Search Results (47)

Gamma-aminobutyric acid (GABA) is a non-protein amino acid playing a significant role in the central nervous system and the gut–brain axis. This study investigated the potential to produce GABA by lactic acid bacteria (LAB) isolated from different varieties of organic tomatoes. The isolated LAB were taxonomically identified by 16S rRNA gene sequencing, the presence of the gadB gene (glutamate decarboxylase) was detected, and GABA production was quantified using HPLC. Levilactobacillus brevis CRAI showed the highest GABA production under optimised fermentation conditions with 4% monosodium glutamate (MSG). The genome sequencing of L. brevis CRAI revealed the presence of gadA and gadB isoforms and assessed the strain’s safety profile. The gene expression analysis revealed that the gadA and gadB genes were upregulated in the presence of 4% MSG. The probiotic potential of L. brevis CRAI was also assessed by functional assays. The strain showed strong antimicrobial activity against representative enteropathogens, i.e., Escherichia coli ETEC, Salmonella choleraesuis, and Yersinia enterocolitica, and anti-inflammatory effect, reducing nitric oxide production in LPS-stimulated RAW264.7 macrophages. In addition, its ability to adhere to intestinal epithelial Caco-2 cells was demonstrated. These results highlight L. brevis CRAI as a promising candidate for the development of GABA-enriched functional foods or probiotic supplements with the perspective to modulate the gut-brain axis. Full article

Due to the roles of oxidative stress, inflammation, and neurotransmitter imbalances in cognitive and mental dysfunction, we aimed to develop a functional drink with antioxidant and anti-inflammatory properties as well as the potential to support neurotransmitter balance for improved cognition and mental health. The Teng Mo, Fen Hong Mee, and Hong Chon Su guava varieties were screened for their polyphenol and flavonoid contents, antioxidant and anti-inflammatory effects, and suppressive effects on acetylcholinesterase (AChE), monoamine oxidase (MAO), GABA transaminase (GABA-T), and glutamate decarboxylase (GAD). Juice from the cultivar with the highest potential was selected and mixed with mint and honey syrups, pomelo-derived dietary fiber, ascorbic acid, agar, water, and fruit puree (pear/apple/orange) to create three guava jelly drink formulations. The formulation with pear puree showed the highest biological potential and was selected as the final product. It is rich in vitamin C, gallic acid, and dietary fiber, and provides approximately 37 Kcal/100 g. It also promotes the growth of lactic acid-producing bacteria in the culture. Thus, our drink shows the potential to reduce oxidative stress and inflammation, improve neurotransmitter regulation, and stimulate the gut–brain axis, thereby promoting cognition and mental wellness. However, clinical research is essential to confirm these potential benefits. Full article

Background: The early detection of type 1 diabetes (T1D) through screening for major islet autoantibodies is receiving increasing attention as a public health strategy, exemplified by the recent implementation of a pilot pediatric screening program in Italy. The transition from research-based screening to large-scale population initiatives needs automated and standardized assays that are capable of processing extensive sample volumes. Hence, this study aimed to evaluate the analytical performance and comparability of a fully automated chemiluminescence immunoassay (CLIA) compared to a conventional enzyme-linked immunosorbent assay (ELISA) for the detection of three classes of major islet antibodies—anti-GAD (GADA), anti-IA-2 (IA-2A), and anti-ZnT8 (ZnT8A). Methods: A total of 104 serum specimens were analyzed for each autoantibody using both ELISA (RSR and Medyzim, DYNES, DSX) and CLIA (MAGLUMI 800). Assay precision and linearity were assessed through intra-assay variability studies and dilution protocols. Methods agreement was evaluated with Passing–Bablok regression, Spearman’s correlation, Bland–Altman analysis, and Cohen’s kappa statistics. Results: The CLIA showed good precision and excellent linearity across clinically relevant concentration ranges of all islet antibodies. Correlation coefficients and categorical agreement between CLIA and ELISA were high (r > 0.96 and Cohen’s kappa >0.8 for all), with ZnT8A exhibiting the highest concordance. However, proportional biases were found, as CLIA systematically underestimated GADA and ZnT8A levels, while overestimated IA-2A compared to the ELISA. Conclusions: The CLIA displayed satisfactory precision and agreement with ELISA for GADA, IA-2A, and ZnT8A detection. Our findings support the use of these automated immunoassays in large-scale population initiatives for diagnosing T1D, but we also highlight the need for further efforts to achieve better inter-assay harmonization. Full article

SPS is characterized by progressive spasmodic muscular rigidity. SPS is thought to be an autoimmune disease with a prominent feature of antibodies against glutamic acid decarboxylase (GAD). GAD is responsible for the enzymatic conversion of glutamic acid (glutamate) into the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Reduced GABA activity leads to increased excitability in the central nervous system, resulting in muscle rigidity and spasms characteristic of SPS. While SPS is rare, anti-GAD antibodies seen in SPS are also seen in the much more common autoimmune disease, type 1 diabetes (T1D). There is evolving research showing that the anti-GAD antibodies of T1D are produced in response to the presence of mycobacterial heat shock protein 65 (mHSP65), and the mHSP65 is produced in response to an occult infection by a bacterium, Mycobacterium avium subspecies Paratuberculosis (MAP). Humans are broadly exposed to MAP in food, water, and air. There are linear and conformational similarities between the epitopes of GAD and mHSP65. This article proposes that MAP is also an infectious trigger for SPS. Dehydroepiandrosterone (DHEA) is a principal component of the steroid metabolome; it plateaus in young adults and then steadily declines. Bromo-epi-androsterone (BEA) is a potent synthetic analog of DHEA; unlike DHEA, it is non-androgenic, non-anabolic, and an effective modulator of immune dysregulation. BEA is also an anti-infective agent and has been shown to benefit mycobacterial infections, including tuberculosis and leprosy. With the immune stabilizing capacity of BEA as well as its anti-mycobacterial properties, there is reason to believe that a randomized clinical trial with BEA may be beneficial for SPS. Full article

Gastrodin (gas) has been shown to promote neuroprotection and reverse Alzheimer’s disease (AD) pathology. However, its high effective dose limits its potential in treating AD. In this study, a bioassay system using PC12 cells and the nerve growth factor (NGF)-mimic effect was employed to investigate the structure–activity relationship of gas derivatives. Among the synthesized compounds, GAD037 demonstrated the highest NGF-mimic activity, surpassing gas. Additionally, GAD037 exhibited significant neuroprotective effects, reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, thereby improving the survival of PC12 cells under oxidative stress. It also protected cells from Aβ-induced toxicity. Target protein identification and mechanistic studies revealed that insulin receptor (INSR) and alpha-actinin-4 (ACTN4) are potential targets of GAD037, confirmed through specific inhibitors, small interfering RNA (siRNA) analysis, a cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS). Moreover, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and rat sarcoma (Ras)/protooncogene serine–threonine protein kinase (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways were found to be involved in the NGF-mimic activity of GAD037. In conclusion, GAD037 exhibits superior NGF-mimic and neuroprotective activities compared to gas, suggesting its potential as a lead compound for anti-AD applications. Full article

Background/Objectives: Recent studies reported that ¹⁸F-Fluorodeoxyglucose (FDG) positron –emission tomography/computed tomography (PET/CT), even in comparison with other traditional methods, can play a role in diagnosing AE and supporting early treatment. In the present study, we further investigated whether ¹⁸F-FDG PET/CT may be a complementary diagnostic tool to conventional procedures in patients with acute symptoms of suspected AE in the early phase. Methods: Eleven consecutive patients with recent acute symptoms suggestive of AE were retrospectively enrolled and underwent brain PET/CT after receiving an intravenous injection of 3.7 MBq/kg of ¹⁸F-FDG. Results: PET/CT showed abnormal FDG uptake in 9/11 patients classified as AE, while it was negative in the remaining 2/11 cases with vascular lesions. Magnetic resonance imaging (MRI), conducted in only 10/11 cases—one patient was a pacemaker wearer—identified suspected AE areas in 3/10 cases, ischemic lesions in another 3/10, and nonspecific data in the remaining 4/10 cases. Cerebrospinal fluid (CSF) tests revealed autoantibody delayed occurrence only in three patients (anti-GAD65, anti-Ma2, and anti-LGI1). After first-line treatment, 3/9 patients showed clinical improvement. Another 3/9 patients experienced partial improvement but with recurrence and new AE brain areas identified by PET/CT, which also detected favorable responses to second-line treatment in 2/3 cases. The remaining 3/9 patients, who were not responsive to treatment, ultimately died. Conclusions: In this study, PET/CT was effective in early identification of AE and enabling rapid therapy, even with inconclusive MRI and persistently negative or delayed positive CSF tests. PET/CT may aid in evaluating treatment response and detecting relapse. Notably, a negative PET/CT was associated with AE absence. Full article

Background: Common mental disorders are an underdiagnosed comorbidity, which can significantly worsen the prognosis of the main disease and decrease the quality of life. We aimed to investigate the prevalence of depression and anxiety in a cohort of irritable bowel syndrome with diarrhea (IBS-D) and ulcerative colitis (UC) patients and to evaluate the risk factors for their occurrence. Materials and Methods: A total of 112 patients were evaluated. Multivariable analysis was used to determine associations between patient factors and common mental disorders, evaluated with PHQ-9 and GAD-7 questionnaires. Results: We found a significantly higher prevalence of moderate and severe anxiety among patients with IBS-D, when compared with the UC group (p < 0.01). Linear regression analysis revealed an inverse association between anti-TNF-alpha monoclonal antibodies treatment and a higher PHQ-9 score (p = 0.02). Multivariate analysis revealed that, in patients with UC, the presence of children has been associated with a higher GAD-7 score (p = 0.01), both individually and in combination with a higher duration of the disease. (p < 0.01). For IBS-D, a combination of active employment status and religious belief, active employment status and higher educational level, as well as religious belief and the presence of children correlated with higher GAD-7 scores (p = 0.03, p = 0.03 and p = 0.02, respectively). Conclusions: Infliximab used in the treatment for UC improved the parameters of depression. Patients with UC who have university education and a longer duration of the disease are at increased risk of developing depression and anxiety, especially if they have children in care. Regarding IBS-D patients who have an active work status, religious beliefs and caregivers are at increased risk of developing anxiety. Full article

Background: Paraneoplastic neurological syndromes (PNSs) are rare conditions characterized by immune-mediated pathogenesis, frequently associated with the presence of a neoplasm. Although a single antineuronal antibody mediates a specific syndrome, atypical manifestations mediated by the same antibody have been described. Methods: The aim of this study was to report on an atypical case of PNS with dual positivity for anti-GAD65 and anti-CRMP5/CV2 antibodies, simultaneously characterized by cognitive decline associated with progressive ataxia and parkinsonism. We also reviewed the current literature for published cases of PNSs with parkinsonism associated with anti-GAD65 and anti- CRMP5/CV2 antibodies. Results: A 68-year-old man with an insidious onset of bradykinesia, cognitive decline, and gait instability that began the year before our evaluation had been diagnosed with parkinsonian syndrome. Analysis of the cerebrospinal fluid showed lymphocytic pleocytosis, and a panel for PNS tested positive for anti-GAD65 and anti- CRMP5/CV2 antibodies. After investigation, a microcitoma was found in the lung. Conclusions: In light of our findings, we suggest considering PNS as an alternative diagnosis to parkinsonism-plus syndromes, in particular if bradykinetic syndrome is accompanied by other clinical manifestations including cognitive decline or ataxia in rapidly deteriorating patients. Earlier detection of PNS would lead to timelier identification of any occult tumors, therein promising improvement in the patient’s prognosis. Full article

We conducted a fundamental evaluation of the 3 Screen ICA ELISA kit, which can simultaneously measure three major anti-islet autoantibodies important in diagnosing and predicting type 1 diabetes, to assess its usefulness as a measuring reagent. In autoantibody-positive samples, the coefficient of variation for intra-assay variation ranged from 1.37% to 2.50%, inter-assay variation from 2.81% to 3.61%, and lot-to-lot variation from 2.01% to 8.61%, demonstrating good reproducibility. Additionally, interfering substances did not affect the autoantibody titers, and satisfying performance was observed in tests examining the sample freeze-thaw stability. Notably, even when the titer of GAD autoantibodies was below the cut-off value of the GAD autoantibody ELISA, the 3 Screen ICA signal was completely absorbed by recombinant GAD65 protein, indicating that the detection sensitivity for GAD autoantibody in the 3 Screen ICA ELISA is higher than that of the GAD autoantibody ELISA kit. Furthermore, in a study using IASP2020 samples from the Immunology and Diabetes Society, which aims to standardize anti-islet autoantibody assays, this kit achieved excellent results with a sensitivity of 96.0%, specificity of 100%, and accuracy of 98.57%. Measuring multiple anti-islet autoantibodies in combination is crucial for diagnosing and predicting type 1 diabetes. The ELISA kit used in this study is highly versatile and can be used in any measurement facility, making it extremely useful for routine testing. Full article

Introduction: Immunotherapy is one of the greatest advancements in oncological patient care. The broader the treatment application, the more common the adverse events associated with the therapy. Immune checkpoint inhibitors (ICI) are currently used in numerous malignancies. These drugs influence the immune cells’ interactions, which translates to interruption of immune evasion and increased anti-tumor activity. However, the disruption of immunological signaling pathways often leads to adverse events, such as endocrinological insufficiencies, among which thyroid is the most common. Moreover, the co-appearance of several insufficiencies has been previously described. Case report: A 73-year-old female treated with durvalumab due to non-small cell lung carcinoma was admitted to the emergency unit due to symptoms of ketoacidosis. She had a history of well-controlled type 2 diabetes mellitus and autoimmune thyroiditis. Laboratory results showed increased anti-GAD antibodies, while the low C-peptide level indicated type 1 diabetes mellitus. Moreover, over the course of longer observation, the patient presented with abrupt aggravation of her autoimmune thyroiditis. Conclusions: The new onset of endocrinological insufficiencies is a rare adverse event of immunotherapy. Clinicians must pay particular attention to any signs indicating these life-threatening conditions. In case of the appearance of any endocrinological adverse event, the close cooperation of oncologists and endocrinologists is required to enhance patients’ quality of life. Full article

Background and Objectives: Although physical health is always studied for women with diabetes, the mental health aspect is generally overlooked for this chronic disease. The present study aimed to examine the prevalence of psychosomatic symptoms, namely, fibromyalgia syndrome, depression, anxiety, and insomnia, and how these symptoms related to the medications used in a cohort of women diagnosed with type 2 diabetes (DM) in Jordan. Materials and Methods: This cross-sectional study recruited women diagnosed with type 2 diabetes, and validated scales (PSRS, PHQ-9, GAD-7, and ISI-A) for fibromyalgia syndrome, depression, anxiety, and insomnia were used. The associations between the different medications used and the dependent variables were examined using four separate multivariate logistic regression models. Results: Data were analyzed from 213 participants. Of them, 27.2% met the threshold for fibromyalgia syndrome diagnosis, 38% met the threshold for severe depression, 36.2% met the threshold for severe anxiety, and 39.9% met the threshold for severe insomnia. Fibromyalgia syndrome symptoms were significantly associated with glimepiride (OR = 1.92, CI = 1.00–3.68), β-blockers (OR = 2.21, CI = 1.03–4.70), diuretics (OR = 3.13, CI = 1.26–7.78), herbal remedies (OR = 2.12, CI = 0.98–4.55), and prescriptions for centrally acting medication (OR = 2.78, CI = 1.24–6.29). Significant associations were found between depression and diuretics (OR = 2.62, CI = 1.05–6.67), over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 3.49, CI = 1.69–7.23), and herbal remedies (OR = 5.07, CI = 2.40–10.69). In addition, anxiety was significantly related to diuretics (OR = 2.48, CI = 1.02–6.02), and OTC NSAIDs (OR = 2.60, CI = 1.29–5.21). Significant associations were evident between insomnia and β-blockers (OR = 3.23, CI = 1.51–6.95), acetaminophen (OR = 2.09, CI = 1.06–4.08), NSAIDs (OR = 4.61, CI = 2.18–9.76), and herbal remedies (OR = 5.95, CI = 2.71–13.07). Conclusions: Medications are associated with high burden of fibromyalgia syndrome, depression, anxiety, and insomnia. These findings underscore the importance of revising and optimizing the pharmacotherapy of these vulnerable patients, performing close mental health monitoring and the implementation of non-pharmacological interventions by integrating mental health services for women with chronic diseases such as diabetes. Full article

The need to increase food safety and improve human health has led to a worldwide increase in interest in gamma-aminobutyric acid (GABA), produced by lactic acid bacteria (LABs). GABA, produced from glutamic acid in a reaction catalyzed by glutamate decarboxylase (GAD), is a four-carbon, non-protein amino acid that is increasingly used in the food industry to improve the safety/quality of foods. In addition to the possible positive effects of GABA, called a postbiotic, on neuroprotection, improving sleep quality, alleviating depression and relieving pain, the various health benefits of GABA-enriched foods such as antidiabetic, antihypertension, and anti-inflammatory effects are also being investigated. For all these reasons, it is not surprising that efforts to identify LAB strains with a high GABA productivity and to increase GABA production from LABs through genetic engineering to increase GABA yield are accelerating. However, GABA’s contributions to food safety/quality and human health have not yet been fully discussed in the literature. Therefore, this current review highlights the synthesis and food applications of GABA produced from LABs, discusses its health benefits such as, for example, alleviating drug withdrawal syndromes and regulating obesity and overeating. Still, other potential food and drug interactions (among others) remain unanswered questions to be elucidated in the future. Hence, this review paves the way toward further studies. Full article

Obesity impacts mental health greatly. Psychological factors may influence the effectiveness of its treatment. This study aimed to compare symptoms of generalised anxiety disorder and depression among adult women across different weight categories. The study sample comprised 1105 adult women. The computer-assisted web interview (CAWI) utilising the seven-item Generalised Anxiety Disorders Scale (GAD-7) and the nine-item Patient Health Questionnaire (PHQ-9) was used. Both GAD-7 and PHQ-9 scores correlated positively with BMI (r = 0.121, p < 0.001 and r = 0.173, p < 0.001, respectively) and negatively with age (r = −0.106, p < 0.001 and r = −0.103, p < 0.001, respectively). Patients undergoing treatment with semaglutide scored lower for both anxiety symptoms (8.71 ± 6.16, p = 0.013) and depression symptoms (9.76 ± 6.37, p = 0.013). Women who underwent bariatric surgery screened less frequently for anxiety (8.03 ± 6.27, p = 0.002) but not for depression. An interdisciplinary approach involving mental health professionals within the therapeutic team can comprehensively address factors contributing to obesity development and treatment outcomes. Further investigation of semaglutide’s use is needed due to the promising evidence suggesting a positive effect on decreasing the severity of depression and anxiety symptoms to assess the direct or indirect character of this influence. Full article

Introduction: Anti-GAD65 antibodies are associated with several neurological phenotypes. Antibody titers are increasingly recognized as useful in diagnosis and prognosis. Objective: To describe a Portuguese cohort of patients with anti-GAD65-associated neurological syndromes. Methods: Retrospective analysis of all patients with positive anti-GAD65 antibodies and associated neurological syndromes followed in a tertiary referral center. Results: Nineteen anti-GAD65 antibody-positive neurological patients were identified, 62.3% female, with a mean age of onset of 56.0 (SD = 13.3) years. Comorbid autoimmune disorders were present in seven patients. Six patients had limbic encephalitis (31.6%), four had epilepsy (21.1%), four had cerebellar ataxia (21.1%), and three had stiff-person syndrome (15.8%). Two patients presented with isolated cognitive dysfunction (executive and mnesic) in the absence of other neurological symptoms. The mean follow-up time was 24.0 (14.0–42.0) months, at the end of which the mean modified Rankin Scale (mRS) value was 2.0 (1.0–4.0). Screening for malignancies was negative in all patients. Serum quantitative analysis was carried out in 18 patients, 10 of whom showed titers above previously defined cut-off points (>10,000 IU/L for ELISA and >20 mmol/L for RIA). Quantitative CSF analysis was performed in nine patients, with four showing above-threshold titers. There was no association between anti-GAD65 levels and clinical phenotype or the final mRS values. High-dose intravenous methylprednisolone and oral prednisolone were the most common acute and chronic treatment regimens, respectively. Conclusion: Anti-GAD65 antibodies are associated with varied neurological syndromes, and antibody titers alone should not be used to exclude a disease. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder identified by impairments in common social interactions and repetitive behaviors. In ASD patients, substantial morphological alterations have been observed in the hippocampus, which represents an important region for the development of social skills. Melatonin, commonly found in many foods and plants, is also produced by the pineal gland. This indolamine, known to regulate the circadian rhythm, shows antioxidant and anti-inflammatory properties. We therefore hypothesized that melatonin may reduce oxidative stress and inflammation in the hippocampus of ASD patients. We explored our hypothesis using the BTBR mouse, a well-regarded murine transgenic model for ASD. Immediately after weaning, male BTBR and C57BL/6 mice underwent an 8-week treatment with melatonin or vehicle. Later, through immunohistochemistry and the immunoblotting analysis of the hippocampus, we evaluated the overall expression and cellular localization of Nrf2 and SOD1, two enzymes involved in the oxidative stress response. Similarly, we evaluated NLRP3 and NFkB, two mediators of inflammation, and GAD67, an enzyme responsible for the synthesis of GABA. Ultimately, we addressed melatonin’s potential to regulate iron metabolism through a DAB-enhanced Perls reaction assay. Results showed melatonin’s potential for modulating the analyzed markers in BTBR mice, suggesting a potential neuroprotective effect in ASD patients. Full article