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Turkish Journal of Medical Sciences 2023This study was designed to evaluate the relationship of two new biomarkers [tribbles homolog 3 (TRB3) and sestrin 2 levels], which were previously associated with...
BACKGROUND/AIM
This study was designed to evaluate the relationship of two new biomarkers [tribbles homolog 3 (TRB3) and sestrin 2 levels], which were previously associated with obesity, with metabolic parameters in obese and nonobese women with polycystic ovary syndrome (PCOS).
MATERIALS AND METHODS
This cross-sectional case control study was conducted between September 2017 and August 2019 in the gynecology department of a tertiary referral hospital. The values of the plasma sestrin 2, TRB3, insulin, fasting plasma glucose, lipid profile, and homeostasis model assessment of insulin resistance (HOMA-IR) were compared in 90 obese women with PCOS (BMI > 30), 90 women with nonobese PCOS (BMI < 30), and 90 control patients (BMI < 30).
RESULTS
The mean age of the study group consisting of all PCOS patients (26.11 ± 4.64 years) and the mean age of the control group (26.3 ± 4.4 years) were statistically similar (p = 0.239). The serum sestrin 2 values of the obese PCOS group were found to be statistically significantly lower than the control and non-obese PCOS groups (p = 0.001, p = 0.0001), while the sestrin 2 values of the nonobese PCOS group were found to be statistically significantly lower than the control group (p = 0.0001). The TRB3 values of the control group were found to be statistically significantly lower than the obese and nonobese PCOS groups (p = 0.0001), while the TRB3 values of the nonobese PCOS group were found to be statistically significantly lower than the obese PCOS group (p = 0.0001). A negative correlation was observed between the sestrin 2 level and BMI (r = -0.272 p = 0.0001), insulin (r = -0.261 p = 0.0001), and HOMA-IR levels (r = -0.250 p = 0.0001). A positive correlation was observed between the TRB3 values and TG (r = 0.248 p = 0.0001), and LDL-C values (r = 0.235 p = 0.0001).
CONCLUSION
According to the findings in this study, low sestrin 2 and high TRB3 levels may be related to impaired metabolic status in the obese PCOS group. Thus, it may be promising for the development of treatment of PCOS and associated metabolic disorder in the future.
Topics: Humans; Female; Polycystic Ovary Syndrome; Obesity; Adult; Case-Control Studies; Cross-Sectional Studies; Protein Serine-Threonine Kinases; Biomarkers; Insulin Resistance; Nuclear Proteins; Young Adult; Blood Glucose; Sestrins; Repressor Proteins; Cell Cycle Proteins
PubMed: 38813505
DOI: 10.55730/1300-0144.5738 -
Turkish Journal of Medical Sciences 2023To reveal the impacts of dapagliflozin, a sodium glucose transporter-2 inhibitor (SGLT-2i), on body weight and body composition, cardiovascular risk indices, and carotid...
BACKGROUND/AIM
To reveal the impacts of dapagliflozin, a sodium glucose transporter-2 inhibitor (SGLT-2i), on body weight and body composition, cardiovascular risk indices, and carotid intima-media thickness (CIMT).
MATERIALS AND METHODS
The data of patients with type-2 diabetes mellitus (T2DM) who applied to Department of Endocrinology and Metabolic Disorders between September 2019 and 2020, and had started dapagliflozin treatment along with their current medications were recorded retrospectively. Body weights, body compositions measured through bioelectrical impedance, and CIMT with T2DM receiving SGLT-2i treatment and medication were measured at weeks 1, 12, and 24 of 42. The visceral adiposity index (VAI), lipid accumulation product (LAP), and atherogenic index of plasma (AIP) were used to determine the lipid measurements and anthropometric values.
RESULTS
The mean change in the total body weight and total fat mass was -2.96 and -1.97 kg, respectively (p < 0.001). There was a reduction in total fat mass of 1.23 kg (from 31.4 to 29.3 kg, p < 0.001) and in body fat percentage of 2.5% (from 35.8% to 34.4%, p < 0.001) in the first 12 weeks. A mild increase was observed in both the total fat mass and body fat percentage between weeks 12 and 24, which was not statistically significant (p = 0.783 and p = 0.925, respectively), whereas there was a statistically significant reduction in high-sensitive C-reactive protein (hsCRP), AIP, and CIMT values (p = 0.006, p = 0.035, and p = 0.007, respectively). No changes were observed in the VAI and LAP values (p = 0.985 and p = 0.636, respectively).
CONCLUSION
It was observed that dapagliflozin not only contributes to weight and fat loss but also has positive impacts on cardiovascular and atherosclerotic indicators.
Topics: Humans; Glucosides; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Male; Female; Middle Aged; Body Composition; Sodium-Glucose Transporter 2 Inhibitors; Body Weight; Retrospective Studies; Carotid Intima-Media Thickness; Cardiovascular Diseases; Adult; Aged; Heart Disease Risk Factors
PubMed: 38813008
DOI: 10.55730/1300-0144.5683 -
Frontiers in Cellular and Infection... 2024To investigate the structure, composition, and functions of the gut microbiota in elderly patients with hyperlipidemia.
OBJECTIVE
To investigate the structure, composition, and functions of the gut microbiota in elderly patients with hyperlipidemia.
METHODS
Sixteen older patients diagnosed with hyperlipidemia (M group) and 10 healthy, age-matched normal volunteers (N group) were included. These groups were further subdivided by sex into the male normal (NM, n = 5), female normal (NF, n = 5), male hyperlipidemia (MM, n = 8), and female hyperlipidemia (MF, n = 8) subgroups. Stool samples were collected for high-throughput sequencing of 16S rRNA genes. Blood samples were collected for clinical biochemical index testing.
RESULTS
Alpha- and beta-diversity analyses revealed that the structure and composition of the gut microbiota were significantly different between the M and N groups. The relative abundances of , , , , and were significantly decreased, while those of , , and were significantly higher in the M group. There were also significant sex-related differences in microbial structure between the NM and NF groups, and between the MM and MF groups. Through functional prediction with PICRUSt 2, we observed distinct between-group variations in metabolic pathways associated with the gut microbiota and their impact on the functionality of the nervous system. Pearson's correlation coefficient was used as a distance metric to build co-abundance networks. A hypergeometric test was used to detect taxonomies with significant enrichment in specific clusters. We speculated that modules with and as the core microbes play an important ecological role in the intestinal microbiota of the M group. The relative intestinal abundances of and in the M group were positively correlated with serum triglyceride and low-density lipoprotein levels, while the relative abundance of was negatively correlated with the serum lipoprotein a level.
Topics: Humans; Gastrointestinal Microbiome; Male; Female; Aged; Hyperlipidemias; RNA, Ribosomal, 16S; Feces; Bacteria; High-Throughput Nucleotide Sequencing; Middle Aged; Aged, 80 and over
PubMed: 38812752
DOI: 10.3389/fcimb.2024.1333145 -
BMC Psychiatry May 2024Motor alterations and lowered physical activity are common in affective disorders. Previous research has indicated a link between depressive symptoms and declining... (Observational Study)
Observational Study
The association between maximal muscle strength, disease severity and psychopharmacotherapy among young to middle-aged inpatients with affective disorders - a prospective pilot study.
BACKGROUND
Motor alterations and lowered physical activity are common in affective disorders. Previous research has indicated a link between depressive symptoms and declining muscle strength primarily focusing on the elderly but not younger individuals. Thus, we aimed to evaluate the relationship between mood and muscle strength in a sample of N = 73 young to middle-aged hospitalized patients (18-49 years, mean age 30.7 years) diagnosed with major depressive, bipolar and schizoaffective disorder, with a focus on moderating effects of psychopharmacotherapy. The study was carried out as a prospective observational study at a German psychiatric university hospital between September 2021 and March 2022.
METHODS
Employing a standardized strength circuit consisting of computerized strength training devices, we measured the maximal muscle strength (F) using three repetitions maximum across four muscle regions (abdomen, arm, back, leg) at three time points (t-t) over four weeks accompanied by psychometric testing (MADRS, BPRS, YRMS) and blood lipid profiling in a clinical setting. For analysis of psychopharmacotherapy, medication was split into activating (AM) and inhibiting (IM) medication and dosages were normalized by the respective WHO defined daily dose.
RESULTS
While we observed a significant decrease of the MADRS score and increase of the relative total F (rTF) in the first two weeks (t-t) but not later (both p < .001), we did not reveal a significant bivariate correlation between disease severity (MADRS) and muscle strength (rTF) at any of the timepoints. Individuals with longer disease history displayed reduced rTF (p = .048). IM was significantly associated with decreased rTF (p = .032). Regression models provide a more substantial effect of gender, age, and IM on muscle strength than the depressive episode itself (p < .001).
CONCLUSIONS
The results of the study indicate that disease severity and muscle strength are not associated in young to middle-aged inpatients with affective disorders using a strength circuit as observational measurement. Future research will be needed to differentiate the effect of medication, gender, and age on muscle strength and to develop interventions for prevention of muscle weakness, especially in younger patients with chronic affective illnesses.
Topics: Humans; Muscle Strength; Male; Pilot Projects; Adult; Female; Prospective Studies; Middle Aged; Young Adult; Adolescent; Inpatients; Bipolar Disorder; Depressive Disorder, Major; Psychotic Disorders; Severity of Illness Index
PubMed: 38811916
DOI: 10.1186/s12888-024-05849-2 -
Science Advances May 2024Lipid droplets (LDs) comprise a triglyceride core surrounded by a lipid monolayer enriched with proteins, many of which function in LD homeostasis. How proteins are...
Lipid droplets (LDs) comprise a triglyceride core surrounded by a lipid monolayer enriched with proteins, many of which function in LD homeostasis. How proteins are targeted to the growing LD is still unclear. Rab1b, a GTPase regulating secretory transport, was recently associated with targeting proteins to LDs in a Drosophila RNAi screen. LD formation was prevented in human hepatoma cells overexpressing dominant-negative Rab1b. We thus hypothesized that Rab1b recruits lipid-synthesizing enzymes, facilitating LD growth. Here, FRET between diacylglycerol acyltransferase 2 (DGAT2) and Rab1b and activity mutants of the latter demonstrated that Rab1b promotes DGAT2 ER to the LD surface redistribution. Last, alterations in LD metabolism and DGAT2 redistribution, consistent with Rab1b activity, were caused by mutations in the Rab1b-GTPase activating protein TBC1D20 in Warburg Micro syndrome (WARBM) model mice fibroblasts. These data contribute to our understanding of the mechanism of Rab1b in LD homeostasis and WARBM, a devastating autosomal-recessive disorder caused by mutations in TBC1D20.
Topics: Lipid Droplets; Animals; Humans; rab1 GTP-Binding Proteins; Diacylglycerol O-Acyltransferase; Mice; Endoplasmic Reticulum; Mutation; Lipid Metabolism; GTPase-Activating Proteins
PubMed: 38809969
DOI: 10.1126/sciadv.ade7753 -
Revista Paulista de Pediatria : Orgao... 2024To report the case of a girl presenting a severe phenotype of mandibuloacral dysplasia type A (MADA) characterized by prominent osteolytic changes and ectodermal...
OBJECTIVE
To report the case of a girl presenting a severe phenotype of mandibuloacral dysplasia type A (MADA) characterized by prominent osteolytic changes and ectodermal defects, associated with a rare homozygous LMNA missense mutation (c.1579C>T).
CASE DESCRIPTION
A 6-year-old girl was evaluated during hospitalization exhibiting the following dysmorphic signs: subtotal alopecia, dysmorphic facies with prominent eyes, marked micrognathia and retrognathia, small beaked nose, teeth crowding and thin lips, generalized lipodystrophy, narrow and sloping shoulders, generalized joint stiffness and bone reabsorption in the terminal phalanges. In dermatological examination, atrophic skin, loss of cutaneous elasticity, hyperkeratosis, dermal calcinosis, and hyperpigmented and hypochromic patches were observed. Radiology exams performed showed bilateral absence of the mandibular condyles, clavicle resorption with local amorphous bone mass confluence with the scapulae, shoulder joints with subluxation and severe bone dysplasia, hip dysplasia, osteopenia and subcutaneous calcifications.
COMMENTS
MADA is a rare autosomal recessive disease caused by mutations in LMNA gene. It is characterized by craniofacial deformities, skeletal anomalies, skin alterations, lipodystrophy in certain regions of the body and premature ageing. Typical MADA is caused by the p.R527H mutation in the LMNA gene. However, molecular analysis performed from oral epithelial cells obtained from the patient showed the rare mutation c.1579C>T, p. R527C in the exon 9 of LMNA. This is the sixth family identified with this mutation described in the literature.
Topics: Humans; Female; Mutation, Missense; Lamin Type A; Child; Phenotype; Mandible; Lipodystrophy; Acro-Osteolysis
PubMed: 38808865
DOI: 10.1590/1984-0462/2024/42/2022189 -
Contact (Thousand Oaks (Ventura County,... 2024One means by which cells reutilize neutral lipids stored in lipid droplets is to degrade them by autophagy. This process involves spartin, mutations of which cause the...
One means by which cells reutilize neutral lipids stored in lipid droplets is to degrade them by autophagy. This process involves spartin, mutations of which cause the rare inherited disorder Troyer syndrome (or spastic paraplegia-20, SPG20). A recently published paper from the team led by Karin Reinsich (Yale) suggests that the molecular function of spartin and its unique highly conserved "senescence" domain is as a lipid transfer protein. Spartin binds to and transfers all lipid species found in lipid droplets, from phospholipids to triglycerides and sterol esters. This lipid transfer activity correlates with spartin's ability to sustain lipid droplet turnover. The senescence domain poses an intriguing question around the wide range of its cargoes, but intriguingly it has yet to yield up its secrets because attempts at crystallization failed and AlphaFold's prediction is unconvincing.
PubMed: 38808280
DOI: 10.1177/25152564241255782 -
Frontiers in Endocrinology 2024A recent cross-sectional study showed that both comorbidities and mortality in patients with adrenal incidentaloma (AI) are tied to sex. However, few longitudinal...
BACKGROUND
A recent cross-sectional study showed that both comorbidities and mortality in patients with adrenal incidentaloma (AI) are tied to sex. However, few longitudinal studies evaluated the development of arterial hypertension, hyperglycemia, dyslipidemia and bone impairment in patients with AI. The aim of this study is to analyze the impact of sex in the development of these comorbidities during long-term follow-up.
METHODS
We retrospectively evaluated 189 patients (120 females, 69 males) with AI, from four referral centers in Italy and Croatia. Clinical characteristics, comorbidities and cortisol after 1-mg dexamethasone suppression test (1-mg DST) were assessed at baseline and at last follow-up visit (LFUV). Median follow-up was 52 (Interquartile Range 25-86) months.
RESULTS
The rates of arterial hypertension and hyperglycemia increased over time both in females (65.8% at baseline 77.8% at LFUV, =0.002; 23.7% at baseline 39.6% at LFUV, <0.001; respectively) and males (58.0% at baseline 69.1% at LFUV, =0.035; 33.8% at baseline 54.0% at LFUV, <0.001; respectively). Patients were stratified in two groups using 1.8 µg/dl as cut-off of cortisol following 1-mg DST: non-functional adrenal tumors (NFAT) and tumors with mild autonomous cortisol secretion (MACS). In the NFAT group (99 patients, females 62.6%), at baseline, we did not observe any difference in clinical characteristics and comorbidities between males and females. At LFUV, males showed a higher frequency of hyperglycemia than females (57.6% 33.9%, =0.03). In the MACS group (89 patients, females 64.0%), at baseline, the prevalence of hypertension, hyperglycemia and dyslipidemia was similar between sexes, despite females were younger (60, IQR 55-69 67.5, IQR 61-73, years; =0.01). Moreover, females presented higher rates of bone impairment (89.3% 54.5%, =0.02) than males. At LFUV, a similar sex-related pattern was observed.
CONCLUSION
Patients with AI frequently develop arterial hypertension and hyperglycemia and should be periodically checked for these comorbidities, regardless of sex. In patients with MACS, the lack of difference between sexes in the frequency of cardiometabolic comorbidities despite that females are younger, and the higher frequency of bone impairment in females, suggest a sex-specific effect of cortisol.
Topics: Humans; Female; Male; Adrenal Gland Neoplasms; Middle Aged; Retrospective Studies; Aged; Comorbidity; Hypertension; Sex Factors; Hyperglycemia; Dyslipidemias; Follow-Up Studies; Italy; Cross-Sectional Studies
PubMed: 38808113
DOI: 10.3389/fendo.2024.1385808 -
Respiratory Research May 2024Pulmonary hypertension (PH) is regarded as cardiovascular disease with an extremely poor prognosis, primarily due to irreversible vascular remodeling. Despite decades of... (Review)
Review
Pulmonary hypertension (PH) is regarded as cardiovascular disease with an extremely poor prognosis, primarily due to irreversible vascular remodeling. Despite decades of research progress, the absence of definitive curative therapies remains a critical challenge, leading to high mortality rates. Recent studies have shown that serious metabolic disorders generally exist in PH animal models and patients of PH, which may be the cause or results of the disease. It is imperative for future research to identify critical biomarkers of metabolic dysfunction in PH pathophysiology and to uncover metabolic targets that could enhance diagnostic and therapeutic strategies. Metabolomics offers a powerful tool for the comprehensive qualitative and quantitative analysis of metabolites within specific organisms or cells. On the basis of the findings of the metabolomics research on PH, this review summarizes the latest research progress on metabolic pathways involved in processes such as amino acid metabolism, carbohydrate metabolism, lipid metabolism, and nucleotide metabolism in the context of PH.
Topics: Humans; Metabolomics; Hypertension, Pulmonary; Animals; Lipid Metabolism
PubMed: 38807129
DOI: 10.1186/s12931-024-02775-5 -
Scientific Reports May 2024Extracellular vesicles (EVs) are lipid-membrane enclosed structures that are associated with several diseases, including those of genitourinary tract. Urine contains EVs...
Extracellular vesicles (EVs) are lipid-membrane enclosed structures that are associated with several diseases, including those of genitourinary tract. Urine contains EVs derived from urinary tract cells. Owing to its non-invasive collection, urine represents a promising source of biomarkers for genitourinary disorders, including cancer. The most used method for urinary EVs separation is differential ultracentrifugation (UC), but current protocols lead to a significant loss of EVs hampering its efficiency. Moreover, UC protocols are labor-intensive, further limiting clinical application. Herein, we sought to optimize an UC protocol, reducing the time spent and improving small EVs (SEVs) yield. By testing different ultracentrifugation times at 200,000g to pellet SEVs, we found that 48 min and 60 min enabled increased SEVs recovery compared to 25 min. A step for pelleting large EVs (LEVs) was also evaluated and compared with filtering of the urine supernatant. We found that urine supernatant filtering resulted in a 1.7-fold increase on SEVs recovery, whereas washing steps resulted in a 0.5 fold-decrease on SEVs yield. Globally, the optimized UC protocol was shown to be more time efficient, recovering higher numbers of SEVs than Exoquick-TC (EXO). Furthermore, the optimized UC protocol preserved RNA quality and quantity, while reducing SEVs separation time.
Topics: Ultracentrifugation; Humans; Extracellular Vesicles; Biomarkers; Urine; Female
PubMed: 38806574
DOI: 10.1038/s41598-024-62783-9