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Frontiers in Immunology 2024Cynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in...
INTRODUCTION
Cynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in methotrexate (MTX)-induced intestinal inflammation remains inadequately understood. Thus, we investigated the impact of cynaroside on MTX-induced intestinal inflammation and its potential mechanisms.
METHODS
To assess the protective potential of cynaroside against intestinal inflammation, Sprague-Dawley rats were subjected to a regimen of 7 mg/kg MTX for 3 days, followed by treatment with cynaroside at varying doses (10, 20, or 40 mg/kg). Histopathological evaluations were conducted alongside measurements of inflammatory mediators to elucidate the involvement of the NLRP3 inflammasome in alleviating intestinal inflammation.
RESULTS
Administration of 7 mg/kg MTX resulted in decreased daily food intake, increased weight loss, and elevated disease activity index in rats. Conversely, treatment with cynaroside at 20 or 40 mg/kg ameliorated the reductions in body weight and daily food intake and suppressed the MTX-induced elevation in the disease activity index. Notably, cynaroside administration at 20 or 40 mg/kg attenuated inflammatory cell infiltration, augmented goblet cell numbers and lowered serum levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-18, as well as the CD68-positive cell rate in the intestines of MTX-induced rats. Furthermore, cynaroside downregulated the expression levels of NLRP3, cleaved caspase 1, and cleaved IL-1β in MTX-induced rats.
DISCUSSION
Collectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats.
Topics: Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Methotrexate; Rats; Rats, Sprague-Dawley; Male; Enteritis; Anti-Inflammatory Agents; Cytokines; Glucosides; Disease Models, Animal
PubMed: 38835771
DOI: 10.3389/fimmu.2024.1405084 -
Journal of Medical Case Reports Jun 2024Immunoglobulin G4-related disease is marked by extensive inflammation and fibrosis of an unknown autoimmune component, with an overall incidence ranging from 0.78 to...
BACKGROUND
Immunoglobulin G4-related disease is marked by extensive inflammation and fibrosis of an unknown autoimmune component, with an overall incidence ranging from 0.78 to 1.39 per 10 person-years. Sinonasal immunoglobulin G4-related disease is atypical and exceedingly uncommon in the existing literature, frequently manifesting clinically as chronic rhinosinusitis, epistaxis, and facial pain.
CASE PRESENTATION
This report describes a 25-year-old Iraqi female who has been suffering from symptoms of chronic rhinosinusitis for 8 years. Despite undergoing several surgeries, there has been no improvement in her symptoms. A tissue biopsy that revealed dense lymphoplasmocytosis with noticeable plasma cell infiltration, storiform fibrosis, and obliterative angitis, along with positive immunohistochemical staining for Immunoglobulin G4 plasma cells, finally confirmed the diagnosis of sinonasal immunoglobulin G4-related disease. The patient responded well to oral prednisolone and methotrexate treatments.
CONCLUSIONS
The main objective of the current report is to raise awareness among physicians about the significance of promptly identifying and diagnosing this rarity, thus preventing the adverse consequences linked to delayed diagnosis and treatment initiation.
Topics: Humans; Female; Immunoglobulin G4-Related Disease; Adult; Sinusitis; Prednisolone; Rhinitis; Methotrexate; Chronic Disease; Biopsy; Treatment Outcome
PubMed: 38835063
DOI: 10.1186/s13256-024-04594-0 -
PloS One 2024Clinical studies showed that prolonged infusion of methotrexate (MTX) leads to more severe adverse reactions than short infusion of MTX at the same dose. We hypothesized...
BACKGROUND AND PURPOSE
Clinical studies showed that prolonged infusion of methotrexate (MTX) leads to more severe adverse reactions than short infusion of MTX at the same dose. We hypothesized that it is the saturation of folate polyglutamate synthetase (FPGS) at high MTX concentration that limits the intracellular synthesis rate of methotrexate polyglutamate (MTX-PG). Due to a similar accumulation rate, a longer infusion duration may increase the concentration of MTX-PG and, result in more serious adverse reactions. In this study, we validated this hypothesis.
EXPERIMENTAL APPROACH
A549, BEL-7402 and MHCC97H cell lines were treated with MTX at gradient concentrations. Liquid chromatograph-mass spectrometer (UPLC-MS/MS) was used to quantify the intracellular concentration of MTX-PG and the abundance of FPGS and γ-glutamyl hydrolase (GGH). High quality data were used to fit the cell pharmacokinetic model.
KEY RESULTS
Both cell growth inhibition rate and intracellular MTX-PG concentration showed a nonlinear relationship with MTX concentration. The parameter Vmax in the model, which represents the synthesis rate of MTX-PG, showed a strong correlation with the abundance of intracellular FPGS.
CONCLUSION AND IMPLICATIONS
According to the model fitting results, it was confirmed that the abundance of FPGS is a decisive factor limiting the synthesis rate of MTX-PG. The proposed hypothesis was verified in this study. In addition, based on the intracellular metabolism, a reasonable explanation was provided for the correlation between the severity of adverse reactions of MTX and infusion time. This study provides a new strategy for the individualized treatment and prediction of efficacy/side effects of MTX.
Topics: Methotrexate; gamma-Glutamyl Hydrolase; Peptide Synthases; Humans; Cell Line, Tumor; Polyglutamic Acid; Tandem Mass Spectrometry; Cell Proliferation; Antimetabolites, Antineoplastic
PubMed: 38833640
DOI: 10.1371/journal.pone.0302663 -
Environmental Health : a Global Access... Jun 2024Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies...
BACKGROUND
Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother's arsenic exposure, folic acid, and spina bifida risk in Bangladesh.
METHODS
We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure.
RESULTS
We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother's arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52-2.29, p = 0.82).
CONCLUSIONS
Mother's arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.
Topics: Humans; Folic Acid; Bangladesh; Spinal Dysraphism; Case-Control Studies; Female; Arsenic; Infant; Male; Adult; Infant, Newborn; Pregnancy; Water Pollutants, Chemical; Maternal Exposure; Young Adult; Drinking Water
PubMed: 38831396
DOI: 10.1186/s12940-024-01091-1 -
International Journal of Biological... Jun 2024Cellulose nanofibres (CNFs), also known as nano-fibrillated cellulose, have emerged as highly promising sustainable biomaterials owing to their numerous advantages,...
Cellulose nanofibres (CNFs), also known as nano-fibrillated cellulose, have emerged as highly promising sustainable biomaterials owing to their numerous advantages, including high accessibility, long-term sustainability, low toxicity, and mechanical properties. Recently, marine organisms have been explored as novel and environmentally friendly sources of cellulose fibers (CFs) due to their easy cultivation, extraction and biocompatibility. Dinoflagellates, a group of marine phytoplankton, have gained particular attention due to their unique cellulosic morphology and lignin-free biomass. Previously, we showed that the unique amorphous nature of dinoflagellate-derived cellulose offers various benefits. This study further explores the potential of dinoflagellate-derived CFs as a sustainable and versatile CNF source. Extracted dinoflagellate cellulose is effectively converted into CNFs via one-step TEMPO oxidation without significant polymer degradation. In addition, the biological compatibility of the CNFs is improved by amine-grafting using putrescine and folic acid. The products are characterised by conductometric titration, zeta potential measurements, TGA, GPC, FTIR, SEM/TEM, XRD, and XPS. Finally, in a proof-of-principle study, the application of the functionalised CNFs in drug delivery is tested using methylene blue as a drug model. Our findings suggest that dinoflagellate-derived CNFs provide an eco-friendly platform that can be easily functionalised for various applications, including drug delivery.
Topics: Dinoflagellida; Cellulose; Nanofibers; Cyclic N-Oxides; Folic Acid
PubMed: 38825272
DOI: 10.1016/j.ijbiomac.2024.132804 -
Microbial Cell Factories May 2024Bacillus subtilis is widely used in industrial-scale riboflavin production. Previous studies have shown that targeted mutagenesis of the ribulose 5-phosphate 3-epimerase...
BACKGROUND
Bacillus subtilis is widely used in industrial-scale riboflavin production. Previous studies have shown that targeted mutagenesis of the ribulose 5-phosphate 3-epimerase in B. subtilis can significantly enhance riboflavin production. This modification also leads to an increase in purine intermediate concentrations in the medium. Interestingly, B. subtilis exhibits remarkable efficiency in purine nucleoside synthesis, often exceeding riboflavin yields. These observations highlight the importance of the conversion steps from inosine-5'-monophosphate (IMP) to 2,5-diamino-6-ribosylamino-4(3 H)-pyrimidinone-5'-phosphate (DARPP) in riboflavin production by B. subtilis. However, research elucidating the specific impact of these reactions on riboflavin production remains limited.
RESULT
We expressed the genes encoding enzymes involved in these reactions (guaB, guaA, gmk, ndk, ribA) using a synthetic operon. Introduction of the plasmid carrying this synthetic operon led to a 3.09-fold increase in riboflavin production compared to the control strain. Exclusion of gmk from the synthetic operon resulted in a 36% decrease in riboflavin production, which was further reduced when guaB and guaA were not co-expressed. By integrating the synthetic operon into the genome and employing additional engineering strategies, we achieved riboflavin production levels of 2702 mg/L. Medium optimization further increased production to 3477 mg/L, with a yield of 0.0869 g riboflavin per g of sucrose.
CONCLUSION
The conversion steps from IMP to DARPP play a critical role in riboflavin production by B. subtilis. Our overexpression strategies have demonstrated their effectiveness in overcoming these limiting factors and enhancing riboflavin production.
Topics: Riboflavin; Bacillus subtilis; Purines; Metabolic Engineering; Biosynthetic Pathways; Operon; Bacterial Proteins
PubMed: 38822377
DOI: 10.1186/s12934-024-02426-w -
BMC Oral Health May 2024The present study aimed to evaluate nutritional intake among a group of male patients in the dental clinic with and without periodontal disease to search for...
BACKGROUND
The present study aimed to evaluate nutritional intake among a group of male patients in the dental clinic with and without periodontal disease to search for associations between nutritional profile and periodontal health.
METHODS
To this purpose, nutritional intake of macronutrients, fiber, vitamins, and minerals were compared evaluating both clinical parameters and periodontal status. Non periodontitis patients were compared with stage III and IV periodontitis and its extension according to the 2017 classification.
RESULTS
After multivariate analysis, statistically significant associations were found between the dietary intake of energy, total fat, cholesterol, calcium, saturated fat, monounsaturated fat and folic acid and iodine and periodontitis status. This study reports an inverse association between cholesterol and iodine and periodontitis and a direct association with saturated fat, monounsaturated fat, and folic acid.
CONCLUSIONS
Maintaining an adequate intake of fat, iodine, calcium, and cholesterol and avoiding an excessive intake of energy, saturated fat, monounsaturated fat, and folic acid could be important to controlling periodontitis.
Topics: Humans; Male; Periodontitis; Middle Aged; Adult; Energy Intake; Nutritional Status; Folic Acid; Diet; Dietary Fats; Dietary Fiber
PubMed: 38816851
DOI: 10.1186/s12903-024-04384-6 -
Scientific Reports May 2024Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent... (Observational Study)
Observational Study
Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38-85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64-1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings.
Topics: Humans; Fluorouracil; Aged; Leucovorin; Irinotecan; Female; Middle Aged; Male; Pancreatic Neoplasms; Aged, 80 and over; Retrospective Studies; Adult; Liposomes; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Prospective Studies
PubMed: 38816500
DOI: 10.1038/s41598-024-63172-y -
World Journal of Gastroenterology May 2024The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of...
BACKGROUND
The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated.
AIM
To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC.
METHODS
We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.
RESULTS
The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs).
CONCLUSION
The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Fluorouracil; Infusions, Intra-Arterial; Leucovorin; Aged; Adult; Hepatic Artery; Organoplatinum Compounds; Treatment Outcome; Molecular Targeted Therapy; Progression-Free Survival; Retrospective Studies; Immunotherapy; Combined Modality Therapy
PubMed: 38813052
DOI: 10.3748/wjg.v30.i17.2321 -
Turkish Journal of Medical Sciences 2023Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint...
BACKGROUND/AIM
Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint destruction. In this study, the relationship between CD39 expression and the treatment response of RA patients was examined to investigate its potential as a biomarker that demonstrates treatment response.
MATERIALS AND METHODS
This study included 77 RA patients and 40 healthy controls (HC). The RA patients were divided into 2 groups based on their response to RA treatment, those with a good response to methotrexate (MTX) monotherapy and those with an inadequate response based on the American College of Rheumatology and the European League Against Rheumatism response criteria. Various immunological parameters and Disease Activity Score in 28 Joints (DAS28) were examined between the groups using the Student's t-test.
RESULTS
The monocytic myeloid-derived suppressor cell (M-MDSC) percentage was higher in the RA patient group versus the HC group. The CD39 expression in the T lymphocytes were higher in patients that responded well to the MTX compared to those showing inadequate response. Additionally, s negative correlation was found between the DAS28 and CD39 in the T cells.
CONCLUSION
The results showed that the improvement in treatment response to the therapy in RA patients could be because of the enhancement in the CD39/adenosine (ADO) pathway. Therefore, therapies targeting the CD39/ADO pathway in T cells may improve RA treatments.
Topics: Humans; Arthritis, Rheumatoid; Methotrexate; Female; Male; Apyrase; Middle Aged; Antirheumatic Agents; Adult; Biomarkers; Treatment Outcome; Antigens, CD; Case-Control Studies; Aged; T-Lymphocytes
PubMed: 38813034
DOI: 10.55730/1300-0144.5672