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Search Results (12,955)

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Keywords = Healthy Aging

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17 pages, 1471 KiB  
Article
RANKL/OPG Axis and Bone Mineral Density in Pediatric Inflammatory Bowel Disease
by Mariusz Olczyk, Agnieszka Frankowska, Marcin Tkaczyk, Anna Socha-Banasiak, Renata Stawerska, Anna Łupińska, Zuzanna Gaj, Ewa Głowacka and Elżbieta Czkwianianc
J. Clin. Med. 2025, 14(15), 5440; https://doi.org/10.3390/jcm14155440 (registering DOI) - 1 Aug 2025
Abstract
Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population [...] Read more.
Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population remain limited. Methods: A single-center, prospective observational study included 100 children aged 4–18 years, with a comparable number of girls and boys. Among them, 72 had IBD (27 CD, 45 UC) and 28 were healthy controls. Anthropometric, biochemical, and densitometric assessments were performed, including serum levels of RANKL and OPG, and markers of inflammation and bone turnover. Results: Children with CD had significantly lower height and weight percentiles compared to UC and controls. Serum RANKL and the RANKL/OPG ratio were significantly elevated in IBD patients, particularly in CD (p < 0.01). Total body BMD Z-scores were lower in IBD compared to controls (p = 0.03). Low BMD was found in 14.7% of UC and 26.3% of CD patients. In both groups, over 30% had values in the “gray zone” (−1.0 to −2.0). A positive correlation was observed between height and weight and bone density (p < 0.01). Higher OPG was associated with lower body weight (p < 0.001), while increased RANKL correlated with osteocalcin (p = 0.03). Patients receiving biological therapy had significantly lower BMD. Conclusions: Pediatric IBD is associated with significant alterations in the RANKL/OPG axis and reduced bone density. These findings support early screening and suggest RANKL/OPG as a potential biomarker of skeletal health. Full article
12 pages, 470 KiB  
Article
Validity and Reliability of the Turkish Version of the Healthy Aging Perception Scale in Older People with Chronic Diseases
by Nihan Türkoğlu, Nur Özlem Kılınç and Esin Kavuran
Behav. Sci. 2025, 15(8), 1048; https://doi.org/10.3390/bs15081048 (registering DOI) - 1 Aug 2025
Abstract
In order to promote healthy aging, it is important to know older people’s perceptions of healthy aging. The aim of this study is to conduct a Turkish validity and reliability study of the Healthy Aging Perception Scale for Older People with Chronic Diseases. [...] Read more.
In order to promote healthy aging, it is important to know older people’s perceptions of healthy aging. The aim of this study is to conduct a Turkish validity and reliability study of the Healthy Aging Perception Scale for Older People with Chronic Diseases. This study was conducted between November and December 2023 with older adult people living in a region in eastern Turkey. A total of 210 older people were included in the sample for the exploratory factor analysis and 214 for the confirmatory factor analysis. A Sociodemographic Information Form and Healthy Aging Perception Scale was used to collect the data of the study. The collected data were analyzed using SPSS 27.0 and AMOS 22.0. Confirmatory factor analysis for the 18-item scale, a four-factor structure with an eigenvalue exceeding 1, was obtained, and it was determined that the factor loadings ranged between 0.834 and 0.637 and the total variance explained was 64.619%. The confirmatory factor analysis of the goodness of fit indices was found to be at an acceptable level. CMIN/DF = 2.834, RMSEA = 0.05, CFI = 0.929, TLI = 0.910, NFI = 0.920, and GFI = 0.901. Cronbach’s alpha of the scale was determined to be 0.826, and the test–retest reliability coefficient was determined to be 0.822. Factor analysis showed a better model fit, and it was determined that the Healthy Aging Perception Scale is a valid and reliable measurement tool in determining the perceptions of the healthy aging of older people with chronic diseases. Full article
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20 pages, 4292 KiB  
Article
A Novel Method for Analysing the Curvature of the Anterior Lens: Multi-Radial Scheimpflug Imaging and Custom Conic Fitting Algorithm
by María Arcas-Carbonell, Elvira Orduna-Hospital, María Mechó-García, Guisela Fernández-Espinosa and Ana Sanchez-Cano
J. Imaging 2025, 11(8), 257; https://doi.org/10.3390/jimaging11080257 (registering DOI) - 1 Aug 2025
Abstract
This study describes and validates a novel method for assessing anterior crystalline lens curvature along vertical and horizontal meridians using radial measurements derived from Scheimpflug imaging. The aim was to evaluate whether pupil diameter (PD), anterior lens curvature, and anterior chamber depth (ACD) [...] Read more.
This study describes and validates a novel method for assessing anterior crystalline lens curvature along vertical and horizontal meridians using radial measurements derived from Scheimpflug imaging. The aim was to evaluate whether pupil diameter (PD), anterior lens curvature, and anterior chamber depth (ACD) change during accommodation and whether these changes are age-dependent. A cross-sectional study was conducted on 104 right eyes from healthy participants aged 21–62 years. Sixteen radial images per eye were acquired using the Galilei Dual Scheimpflug Placido Disk Topographer under four accommodative demands (0, 1, 3, and 5 dioptres (D)). Custom software analysed lens curvature by calculating eccentricity in both meridians. Participants were analysed as a total group and by age subgroups. Accommodative amplitude and monocular accommodative facility were inversely correlated with age. Both PD and ACD significantly decreased with higher accommodative demands and age. Relative eccentricity decreased under accommodation, indicating increased lens curvature, especially in younger participants. Significant curvature changes were detected in the horizontal meridian only, although no statistically significant differences between meridians were found overall. The vertical meridian showed slightly higher eccentricity values, suggesting that it remained less curved. By enabling detailed, meridionally stratified in vivo assessment of anterior lens curvature, this novel method provides a valuable non-invasive approach for characterizing age-related biomechanical changes during accommodation. The resulting insights enhance our understanding of presbyopia progression, particularly regarding the spatial remodelling of the anterior lens surface. Full article
(This article belongs to the Special Issue Current Progress in Medical Image Segmentation)
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18 pages, 3360 KiB  
Article
Hydrogen Sulfide Has a Minor Impact on Human Gut Microbiota Across Age Groups
by Linshu Liu, Johanna M. S. Lemons, Jenni Firrman, Karley K. Mahalak, Venkateswari J. Chetty, Adrienne B. Narrowe, Stephanie Higgins, Ahmed M. Moustafa, Aurélien Baudot, Stef Deyaert and Pieter Van den Abbeele
Sci 2025, 7(3), 102; https://doi.org/10.3390/sci7030102 (registering DOI) - 1 Aug 2025
Abstract
Hydrogen sulfide (H2S) can be produced from the metabolism of foods containing sulfur in the gastrointestinal tract (GIT). At low doses, H2S regulates the gut microbial community and supports GIT health, but depending on dose, age, and individual health [...] Read more.
Hydrogen sulfide (H2S) can be produced from the metabolism of foods containing sulfur in the gastrointestinal tract (GIT). At low doses, H2S regulates the gut microbial community and supports GIT health, but depending on dose, age, and individual health conditions, it may also contribute to inflammatory responses and gut barrier dysfunction. Controlling H2S production in the GIT is important for maintaining a healthy gut microbiome. However, research on this subject is limited due to the gaseous nature of the chemical and the difficulty of accessing the GIT in situ. In the present ex vivo experiment, we used a single-dose sodium sulfide preparation (SSP) as a H2S precursor to test the effect of H2S on the human gut microbiome across different age groups, including breastfed infants, toddlers, adults, and older adults. Metagenomic sequencing and metabolite measurements revealed that the development of the gut microbial community and the production of short-chain fatty-acids (SCFAs) were age-dependent; that the infant and the older adult groups were more sensitive to SSP exposure; that exogeneous SSP suppressed SCFA production across all age groups, except for butyrate in the older adult group, suggesting that H2S selectively favors specific gut microbial processes. Full article
(This article belongs to the Section Biology Research and Life Sciences)
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13 pages, 724 KiB  
Article
Investigating the Diagnostic Utility of LncRNA GAS5 in NAFLD Patients
by Maysa A. Mobasher, Alaa Muqbil Alsirhani, Sahar Abdulrahman Alkhodair, Amir Abd-elhameed, Shereen A. Baioumy, Marwa M. Esawy and Marwa A. Shabana
Biomedicines 2025, 13(8), 1873; https://doi.org/10.3390/biomedicines13081873 (registering DOI) - 1 Aug 2025
Abstract
Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions globally. This study aimed to assess the long non-coding RNAs (lncRNAs) growth arrest-specific 5 (GAS5), miR-29a-3p, and neurogenic locus notch homolog protein 2 (NOTCH2) as biomarkers in [...] Read more.
Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions globally. This study aimed to assess the long non-coding RNAs (lncRNAs) growth arrest-specific 5 (GAS5), miR-29a-3p, and neurogenic locus notch homolog protein 2 (NOTCH2) as biomarkers in patients with NAFLD and find out if they are related to any clinical factors. Subjects and Methods: Thirty-eight age-matched healthy persons and thirty-eight NAFLD patients were enrolled. Patients were split into the following three groups: non-alcoholic steatohepatitis (NASH) (n = 12), patients with NAFLD-related cirrhosis (n = 8), and patients with NAFLD-related simple steatosis (n = 18). Real-time PCR was utilized to examine the expression. Results: The lncRNA GAS5 and NOTCH2 were higher in NAFLD cases in comparison to controls. On the other hand, microRNA-29a-3p was underexpressed in NAFLD cases in comparison to controls. Regarding NAFLD diagnosis, lncRNA GAS5 was the best single marker with a sensitivity of 100% and a specificity of 94.7% at the cutoff values of ≥1.16-fold change. Regarding different stages of the disease, the highest level of lncRNA GAS5 was in cirrhosis. lncRNA GAS5 expression, among other studied parameters, is still a significant predictor of NAFLD (adjusted odds ratio of 162, C.I. = 5.7–4629) (p = 0.003). LncRNA GAS5 has a positive correlation with NOTCH2 and a negative correlation with miR-29a-3p. LncRNA GAS5, NOTCH2, and RNA-29a-3p were significantly different in NAFLD cases compared to controls. Conclusions: lncRNA GAS5 appears to be the most effective single marker for detecting NAFLD. LncRNA GAS5 expression is a significant independent predictor of NAFLD. LncRNA GAS5 can differentiate different NAFLD stages. Full article
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13 pages, 647 KiB  
Article
Reference Values for Liver Stiffness in Newborns by Gestational Age, Sex, and Weight Using Three Different Elastography Methods
by Ángel Lancharro Zapata, Alejandra Aguado del Hoyo, María del Carmen Sánchez Gómez de Orgaz, Maria del Pilar Pintado Recarte, Pablo González Navarro, Perceval Velosillo González, Carlos Marín Rodríguez, Yolanda Ruíz Martín, Manuel Sanchez-Luna, Miguel A. Ortega, Coral Bravo Arribas and Juan Antonio León Luís
J. Clin. Med. 2025, 14(15), 5418; https://doi.org/10.3390/jcm14155418 (registering DOI) - 1 Aug 2025
Abstract
Objective: To determine reference values of liver stiffness during the first week of extrauterine life in healthy newborns, according to gestational age, sex, and birth weight, using three elastography techniques: point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) with convex [...] Read more.
Objective: To determine reference values of liver stiffness during the first week of extrauterine life in healthy newborns, according to gestational age, sex, and birth weight, using three elastography techniques: point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) with convex and linear probes. Materials and Methods: This was a cross-sectional observational study conducted at a single center on a hospital-based cohort of 287 newborns between 24 and 42 weeks of gestation, admitted between January 2023 and May 2024. Cases with liver disease, significant neonatal morbidity, or technically invalid studies were excluded. Hepatic elastography was performed during the first week of life using pSWE and 2D-SWE with both convex and linear probes. Clinical and technical neonatal variables were recorded. Liver stiffness values were analyzed in relation to gestational age, birth weight, and sex. Linear regression models were applied to assess associations, considering p-values < 0.05 as statistically significant. Results: After applying exclusion criteria, valid liver stiffness measurements were obtained in 208 cases with pSWE, 224 with 2D-SWE (convex probe), and 222 with 2D-SWE (linear probe). A statistically significant inverse association between liver stiffness and gestational age (p < 0.03) was observed across all techniques except for 2D-SWE with the linear probe. Only 2D-SWE with the convex probe showed a significant association with birth weight. No significant differences were observed based on neonatal sex. The 2D-SWE technique with the convex probe demonstrated significantly shorter examination times compared to pSWE (p < 0.001). Conclusions: Neonatal liver stiffness measured by pSWE and 2D-SWE with a convex probe shows an inverse correlation with gestational age, potentially reflecting the structural and functional maturation of the liver. These techniques are safe, reliable, and provide useful information for distinguishing normal findings in preterm neonates from early hepatic pathology. The values obtained represent a valuable reference for clinical hepatic assessment in the neonatal period. Full article
(This article belongs to the Special Issue Multiparametric Ultrasound Techniques for Liver Disease Assessments)
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2 pages, 122 KiB  
Correction
Correction: Huang et al. The Safety and Immunogenicity of a Quadrivalent Influenza Subunit Vaccine in Healthy Children Aged 6–35 Months: A Randomized, Blinded and Positive-Controlled Phase III Clinical Trial. Vaccines 2025, 13, 467
by Lili Huang, Guangfu Li, Yuhui Zhang, Xue Zhao, Kai Wang, Chunyu Jia, Wei Zhang, Jiebing Tan, Xiaofen Chen, Qin Li, Hongyan Jiang, Rui An, Wenna Leng, Yongli Yang, Youcai An, Yanxia Wang and Yaodong Zhang
Vaccines 2025, 13(8), 826; https://doi.org/10.3390/vaccines13080826 (registering DOI) - 1 Aug 2025
Abstract
The authors would like to make the following corrections to this published paper [...] Full article
17 pages, 811 KiB  
Article
Implementation of Polygenic Risk Stratification and Genomic Counseling in Colombia: An Embedded Mixed-Methods Study
by Cesar Augusto Buitrago, Melisa Naranjo Vanegas, Harvy Mauricio Velasco, Danny Styvens Cardona, Juan Pablo Valencia-Arango, Sofia Lorena Franco, Lina María Torres, Johana Cañaveral, Diana Patricia Silgado and Andrea López Cáceres
J. Pers. Med. 2025, 15(8), 335; https://doi.org/10.3390/jpm15080335 (registering DOI) - 1 Aug 2025
Abstract
Background: Breast cancer remains a major public health challenge in Latin America, where access to personalized risk assessment tools is still limited. This study aimed to evaluate the implementation of a polygenic risk score (PRS)-based stratification model combined with remote genomic counseling [...] Read more.
Background: Breast cancer remains a major public health challenge in Latin America, where access to personalized risk assessment tools is still limited. This study aimed to evaluate the implementation of a polygenic risk score (PRS)-based stratification model combined with remote genomic counseling in Colombian women with sporadic breast cancer and healthy women. Methods: In 2023, an embedded mixed-methods observational study was conducted in Medellín involving 1997 women aged 40–75 years who underwent clinical PRS testing. The intervention integrated PRS-based risk categorization with individualized risk factor assessment and lifestyle recommendations delivered through a remote counseling platform. Results: PRS analysis classified 9.7% of women as high risk and 46% as low risk. Healthier lifestyle patterns were significantly associated with lower PRS categories (p = 0.034). Physical activity showed a protective effect (OR = 0.60, 95% CI: 0.5–0.8), while prior smoking, elevated BMI, and sedentary behavior were associated with higher risk. The counseling model achieved high delivery (93%) and satisfaction (85%) rates. Qualitative insights revealed improved understanding of genomic risk and greater engagement in preventive behaviors. Only one new case of breast cancer was detected among intermediate-risk participants, with a diagnostic lead time of 12 months. Conclusions: These findings support the feasibility, acceptability, and potential impact of integrating PRS and genomic counseling in cancer prevention strategies in middle-income settings. Full article
(This article belongs to the Special Issue Cancer Risk Assessment in Precision Medicine)
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13 pages, 1454 KiB  
Article
Lower Limb Inter-Joint Coordination and End-Point Control During Gait in Adolescents with Early Treated Unilateral Developmental Dysplasia of the Hip
by Chu-Fen Chang, Tung-Wu Lu, Chia-Han Hu, Kuan-Wen Wu, Chien-Chung Kuo and Ting-Ming Wang
Bioengineering 2025, 12(8), 836; https://doi.org/10.3390/bioengineering12080836 (registering DOI) - 31 Jul 2025
Abstract
Background: Residual deficits after early treatment of developmental dysplasia of the hip (DDH) using osteotomy often led to asymmetrical gait deviations with increased repetitive rates of ground reaction force (GRF) in both hips, resulting in a higher risk of early osteoarthritis. This [...] Read more.
Background: Residual deficits after early treatment of developmental dysplasia of the hip (DDH) using osteotomy often led to asymmetrical gait deviations with increased repetitive rates of ground reaction force (GRF) in both hips, resulting in a higher risk of early osteoarthritis. This study investigated lower limb inter-joint coordination and swing foot control during level walking in adolescents with early-treated unilateral DDH. Methods: Eleven female adolescents treated early for DDH using Pemberton osteotomy were compared with 11 age-matched healthy controls. The joint angles and angular velocities of the hip, knee, and ankle were measured, and the corresponding phase angles and continuous relative phase (CRP) for hip–knee and knee–ankle coordination were obtained. The variability of inter-joint coordination was quantified using the deviation phase values obtained as the time-averaged standard deviations of the CRP curves over multiple trials. Results: The DDH group exhibited a flexed posture with increased variability in knee–ankle coordination of the affected limb throughout the gait cycle compared to the control group. In contrast, the unaffected limb compensated for the kinematic alterations of the affected limb with reduced peak angular velocities but increased knee–ankle CRP over double-limb support and trajectory variability over the swing phase. Conclusions: The identified changes in inter-joint coordination in adolescents with early treated DDH provide a plausible explanation for the previously reported increased GRF loading rates in the unaffected limb, a risk factor of premature OA. Full article
(This article belongs to the Special Issue Biomechanics and Motion Analysis)
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15 pages, 1825 KiB  
Article
Entropy Analysis of Electroencephalography for Post-Stroke Dysphagia Assessment
by Adrian Velasco-Hernandez, Javier Imaz-Higuera, Jose Luis Martinez-de-Juan, Yiyao Ye-Lin, Javier Garcia-Casado, Marta Gutierrez-Delgado, Jenny Prieto-House, Gemma Mas-Sese, Araceli Belda-Calabuig and Gema Prats-Boluda
Entropy 2025, 27(8), 818; https://doi.org/10.3390/e27080818 (registering DOI) - 31 Jul 2025
Abstract
Affecting over 50% of stroke patients, dysphagia is still challenging to diagnose and manage due to its complex multifactorial nature and can be the result of disruptions in the coordination of cortical and subcortical neural activity as reflected in electroencephalographic (EEG) signal patterns. [...] Read more.
Affecting over 50% of stroke patients, dysphagia is still challenging to diagnose and manage due to its complex multifactorial nature and can be the result of disruptions in the coordination of cortical and subcortical neural activity as reflected in electroencephalographic (EEG) signal patterns. Sample Entropy (SampEn), a signal complexity or predictability measure, could serve as a tool to identify any abnormalities associated with dysphagia. The present study aimed to identify quantitative dysphagia biomarkers using SampEn from EEG recordings in post-stroke patients. Sample entropy was calculated in the theta, alpha, and beta bands of EEG recordings in a repetitive swallowing task performed by three groups: 22 stroke patients without dysphagia (controls), 36 stroke patients with dysphagia, and 21 healthy age-matched individuals. Post-stroke patients, both with and without dysphagia, exhibited significant differences in SampEn compared to healthy subjects in the alpha and theta bands, suggesting widespread alterations in brain dynamics. These changes likely reflect impairments in sensorimotor integration and cognitive control mechanisms essential for effective swallowing. A significant cluster was identified in the left parietal region during swallowing in the beta band, where dysphagic patients showed higher entropy compared to healthy individuals and controls. This finding suggests altered neural dynamics in a region crucial for sensorimotor integration, potentially reflecting disrupted cortical coordination associated with dysphagia. The precise quantification of these neurophysiological alterations offers a robust and objective biomarker for diagnosing neurogenic dysphagia and monitoring therapeutic interventions by means of EEG, a non-invasive and cost-efficient technique. Full article
(This article belongs to the Section Multidisciplinary Applications)
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17 pages, 1893 KiB  
Systematic Review
Attention Deficit and Memory Function in Children with Bronchial Asthma: A Systematic Review and Meta-Analysis of 104,975 Patients with Trial Sequential Analysis
by Plamen Penchev, Daniela Milanova-Ilieva, Lyubomir Gaydarski, Petar-Preslav Petrov, Kostadin Ketev, Pavel Stanchev, Noor Husain and Nikolai Ramadanov
Children 2025, 12(8), 1013; https://doi.org/10.3390/children12081013 - 31 Jul 2025
Abstract
Introduction: Asthma is a chronic respiratory disease affecting approximately 5 million children in the US, but little is known about whether asthma alters children’s attention and memory functions. Most studies on this topic focus on psychiatric and QoL outcomes rather than cognitive functions, [...] Read more.
Introduction: Asthma is a chronic respiratory disease affecting approximately 5 million children in the US, but little is known about whether asthma alters children’s attention and memory functions. Most studies on this topic focus on psychiatric and QoL outcomes rather than cognitive functions, leaving a gap in the literature. We aimed to conduct a systematic review and meta-analysis to evaluate the attention deficit and memory function outcomes in children with bronchial asthma. Methods: A systematic search was conducted in PubMed, Web of Science, and Cochrane Library from inception to 28 February 2025 for studies evaluating attention deficit and memory function in children with bronchial asthma. Outcomes of interest included attention deficit and memory function. Statistical analysis was performed with R 4.3.1. Heterogeneity was accessed using the I2 statistics and Cochrane Q test. The standardized mean difference (SMD) with restricted maximum-likelihood estimator random-effects method was computed for all outcomes. Results: A total of seven studies were included in the final meta-analysis, comprising 104,975 patients, of whom 10,200 (9.7%) had bronchial asthma (mean age ± 8.98 years, mean 45% females). In the pooled analysis, children with asthma had a worsened attention deficit compared to the healthy group (SMD 0.29; 95% CI [0.07; 0.51]; p = 0.01; I2 = 92%). However, no statistically significant difference was found in memory function between groups (SMD −0.24; 95% CI [−1.81; 1.33]; p = 0.77; I2 = 96%). Conclusions: Children with asthma showed significantly higher attention deficit scores compared to healthy children. No statistically significant differences were observed in memory function between the groups. These findings may have implications for early cognitive screening in pediatric asthma management. Full article
(This article belongs to the Special Issue Attention Deficit/Hyperactivity Disorder in Children and Adolescents)
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34 pages, 1782 KiB  
Review
Synthalin, Buformin, Phenformin, and Metformin: A Century of Intestinal “Glucose Excretion” as Oral Antidiabetic Strategy in Overweight/Obese Patients
by Giuliano Pasquale Ramadori
Livers 2025, 5(3), 35; https://doi.org/10.3390/livers5030035 (registering DOI) - 31 Jul 2025
Abstract
After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have [...] Read more.
After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article
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15 pages, 6719 KiB  
Article
circSATB1 Modulates Cell Senescence in Age-Related Acute Myeloid Leukemia: A Mechanistic Proposal
by Linxiang Han, Xi Wen, Ling Zhang, Xingcheng Yang, Ziyan Wei, Haodong Wu, Yichen Zhan, Huiting Wang and Yu Fang
Cells 2025, 14(15), 1181; https://doi.org/10.3390/cells14151181 - 31 Jul 2025
Abstract
Acute myeloid leukemia (AML) is a malignant hematological tumor with a high prevalence in elderly people, and circular RNA (circRNA) plays an important role in age-related diseases. Induction of cancer cell senescence is a highly promising therapeutic strategy; however, the presence of senescence-associated [...] Read more.
Acute myeloid leukemia (AML) is a malignant hematological tumor with a high prevalence in elderly people, and circular RNA (circRNA) plays an important role in age-related diseases. Induction of cancer cell senescence is a highly promising therapeutic strategy; however, the presence of senescence-associated circRNAs in AML remains to be elucidated. Here, we show that the expression patterns of circRNAs differed between elderly AML patients and healthy volunteers. circSATB1 was significantly overexpressed in elderly patients and AML cells. Knockdown of circSATB1 resulted in the inhibition of proliferation and arrest of the cell cycle in the G0/G1 phase; no effect on apoptosis or DNA integrity was observed, and precocious cellular senescence was promoted, characterized by no change in telomere length. Database analysis revealed that there may be two miRNA and nine RNA-binding proteins (RBPs) involved in regulating the cellular functions of circSATB1. Our observations uncover circSATB1-orchestrated cell senescence in AML, which provides clues for finding more modest therapeutic targets for AML. Full article
(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)
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25 pages, 2786 KiB  
Review
Mechanisms Underlying Muscle-Related Diseases and Aging: Insights into Pathophysiology and Therapeutic Strategies
by Jialin Fan, Zara Khanzada and Yunpeng Xu
Muscles 2025, 4(3), 26; https://doi.org/10.3390/muscles4030026 (registering DOI) - 31 Jul 2025
Abstract
Skeletal muscle aging and related diseases are characterized by progressive loss of muscle mass, strength, and metabolic function. Central to these processes is mitochondrial dysfunction, which impairs energy metabolism, redox homeostasis, and proteostasis. In addition, non-mitochondrial factors such as muscle stem cell exhaustion, [...] Read more.
Skeletal muscle aging and related diseases are characterized by progressive loss of muscle mass, strength, and metabolic function. Central to these processes is mitochondrial dysfunction, which impairs energy metabolism, redox homeostasis, and proteostasis. In addition, non-mitochondrial factors such as muscle stem cell exhaustion, neuromuscular junction remodeling, and chronic inflammation also contribute significantly to muscle degeneration. This review integrates recent advances in understanding mitochondrial and non-mitochondrial mechanisms underlying muscle aging and disease. Additionally, we discuss emerging therapeutic approaches targeting these pathways to preserve muscle health and promote healthy aging. Full article
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13 pages, 806 KiB  
Article
Structural Brain Changes in Patients with Congenital Anosmia: MRI-Based Analysis of Gray- and White-Matter Volumes
by Shun-Hung Lin, Hsian-Min Chen and Rong-San Jiang
Diagnostics 2025, 15(15), 1927; https://doi.org/10.3390/diagnostics15151927 - 31 Jul 2025
Abstract
Background: Congenital anosmia (CA) is a rare condition characterized by a lifelong inability to perceive odors, which significantly affects daily life and may be linked to broader neurodevelopmental alterations. This study aimed to investigate structural brain differences in patients with CA using MRI, [...] Read more.
Background: Congenital anosmia (CA) is a rare condition characterized by a lifelong inability to perceive odors, which significantly affects daily life and may be linked to broader neurodevelopmental alterations. This study aimed to investigate structural brain differences in patients with CA using MRI, focusing on gray matter (GM) and white matter (WM) changes and their implications for neurodevelopment. Methods: This retrospective study included 28 patients with CA and 28 age- and gender-matched healthy controls. Patients with CA were diagnosed at a single medical center between 1 January 2001 and 30 August 2024. Controls were randomly selected from an imaging database and had no history of olfactory dysfunction. Brain Magnetic Resonance Imaging (MRI)was analyzed using volumetric analysis in SPM12.GM and WM volumes were quantified across 11 anatomical brain regions based on theWFU_PickAtlas toolbox, including frontal, temporal, parietal, occipital, limbic, sub-lobar, cerebellum (anterior/posterior), midbrain, the pons, and the frontal–temporal junction. Left–right hemispheric comparisons were also conducted. Results: Patients with CA exhibited significantly smaller GM volumes compared to healthy controls (560.6 ± 114.7 cc vs. 693.7 ± 96.3 cc, p < 0.001) but larger WM volumes (554.2 ± 75.4 cc vs. 491.1 ± 79.7 cc, p = 0.015). Regionally, GM reductions were observed in the frontal (131.9 ± 33.7 cc vs. 173.7 ± 27.0 cc, p < 0.001), temporal (81.1 ± 18.4 cc vs. 96.5 ± 14.1 cc, p = 0.001), parietal (52.4 ± 15.2 cc vs. 77.2 ± 12.4 cc, p < 0.001), sub-lobar (57.8 ± 9.7 cc vs. 68.2 ± 10.2 cc, p = 0.001), occipital (39.1 ± 13.0 cc vs. 57.8 ± 8.9 cc, p < 0.001), and midbrain (2.0 ± 0.5 cc vs. 2.3 ± 0.4 cc, p = 0.006) regions. Meanwhile, WM increases were notable in the frontal(152.0 ± 19.9 cc vs. 139.2 ± 24.0 cc, p = 0.027), temporal (71.5 ± 11.5 cc vs. 60.8 ± 9.5 cc, p = 0.001), parietal (75.8 ± 12.4 cc vs. 61.9 ± 11.5 cc, p < 0.001), and occipital (58.7 ± 10.3 cc vs. 41.9 ± 7.9 cc, p < 0.001) lobes. A separate analysis of the left and right hemispheres revealed similar patterns of reduced GM and increased WM volumes in patients with CA across both sides. An exception was noted in the right cerebellum-posterior, where patients with CA showed significantly greater WM volume (5.625 ± 1.667 cc vs. 4.666 ± 1.583 cc, p = 0.026). Conclusions: This study demonstrates widespread structural brain differences in individuals with CA, including reduced GM and increased WM volumes across multiple cortical and sub-lobar regions. These findings suggest that congenital olfactory deprivation may impact brain maturation beyond primary olfactory pathways, potentially reflecting altered synaptic pruning and increased myelination during early neurodevelopment. The involvement of the cerebellum further implies potential adaptations beyond motor functions. These structural differences may serve as potential neuroimaging markers for monitoring CA-associated cognitive or emotional comorbidities. Full article
(This article belongs to the Special Issue Brain/Neuroimaging 2025)
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