The Role of Cobalamin in Multiple Sclerosis: An Update.

Multiple sclerosis (MS) is a neurodegenerative condition that results in axonal and permanent damage to the central nervous system, necessitating healing owing to autoimmune reactions and persistent neuroinflammation. Antioxidant and anti-inflammatory drugs are essential for the management of oxidative stress and neuroinflammation. Additionally, multivitamin supplementation, particularly vitamin B12 (cobalamin), may be beneficial for neuronal protection. Although there is no documented connection between vitamin B12 deficiency and MS, researchers have explored its potential as a metabolic cause. This review highlights the therapeutic benefits of cobalamin (Cbl) in patients with MS.

Associations of dual-task walking costs with cognition in Parkinson's disease.

BACKGROUND: Gait and cognition are closely associated in Parkinson's disease (PD), with specific cognitive domains being associated with different motor symptoms. By identifying gait parameters affected by cognition, clinicians can develop targeted interventions that address cognitive impairment, improve gait, and reduce the risk of injury in PD patients. RESEARCH QUESTION: What gait parameters are affected by cognition in PD patients during dual-task walking, and how are these parameters related to cognitive function as measured by the Montreal Cognitive Assessment (MoCA)? METHODS: 36 patients with available gait data and cognitive assessments were enrolled. Gait data of usual and dual-task walking sessions were recorded using lightweight wireless wearable sensors attached to trunk, lower, and upper extremities. Dual-task costs were calculated from usual and dual-task measures. Statistical analysis included non-parametric tests, Wilcoxon signed-rank test, Spearman's correlation, and stepwise linear regression models. RESULTS: Walking speed, cadence, asymmetry in arm swing (ASA), between arms' amplitude symmetry (BAS), average stride time, and jerk of the acceleration movement of the legs were found to be affected during the dual-task walking session (P<0.05). Spearman's correlation showed significant correlations between MoCA scores and ASA (ρ=-0.469, P=0.036) and BAS (ρ=-0.448, P=0.036) costs. Stepwise linear regression models found that MoCA scores were significant predictors of BAS and ASA costs (P<0.05). SIGNIFICANCE: This study found a significant association between global cognitive ability and several gait parameters costs under cognitive load caused by dual-task walking in PD patients. The study identified the gait parameters that were affected by cognitive load and found that MoCA scores were significant predictors of those gait parameters. Identifying gait parameters affected by cognition can lead to more targeted interventions for improving gait and reducing injury risk in PD patients.

Microbiome as a biomarker and therapeutic target in pancreatic cancer.

Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.

Efficacy of Rituximab on Refractory Organ Involvements in Granulomatosis with Polyangiitis: A Systematic Review of Case Reports.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a type of Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterized by necrotizing vasculitis affecting small and medium-sized blood vessels. GPA affects various organs, with respiratory tract, vasculitis and glomerulonephritis being the most common triad. Remission induction and maintenance therapy for GPA traditionally involves corticosteroids and cyclophosphamide. However, treatment with rituximab, a monoclonal antibody that depletes B-cells involved in autoimmune disease, has been successful in inducing remission in several studies. The purpose of this systematic review was to investigate the efficacy of rituximab in treating various clinical manifestations of GPA. METHODS: In adherence to PRISMA guidelines for systematic reviews and meta-analyses, we carried out a comprehensive review to investigate the effectiveness of rituximab on particular organ involvement in GPA. We searched three databases (PubMed, Scopus, and Embase) up until November 6, 2022, for case reports on the topic. To ensure all relevant studies were included, we manually screened the first 50 pages of Google Scholar's search results. RESULTS: The review identified a total of 64 case reports and a case series of 113 cases, highlighting the effectiveness of rituximab in treating refractory organ involvement in GPA. The review also analyzed the effectiveness of rituximab in treating ocular, CNS, cardiac, pulmonary, cutaneous, gastrointestinal, renal, and other organ involvements in GPA. CONCLUSIONS: Our results indicated that rituximab can be a promising therapy for treating specific clinical manifestations of several organ involvements. However, more research is needed to determine the long-term efficacy of rituximab in treating GPA.

Bioactive Peptides: Potential Impact on the Treatment of Gastrointestinal Cancers.

We have reviewed the potential use of bioactive peptides in the treatment of gastrointestinal (GI) malignancies, which are a significant cause of morbidity and mortality globally. Conventional therapies, such as surgery, chemotherapy, and radiotherapy, are associated with numerous side effects that may lead to longterm complications. Bioactive peptides are short-chain amino acids that can be extracted from natural sources or synthesized, and they have various potential health benefits, including anti-inflammatory, anti-hypertensive, antioxidant, antimicrobial, and anti-cancer properties. Bioactive peptides can be acquired from animal or plant sources, and can be classified based on their function, such as ACE-inhibiting, antimicrobial, and electrolyte- regulating peptides. Recent studies have demonstrated the promising role of bioactive peptides in tumor suppression, especially when combined with conventional therapies. In this study, we have reviewed the beneficial properties of bioactive peptides and their role in suppressing tumor activity. The mechanisms of bioactive peptides in tumor suppression are discussed. We have further reviewed the findings of preclinical and clinical studies that have investigated the application of bioactive peptides in the treatment of GI cancers. This review highlights the potential use of bioactive peptides as a promising treatment method for GI malignancies to increase the quality of life of GI cancer patients.

The circadian clock as a potential biomarker and therapeutic target in pancreatic cancer.

Pancreatic cancer (PC) has a very high mortality rate globally. Despite ongoing efforts, its prognosis has not improved significantly over the last two decades. Thus, further approaches for optimizing treatment are required. Various biological processes oscillate in a circadian rhythm and are regulated by an endogenous clock. The machinery controlling the circadian cycle is tightly coupled with the cell cycle and can interact with tumor suppressor genes/oncogenes; and can therefore potentially influence cancer progression. Understanding the detailed interactions may lead to the discovery of prognostic and diagnostic biomarkers and new potential targets for treatment. Here, we explain how the circadian system relates to the cell cycle, cancer, and tumor suppressor genes/oncogenes. Furthermore, we propose that circadian clock genes may be potential biomarkers for some cancers and review the current advances in the treatment of PC by targeting the circadian clock. Despite efforts to diagnose pancreatic cancer early, it still remains a cancer with poor prognosis and high mortality rates. While studies have shown the role of molecular clock disruption in tumor initiation, development, and therapy resistance, the role of circadian genes in pancreatic cancer pathogenesis is not yet fully understood and further studies are required to better understand the potential of circadian genes as biomarkers and therapeutic targets.

Association of Total Bilirubin with Motor Signs in Early Parkinson's Disease in LRRK2 Variant Carriers.

Oxidative stress is considered a possible mechanism in Parkinson's disease (PD) progression. Bilirubin has been recognized as a powerful antioxidant that increases due to heme-oxygenase activity. We aimed to investigate the association of total bilirubin (TB) with motor signs and asymmetry in different stages of early PD. A case-control study was performed to investigate the differences in TB levels in PD patients and healthy controls (HC) both carrying LRRK2 variants. We compared TB levels in HC and Hoehn and Yahr (HY) I and II cohorts separately, followed by multiple linear regression analysis to evaluate the association between TB and motor dysfunction in each stage. We used Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (UPDRS) part III scores and asymmetry scores to address motor disability. Asymmetry scores were calculated from the corresponding UPDRS III tasks. TB was significantly increased in HY II compared to HC (P < 0.001). Positive correlations with TB were found for UPDRS III total score (ρ = 0.303, P = 0.034) and asymmetry score (ρ = 0.418, P = 0.003) in HY I. Multiple linear regression found a significant relationship between TB and asymmetry scores in HY I (R2 = 0.261, P = 0.037), but no relationship was achieved with UPDRS III total scores. Increased TB serves as an important diagnostic marker in earlier stages of PD. A significant relationship was found between TB and motor asymmetry in HY I patients. According to our findings, bilirubin mainly exhibits its protective effects in HY I population.