The Oxidative Stress and Nervous Distress Connection in Gastrointestinal Disorders.

Oxidative stress is increasingly recognized as a central player in a range of gastrointestinal (GI) disorders, as well as complications stemming from therapeutic interventions. This article presents an overview of the mechanisms of oxidative stress in GI conditions and highlights a link between oxidative insult and disruption to the enteric nervous system (ENS), which controls GI functions. The dysfunction of the ENS is characteristic of a spectrum of disorders, including neurointestinal diseases and conditions such as inflammatory bowel disease (IBD), diabetic gastroparesis, and chemotherapy-induced GI side effects. Neurons in the ENS, while essential for normal gut function, appear particularly vulnerable to oxidative damage. Mechanistically, oxidative stress in enteric neurons can result from intrinsic nitrosative injury, mitochondrial dysfunction, or inflammation-related pathways. Although antioxidant-based therapies have shown limited efficacy, recognizing the multifaceted role of oxidative stress in GI diseases offers a promising avenue for future interventions. This comprehensive review summarizes the literature to date implicating oxidative stress as a critical player in the pathophysiology of GI disorders, with a focus on its role in ENS injury and dysfunction, and highlights opportunities for the development of targeted therapeutics for these diseases.

Oxidative Stress and Neural Dysfunction in Gastrointestinal Diseases: Can Stem Cells Offer a Solution?

Oxidative stress is involved in many gastrointestinal (GI) disorders as either the primary pathogenesis (radiation, chemotherapy, toxicity, ischemia-reperfusion) or a secondary driving force of disease progression (inflammation and diabetes). The GI tract is innervated intrinsically by the enteric nervous system (ENS) with a diverse role in maintaining gut homeostasis and GI motility. Complications in the physiological functioning of the ENS results in GI dysfunction that can result in debilitating sequelae from dysmotility greatly impacting quality of life and leading to potentially fatal complications. Therapeutics to remedy either oxidative stress or enteric neuronal dysfunction are severely limited, resulting in a critical gap in clinical care for GI disease and neurointestinal complications. Stem cell therapies have shown great promise in the treatment of several gut disorders via mechanisms including cell regeneration, anti-inflammatory activity, providing trophic support, and emerging evidence of antioxidant and neuroprotective functions. The potential of mesenchymal stem cell (MSC) therapies and recent evidence of their antioxidant and neuroprotective activity in several GI conditions are discussed. Finally, future therapeutic aspects of stem cell-based tools for combatting oxidative stress and enteric neuropathies in GI disease are considered.

Improving behavioral test data collection and analysis in animal models with an image processing program.

Behavioral studies are commonly used as a standard procedure to evaluate anxiety and depression in animal models. Recently, different methods have been developed to improve data collection and analysis of the behavioral tests. Currently available methods, including manual analysis and commercially available products, are either time-consuming or costly. The objective of this study was to improve the collection and analysis of behavioral test data in animal models by developing an image processing program. Eleven behavioral parameters were evaluated by three different methods, including (i) manual detection, (ii) commercially available TopScan software (CleverSys Inc, USA), and (iii) In-housed-developed Advanced Move Tracker (AMT) software. Results obtained from different methods were compared to validate the accuracy and efficiency of AMT. Results showed that AMT software provides highly accurate and reliable data analysis compared to other methods. Less than 5% tolerance was reported between results obtained from AMT compared to TopScan. In addition, the analysis processing time was remarkably reduced (68.3%) by using AMT compared to manual detection. Overall, the findings confirmed that AMT is an efficient program for automated data analysis, significantly enhancing research outcomes through accurate analysis of behavioral test data in animal models.

Tryptophan and Substance Abuse: Mechanisms and Impact.

Addiction, the continuous misuse of addictive material, causes long-term dysfunction in the neurological system. It substantially affects the control strength of reward, memory, and motivation. Addictive substances (alcohol, marijuana, caffeine, heroin, methamphetamine (METH), and nicotine) are highly active central nervous stimulants. Addiction leads to severe health issues, including cardiovascular diseases, serious infections, and pulmonary/dental diseases. Drug dependence may result in unfavorable cognitive impairments that can continue during abstinence and negatively influence recovery performance. Although addiction is a critical global health challenge with numerous consequences and complications, currently, there are no efficient options for treating drug addiction, particularly METH. Currently, novel treatment approaches such as psychological contingency management, cognitive behavioral therapy, and motivational enhancement strategies are of great interest. Herein, we evaluate the devastating impacts of different addictive substances/drugs on users' mental health and the role of tryptophan in alleviating unfavorable side effects. The tryptophan metabolites in the mammalian brain and their potential to treat compulsive abuse of addictive substances are investigated by assessing the functional effects of addictive substances on tryptophan. Future perspectives on developing promising modalities to treat addiction and the role of tryptophan and its metabolites to alleviate drug dependency are discussed.

MicroRNAs induced by Listeria monocytogenes and their role in cells.

Listeria monocytogenes (Lm) causes abortions at high rates and threatens newborns' lives. Also, the elderly and immunocompromised individuals are particularly vulnerable neurologically. The bacterium exerts its pathogenesis intracellularly by manipulating cell organs. It manipulates nucleus elements, microRNAs (miRNAs), in order to increase survival and evade immunity. miRNAs are small non-coding RNAs that degrade gene expression post-transcriptionally. Any alteration to the expression of miRNAs affects various cascades in cells, especially immunity-related responses. Thus, utilizing miRNAs as a novel therapeutic agent not only restricts infection but enhances immunity reactions. This review provides an overview of miRNAs in listeriosis, their role in cells, and their prospects as therapy.

Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut-Immune-Brain Axis.

Methamphetamine (METH) is a highly addictive drug abused by millions of users worldwide, thus becoming a global health concern with limited management options. The inefficiency of existing treatment methods has driven research into understanding the mechanisms underlying METH-induced disorders and finding effective treatments. This study aims to understand the complex interactions of the gastrointestinal-immune-nervous systems following an acute METH dose administration as one of the potential underlying molecular mechanisms concentrating on the impact of METH abuse on gut permeability. Findings showed a decreased expression of tight junction proteins ZO-1 and EpCAm in intestinal tissue and the presence of FABP-1 in sera of METH treated mice suggests intestinal wall disruption. The increased presence of CD45+ immune cells in the intestinal wall further confirms gut wall inflammation/disruption. In the brain, the expression of inflammatory markers Ccl2, Cxcl1, IL-1ß, TMEM119, and the presence of albumin were higher in METH mice compared to shams, suggesting METH-induced blood-brain barrier disruption. In the spleen, cellular and gene changes are also noted. In addition, mice treated with an acute dose of METH showed anxious behavior in dark and light, open field, and elevated maze tests compared to sham controls. The findings on METH-induced inflammation and anxiety may provide opportunities to develop effective treatments for METH addiction in the future.

The Role of Tryptophan Metabolites in Neuropsychiatric Disorders.

In recent decades, neuropsychiatric disorders such as major depressive disorder, schizophrenia, bipolar, etc., have become a global health concern, causing various detrimental influences on patients. Tryptophan is an important amino acid that plays an indisputable role in several physiological processes, including neuronal function and immunity. Tryptophan's metabolism process in the human body occurs using different pathways, including the kynurenine and serotonin pathways. Furthermore, other biologically active components, such as serotonin, melatonin, and niacin, are by-products of Tryptophan pathways. Current evidence suggests that a functional imbalance in the synthesis of Tryptophan metabolites causes the appearance of pathophysiologic mechanisms that leads to various neuropsychiatric diseases. This review summarizes the pharmacological influences of tryptophan and its metabolites on the development of neuropsychiatric disorders. In addition, tryptophan and its metabolites quantification following the neurotransmitters precursor are highlighted. Eventually, the efficiency of various biomarkers such as inflammatory, protein, electrophysiological, genetic, and proteomic biomarkers in the diagnosis/treatment of neuropsychiatric disorders was discussed to understand the biomarker application in the detection/treatment of various diseases.

Comprehensive study of antimicrobial susceptibility pattern and extended spectrum beta-lactamase (ESBL) prevalence in bacteria isolated from urine samples.

Nowadays, increasing extended-spectrum ß-lactamase (ESBL)-producing bacteria have become a global concern because of inducing resistance toward most of the antimicrobial classes and making the treatment difficult. In order to achieve an appropriate treatment option, identification of the prevalent species which generate ESBL as well as their antibiotic susceptibility pattern is essential worldwide. Hence, this study aimed to investigate the prevalence of ESBL-producing bacteria and assess their drug susceptibility in Fardis Town, Iran. A total of 21,604 urine samples collected from patients suspected to have urinary tract infection (UTI) were processed in the current study. The antimicrobial susceptibility of the isolates was tested by the disk diffusion method. The ESBL producing bacteria were determined by Double Disc Synergy Test (DDST) procedure. Bacterial growth was detected in 1408 (6.52%) cases. The most common bacterial strains causing UTI were found E. coli (72.16%), followed by K. pneumoniae (10.3%) and S. agalactiae (5.7%). Overall, 398 (28.26%) were ESBL producer. The highest ESBL production was observed in E. coli, followed by Klebsiella species. ESBL producers revealed a higher level of antibiotic resistance compared with non-ESBLs. In conclusion, ESBL production in uropathogens was relatively high. Carbapenems and Aminoglycosides were confirmed as the most effective treatment options for these bacteria.

Relationship Among Antibiotic Resistance, Biofilm Formation and lasB Gene in Pseudomonas Aeruginosa Isolated from Burn Patients.

BACKGROUND: Pseudomonas aeruginosa is a major cause of hospital-acquired infection due to its high antibiotic resistance and biofilm formation ability. P. aeruginosa produces elastase lasB during biofilm formation, which can influence properties of biofilm. This study was carried out to evaluate the antibiotic resistance and distribution of the lasB gene among biofilm-producing P. aeruginosa strains isolated from burn patients. METHODS: A total of 128 clinical samples were collected from burn patients. The P. aeruginosa isolates were identified using standard bacteriological procedures. Antibiotic susceptibility test was performed by the disk diffusion method. Biofilm formation was measured by microtiter plate assay. The presence of lasB gene was detected by PCR. RESULTS: A total of 75 samples were positive for P. aeruginosa. A high rate of resistance was seen against ceftriaxone, cefotaxime, and piperacillin/tazobactam. Biofilm formation was seen in 57.3% of the isolates and the prevalence of the lasB gene was 85.3%. Biofilm formation in isolates without lasB was lower and these isolates were more sensitive to imipenem and piperacillin/tazobactam. CONCLUSIONS: In the present study, we did not find a statistically significant relationship among elastase gene (lasB) presence, antibiotic resistance, and biofilm formation in P. aeruginosa strains isolated from burn patients.

The study of H. pylori putative candidate factors for single- and multi-component vaccine development.

Helicobacter pylori has grown to colonize inside the stomach of nearly half of the world's population, turning into the most prevalent infections in the universe. Medical care failures noticeably confirm the need for a vaccine to hinder or deal with H. pylori. This review is planned to discuss the most known factors as a vaccine candidate, including single (AhpC, BG, CagA, KatA, Fla, Hsp, HWC, Lpp, LPS, NAP, OMP, OMV, SOD, Tpx, Urease, VacA) and multi-component vaccines. Many promising results in the field of single and multivalent vaccine can be seen, but there is no satisfactory outcome and neither a prophylactic nor a therapeutic vaccine to treat or eradicate the infection in human has been acquired. Hence, selecting suitable antigen is an important factor as an appropriate adjuvant. Taken all together, the development of efficient anti-H. pylori vaccines relies on the fully understanding of the interactions between H. pylori and its host immune system. Therefore, more work should be done on epitope mapping, analysis of molecular structure, and determination of the antigen determinant region as well due to design a vaccine, preferably a multi-component vaccine to elicit specific CD4 T-cell responses that are required for H. pylori vaccine efficacy.

Production of IFN-γ and IL-4 Against Intact Catalase and Constructed Catalase Epitopes of Helicobacter pylori From T-Cells.

BACKGROUND: Helicobacter pylori infection is highly prevalent in the developing countries. It causes gastritis, peptic ulcer disease, and gastrocarcinoma. Treatment with drugs and antibiotics is problematic due to the following reasons: cost, resistance to antibiotics, prolonged treatment and using multiple drugs. Catalase is highly conserved among the Helicobacter species and is important to the survival of the organism. It is expressed in high amounts and is exposed to the surface of this bacterium; therefore it represents a suitable candidate vaccine antigen. OBJECTIVES: A suitable approach in H. pylori vaccinology is the administration of epitope based vaccines. Therefore the responses of T-cells (IFN-γ and IL-4 production) against the catalase of H. pylori were determined. Then the quality of the immune responses against intact catalase and three epitopes of catalase were compared. MATERIALS AND METHODS: In this study, a composition of three epitopes of the H. pylori catalase was selected based on Propred software. The effect of catalase epitopes on T-cells were assayed and immune responses identified. RESULTS: The results of IFN-γ, IL-4 production against antigens, epitopes, and recombinant catalase by T-cells were compared for better understanding of epitope efficiency. CONCLUSIONS: The current research demonstrated that epitope sequence stimulates cellular immune responses effectively. In addition, increased safety and potency as well as a reduction in time and cost were advantages of this method. Authors are going to use this sequence as a suitable vaccine candidate for further research on animal models and humans in future.