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Molecular Nutrition & Food Research May 2024Patients with Type 2 diabetes mellitus (T2DM) have lower levels of vitamin D. An elevation in uric acid (UA) contributes to T2DM via an increase in oxidative stress....
SCOPE
Patients with Type 2 diabetes mellitus (T2DM) have lower levels of vitamin D. An elevation in uric acid (UA) contributes to T2DM via an increase in oxidative stress. Adenosine deaminase (ADA) is an enzyme of the purine degradation pathway. It is hypothesized that a reduction of ADA activity via vitamin D supplementation reduces UA and oxidative stress.
METHODS AND RESULTS
A total of 162 participants (81 with T2DM and 81 controls) are enrolled in a case-control study. A follow-up interventional study is performed on 30 patients with vitamin D deficiency. These patients receive 50 000 IU (international units) of vitamin D3 on a weekly basis for 12 weeks. This intervention is followed by the measurement of several markers. T2DM patients has higher ADA activity, UA, and lipid peroxidation but lower 25-hydroxy-vitamin D (25 (OH) vitamin D) and GSH/GSSG ratio (p < 0.05). Vitamin D supplementation results in a reduction of ADA activity and UA levels (p < 0.05) along with an increase in GSH/GSSG ratio (p < 0.05).
CONCLUSION
The results highlight the presence of an axis in T2DM patients between ADA, UA, and oxidative stress. Modulation of this axis can be achieved by clinically approved vitamin D supplementation protocols.
PubMed: 38816753
DOI: 10.1002/mnfr.202300870 -
Journal of Paediatrics and Child Health May 2024
PubMed: 38804661
DOI: 10.1111/jpc.16572 -
Purinergic Signalling May 2024Cutaneous melanoma (CM) poses a therapeutic challenge due to its aggressive nature and often limited response to conventional treatments. Exploring novel therapeutic...
Cutaneous melanoma (CM) poses a therapeutic challenge due to its aggressive nature and often limited response to conventional treatments. Exploring novel therapeutic targets is essential, and natural compounds have emerged as potential candidates. This study aimed to elucidate the impact of curcumin, a natural compound known for its anti-inflammatory, antioxidant, and anti-tumor properties, on metastatic melanoma cells, focusing on the purinergic system and immune responses. Human melanoma cell line SK-Mel-28 were exposed to different curcumin concentrations for either 6 or 24 h, after which we assessed components related to the purinergic system and the inflammatory cascade. Using RT-qPCR, we assessed the gene expression of CD39 and CD73 ectonucleotidases, as well as adenosine deaminase (ADA). Curcumin effectively downregulated CD39, CD73, and ADA gene expression. Flow cytometry analysis revealed that curcumin significantly reduced CD39 and CD73 protein expression at specific concentrations. Moreover, the A2A receptor's protein expression decreased across all concentrations. Enzymatic activity assays demonstrated that curcumin modulated CD39, CD73, and ADA activities, with effects dependent on concentration and duration of treatment. Extracellular ATP levels increased after 24 h of curcumin treatment, emphasizing its role in modulating hydrolytic activity. Curcumin also displayed anti-inflammatory properties by reducing NLRP3 gene expression and impacting the levels of key inflammatory cytokines. In conclusion, this study unveils the potential of curcumin as a promising adjuvant in CM treatment. Curcumin modulates the expression and activity of crucial components of the purinergic system and exhibits anti-inflammatory effects, indicating its potential therapeutic role in combating CM. These findings underscore curcumin's promise and warrant further investigation in preclinical and clinical settings for melanoma management.
PubMed: 38801619
DOI: 10.1007/s11302-024-10023-0 -
Cureus Apr 2024Pericarditis can be a common complication of tuberculosis (TB) in developing countries like India. It is associated with fever, fatigue, and weight loss and can often be...
Pericarditis can be a common complication of tuberculosis (TB) in developing countries like India. It is associated with fever, fatigue, and weight loss and can often be accompanied by shortness of breath and chest pain. Other common causes of pericardial effusion include malignancy, renal failure, autoimmune disease, and viral and bacterial infections. When the pericardial fluid is bloody, TB is likely to be present in developing countries. It can often get complicated with cardiac tamponade, which has a high mortality rate. We present a case of a 55-year-old female with no co-morbidities who presented with shortness of breath, fatigue for two weeks, and chest pain for one week. She had no history of fever, chills, or rigour, and no history of TB contact. Clinical examination revealed low blood pressure with raised jugular venous pressure (JVP). Her electrocardiography (ECG) showed sinus tachycardia with a low-voltage complex. Echocardiography (ECHO) showed a large pericardial effusion, compromising ventricular function. We performed pericardiocentesis, drained 1.4 L of bloody fluid, and sent the pericardial fluid for analysis. Pericardial fluid adenosine deaminase (ADA) and cartridge-based nucleic acid amplification testing (CBNAAT) came positive for Mycobacterium TB. The patient was started on anti-tubercular treatment (ATT) and broad-spectrum antibiotics with drainage. Other routine investigations and autoimmune immune workups were normal. The patient also developed ATT-induced hepatitis, for which modified ATT was initiated. The patient improved clinically and symptomatically, was discharged, and was advised to follow up in the outpatient department (OPD).
PubMed: 38800190
DOI: 10.7759/cureus.59050 -
Cureus Apr 2024Tuberculosis (TB), caused by the bacteria , is a highly infectious and prevalent disease. It is the leading cause of death among communicable diseases and the fifth...
Tuberculosis (TB), caused by the bacteria , is a highly infectious and prevalent disease. It is the leading cause of death among communicable diseases and the fifth leading cause of all diseases in India. The diagnosis can be challenging due to the disease's unique appearance and various presentations. Disseminated TB is characterized by the involvement of two or more non-contiguous sites resulting from hematogenous extension of the disease. Clinical confirmation of the diagnosis of disseminated TB is based on bacteriological or histological evidence. Based on various studies, there is evidence that satisfactory results are obtained from treatment with first-line anti-tubercular drugs. When there is a delay in diagnosis and treatment, it can become a life-threatening condition. We present a case of a 38-year-old alcoholic male who presented with generalized edema, pain, and distension of the abdomen. According to the initial presentation, the provisional diagnosis made was alcoholic liver disease, but it was later diagnosed as disseminated TB with sputum-positive pulmonary TB with abdominal involvement in the form of ascites and hepatosplenomegaly along with hematological involvement as pancytopenia. The patient started showing drastic improvement after the initiation of anti-tubercular therapy.
PubMed: 38800156
DOI: 10.7759/cureus.58902 -
International Journal of Rheumatic... May 2024
Chest trauma-induced pleuritis with elevated pleural rheumatoid factor and adenosine deaminase levels in a patient subsequently diagnosed with rheumatoid arthritis: A case report.
Topics: Humans; Arthritis, Rheumatoid; Adenosine Deaminase; Pleurisy; Rheumatoid Factor; Biomarkers; Thoracic Injuries; Male; Treatment Outcome; Predictive Value of Tests; Up-Regulation; Tomography, X-Ray Computed; Middle Aged
PubMed: 38794838
DOI: 10.1111/1756-185X.15191 -
Communications Biology May 2024Deficiency of adenosine deaminase 2 (DADA2) is an inborn error of immunity caused by loss-of-function mutations in the adenosine deaminase 2 (ADA2) gene. Clinical...
Deficiency of adenosine deaminase 2 (DADA2) is an inborn error of immunity caused by loss-of-function mutations in the adenosine deaminase 2 (ADA2) gene. Clinical manifestations of DADA2 include vasculopathy and immuno-hematological abnormalities, culminating in bone marrow failure. A major gap exists in our knowledge of the regulatory functions of ADA2 during inflammation and hematopoiesis, mainly due to the absence of an ADA2 orthologue in rodents. Exploring these mechanisms is essential for understanding disease pathology and developing new treatments. Zebrafish possess two ADA2 orthologues, cecr1a and cecr1b, with the latter showing functional conservation with human ADA2. We establish a cecr1b-loss-of-function zebrafish model that recapitulates the immuno-hematological and vascular manifestations observed in humans. Loss of Cecr1b disrupts hematopoietic stem cell specification, resulting in defective hematopoiesis. This defect is caused by induced inflammation in the vascular endothelium. Blocking inflammation, pharmacological modulation of the Ar pathway, or the administration of the recombinant human ADA2 corrects these defects, providing insights into the mechanistic link between ADA2 deficiency, inflammation and immuno-hematological abnormalities. Our findings open up potential therapeutic avenues for DADA2 patients.
Topics: Animals; Zebrafish; Adenosine Deaminase; Hematopoietic Stem Cells; Inflammation; Hematopoiesis; Zebrafish Proteins; Humans; Signal Transduction; Intercellular Signaling Peptides and Proteins
PubMed: 38777862
DOI: 10.1038/s42003-024-06286-3 -
Frontiers in Immunology 2024Thyroid immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment appear to correlate with a better prognosis. We aimed to...
BACKGROUND
Thyroid immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment appear to correlate with a better prognosis. We aimed to investigate clinical biomarkers associated with thyroid irAEs.
METHODS
We retrospectively analyzed data from 129 patients receiving programmed cell death protein 1 (PD-1) inhibitors for stage III and IV gastrointestinal tumors. Patients were divided into two groups: "thyroid irAEs" group and "no thyroid irAEs" group. We compared continuous variables using Mann-Whitney U and Kruskal-Wallis tests and categorical variables using Pearson's chi-square test. Survival curves were generated using the Kaplan-Meier method, and associations between clinical features and thyroid irAEs were assessed using univariate and multivariate logistic regression models. Associations for thyroid irAEs and outcomes [progression-free survival (PFS), overall survival (OS)] of the patients were performed with a Cox proportional hazard model.
RESULTS
A total of 129 patients, including 66 gastric cancer, 30 esophageal squamous cell carcinoma, and 33 hepatocellular carcinoma (HCC), were involved in this analysis with 47 cases of thyroid irAEs occurrence. The Cox proportional hazard model analysis confirmed the extended PFS [hazard rate (HR) = 0.447, 95% confidence interval (CI): 0.215 to 0.931, = 0.031] and OS (HR = 0.424, 95% CI: 0.201 to 0.893, = 0.024) for thyroid irAEs group when compared with those of the no thyroid irAEs group. Association between thyroid irAEs and clinical characteristics at baseline was analyzed subsequently by univariate analysis. Higher body mass index ( = 0.005), increased eosinophil count ( = 0.014), increased lactate dehydrogenase ( = 0.008), higher baseline thyroid stimulating hormone (TSH) ( = 0.001), HCC ( = 0.001) and increased adenosine deaminase (ADA) ( = 0.001) were linked with thyroid irAEs occurrence. The multivariable logistic regression model indicated that ADA [odds rate (OR) = 4.756, 95% CI: 1.147 to 19.729, = 0.032] was independently associated with thyroid irAEs occurrence.
CONCLUSIONS
Increased baseline level of ADA was associated with thyroid irAEs occurrence in patients with advanced gastrointestinal tumors who received ICI treatment. In the case of abnormal ADA, attention should be paid to the risk of thyroid irAEs.
Topics: Humans; Female; Male; Gastrointestinal Neoplasms; Middle Aged; Aged; Retrospective Studies; Immune Checkpoint Inhibitors; Neoplasm Staging; Adult; Thyroid Gland; Prognosis; Biomarkers, Tumor
PubMed: 38774877
DOI: 10.3389/fimmu.2024.1381061 -
Porcine Health Management May 2024Identification of animals in need of medical treatment is important in porcine health management, where analytical samples applicable at farm level could be utilized....
BACKGROUND
Identification of animals in need of medical treatment is important in porcine health management, where analytical samples applicable at farm level could be utilized. Several biomarkers are measurable in saliva, which is less stressful to collect than blood. Saliva sampling is easy to learn and repeatable, making it suitable for monitoring purposes. Previous research suggests that porcine health biomarkers are dependent on production stage and gender, and that combining biomarkers improves diagnostic sensitivity. However, proper monitoring of biomarkers during the complete production cycle has not been studied. We aimed to describe the dynamics of salivary and serum haptoglobin (Hp), adenosine deaminase (ADA), and immunoglobulin G (IgG) in four production stages (suckling, early growing, late growing, finishing), on commercial Finnish pig farms using a total of 117 piglets. The relationship between gender and biomarker dynamics was investigated, as well as the relationships between these biomarkers in saliva and serum.
RESULTS
The highest salivary concentrations of Hp, ADA and IgG were measured in suckling piglets. The differences between production stages were generally larger in saliva than for the corresponding serum biomarkers. All correlation coefficients between salivary biomarkers were positive in each production stage and the strength of the correlation varied from 0.245 to 0.762. No similar trend was observed regarding correlation coefficients either between serum biomarkers or between salivary and serum biomarkers. Gender was associated with some biomarker concentrations.
CONCLUSIONS
The biomarker dynamics supported previous findings that collection of analytical samples should be conducted in age-matched populations. Positive and even strong relationships between salivary biomarkers indicate the potential to use especially saliva for health monitoring. Our results also suggest the importance of considering gender effects when assessing some salivary or serum biomarkers.
PubMed: 38773547
DOI: 10.1186/s40813-024-00368-8 -
Neoplasma Apr 2024It has been demonstrated that calreticulin (CALR) is expressed abnormally in various tumors and is involved in the occurrence and development of tumors. In this study,...
It has been demonstrated that calreticulin (CALR) is expressed abnormally in various tumors and is involved in the occurrence and development of tumors. In this study, CALR and EIF2AK2 expression was measured in the clinical specimens of 39 patients with melanoma. Then, we constructed knockdown and overexpression cell models of CALR and EIF2AK2 and used wound healing and Transwell assays to observe cell migration and invasion. Apoptosis, EDU, and ROS assays were used to measure cell apoptosis and proliferation, as well as ROS levels. The effect of CALR on endoplasmic reticulum stress was detected using endoplasmic reticulum fluorescent probes. Western blotting was used to detect protein levels of CALR, EIF2AK2, ADAR1, and MMP14. The results indicated that CALR and EIF2AK2 expression levels were significantly higher in human melanoma tissues than in adjacent non-tumor tissue. In addition, we found a correlation between CALR and the expression of EIF2AK2 and MMP14, and the experimental results indicated that overexpression of CALR significantly upregulated the expression of EIF2AK2, MMP14, and ADAR1, while knockdown of CALR inhibited their expression. Notably, the knockdown of EIF2AK2 in the CALR overexpression group blocked the upregulation of MMP14 and ADAR1 expression by CALR, and the knockdown of both CALR and EIF2AK2 significantly inhibited MMP14 and ADAR1 expression. In conclusion, CALR and EIF2AK2 play a promoting role in melanoma progression, and knockdown of CALR and EIF2AK2 may be an effective anti-tumor target, and its mechanism may be through MMP14, ADAR1 signaling.
Topics: Humans; Adenosine Deaminase; Melanoma; eIF-2 Kinase; RNA-Binding Proteins; Calreticulin; Cell Proliferation; Signal Transduction; Cell Line, Tumor; Matrix Metalloproteinase 14; Cell Movement; Apoptosis; Endoplasmic Reticulum Stress; Female; Disease Progression; Male; Gene Expression Regulation, Neoplastic; Middle Aged
PubMed: 38766853
DOI: 10.4149/neo_2024_240116N24