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Genome Medicine Jan 2024The impact of the gut microbiome on the initiation and intensity of immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely...
BACKGROUND
The impact of the gut microbiome on the initiation and intensity of immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely acknowledged. Nevertheless, there is inconsistency in the gut microbial associations with irAEs reported across various studies.
METHODS
We performed a comprehensive analysis leveraging a dataset that included published microbiome data (n = 317) and in-house generated data from 16S rRNA and shotgun metagenome samples of irAEs (n = 115). We utilized a machine learning-based approach, specifically the Random Forest (RF) algorithm, to construct a microbiome-based classifier capable of distinguishing between non-irAEs and irAEs. Additionally, we conducted a comprehensive analysis, integrating transcriptome and metagenome profiling, to explore potential underlying mechanisms.
RESULTS
We identified specific microbial species capable of distinguishing between patients experiencing irAEs and non-irAEs. The RF classifier, developed using 14 microbial features, demonstrated robust discriminatory power between non-irAEs and irAEs (AUC = 0.88). Moreover, the predictive score from our classifier exhibited significant discriminative capability for identifying non-irAEs in two independent cohorts. Our functional analysis revealed that the altered microbiome in non-irAEs was characterized by an increased menaquinone biosynthesis, accompanied by elevated expression of rate-limiting enzymes menH and menC. Targeted metabolomics analysis further highlighted a notably higher abundance of menaquinone in the serum of patients who did not develop irAEs compared to the irAEs group.
CONCLUSIONS
Our study underscores the potential of microbial biomarkers for predicting the onset of irAEs and highlights menaquinone, a metabolite derived from the microbiome community, as a possible selective therapeutic agent for modulating the occurrence of irAEs.
Topics: Humans; Neoplasms; Immune Checkpoint Inhibitors; Gastrointestinal Microbiome; Antineoplastic Agents, Immunological; RNA, Ribosomal, 16S; Vitamin K 2; Drug-Related Side Effects and Adverse Reactions; Immunotherapy; Programmed Cell Death 1 Receptor; Immune System Diseases; Retrospective Studies; Lung Neoplasms
PubMed: 38243343
DOI: 10.1186/s13073-024-01285-9 -
BMC Musculoskeletal Disorders Jan 2024We aimed to assess the associations of vitamins intake with osteoporosis based on a national sample from US adults.
BACKGROUND
We aimed to assess the associations of vitamins intake with osteoporosis based on a national sample from US adults.
METHODS
A total of 1536 participants were included in this cross-sectional study to investigate the relationship between vitamins intake and osteoporosis from National Health and Nutrition Examination Survey, including vitamin A, C, D. Logistic regression models were used to assess the associations between dietary vitamin intake and osteoporosis.
RESULTS
We found that vitamins intake were negatively associated with osteoporosis. For vitamin A, compared with the first tertile, the odds ratios (ORs) and 95% confidential intervals (CIs) were 0.93 (0.81-1.04) for the second tertile and 0.85 (0.78-0.96) for the third tertile (P < 0.01). For vitamin C, compared with the first tertile, the ORs and 95% CIs were 0.89 (0.78-1.05) for the second tertile and 0.79 (0.67-0.93) for the third tertile (P < 0.01). For vitamin D, compared with the first tertile, the odds ratios (ORs) and 95% confidential intervals (CIs) were 0.94 (0.82-1.07) for the second tertile and 0.88 (0.75-0.98) for the third tertile (P < 0.01). And the negative association between vitamins intake and osteoporosis were more evident for female, aged ≥ 60, and BMI > 30, including vitamin A, C and D.
CONCLUSIONS
Our findings provide evidence that vitamins intake is linked with decreased prevalence of osteoporosis, including vitamin A, C, D. Further large-scale prospective cohort studies are needed to verify our findings.
Topics: Adult; Female; Humans; Bone Density; Vitamins; Absorptiometry, Photon; Cross-Sectional Studies; Vitamin A; Nutrition Surveys; Prospective Studies; Osteoporosis; Vitamin K
PubMed: 38233761
DOI: 10.1186/s12891-024-07173-y -
Trials Jan 2024Cystic fibrosis is an inherited disease, which is caused by the CFTR protein defects due to mutations in the CFTR gene. Along with CFTR dysfunction, exocrine pancreatic...
BACKGROUND
Cystic fibrosis is an inherited disease, which is caused by the CFTR protein defects due to mutations in the CFTR gene. Along with CFTR dysfunction, exocrine pancreatic insufficiency plays a key role in persistent fat malabsorption in CF patients; therefore, deficiency of fat-soluble vitamins (A, D, E, and K) is still a therapeutic challenge. Even with efficient pancreatic enzyme medication and CF-specific vitamins, many patients with CF have fat-soluble vitamins deficiency. The present study aims to evaluate the efficiency of nanomicelle formulation of fat-soluble vitamins in children with CF in order to achieve the appropriate serum levels of these vitamins.
METHODS
This prospective, single-blind control trial will be conducted at the Akbar Children's Hospital in Mashhad, Iran. Patients with CF will be enrolled based on the eligibility criteria. The control group will receive the standard formulation of fat-soluble vitamins similar to the routine CF treatment, and for the intervention group, the nanomicelle formulation of fat-soluble vitamins will be administered for 3 months. The primary outcome of this study is the measurement of serum levels of fat-soluble vitamins. The secondary outcomes are clinical assessment by the Shwachman-Kulczycki score, anthropometrics, and quality of life. Outcomes will be assessed before and after 3 months.
DISCUSSION
Due to persistent fat-soluble vitamin deficiency in CF disease, the nanomicelle formulation could be proposed as a new delivery method of fat-soluble vitamins in the treatment of cystic fibrosis.
TRIAL REGISTRATION
Iranian Registry of Clinical Trials IRCT20220415054541N1. Registered on July 23, 2022.
Topics: Child; Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Quality of Life; Iran; Prospective Studies; Single-Blind Method; Dietary Supplements; Vitamins; Vitamin A; Vitamin K; Randomized Controlled Trials as Topic
PubMed: 38229125
DOI: 10.1186/s13063-023-07896-8 -
Veterinary Research Jan 2024Carbonyl-reducing enzymes (CREs) catalyse the reduction of carbonyl groups in many eobiotic and xenobiotic compounds in all organisms, including helminths. Previous...
Flubendazole carbonyl reduction in drug-susceptible and drug-resistant strains of the parasitic nematode Haemonchus contortus: changes during the life cycle and possible inhibition.
Carbonyl-reducing enzymes (CREs) catalyse the reduction of carbonyl groups in many eobiotic and xenobiotic compounds in all organisms, including helminths. Previous studies have shown the important roles of CREs in the deactivation of several anthelmintic drugs (e.g., flubendazole and mebendazole) in adults infected with the parasitic nematode Haemonchus contortus, in which the activity of a CRE is increased in drug-resistant strains. The aim of the present study was to compare the abilities of nematodes of both a drug-susceptible strain (ISE) and a drug-resistant strain (IRE) to reduce the carbonyl group of flubendazole (FLU) in different developmental stages (eggs, L1/2 larvae, L3 larvae, and adults). In addition, the effects of selected CRE inhibitors (e.g., glycyrrhetinic acid, naringenin, silybin, luteolin, glyceraldehyde, and menadione) on the reduction of FLU were evaluated in vitro and ex vivo in H. contortus adults. The results showed that FLU was reduced by H. contortus in all developmental stages, with adult IRE females being the most metabolically active. Larvae (L1/2 and L3) and adult females of the IRE strain reduced FLU more effectively than those of the ISE strain. Data from the in vitro inhibition study (performed with cytosolic-like fractions of H. contortus adult homogenate) revealed that glycyrrhetinic acid, naringenin, mebendazole and menadione are effective inhibitors of FLU reduction. Ex vivo study data showed that menadione inhibited FLU reduction and also decreased the viability of H. contortus adults to a similar extent. Naringenin and mebendazole were not toxic at the concentrations tested, but they did not inhibit the reduction of FLU in adult worms ex vivo.
Topics: Female; Animals; Mebendazole; Haemonchus; Vitamin K 3; Anthelmintics; Larva; Glycyrrhetinic Acid
PubMed: 38225645
DOI: 10.1186/s13567-023-01264-9 -
Nutrients Dec 2023Multiple myeloma (MM) is a plasma cell malignancy that, despite recent advances in therapy, continues to pose a major challenge to hematologists. Currently, different...
Vitamin D and K Supplementation Is Associated with Changes in the Methylation Profile of U266-Multiple Myeloma Cells, Influencing the Proliferative Potential and Resistance to Bortezomib.
Multiple myeloma (MM) is a plasma cell malignancy that, despite recent advances in therapy, continues to pose a major challenge to hematologists. Currently, different classes of drugs are applied to treat MM, among others, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Most of them participate in an interplay with the immune system, hijacking its effector functions and redirecting them to anti-MM activity. Therefore, adjuvant therapies boosting the immune system may be potentially beneficial in MM therapy. Vitamin D (VD) and vitamin K (VK) have multiple so called "non-classical" actions. They exhibit various anti-inflammatory and anti-cancer properties. In this paper, we investigated the influence of VD and VK on epigenetic alterations associated with the proliferative potential of MM cells and the development of BTZ resistance. Our results showed that the development of BTZ resistance is associated with a global decrease in DNA methylation. On the contrary, both control MM cells and BTZ-resistant MM cells exposed to VD alone and to the combination of VD and VK exhibit a global increase in methylation. In conclusion, VD and VK in vitro have the potential to induce epigenetic changes that reduce the proliferative potential of plasma cells and may at least partially prevent the development of resistance to BTZ. However, further ex vivo and in vivo studies are needed to confirm the results and introduce new supplementation recommendations as part of adjuvant therapy.
Topics: Humans; Vitamin D; Bortezomib; Multiple Myeloma; Vitamins; Vitamin K; DNA Methylation; Dietary Supplements
PubMed: 38201971
DOI: 10.3390/nu16010142 -
Nutrients Dec 2023The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a... (Review)
Review
The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a strong relationship between the recommended daily dose of selected B vitamins and a functional immune system. Regarding specific B vitamins: (1) Riboflavin is necessary for the optimization of reactive oxygen species (ROS) in the fight against bacterial infections caused by and . (2) Niacin administered within normal doses to obese rats can change the phenotype of skeletal fibers, and thereby affect muscle metabolism. This metabolic phenotype induced by niacin treatment is also confirmed by stimulation of the expression of genes involved in the metabolism of free fatty acids (FFAs) and oxidative phosphorylation at this level. (3) Vitamin B5 effects depend primarily on the dose, thus large doses can cause diarrhea or functional disorders of the digestive tract whereas normal levels are effective in wound healing, liver detoxification, and joint health support. (4) High vitamin B6 concentrations (>2000 mg per day) have been shown to exert a significant negative impact on the dorsal root ganglia. Whereas, at doses of approximately 70 ng/mL, sensory symptoms were reported in 80% of cases. (5) Chronic increases in vitamin B12 have been associated with the increased incidence of solid cancers. Additionally, glucuronolactone, whose effects are not well known, represents a controversial compound. (6) Supplementing with D-glucarates, such as glucuronolactone, may help the body's natural defense system function better to inhibit different tumor promoters and carcinogens and their consequences. Cumulatively, the present review aims to evaluate the relationship between the selected B vitamins group, glucuronolactone, and the immune system and their associations to bioavailability, doses, and efficiency.
Topics: Animals; Rats; Vitamin B Complex; Niacin; Biological Availability; Glucuronates; Vitamin A; Vitamin K; Carcinogens
PubMed: 38201854
DOI: 10.3390/nu16010024 -
Cells Dec 2023Besides its role in coagulation, vitamin K seems to be involved in various other mechanisms, including inflammation and age-related diseases, also at the level of gene...
Amyloidogenic and Neuroinflammatory Molecular Pathways Are Contrasted Using Menaquinone 4 (MK4) and Reduced Menaquinone 7 (MK7R) in Association with Increased DNA Methylation in SK-N-BE Neuroblastoma Cell Line.
Besides its role in coagulation, vitamin K seems to be involved in various other mechanisms, including inflammation and age-related diseases, also at the level of gene expression. This work examined the roles of two vitamin K2 (menaquinones) vitamers, namely, menaquinone-4 (MK4) and reduced menaquinone-7 (MK7R), as gene modulator compounds, as well as their potential role in the epigenetic regulation of genes involved in amyloidogenesis and neuroinflammation. The SK-N-BE human neuroblastoma cells provided a "first-line" model for screening the neuroinflammatory and neurodegenerative molecular pathways. MK7R, being a new vitamin K form, was first tested in terms of solubilization, uptake and cell viability, together with MK4 as an endogenous control. We assessed the expression of key factors in amyloidogenesis and neuroinflammation, observing that the MK7R treatment was associated with the downregulation of neurodegeneration- ( and ) and neuroinflammation- ( and ) associated genes, whereas genes retaining protective roles toward amiloidogenesis were upregulated ( and ). By profiling the DNA methylation patterns of genes known to be epigenetically regulated, we observed a correlation between hypermethylation and the downregulation of , and These results suggest a possible role of MK7R in the treatment of cognitive impairment, giving a possible base for further preclinical experiments in animal models of neurodegenerative disease.
Topics: Animals; Humans; Vitamin K 2; Neuroinflammatory Diseases; Amyloid Precursor Protein Secretases; DNA Methylation; Epigenesis, Genetic; Interleukin-6; Neurodegenerative Diseases; Aspartic Acid Endopeptidases; Vitamin K; Neuroblastoma; Cell Line
PubMed: 38201262
DOI: 10.3390/cells13010058 -
Scientific Reports Jan 2024Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is avitamin K (VK) deficiency indicator in neonates. However, PIVKA-II detection frequency in neonatal...
Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is avitamin K (VK) deficiency indicator in neonates. However, PIVKA-II detection frequency in neonatal blood at birth and the correlation between PIVKA-II and gestational age are unclear. We retrospectively analyzed infants admitted to our institution between June 1, 2018, and March 31, 2022, whose clinical and PIVKA-II data were available, and classified them into preterm and term infant groups. Overall incidence of PIVKA-II-positive cases (≥ 50 mAU/mL) was 42.8%, including 0.6% apparent VK deficiency (≥ 5000 mAU/mL), 3.1% experimental VK deficiency (1000-4999 mAU/mL), and 10.7% latent VK deficiency (200-999 mAU/mL) cases. Incidence of PIVKA-II-positive cases was significantly higher in the term group than in the preterm group (49.4% vs. 29.7%, p < 0.001). Gestational age correlated with PIVKA-II levels (r = 0.117, p < 0.0001). Median serum PIVKA-II levels and incidence of PIVKA-II-positive cases (≥ 50 mAU/mL, 16.4%) were lower at 5 days after birth than at birth, possibly reflecting the postnatal VK prophylaxis impact. Only one infant was diagnosed with VK deficiency bleeding (PIVKA-II levels, at birth: 10,567 mAU/mL; at day 5: 2418 mAU/mL). Thus, serum PIVKA-II levels after birth weakly correlated with gestational age. VK deficiency was more common in term infants than in preterm infants.
Topics: Infant, Newborn; Infant; Humans; Vitamin K; Infant, Premature; Retrospective Studies; Gestational Age; Health Facilities
PubMed: 38195988
DOI: 10.1038/s41598-024-51674-8 -
Acta Veterinaria Scandinavica Jan 2024Tail biting (TB) is a welfare issue with economic consequences due to infections and ill-thrift. This study aimed to reduce tail injuries in a high-performing...
BACKGROUND
Tail biting (TB) is a welfare issue with economic consequences due to infections and ill-thrift. This study aimed to reduce tail injuries in a high-performing non-tail-docking pig herd.
RESULTS
During eleven years preceding the trial, the annual incidence of tail injuries registered at slaughter in pigs from the herd increased from 3% (equivalent to the national mean) to 10%. It was positively correlated to a high weight gain and negatively correlated to daylight length. The overall incidence of tail injuries during the four years preceding the trial was 9.2% with significant differences between four identically structured buildings for fatteners (I < II < III < IV). The feed was enriched with amino acids, minerals and fibres. The buildings used different illumination strategies, I: standard fluorescent tubes with an invisible flickering light of 30-40% for 14 h daily, II: non-flickering led light for 14 h daily, III (control) and IV: standard fluorescent tubes for 2 h daily. IV had free access to manipulable material (hay-silage), while I-III was offered 100-200 g daily. During the adaptation period (6 months), the incidence of tail injuries decreased significantly in all buildings to a mean of 5.4%. The largest decrease (from 11.4 to 4.3%) was obtained in IV. During the trial period (12 months), the mean incidence of tail injuries decreased in all groups to a mean of 3.0%. There were no differences in treatment incidences of individual pigs due to TB between groups, but the use of enriched pellets due to TB in pens was lowest in II. The low incidence of tail injuries was retained during the post-trial period (6 months) when all buildings used artificial illumination for two hours per day.
CONCLUSIONS
The incidence of TB in fast growing non-tail-docked pigs in the herd was successfully reduced by supplementing the feed with amino acids, minerals, vitamins and fibres. Additional manipulable material accelerated that process and non-flickering illumination may have had an impact in preventing TB. The results obtained do not support the need for tail-docking of pigs, provided that the needs of the pigs in terms of feed ingredients, stocking density and access to manipulable materials are fulfilled.
Topics: Animals; Amino Acids; Minerals; Swine; Tail; Vitamin A; Vitamin K; Animal Welfare
PubMed: 38195502
DOI: 10.1186/s13028-023-00716-8 -
Analytical and Bioanalytical Chemistry May 2024In this study, arsenic (As) speciation was investigated in the freshwater alga Chlamydomonas reinhardtii treated with 20 μg/L arsenate using fractionation as well as...
In this study, arsenic (As) speciation was investigated in the freshwater alga Chlamydomonas reinhardtii treated with 20 μg/L arsenate using fractionation as well as ICP-MS/ESI-MS analyses and was compared with the known As metabolite profile of wild-grown Saccharina latissima. While the total As accumulation in C. reinhardtii was about 85% lower than in S. latissima, the relative percentage of arsenolipids was significantly higher in C. reinhardtii (57.0% vs. 5.01%). As-containing hydrocarbons and phospholipids dominated the hydrophobic As profile in S. latissima, but no As-containing hydrocarbons were detectable in C. reinhardtii. Instead for the first time, an arsenoriboside-containing phytol (AsSugPhytol) was found to dominate the hydrophobic arsenicals of C. reinhardtii. Interestingly, this compound and its relatives had so far been only found in green marine microalgae, open sea plankton (mixed assemblage), and sediments but not in brown or red macroalgae. This compound family might therefore relate to differences in the arsenic metabolism between the algae phyla.
Topics: Arsenicals; Arsenic; Chlamydomonas reinhardtii; Hydrocarbons; Edible Seaweeds; Laminaria
PubMed: 38189919
DOI: 10.1007/s00216-023-05122-7