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Medicina (Kaunas, Lithuania) Jun 2024: The objective of this study is to investigate how different therapies modulating insulin resistance, either causally or consequently, affect metabolic parameters in...
: The objective of this study is to investigate how different therapies modulating insulin resistance, either causally or consequently, affect metabolic parameters in treatment-naïve subjects with T2DM. : A total of 212 subjects were assigned to receive either a tight Japanese diet ( = 65), pioglitazone at doses ranging from 15-30 mg/day ( = 70), or canagliflozin at doses ranging from 50-100 mg/day ( = 77) for a duration of three months. Correlations and changes (Δ) in metabolic parameters relative to insulin resistance were investigated. : Across these distinct therapeutic interventions, ΔHOMA-R exhibited significant correlations with ΔFBG and ΔHOMA-B, while demonstrating a negative correlation with baseline HOMA-R. However, other parameters such as ΔHbA1c, ΔBMI, ΔTC, ΔTG, Δnon-HDL-C, or ΔUA displayed varying patterns depending on the treatment regimens. Participants were stratified into two groups based on the median value of ΔHOMA-R: the lower half (X) and upper half (Y). Group X consistently demonstrated more pronounced reductions in FBG compared to Group Y across all treatments, while other parameters including HbA1c, HOMA-B, TC, TG, HDL-C, non-HDL-C, TG/HDL-C ratio, or UA exhibited distinct regulatory responses depending on the treatment administered. : These findings suggest that (1) regression to the mean is observed in the changes in insulin resistance across these therapies and (2) the modulation of insulin resistance with these therapies, either causally or consequentially, results in differential effects on glycemic parameters, beta-cell function, specific lipids, body weight, or UA.
Topics: Humans; Diabetes Mellitus, Type 2; Insulin Resistance; Male; Female; Middle Aged; Pioglitazone; Hypoglycemic Agents; Canagliflozin; Blood Glucose; Aged; Glycated Hemoglobin; Adult
PubMed: 38929608
DOI: 10.3390/medicina60060991 -
Medicina (Kaunas, Lithuania) May 2024: Ketogenic diet therapy (KDT) has been used as a non-pharmacological treatment for childhood refractory epilepsy. Its efficacy and safety have been described in...
: Ketogenic diet therapy (KDT) has been used as a non-pharmacological treatment for childhood refractory epilepsy. Its efficacy and safety have been described in numerous studies and reviews. However, there have been fewer studies evaluating the challenges experienced by patients and their family members when starting KDT. When implementing a new treatment method, challenges arise for both the healthcare professionals and patients, making it important to summarize the initial results and compare them with the experiences of other centers. To analyze and evaluate the efficacy and safety of KDT in children with epilepsy, as well as to consider the challenges faced by their parents/caregivers. : A retrospective analysis of patients' data (N = 30) and an analysis of the completed questionnaires of the parents/caregivers (N = 22) occurred. : In the study group, 66.7% of the patients had a >50% decrease in seizure frequency, and 2/3 of them had a >90% decrease in seizure frequency or were seizure-free, which enabled reducing the anti-seizure medications in 36.4% of the patients, as well as reducing the hospital visits. Cognitive improvement and better alertness were subjectively reported by 59.1% of the parents/caregivers. No dangerous long-term adverse effects of KDT have been observed in the study group. The patients with generalized epilepsy experienced significantly more adverse events. Most of the adverse effects of KDT were related to the digestive system, but usually they were temporary and controllable. The challenges of the parents/caregivers were mostly related to social life issues and financial difficulties; the medical-related challenges were minimal. : KDT is an effective and safe treatment option for children with drug-resistant epilepsy, and the challenges faced by families are resolvable. In order to ensure effective KDT, a multidisciplinary team is required. This would ensure smooth and comprehensive care and the timely resolution of emerging problems. The cooperation of the families undergoing KDT is also important, enabling them to share their experiences.
Topics: Humans; Diet, Ketogenic; Retrospective Studies; Male; Female; Child; Child, Preschool; Epilepsy; Treatment Outcome; Surveys and Questionnaires; Adolescent; Infant
PubMed: 38929536
DOI: 10.3390/medicina60060919 -
Antioxidants (Basel, Switzerland) May 2024Microbial community control is crucial for maintaining homeostasis of the gut-liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we...
Microbial community control is crucial for maintaining homeostasis of the gut-liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)- (nopal), (cocoa) and (crickets)-enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, and expression, and decreased and expression. MexMix significantly reduced steatosis in the mice's liver and modified the expression of 1668 genes. By PCR, we corroborated a and decrease, and a and increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.
PubMed: 38929103
DOI: 10.3390/antiox13060664 -
International Journal of Molecular... Jun 2024Sleep problems are a significant phenotype in children with fragile X syndrome. Our prior work assessed sleep-wake cycles in male mice and wild type (WT) littermate...
Sleep problems are a significant phenotype in children with fragile X syndrome. Our prior work assessed sleep-wake cycles in male mice and wild type (WT) littermate controls in response to ketogenic diet therapy where mice were treated from weaning (postnatal day 18) through study completion (5-6 months of age). A potentially confounding issue with commencing treatment during an active period of growth is the significant reduction in weight gain in response to the ketogenic diet. The aim here was to employ sleep electroencephalography (EEG) to assess sleep-wake cycles in mice in response to the genotype and a ketogenic diet, with treatment starting at postnatal day 95. EEG results were compared with prior sleep outcomes to determine if the later intervention was efficacious, as well as with published rest-activity patterns to determine if actigraphy is a viable surrogate for sleep EEG. The data replicated findings that mice exhibit sleep-wake patterns similar to wild type littermates during the dark cycle when maintained on a control purified-ingredient diet but revealed a genotype-specific difference during hours 4-6 of the light cycle of the increased wake (decreased sleep and NREM) state in mice. Treatment with a high-fat, low-carbohydrate ketogenic diet increased the percentage of NREM sleep in both wild type and mice during the dark cycle. Differences in sleep microstructure (length of wake bouts) supported the altered sleep states in response to ketogenic diet. Commencing ketogenic diet treatment in adulthood resulted in a 15% (WT) and 8.6% () decrease in body weight after 28 days of treatment, but not the severe reduction in body weight associated with starting treatment at weaning. We conclude that the lack of evidence for improved sleep during the light cycle (mouse sleep time) in mice in response to ketogenic diet therapy in two studies suggests that ketogenic diet may not be beneficial in treating sleep problems associated with fragile X and that actigraphy is not a reliable surrogate for sleep EEG in mice.
Topics: Animals; Diet, Ketogenic; Mice; Fragile X Syndrome; Mice, Inbred C57BL; Male; Sleep; Fragile X Mental Retardation Protein; Mice, Knockout; Electroencephalography; Disease Models, Animal
PubMed: 38928388
DOI: 10.3390/ijms25126679 -
International Journal of Molecular... Jun 2024The aryl hydrocarbon receptor (AhR) is a transcription factor that regulates the immune system through complicated transcriptional programs. Genistein, an AhR ligand,...
The aryl hydrocarbon receptor (AhR) is a transcription factor that regulates the immune system through complicated transcriptional programs. Genistein, an AhR ligand, exhibits anti-inflammatory properties. However, its role in modulating immune responses via the AhR signaling pathway remains unclear. In this study, 360 male Arbor Acre broilers (1-day-old) were fed a basal diet supplemented with 40 or 80 mg/kg genistein and infected with or without (). Our results demonstrated that genistein ameliorated -induced intestinal damage, as reflected by the reduced intestinal lesion scores and improved intestinal morphology and feed-to-gain ratio. Moreover, genistein increased intestinal sIgA, TGF-β, and IL-10, along with elevated serum IgG, IgA, and lysozyme levels. Genistein improved intestinal AhR and cytochrome P450 family 1 subfamily A member 1 (CYP1A1) protein levels and AhR cell numbers in -challenged broilers. The increased number of AhRCD163 cells in the jejunum suggested a potential association between genistein-induced AhR activation and anti-inflammatory effects mediated through M2 macrophage polarization. In IL-4-treated RAW264.7 cells, genistein increased the levels of AhR, CYP1A1, CD163, and arginase (Arg)-1 proteins, as well as IL-10 mRNA levels. This increase was attenuated by the AhR antagonist CH223191. In summary, genistein activated the AhR signaling pathway in M2 macrophages, which enhanced the secretion of anti-inflammatory cytokines and attenuated intestinal damage in -infected broilers .
Topics: Animals; Receptors, Aryl Hydrocarbon; Genistein; Chickens; Macrophages; Mice; Enteritis; Male; RAW 264.7 Cells; Poultry Diseases; Intestines; Clostridium perfringens; Clostridium Infections; Necrosis; Macrophage Activation; Inflammation; Signal Transduction
PubMed: 38928362
DOI: 10.3390/ijms25126656 -
International Journal of Molecular... Jun 2024Bosentan, an endothelin receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin...
Bosentan, an endothelin receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin, and mice were randomized into four groups: (1) control/COG: no intervention; (2) ΒOG: bosentan 100 mg/kg/day per os; (3) ATG: atorvastatin 20 mg/kg/day per os; and (4) BO + ATG: combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix metalloproteinases (MMP-2, -3, -9), and TIMP-1 were determined. The percentage of lumen stenosis was significantly lower across all treated groups: BOG: 19.5 ± 2.2%, ATG: 12.8 ± 4.8%, and BO + ATG: 9.1 ± 2.7% compared to controls (24.6 ± 4.8%, < 0.001). The administration of both atorvastatin and bosentan resulted in significantly higher collagen content and thicker fibrous cap versus COG ( < 0.01). All intervention groups showed lower relative intra-plaque concentrations of MCP-1, MMP-3, and MMP-9 and a higher TIMP-1concentration compared to COG ( < 0.001). Importantly, latter parameters presented lower levels when bosentan was combined with atorvastatin compared to COG ( < 0.05). Bosentan treatment in diabetic, atherosclerotic mice delayed the atherosclerosis progression and enhanced plaques' stability, showing modest but additive effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.
Topics: Animals; Bosentan; Atorvastatin; Mice; Male; Atherosclerosis; Endothelin Receptor Antagonists; Diabetes Mellitus, Experimental; Drug Therapy, Combination; Collagen; Diet, High-Fat; Chemokine CCL2; Tumor Necrosis Factor-alpha; Plaque, Atherosclerotic; Mice, Knockout; Tissue Inhibitor of Metalloproteinase-1
PubMed: 38928320
DOI: 10.3390/ijms25126614 -
International Journal of Molecular... Jun 2024Atopic dermatitis (AD) is a chronic inflammatory skin condition with a high prevalence worldwide. AD pathogenesis is complex and consists of immune system dysregulation... (Review)
Review
Atopic dermatitis (AD) is a chronic inflammatory skin condition with a high prevalence worldwide. AD pathogenesis is complex and consists of immune system dysregulation and impaired skin barrier, influenced by genetic and environmental factors. The purpose of the review is to show the complex interplay between atopic dermatitis and the microbiota. Human microbiota plays an important role in AD pathogenesis and the course of the disease. Dysbiosis is an important factor contributing to the development of atopic diseases, including atopic dermatitis. The gut microbiota can influence the composition of the skin microbiota, strengthening the skin barrier and regulating the immune response via the involvement of bacterial metabolites, particularly short-chain fatty acids, in signaling pathways of the gut-skin axis. AD can be modulated by antibiotic intake, dietary adjustments, hygiene, and living conditions. One of the promising strategies for modulating the course of AD is probiotics. This review offers a summary of how the microbiota influences the development and treatment of AD, highlighting aspects that warrant additional investigation.
Topics: Dermatitis, Atopic; Humans; Dysbiosis; Gastrointestinal Microbiome; Probiotics; Microbiota; Skin; Animals
PubMed: 38928245
DOI: 10.3390/ijms25126539 -
Genes Jun 2024Brain lipid homeostasis is an absolute requirement for proper functionality of nerve cells and neurological performance. Current evidence demonstrates that lipid...
Multifactor Analyses of Frontal Cortex Lipids in the APP/PS1 Model of Familial Alzheimer's Disease Reveal Anomalies in Responses to Dietary n-3 PUFA and Estrogenic Treatments.
Brain lipid homeostasis is an absolute requirement for proper functionality of nerve cells and neurological performance. Current evidence demonstrates that lipid alterations are linked to neurodegenerative diseases, especially Alzheimer's disease (AD). The complexity of the brain lipidome and its metabolic regulation has hampered the identification of critical processes associated with the onset and progression of AD. While most experimental studies have focused on the effects of known factors on the development of pathological hallmarks in AD, e.g., amyloid deposition, tau protein and neurofibrillary tangles, neuroinflammation, etc., studies addressing the causative effects of lipid alterations remain largely unexplored. In the present study, we have used a multifactor approach combining diets containing different amounts of polyunsaturated fatty acids (PUFAs), estrogen availabilities, and genetic backgrounds, i.e., wild type (WT) and APP/PS1 (FAD), to analyze the lipid phenotype of the frontal cortex in middle-aged female mice. First, we observed that severe n-3 PUFA deficiency impacts the brain n-3 long-chain PUFA (LCPUFA) composition, yet it was notably mitigated by hepatic de novo synthesis. n-6 LCPUFAs, ether-linked fatty acids, and saturates were also changed by the dietary condition, but the extent of changes was dependent on the genetic background and hormonal condition. Likewise, brain cortex phospholipids were mostly modified by the genotype (FAD>WT) with nuanced effects from dietary treatment. Cholesterol (but not sterol esters) was modified by the genotype (WT>FAD) and dietary condition (higher in DHA-free conditions, especially in WT mice). However, the effects of estrogen treatment were mostly observed in relation to phospholipid remodeling in a genotype-dependent manner. Analyses of lipid-derived variables indicate that nerve cell membrane biophysics were significantly affected by the three factors, with lower membrane microviscosity (higher fluidity) values obtained for FAD animals. In conclusion, our multifactor analyses revealed that the genotype, diet, and estrogen status modulate the lipid phenotype of the frontal cortex, both as independent factors and through their interactions. Altogether, the outcomes point to potential strategies based on dietary and hormonal interventions aimed at stabilizing the brain cortex lipid composition in Alzheimer's disease neuropathology.
Topics: Alzheimer Disease; Animals; Fatty Acids, Omega-3; Mice; Frontal Lobe; Female; Disease Models, Animal; Amyloid beta-Protein Precursor; Estrogens; Mice, Transgenic; Presenilin-1; Lipid Metabolism; Humans
PubMed: 38927745
DOI: 10.3390/genes15060810 -
Biomolecules May 2024Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and...
Reduced Insulin Resistance and Oxidative Stress in a Mouse Model of Metabolic Syndrome following Twelve Weeks of Citrus Bioflavonoid Hesperidin Supplementation: A Dose-Response Study.
Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg/kg/day), mid- (140 mg/kg/day), or high-dose (280 mg/kg/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice ( < 0.0001). Fasting blood glucose (FBG) increased by 40% ( < 0.0001), plasma insulin by 100% ( < 0.05), and HOMA-IR by 150% ( < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day ( < 0.0001) and 50% at 280 mg/kg/day ( < 0.005). HOMA-IR decreased by 45% at both doses ( < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups ( < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice ( < 0.001) and reduced by 20% with all hesperidin doses ( < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS.
Topics: Animals; Hesperidin; Oxidative Stress; Insulin Resistance; Metabolic Syndrome; Male; Mice; Citrus; Mice, Inbred C57BL; Dietary Supplements; Disease Models, Animal; Dose-Response Relationship, Drug; Blood Glucose; Diet, High-Fat; Antioxidants
PubMed: 38927040
DOI: 10.3390/biom14060637 -
Biomolecules May 2024Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks the colon, leading to ulcer development, loss of colon function, and bloody diarrhea.... (Review)
Review
Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks the colon, leading to ulcer development, loss of colon function, and bloody diarrhea. The human gut ecosystem consists of almost 2000 different species of bacteria, forming a bioreactor fueled by dietary micronutrients to produce bioreactive compounds, which are absorbed by our body and signal to distant organs. Studies have shown that the Western diet, with fewer short-chain fatty acids (SCFAs), can alter the gut microbiome composition and cause the host's epigenetic reprogramming. Additionally, overproduction of HS from the gut microbiome due to changes in diet patterns can further activate pro-inflammatory signaling pathways in UC. This review discusses how the Western diet affects the microbiome's function and alters the host's physiological homeostasis and susceptibility to UC. This article also covers the epidemiology, prognosis, pathophysiology, and current treatment strategies for UC, and how they are linked to colorectal cancer.
Topics: Humans; Gastrointestinal Microbiome; Colitis, Ulcerative; Colorectal Neoplasms; Epigenesis, Genetic; Diet, Western; Animals
PubMed: 38927037
DOI: 10.3390/biom14060633