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Nutrients Jun 2024While the exact pathogenesis of IBD remains unclear, genetic, environmental and nutritional factors as well as the composition of the gut microbiome play crucial roles.... (Review)
Review
While the exact pathogenesis of IBD remains unclear, genetic, environmental and nutritional factors as well as the composition of the gut microbiome play crucial roles. Food additives, which are increasingly consumed in the Western diet, are being investigated for their potential effects on IBD. These additives can affect gut health by altering the composition of the microbiota, immune responses, and intestinal permeability, contributing to autoimmune diseases and inflammation. Despite the growing number of studies on food additives and IBD, the specific effects of carrageenan have not yet been sufficiently researched. This review addresses this gap by critically analyzing recent studies on the effects of carrageenan on the gut microbiota, intestinal permeability, and inflammatory processes. We searched the MEDLINE and SCOPUS databases using the following terms: carrageenan, carrageenan and inflammatory bowel disease, carrageenan and cancer, food additives and microbiome, food additives and intestinal permeability, and food additives and autoimmune diseases. In animal studies, degraded carrageenan has been shown to trigger intestinal ulceration and inflammation, highlighting its potential risk for exacerbating IBD. It can affect the gut microbiota, reduce bacterial diversity, and increase intestinal permeability, contributing to "leaky gut" syndrome. Some studies suggest that carrageenan may inhibit the growth of cancer cells by influencing the progression of the cell cycle, but the anti-cancer effect is still unclear. Carrageenan may also increase glucose intolerance and insulin resistance. Further research is needed to determine whether carrageenan should be excluded from the diet of individuals with IBD.
Topics: Humans; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Carrageenan; Animals; Diet; Food Additives; Permeability
PubMed: 38892712
DOI: 10.3390/nu16111780 -
Nutrients May 2024In people with obesity, diabetes, and hypertension, lipid and glucose metabolism and oxidative stress generation interact. This condition, known as a "metabolic... (Review)
Review
In people with obesity, diabetes, and hypertension, lipid and glucose metabolism and oxidative stress generation interact. This condition, known as a "metabolic syndrome" (MetS), presents a global challenge and appears to be the underlying mechanism for the development of cardiovascular diseases (CVDs). This review is designed based on evidence indicating the pathogenic mechanisms of MetS. In detail, we will look at the mechanisms of oxidative stress induction in MetS, the effects of elevated oxidative stress levels on the condition's pathophysiology, and matters related to endothelial function. According to different components of the MetS pathophysiological network, the effects of antioxidants and endothelial dysfunction are reviewed. After considering the strategic role of oxidative stress in the pathophysiology of MetS and its associated CVDs, oxidative stress management by antioxidant supplementation seems an appropriate therapeutic approach.
Topics: Metabolic Syndrome; Humans; Antioxidants; Cardiovascular Diseases; Oxidative Stress; Dietary Supplements; Endothelium, Vascular
PubMed: 38892574
DOI: 10.3390/nu16111641 -
Nutrients May 2024Variants in fat mass and the obesity-associated protein () gene have long been recognized as the most significant genetic predictors of body fat mass and obesity....
BACKGROUND
Variants in fat mass and the obesity-associated protein () gene have long been recognized as the most significant genetic predictors of body fat mass and obesity. Nevertheless, despite the overall evidence, there are conflicting reports regarding the correlation between different polymorphisms of the gene and body mass index (BMI). Additionally, it is unclear whether influences metabolic syndrome (MetS) through mechanisms other than BMI's impact. In this work, we aimed to analyze the impact of the following polymorphisms on the BMI as well as MetS components in a population of young adult men.
METHODS
The patient group consisted of 279 Polish young adult men aged 28.92 (4.28) recruited for the MAGNETIC trial. The single-nucleotide polymorphisms (SNPs), located in the first intron of the gene, were genotyped, and the results were used to identify "protective" and "risk" haplotypes and diplotypes based on the literature data. Laboratory, as well as anthropometric measurements regarding MetS, were performed. Measured MetS components included those used in the definition in accordance with the current guidelines. Data regarding dietary patterns were also collected, and principal components of the dietary patterns were identified.
RESULTS
No statistically significant correlations were identified between the analyzed diplotypes and BMI ( = 0.53) or other MetS components (waist circumference = 0.55; triglycerides = 0.72; HDL cholesterol = 0.33; blood glucose = 0.20; systolic blood pressure = 0.06; diastolic blood pressure = 0.21). Stratification by the level of physical activity or adherence to the dietary patterns also did not result in any statistically significant result.
CONCLUSIONS
Some studies have shown that SNPs such as rs1421085, rs1121980, rs8050136, rs9939609, and rs9930506 have an impact on the BMI or other MetS components; nevertheless, this was not replicated in this study of Polish young adult males.
Topics: Humans; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Male; Metabolic Syndrome; Body Mass Index; Adult; Poland; Polymorphism, Single Nucleotide; Young Adult; Haplotypes; Life Style; Diet; Genetic Predisposition to Disease; Feeding Behavior; Dietary Patterns
PubMed: 38892547
DOI: 10.3390/nu16111615 -
International Journal of Molecular... May 2024The role of programmed death cell protein 1 (PD-1) has already been described in a range of various diseases, including COVID-19. This study provides new, innovative...
Programmed Cell Death Protein-1 Regulation in Response to SARS-CoV-2 in Paediatric Multisystem Inflammatory Syndrome Temporally Associated with SARS-CoV-2: A Prospective Cohort Study.
The role of programmed death cell protein 1 (PD-1) has already been described in a range of various diseases, including COVID-19. This study provides new, innovative data, related to the expression of PD-1 and the risk of Paediatric Inflammatory Multisystem Syndrome, temporally associated with SARS-CoV-2 infection (PIMS-TS)-a rare, but potentially life-threatening complication of COVID-19. In this study, we evaluated the expression of PD-1 protein in patients with PIMS. Blood samples were taken from patients at the time of diagnosis (n = 33), after 6 weeks (n = 33), 3 months (n = 24), 6 months (n = 24) and 12 months (n = 8). The immunophenotypes were evaluated in flow cytometry. The control group consisted of 35 healthy children with negative SARS-CoV-2 antigen/PCR test, who were asymptomatic and had no history of allergic, autoimmune or oncological diseases. The associations between immunophenotypes, biochemical findings and clinical data were analysed. Significant increases in the expression of PD-1 for CD4+ and CD8+ T cells, compared to the control group, were observed in the day of admission, with a gradual decrease during the first weeks from initiation of treatment. This study sheds new light on the pathogenesis of PIMS-TS, emphasizing the role of PD-1 protein. Future research is essential for early risk prediction in SARS-CoV-2 patients and for devising effective clinical prevention and management strategies.
Topics: Humans; COVID-19; Programmed Cell Death 1 Receptor; Systemic Inflammatory Response Syndrome; Male; Child; Female; SARS-CoV-2; Child, Preschool; Prospective Studies; Adolescent; Infant; CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Immunophenotyping
PubMed: 38892153
DOI: 10.3390/ijms25115968 -
International Journal of Molecular... May 2024Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and retinal pigment epithelial atrophy, leading to severe visual...
Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and retinal pigment epithelial atrophy, leading to severe visual impairment or blindness. RP can be classified as nonsyndromic or syndromic with complex clinical phenotypes. Three unrelated Polish probands affected with retinitis pigmentosa coexisting with cerebellar ataxia were recruited for this study. Clinical heterogeneity and delayed appearance of typical disease symptoms significantly prolonged the patients' diagnostic process. Therefore, many clinical and genetic tests have been performed in the past. Here, we provide detailed clinical and genetic analysis results of the patients. Whole-exome sequencing (WES) and targeted NGS analysis allow the identification of four novel and two previously reported variants in the following genes: , , and The use of next-generation sequencing (NGS) methods finally allowed for confirmation of the clinical diagnosis. Ultra-rare diseases such as PHARC, PCARP, and Oliver-McFarlane syndromes were diagnosed in patients, respectively. Our findings confirmed the importance of the application of next-generation sequencing methods, especially in ultra-rare genetic disorders with overlapping features.
Topics: Humans; Retinitis Pigmentosa; Male; Female; Exome Sequencing; Pedigree; High-Throughput Nucleotide Sequencing; Adult; Cerebellar Ataxia; Membrane Transport Proteins; Monoacylglycerol Lipases; Mutation; Ataxia; Phenotype; Acyltransferases; Cataract; Phospholipases; Polyneuropathies
PubMed: 38891946
DOI: 10.3390/ijms25115759 -
International Journal of Molecular... May 2024Gilles de la Tourette syndrome (GTS) is a neurodevelopmental psychiatric disorder with complex and elusive etiology with a significant role of genetic factors. The aim...
Gilles de la Tourette syndrome (GTS) is a neurodevelopmental psychiatric disorder with complex and elusive etiology with a significant role of genetic factors. The aim of this study was to identify structural variants that could be associated with familial GTS. The study group comprised 17 multiplex families with 80 patients. Structural variants were identified from whole-genome sequencing data and followed by co-segregation and bioinformatic analyses. The localization of these variants was used to select candidate genes and create gene sets, which were subsequently processed in gene ontology and pathway enrichment analysis. Seventy putative pathogenic variants shared among affected individuals within one family but not present in the control group were identified. Only four private or rare deletions were exonic in , , , and genes. Notably, the gene is involved in cochlear development and sensory perception of sound, a process that was associated previously with familial GTS. In addition, two rare variants and three not present in the control group were co-segregating with the disease in two families, and uncommon insertions in and were co-segregating in three families each. Enrichment analysis showed that identified structural variants affected synaptic vesicle endocytosis, cell leading-edge organization, and signaling for neurite outgrowth. The results further support the involvement of the regulation of neurotransmission, neuronal migration, and sound-sensing in GTS.
Topics: Humans; Tourette Syndrome; Male; Female; Pedigree; Genetic Predisposition to Disease; Extracellular Matrix Proteins; Adult; Whole Genome Sequencing
PubMed: 38891944
DOI: 10.3390/ijms25115758 -
Healthcare (Basel, Switzerland) May 2024(1) Background: FABMs (fertility awareness-based methods) are methods that rely on the observation of clinical signs related to fertility found in women, the so-called...
Usefulness of the Sympto-Thermal Method with Standardized Cervical Mucus Assessment (InVivo Method) for Evaluating the Monthly Cycle in Women with Polycystic Ovary Syndrome (PCOS).
(1) Background: FABMs (fertility awareness-based methods) are methods that rely on the observation of clinical signs related to fertility found in women, the so-called fertility bioindicators. They can be a valuable tool for diagnosing monthly cycle disorders and infertility, for example, among patients with PCOS (polycystic ovary syndrome). Until now, it has been difficult for women with PCOS to use FABM, due to the difficulty of describing fertility bioindicators and their disorders due to the biology of the syndrome. The new InVivo sympto-thermal method with standardized cervical mucus assessment may provide a valuable diagnostic and therapeutic tool for observing the monthly cycle in this group of women. (2) Methods: The monthly cycle was evaluated in a group of 32 women of reproductive age. A total of 108 monthly cycle observation cards were analyzed: 35 monthly cycle cards were collected from 18 women with PCOS, and 73 monthly cycle cards collected from 14 healthy women. In addition, 32 pairs of macroscopic and microscopic images were evaluated: 17 pairs from the study group (four subjects) and 15 pairs from women in the control group (six subjects). (3) Results: We showed that in the group of patients with PCOS, menstruation was longer ( = 0.000814), the number of mucus peaks was statistically higher ( = 0.040747), and the interquartile range (IQR) of the duration of the follicular phase (calculated according to the BBT) was significantly higher (8 days) compared to women in the control group. We also observed that among all the women studied, the microscopic image of cervical mucus correlated with the cycle phase described in the observation card, as determined by reference to the BBT chart, provided that it showed the correct features. (4) Conclusions: Systematic maintenance of monthly cycle observation charts using the InVivo method can be an important supplement to the medical history, as it allows for a thorough assessment of, among others, the timing of monthly bleeding, cervical mucus symptoms, BBT changes, and the duration of the follicular and luteal phases among both healthy and PCOS women.
PubMed: 38891183
DOI: 10.3390/healthcare12111108 -
The Lancet. Haematology Jun 2024A standard of care and optimal duration of therapy have not been established for patients with multiply relapsed or refractory follicular lymphoma. The aim of this study...
BACKGROUND
A standard of care and optimal duration of therapy have not been established for patients with multiply relapsed or refractory follicular lymphoma. The aim of this study was to evaluate epcoritamab, a novel CD3 × CD20 bispecific antibody, in the third-line and later setting of follicular lymphoma.
METHODS
EPCORE NHL-1 is a multicohort, single-arm, phase 1-2 trial conducted at 88 sites across 15 countries. Here, we report the primary analysis of patients with relapsed or refractory follicular lymphoma in the phase 2 part of the trial, which included the pivotal (dose expansion) cohort and the cycle 1 optimisation cohort. Eligible patients were aged 18 years or older, had relapsed or refractory CD20 follicular lymphoma (grade 1-3A), an Eastern Cooperative Oncology Group performance status of up to 2, and had received at least two previous lines of therapy (including an anti-CD20 monoclonal antibody and an alkylating agent or lenalidomide). Patients were treated with subcutaneous epcoritamab 48 mg in 28-day cycles: weekly in cycles 1-3, biweekly in cycles 4-9, and every 4 weeks until disease progression or unacceptable toxicity. To mitigate the risk and severity of cytokine release syndrome, in the pivotal cohort, cycle 1 consisted of a step-up dosing regimen of a 0·16-mg priming dose on day 1 and a 0·80-mg intermediate dose on day 8, followed by subsequent 48-mg full doses and prophylactic prednisolone 100 mg; in the cycle 1 optimisation cohort, a second intermediate dose of 3 mg on day 15, adequate hydration, and prophylactic dexamethasone 15 mg were evaluated during cycle 1 to further reduce risk and severity of cytokine release syndrome. Primary endpoints were independently reviewed overall response rate for the pivotal cohort and the proportion of patients with grade 2 or worse and any-grade cytokine release syndrome for the cycle 1 optimisation cohort. Analyses were done in all enrolled patients who had received at least one dose of epcoritamab. This study is registered with ClinicalTrials.gov, NCT03625037, and is ongoing.
FINDINGS
Between June 19, 2020, and April 21, 2023, 128 patients (median age 65 years [IQR 55-72]; 49 [38%] female and 79 [62%] male) were enrolled and treated in the pivotal cohort (median follow-up 17·4 months [IQR 9·1-20·9]). The overall response rate was 82·0% (105 of 128 patients; 95% CI 74·3-88·3), with a complete response rate of 62·5% (80 of 128; 95% CI 53·5-70·9). The most common grade 3-4 treatment-emergent adverse event was neutropenia in 32 (25%) of 128 patients. Grade 1-2 cytokine release syndrome was reported in 83 (65%) of 128 patients; grade 3 cytokine release syndrome was reported in two (2%). Immune effector cell-associated neurotoxicity syndrome was reported in eight (6%) of 128 patients (five [4%] grade 1; three [2%] grade 2). Between Oct 25, 2022, and Jan 8, 2024, 86 patients (median age 64 years [55-71]; 37 [43%] female and 49 [57%] male) were enrolled and treated in the cycle 1 optimisation cohort. The incidence of cytokine release syndrome was 49% (42 of 86 patients; eight [9%] grade 2; none of grade 3 or worse), with no reported immune effector cell-associated neurotoxicity syndrome.
INTERPRETATION
Epcoritamab monotherapy showed clinically meaningful activity in patients with multiply relapsed or refractory follicular lymphoma, and had a manageable safety profile.
FUNDING
Genmab and AbbVie.
PubMed: 38889737
DOI: 10.1016/S2352-3026(24)00166-2 -
Kardiologia Polska Jun 2024
Comprehensive assessment of Cardiovascular-Kidney-Metabolic (CKM) syndrome: Novel tools for assessment of cardiovascular risk and kidney outcomes in long-term kidney transplant patients.
PubMed: 38887781
DOI: 10.33963/v.phj.101062 -
Kardiologia Polska Jun 2024
Long-term outcomes following paclitaxel-coated balloons versus thin-strut drug eluting stents for treatment of in-stent restenosis in Chronic Coronary Syndrome (CCS Dragon-Registry).
PubMed: 38887780
DOI: 10.33963/v.phj.101064