; Cuprizone; Multiple sclerosis; Nrf2; mTO

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Study of the Effects of Ellagic Acid on Population and Activity of Central Nervous System Neuroglia Cells in the Cuprizone-induced Multiple Sclerosis

Background and Aim: Ellagic acid (EA) is a natural antioxidant with phenolic structure. In this study, we evaluate the effects of EA consumption on population and activation of neuroglia cells in the animal model of MS under oxidative stress. Materials and Methods: Mature male mice with age of between 8 to 9 weeks were kept in the standard conditions. For model induction, animals received powder normal diet containing 0.2% Cuprizone (Cup) for six weeks. Mice were divided into eight groups containing control, control receiving three doses of EA (20, 40 and 80 mg/kg), Cup and Cup receiving three doses of EA. Finally, specific glial cell markers in the animal brain tissues were analyzed by molecular methods such as immunohistochemistry (IHC), western blotting (WB) and Real Time-PCR (RT-PCR). Findings: IHC and WB analysis have shown that only high concentration of EA is able to reduce protein expression of GFAP (activated astrocytes marker), Mac-3 (activated microglial marker), increase protein expression of Olig-2 (oligodendrocytes precursor marker) and ultimately significant reduction on APC (mature oligodendrocytes marker)/Olig-2 ratio in comparison with Cup group. In addition, RT-PCR evaluation indicated that changes in the mRNA expression of target markers were consistent with observed changes in their protein expression and therefore, IHC and WB results were confirmed. Conclusion: Consumption of 80 mg/kg of EA effectively decreased activation of astrocytes and microglial and so appropriates environment for migration of oligodendrocyte precursor cells to the lesion area and shifting from damage course into the repair progressions

Presenilin-1-Derived Circular RNAs: Neglected Epigenetic Regulators with Various Functions in Alzheimer’s Disease

The presenilin-1 (PSEN1) gene is crucial in developing Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the most common cause of dementia. Circular RNAs (circRNAs) are non-coding RNA generated through back-splicing, resulting in a covalently closed circular molecule. This study aimed to investigate PSEN1-gene-derived circular RNAs (circPSEN1s) and their potential functions in AD. Our in silico analysis indicated that circPSEN1s (hsa_circ_0008521 and chr14:73614502-73614802) act as sponge molecules for eight specific microRNAs. Surprisingly, two of these miRNAs (has-mir-4668-5p and has-mir-5584-5p) exclusively interact with circPSEN1s rather than mRNA-PSEN1. Furthermore, the analysis of pathways revealed that these two miRNAs predominantly target mRNAs associated with the PI3K-Akt signaling pathway. With sponging these microRNAs, circPSEN1s were found to protect mRNAs commonly targeted by these miRNAs, including QSER1, BACE2, RNF157, PTMA, and GJD3. Furthermore, the miRNAs sequestered by circPSEN1s have a notable preference for targeting the TGF-β and Hippo signaling pathways. We also demonstrated that circPSEN1s potentially interact with FOXA1, ESR1, HNF1B, BRD4, GATA4, EP300, CBX3, PRDM9, and PPARG proteins. These proteins have a prominent preference for targeting the TGF-β and Notch signaling pathways, where EP300 and FOXA1 have the highest number of protein interactions. Molecular docking analysis also confirms the interaction of these hub proteins and Aβ42 with circPSEN1s. Interestingly, circPSEN1s-targeted molecules (miRNAs and proteins) impacted TGF-β, which served as a shared signaling pathway. Finally, the analysis of microarray data unveiled distinct expression patterns of genes influenced by circPSEN1s (WTIP, TGIF, SMAD4, PPP1CB, and BMPR1A) in the brains of AD patients. In summary, our findings suggested that the interaction of circPSEN1s with microRNAs and proteins could affect the fate of specific mRNAs, interrupt the function of unique proteins, and influence cell signaling pathways, generally TGF-β. Further research is necessary to validate these findings and gain a deeper understanding of the precise mechanisms and significance of circPSEN1s in the context of AD

Evaluation of reactive Epstein–Barr Virus (EBV) in Iranian patient with different subtypes of multiple sclerosis (MS)

AbstractObjectivesEpstein-Barr virus has been recently associated with the onset of multiple sclerosis, yet understanding how it elicits autoimmunity remains elusive. We investigated the relation between Epstein-Barr virus reactivation and disease development in different subtypes of multiple sclerosis.MethodsIn the present research, we have determined the Epstein-Barr virus-DNA load by quantitative real-time polymerase chain reaction and Epstein-Barr virus antibody levels by EIA technique in both multiple sclerosis patients (n=78) and healthy controls (n=123).ResultsOur results demonstrated increased titer of both anti-Epstein-Barr virus-IgG and IgM antibodies in patients (91.02% vs 82.11% in controls, p<0.001 and 14.1% vs 4.06% in controls, p<0.001, respectively). Overall, Epstein-Barr virus reactivation was found in 68.75% of subtypes of multiple sclerosis, 4.54% of multiple sclerosis primary subtype, and in only 3.25% of healthy control subjects. Moreover, in samples of patients with disease relapse (exacerbation) cell free viral DNA was elevated in contrast to other patients (p<0.001).ConclusionsThese findings provide further support for the detrimental effects of Epstein-Barr virus in the reactivation of multiple sclerosis attacks

Human Herpesvirus-6 and Epstein-Barr Virus Infections at Different Histopathological Grades of Oral Squamous Cell Carcinomas

Background: The aim of this study was to determine the prevalence and viral load of Epstein-Barr virus (EBV) and Human herpesvirus-6 (HHV-6) in different histopathologic grades of oral squamous cell carcinoma (OSCC). Methods: Forty-five formalin-fixed paraffin-embedded tissue section of OSCC patients were analyzed by quantitative real-time polymerase chain reaction for detection of EBV and HHV-6. Results: The mean age of the patients was 58.6 years, 69% of whom were female, and 31% were male. Overall, the positive rate for EBV and HHV-6 were 16.7% and 27.1%, respectively; and the mean viral load EBV was 27.9 × 10 3 and 38.5 × 10 3 for HHV-6. No correlation was demonstrated between the viral load of EBV DNA (P = 0.35) and HHV-6 (P = 0.38) at the different OSCC histopathologic grades. Conclusions: These findings neither lend support to the hypothesis that EBV and HHV-6 are directly involved in OSCC nor rule out the possibility that these viruses play an indirect role in carcinogenesis in this area

Evaluation of reactive Epstein-Barr virus (EBV) in Iranian patient with different subtypes of multiple sclerosis (MS)

OBJECTIVES: Epstein-Barr virus has been recently associated with the onset of multiple sclerosis, yet understanding how it elicits autoimmunity remains elusive. We investigated the relation between Epstein-Barr virus reactivation and disease development in different subtypes of multiple sclerosis. METHODS: In the present research, we have determined the Epstein-Barr virus-DNA load by quantitative real-time polymerase chain reaction and Epstein-Barr virus antibody levels by EIA technique in both multiple sclerosis patients (n = 78) and healthy controls (n = 123). RESULTS: Our results demonstrated increased titer of both anti-Epstein-Barr virus-IgG and IgM antibodies in patients (91.02% vs 82.11% in controls, p < 0.001 and 14.1% vs 4.06% in controls, p < 0.001, respectively). Overall, Epstein-Barr virus reactivation was found in 68.75% of subtypes of multiple sclerosis, 4.54% of multiple sclerosis primary subtype, and in only 3.25% of healthy control subjects. Moreover, in samples of patients with disease relapse (exacerbation) cell free viral DNA was elevated in contrast to other patients (p < 0.001). CONCLUSIONS: These findings provide further support for the detrimental effects of Epstein- Barr virus in the reactivation of multiple sclerosis attacks