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Current Issues in Molecular Biology May 2024Physical activity is integral to metabolic health, particularly in addressing insulin resistance and related disorders such as type 2 diabetes mellitus (T2DM). Studies... (Review)
Review
Physical activity is integral to metabolic health, particularly in addressing insulin resistance and related disorders such as type 2 diabetes mellitus (T2DM). Studies consistently demonstrate a strong association between physical activity levels and insulin sensitivity. Regular exercise interventions were shown to significantly improve glycemic control, highlighting exercise as a recommended therapeutic strategy for reducing insulin resistance. Physical inactivity is closely linked to islet cell insufficiency, exacerbating insulin resistance through various pathways including ER stress, mitochondrial dysfunction, oxidative stress, and inflammation. Conversely, physical training and exercise preserve and restore islet function, enhancing peripheral insulin sensitivity. Exercise interventions stimulate β-cell proliferation through increased circulating levels of growth factors, further emphasizing its role in maintaining pancreatic health and glucose metabolism. Furthermore, sedentary lifestyles contribute to elevated oxidative stress levels and ceramide production, impairing insulin signaling and glucose metabolism. Regular exercise induces anti-inflammatory responses, enhances antioxidant defenses, and promotes mitochondrial function, thereby improving insulin sensitivity and metabolic efficiency. Encouraging individuals to adopt active lifestyles and engage in regular exercise is crucial for preventing and managing insulin resistance and related metabolic disorders, ultimately promoting overall health and well-being.
PubMed: 38920999
DOI: 10.3390/cimb46060327 -
Journal of Mother and Child Feb 2024Van der Woude syndrome (VWS) is a rare congenital malformation characterized by lower lip pits among patients with a lip and/or palate cleft. It is transmitted by an...
BACKGROUND
Van der Woude syndrome (VWS) is a rare congenital malformation characterized by lower lip pits among patients with a lip and/or palate cleft. It is transmitted by an autosomal dominant inheritance with variable expressivity.
METHODS
The study group consisted of 24 consecutive patients (13 males and 11 females) with VWS operated on at a single center between 2009 and 2022. They suffered from: bilateral cleft lip and palate - 6 patients; unilateral cleft lip and palate - 9 patients; cleft lip - 1 patient; and isolated cleft palate - 8 patients.
RESULTS
In 16 (66%) cases pits of lower lip occurred on both side of midline, while in 8 (34%) the pits were detected unilaterally. The primary cleft repairs were performed according to one-stage principle at the mean age of 8.6 months (SD 1.4, range 6-12). In all patients lower lip pits repairs were performed after the primary cleft repairs as a separate procedure at the mean age of 37 months (SD 11.3 range 14-85). The mean number of all primary repairs of the syndrome-both cleft defect and lower lip pits repairs-was 2.46. Nine patients (37.5%) required additional secondary corrections of the lower lip due to the poor aesthetic post-operative outcome.
CONCLUSIONS
The frequent need for secondary corrections of residual lower lip deformities indicates the considerable difficulties in obtaining a satisfactory outcome of the repairs to lip pits caused by VWS. The average number of the primary surgical interventions in evaluated material remained low.
Topics: Humans; Cleft Lip; Female; Cleft Palate; Male; Retrospective Studies; Lip; Abnormalities, Multiple; Child, Preschool; Infant; Child; Treatment Outcome; Plastic Surgery Procedures; Cysts
PubMed: 38920016
DOI: 10.34763/jmotherandchild.20242801.d-24-00020 -
Scientific Reports Jun 2024Short-term exposure to air pollutants may contribute to an increased risk of acute coronary syndrome (ACS). This study assessed the role of short-term exposure to fine...
Short-term exposure to air pollutants may contribute to an increased risk of acute coronary syndrome (ACS). This study assessed the role of short-term exposure to fine particulate matter (PM) as well as fine and coarse PM (PM) air pollution in ACS events and the effect of blood groups on this phenomenon. A retrospectively collected database of 9026 patients was evaluated. The study design was a case-crossover using a conditional logistic regression model. The main analysis focused on PM levels with a 1 day lag until the ACS event, using threshold-modelled predictor for all patients. Secondary analyses utilized separate threshold-modelled predictors for 2-7-days moving averages and for patients from specific ABO blood groups. Additional analysis was performed with the non-threshold models and for PM levels. Short-term exposure to increased PM and PM levels at a 1-day lag was associated with elevated risks of ACS (PM: OR = 1.012 per + 10 µg/m, 95% CI 1.003, 1.021; PM: OR = 1.014 per + 10 µg/m, CI 1.002, 1.025) for all patients. Analysis showed that exposure to PM was associated with increased risk of ACS at a 1-day lag for the A, B or AB group (OR = 1.012 per + 10 µg/m, CI 1.001, 1.024), but not O group (OR = 1.011 per + 10 µg/m, CI 0.994, 1.029). Additional analysis showed positive associations between exposure to PM and risk of ACS, with 7-days moving average models stratified by blood group revealing that exposures to PM and PM were associated with elevated risk of ACS for patients with group O. Short-term exposures to PM and PM were associated with elevated risk of ACS. Short-term exposure to PM was positively associated with the risk of ACS for patients with A, B, or AB blood groups for a 1-day lag, while risk in O group was delayed to 7 days.
Topics: Humans; Acute Coronary Syndrome; Male; Female; Particulate Matter; Air Pollution; Middle Aged; Aged; Cross-Over Studies; Retrospective Studies; Air Pollutants; ABO Blood-Group System; Environmental Exposure; Risk Factors
PubMed: 38918482
DOI: 10.1038/s41598-024-65506-2 -
Pharmacological Reports : PR Jun 2024
Correction: Liquid chromatography-tandem mass spectrometry method for mycophenolic acid and its glucuronide determination in saliva samples from children with nephrotic syndrome.
PubMed: 38916851
DOI: 10.1007/s43440-024-00617-1 -
Journal of Neural Transmission (Vienna,... Jun 2024Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In... (Review)
Review
Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In most reported cases, the inheritance of BHC is autosomal dominant but both incomplete penetrance and variable expressivity are observed and can be caused by NKX2-1 mutations. The spectrum contains choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome. The neurological symptoms can be misdiagnosed as Huntington's disease (HD). The two Polish families were diagnosed with NKX2-1 gene mutations and a literature review concerning the NKX2-1-related disorders was conducted. All family members were examined by experienced movement disorders specialists. PubMed database was searched to obtain previously described NKX2-1 cases. Whole exome sequencing (WES) was performed in one proband (Family A) and direct NKX2-1 sequencing in the second (Family B). Two Polish families were diagnosed with NKX2-1 gene mutations (p.Trp208Leu and p.Cys117Alafs*8). In one family, the co-occurrence of HD was reported. Forty-nine publications were included in the literature review and symptoms of 195 patients with confirmed NKX2-1 mutation were analyzed. The most common symptoms were chorea and choreiform movements, and delayed motor milestones. The NKX2-1 mutation should always be considered as a potential diagnosis in families with chorea, even with a family history of HD. Lack of chorea does not exclude the NKX2-1-related disorders.
PubMed: 38916623
DOI: 10.1007/s00702-024-02800-3 -
Cardiology Journal 2024
Topics: Humans; Acute Coronary Syndrome; Platelet Aggregation Inhibitors; Treatment Outcome; Percutaneous Coronary Intervention
PubMed: 38913494
DOI: 10.5603/cj.98301 -
Anthropologischer Anzeiger; Bericht... Jun 2024The growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) is crucial for longitudinal bone growth and exerts several metabolic effects. It is debatable whether...
The growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) is crucial for longitudinal bone growth and exerts several metabolic effects. It is debatable whether and how the recombinant human growth hormone (rhGH) treatment affects the trunk-limb proportions. We aim to evaluate the changes in body proportions and body fat content in short children with growth hormone deficiency (GHD), children born small for gestational age (SGA), and girls with Turner syndrome (TS) during the first year of rhGH therapy. The data of 70 children with GHD, 40 children born SGA, and 36 girls with TS from 1998 to 2019 were analyzed. The following parameters were measured: height, body weight, sitting height, and two skinfolds on the arm above the triceps brachii and below the scapula at the beginning of rhGH therapy and after the first year of treatment. Sitting height and lower limb length were presented as percentages (%) of body height. Fat mass percentage (%FAT) was calculated using the Slaughter formula. At the beginning of rhGH, TS girls had the greatest height deficit (-2.7 SDS), the highest sitting height (%), and the lowest lower limb length (%) compared to children with GHD and children born SGA. Moreover, TS girls had higher body weight SDS, BMI SDS compared to SGA children ( < 0.001), and higher %FAT compared to both GHD and SGA children ( < 0.001 for both). After the first year of rhGH therapy, a significant increase in lower limb share (%) and a decrease in %FAT were observed in all the study groups. TS girls still had significantly higher sitting height (%), shorter lower limbs (%), and higher %FAT, body weight SDS, and BMI SDS compared to children with GHD and children born SGA ( < 0.05 for all variables). Our results show that rhGH treatment could increase lower limb length in relation to height and reduce fat mass in treated children. Girls with TS had the largest baseline body disproportions and the highest body fat content. Despite a satisfactory reduction in height deficit, after the first year of rhGH therapy, these girls had still higher body weight SDS, BMI SDS, %FAT, the highest sitting height (%), and the lowest lower limb length (%) compared to children with GHD and born SGA.
PubMed: 38912850
DOI: 10.1127/anthranz/2024/1763 -
International Journal of Biological... 2024Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges in terms of prognosis and treatment. Recent research has identified splicing deregulation as a new...
Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges in terms of prognosis and treatment. Recent research has identified splicing deregulation as a new cancer hallmark. Herein, we investigated the largely uncharacterized alternative splicing profile and the key splicing factor SF3B1 in PDAC pancreatic cells and tissues as a potential discovery source of plausible drug targets and new predictive biomarkers of clinical outcome. The research involved a transcriptome-wide analysis, comparing profiles of splicing profiles in PDAC primary cells with normal ductal cells. This revealed more than 400 significant differential splicing events in genes involved in regulation of gene expression, primarily related to mRNA splicing, and metabolism of nucleic acids. PDAC cultures were highly sensitive to the SF3B1 modulators, E7107 and Pladienolide-B, showing IC50s in the low nanomolar range. These compounds induced apoptosis, associated to induction of the MCL-1/S splice variant. and reduced cell migration, associated to RON mis-splicing. In an orthotopic mouse model, E7107 showed promising results. Furthermore, we evaluated SF3B1 expression in specimens from 87 patients and found a significant association of SF3B1 expression with progression-free and overall survival. In conclusion, SF3B1 emerges as both a potential prognostic factor and therapeutic target in PDAC, impacting cell proliferation, migration, and apoptosis. These findings warrant future studies on this new therapeutic strategy against PDAC.
Topics: Humans; RNA Splicing Factors; Pancreatic Neoplasms; Animals; Mice; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Epoxy Compounds; Prognosis; Phosphoproteins; Macrolides; Apoptosis; RNA Splicing; Alternative Splicing; Female; Cell Movement
PubMed: 38904016
DOI: 10.7150/ijbs.92671 -
Research Square Jun 2024The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP)...
The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.
PubMed: 38903062
DOI: 10.21203/rs.3.rs-4438861/v1 -
Asian Journal of Surgery Jun 2024
PubMed: 38902171
DOI: 10.1016/j.asjsur.2024.05.206