Search Results (263)

Background/objectives: Polycystic ovary syndrome (PCOS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are common co-morbidities in women of reproductive age. PCOS is highly heterogeneous and is, therefore, divided into four phenotypes. MASLD leads to numerous systemic complications. Studies to date have shown an association between PCOS and MASLD. This study was designed to compare the FIB-4 score (based on age, alanine aminotransferase, aspartate aminotransferase and platelet count) and the results of shear wave elastography in assessing the risk of developing MASLD by patients with PCOS divided by phenotypes. Methods: The study enrolled 242 women age 18–35 years with PCOS diagnosed according to Rotterdam criteria, hospitalized at the Department of Gynaecological Endocrinology of the University Clinical Centre in Katowice. The study subjects were assigned to phenotypes A to D. Clinical and biochemical assessments were performed (including androgens and metabolic parameters), and the FIB-4 index was calculated. Liver fibrosis was evaluated by shear wave elastography. To balance the group sizes of phenotypes, oversampling with replacement was applied (PROC SURVEYSELECT, SAS), increasing the number of observations for phenotypes B, C, and D fivefold. Statistical analyses were performed based on data distribution (Shapiro–Wilk test), using ANOVA or the Kruskal–Wallis test with Dunn’s correction. Statistical significance was set at p < 0.05. Results: The FIB-4 score was the highest in phenotype B patients (0.50 ± 0.15), and the lowest in phenotypes A and C (0.42 ± 0.14). The highest rate of positive elastography findings was recorded in phenotype A patients (34.7%) and the lowest in phenotype C group (13.5%). Significant differences between the phenotypes were also found in terms of androgen levels, insulin, HOMA-IR, and the lipid profile. Among patients with positive elastography, the highest FIB-4 scores were recorded in phenotype C group (0.44 ± 0.06), but the differences between the phenotypes were not statistically significant. Conclusions: The FIB-4 score was the highest in phenotype B patients and differed significantly from phenotypes A, C and D. In the elastography exam, the fibrosis index was statistically significantly higher in phenotype A compared to other phenotypes. No correlation was detected between the FIB-4 index and positive elastography. The findings suggest that the FIB-4 index may be used for MASLD screening, but its usefulness as a predictor of eligibility for elastography requires more research. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD), a recently proposed term to replace non-alcoholic fatty liver disease (NAFLD), emphasizes the critical role of metabolic dysfunction and applies broader diagnostic criteria. Diagnosis of MAFLD requires evidence of hepatic steatosis combined with obesity, type 2 diabetes mellitus, or other metabolic dysregulation conditions, all of which significantly elevate the risk of chronic kidney disease (CKD). This review discusses the pathological mechanisms of lipid accumulation and insulin resistance in MAFLD and CKD, highlighting their mechanistic connections. Specifically, ectopic fat accumulation triggered by metabolic reprogramming, oxidative stress and inflammation induced by energy overload, modified lipids, uremic toxins, and senescence, as well as insulin resistance pathways activated by pro-inflammatory factors and lipotoxic products, collectively exacerbate simultaneous hepatic and renal injury. Moreover, interactions among hyperinsulinemia, the sympathetic nervous system, the renin–angiotensin system (RAS), and altered adipokine and hepatokine profiles further amplify insulin resistance, ectopic lipid deposition, and systemic damage. Finally, the review explores potential therapeutic strategies targeting lipid metabolism, insulin sensitivity, and RAS activity, which offer promise for dual-organ protection and improved outcomes in both hepatic and renal systems. Full article

The advent of effective antiretroviral therapy in the mid-1990s, which successfully prevented the progression to AIDS in people living with HIV (PLWH), was associated with the appearance of the so-called HIV-associated lipodystrophy. This condition involved subcutaneous fat atrophy; abdominal fat hypertrophy; and, in some cases, lipomatosis. It was also associated with systemic metabolic disturbances, primarily insulin resistance and dyslipidemia. Following the replacement of certain antiretroviral drugs, particularly the thymidine-analog reverse transcriptase inhibitors stavudine and zidovudine, with less toxic alternatives, the incidences of lipoatrophy and lipomatosis significantly declined. However, lipodystrophy resulting from first-generation antiretroviral therapy does not always resolve after switching to newer agents. Although the widespread use of modern antiretroviral drugs—especially integrase strand transfer inhibitors and non-lipoatrophic reverse transcriptase inhibitors such as tenofovir alafenamide—has reduced the incidences of severe forms of lipodystrophy, these regimens are not entirely free of adipose tissue-related effects. Notably, they are associated with weight gain that resembles common obesity and can have adverse cardiometabolic consequences. Recent evidence also suggests the hypertrophy of specific fat depots, such as epicardial and perivascular adipose tissue, in PLWH on last-generation treatments, potentially contributing to increased cardiovascular risk. This evolving landscape underscores the persistent vulnerability of PLWH to adipose tissue alterations. While these morphological changes may not be as pronounced as those seen in classic HIV-associated lipodystrophy, they can still pose significant health risks. The continued optimization of treatment regimens and the vigilant monitoring of adipose tissue alterations and metabolic status remain essential strategies to improve the health of PLWH. Full article

Background: Hashimoto’s thyroiditis (HT), the most prevalent autoimmune thyroid disorder in reproductive-age women, has been linked to diminished ovarian reserve and subfertility. This study aimed to evaluate the relationship between HT and key fertility parameters, including hormonal markers and reproductive outcomes, while also exploring the potential impact of thyroid hormone replacement therapy. Methods: A retrospective observational study was conducted on 86 women undergoing fertility evaluation. Participants were divided into two groups based on anti-thyroid peroxidase antibodies (ATPO): the HT group (n = 49) and the control group (n = 37). Among women with HT, 57% were receiving levothyroxine (Euthyrox^®) at the time of assessment. Variables analyzed included serum levels of anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), insulin resistance index (HOMA-IR), number of oocytes retrieved, blastocysts formed, pregnancies achieved, and live births. Statistical methods included t-tests, Mann–Whitney U tests, Pearson/Spearman correlations, and linear regression models. Results: Women in the HT group had slightly lower AMH levels and oocyte counts compared to controls, though these differences did not reach statistical significance. TSH values were higher in the HT group and showed a significant negative correlation with blastocyst formation (p = 0.03). Although TSH also showed negative trends with oocyte count, pregnancies, and live births, these correlations did not reach statistical significance. A post-hoc subgroup analysis revealed that HT patients receiving levothyroxine tended to have higher numbers of oocytes retrieved and blastocysts formed compared to untreated HT patients, suggesting a possible beneficial effect of thyroid hormone replacement, although the differences were not statistically significant. Conclusions: HT is associated with subtle but clinically relevant impairments in ovarian reserve and reproductive potential. Thyroid hormone replacement may offer modest benefits and should be considered in the individualized management of fertility in women with thyroid autoimmunity. Full article

Background/Objectives: Diabetic ketoacidosis (DKA) is an acute and severe complication of diabetes mellitus, marked by hyperglycemia, ketosis, and acidosis. It is associated with significant metabolic and inflammatory adjustments that can impact multiple biochemical pathways. This study aimed to determine the serum sphingolipid profile in DKA and investigate its relationship with neutral sphingomyelinase (N-SMase), pro-inflammatory cytokines, β-hydroxybutyrate (β-OHB), and lactate levels. Methods: Thirty-three participants were divided into three groups: control (BMI ≤ 30, no health issues), obese (BMI > 30), and DKA (BMI ≤ 30). Sphingomyelins (16:0–24:0 SMs) and ceramides (C16–C24 CERs) were measured using ultra-fast liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). N-SMase, interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were assessed by enzyme-linked immunosorbent assay. Evaluations were done in the DKA group before and after standard clinical treatment for DKA (post-DKA group), which included intravenous insulin therapy, fluid resuscitation, and electrolyte replacement, as per established clinical guidelines. Results: β-OHB levels were significantly higher in the DKA group than in the control, obese, and post-DKA groups. Although β-OHB levels decreased in the post-DKA group, they remained elevated compared to the control and obese groups. Lactate levels were also higher in the DKA group, with a significant decrease in the post-DKA group. TNF-α and IL-1β were higher in the obese group compared to control and DKA groups, and TNF-α decreased significantly in the post-DKA group compared to DKA. N-SMase, 16:0–18:0 SMs, and C18-C24 CER levels were lower in the DKA and post-DKA groups compared to obese and control groups. Serum β-OHB and lactate levels were significantly correlated with S1P, total CER, total SM, and N-SMase values. Conclusions: The study reveals significant metabolic and inflammatory differences in DKA and post-DKA states, suggesting a relationship between sphingolipids, N-SMase, and these alterations, which could offer insights into DKA pathophysiology and therapeutic targets. Full article

Background: One of the most debated topics in experimental and clinical endocrinology is the impact of hypo- and hyper-somatotropism on the extension/shortening of the lifespan, the results of experimental, clinical, and epidemiological studies being extremely conflicting. Biological age, a surrogate of lifespan, can be measured through different methods, including the age-related epigenetic modifications of DNA. Objective: The present study aimed to evaluate the biological (epigenetic) age and age acceleration in a group of growth hormone (GH)-deficient (GHD) children (F/M = 5/5; age: 11.0 ± 2.7 years), treated with recombinant human GH (rhGH) for 6 months at a daily dose of 0.025–0.035 mg/kg. Results: Treatment with rhGH significantly increased height velocity and circulating insulin-like growth factor 1 (IGF-1) levels. Biological and chronological ages were significantly correlated at baseline and after 6 months of rhGH replacement therapy. Treatment with rhGH reduced age acceleration, an effect that became significant only after adjustment for IGF-1. In a linear regression model for longitudinal data, after adjustment for rhGH treatment, age acceleration was significantly associated with IGF-1 levels, an effect missing when considering the interaction rhGH treatment × age acceleration at 6 months of rhGH treatment. Conclusions: (rh)GH, when administered to GHD children, exerts anti-ageing effects, which become evident after removal of the presumably pro-ageing effects of IGF-1. Full article

This study was conducted to investigate the effects of replacing fish meal with either whole-fat or defatted krill powder on the growth, body color, immunity, and related gene expression of red–white koi carp. A total of 630 red–white koi carp with an initial body mass of 13.5 ± 0.05 g were randomly divided into seven groups with three replicates per group and 30 fish per replicate. The control group was fed a basic diet (C0). The other six diets were supplemented with different levels of whole krill meal or defatted krill meal as replacements (10% whole fat, 20% whole fat, 30% whole fat, 10% defatted, 20% defatted, and 30% defatted) in the experimental groups, named W10, W20, W30, D10, D20, and D30, respectively, for a total duration of 60 days. The growth, body color, immunity and gene expression indexes were measured in the koi after completion. The results indicate the following. (1) Compared with C0, the experimental groups of koi showed a significant increase in the specific growth rate (SGR) (p < 0.05), while the hepatosomatic index (HSI) and viscerosomatic ratio (VSI) decreased. Additionally, there was a significant increase in the relative expression level of insulin-like growth factor (IGF-1) in both the liver and muscle (p < 0.05). (2) The experimental groups of koi carp exhibited a significant increase in the carotenoid content in the scales and skin, as well as an elevated relative expression level of the tyrosinase (TYR) gene in the muscle (p < 0.05). (3) The lysozyme (LZM) and superoxide dismutase (SOD) activities were significantly increased in the experimental groups compared to C0 (p < 0.05). Additionally, the SOD activity was significantly higher in the defatted groups than in the whole-fat groups (p < 0.05). Furthermore, the liver alkaline phosphatase (AKP) activity was significantly lower in the D20 and D30 groups compared to the other five groups. (4) The expression level of LPL was significantly lower in the liver and muscle of the whole-fat group compared to the defatted group (p < 0.05). Tissue section observation revealed that the hepatocytes in the W20 and W30 groups exhibited a reduced size and an increased lipid droplet count, while the vacuolar degeneration of the hepatocytes increased in the D30 group. In conclusion, replacing fish meal with whole-fat or defatted krill powder or defatted Antarctic krill meal significantly improves the growth performance, body color, and immunity of red–white koi carp. However, excessive addition of krill meal can easily cause liver damage. The recommended replacement level for whole krill powder is 20% to 30%, while defatted krill powder should be replaced at a level of 10% to 20%. Full article

Biochemical alterations linked to metabolic syndrome (MetS), type 2 diabetes (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD) may be brought on by the Western diet. Based on research conducted over the past decade, fructose is one of the main culprits. Over 80% of ingested fructose is metabolized by the liver at first pass, where it stimulates de novo lipogenesis (DNL) to drive hepatic triglyceride (TG) synthesis, which contributes to MASLD, hepatic insulin resistance (IR), and dyslipidemia. Fructose reduction produces quick and significant amelioration in these metabolic disturbances. We hereby propose potential overarching processes that can link these pathways to signaling disruption by the critical metabolic sensor AMP-activated protein kinase (AMPK). We proffer that when large amounts of fructose and glucose enter the liver, triose fluxes may be sufficient to produce transient increases in methylglyoxal (MG), allowing steady-state concentrations between its production and catabolism by glyoxalases to be high enough to modify AMPK-sensitive functional amino acid residues. These reactions would transiently interfere with AMPK activation by both AMP and aldolase. Such a sequence of events would boost the well-documented lipogenic impact of fructose. Given that MG adducts are irreversible, modified AMPK molecules would be less effective in metabolite sensing until they were replaced by synthesis. If proven, this mechanism provides another avenue of possibilities to tackle the problem of fructose in our diet. We additionally discuss potential multimodal treatments and future research avenues for this apparent hepatic AMPK malfunction. Full article

This research investigated the growth, serum biochemistry, antioxidant capability, and immunity impact of black carp fed degossypolled cottonseed protein replacing fishmeal at the levels of 0%, 10%, 20%, 30%, 40%, and 50% (DCP0, DCP10, DCP20, DCP30, DCP40, and DCP50), respectively. The results showed there were no significant changes in growth among these test groups. The activities and mRNA expression levels of amylase and trypsin were heightened in conjunction with 30–40% DCP. Although the insulin contents were reduced with a rise in DCP content, 5-hydroxytryptamino was increased in the DCP40 and DCP50 groups. DCP40 could heighten the levels of low-density lipoprotein cholesterol, triglycerides, total cholesterol, and urea nitrogen. Although lower levels of DCP (≤20%) could increase the total antioxidant capacity compared with the DCP50 group, DCP50 could markedly heighten levels of catalase, glutathione S-transferase, H₂O₂, and malondialdehyde. Meanwhile, the mRNA levels of Mn-superoxide dismutase, glutathione reductase, glutathione peroxidase, glutamate–cysteine ligase regulatory subunit, and nuclear factor E2-related factor 2 were heightened in the DCP30 group compared with the DCP50 group. The levels of alkaline phosphatase, immunoglobulin M, and liver-expressed antimicrobial peptide 2 were markedly heightened in the liver of the DCP20 group compared with the DCP50 group. In conclusion, a suitable level of DCP (20%) could improve serum biochemical indices and hormone variation, enhance antioxidant capability, and increase immunity in black carp. Full article

Background/Objectives: Diabetic ketoacidosis (DKA) is a common acute complication of diabetes with treatment consisting of reversal of cause, insulin administration, fluid resuscitation and electrolyte repletion. Yet, many aspects of DKA management are currently based on low-quality evidence or physiological rationale. This evidence and gap map review presents an overview of the current body of literature and identifies evidence gaps in relation to therapeutic interventions for DKA. Methods: Interventions and outcomes relevant to DKA were identified and iteratively developed to produce a coding model for the proposed evidence and gap map. PubMed was searched with Me SH terms relevant to the identified interventions and outcomes. Studies identified were screened and assigned interventions and outcomes. Interventional research was uploaded to EPPI-Reviewer and EPPI-Mapper to produce the evidence and gap map. Results: The search identified 1131 studies, of which 18 were non-human and 345 were duplicates. A total of 768 unique studies were screened, and 118 were identified as interventions (52 pediatric and 66 adult studies). A total of 26 high-quality studies, 88 medium-quality studies and 4 low-quality studies were identified. These 118 studies were coded into the proposed DKA evidence and gap map. The intervention domains were fluid therapy, insulin therapy, electrolyte replacement, adjunct therapies and admission type. The outcome domains were DKA resolution, insulin duration, length of stay, morbidity and mortality, complications, and biochemical parameters. Conclusions: Fluid type and insulin infusion administration were prominent in the current literature. These studies frequently used DKA resolution and complications associated with DKA such as electrolyte disturbances and cerebral edema as the primary outcomes. Substantial gaps were identified with scant evidence to guide prophylactic electrolyte administration, enteral intake and adjunctive therapy (thiamine, bicarbonate). Even for well-investigated interventions such as fluids and insulin, substantial gaps existed, particularly for patient-centered and healthcare service outcomes. Full article

Muscle satellite (stem) cells (MSCs) reside in skeletal muscle and are essential for myogenesis. Thus, MSCs are widely used in cultured meat research. This study aimed to identify substances that promote MSC proliferation and differentiation while maintaining their intrinsic properties, with the long-term goal of replacing fetal bovine serum (FBS) for bovine MSC cultivation. Therefore, this study evaluated the effects of six growth factors (TGF-β, HGF, PDGF, insulin, IGF-1, and EGF) and the cytokine IL-2 on bovine MSCs. Each factor was applied during the proliferation and differentiation of MSCs, and the proliferation rate, differentiation rate, and expression of relevant mRNA and proteins were analyzed. Insulin most effectively promoted MSC proliferation and differentiation. Specifically, insulin increased cell proliferation rates, proliferation markers Ki67 and PCNA expressions, and markers of differentiation, such as myotube formation and creatine kinase activity, alongside the expressions of MYOD, MYOG, and MYH. Furthermore, insulin suppressed low FBS-induced reductions in proliferation and differentiation markers. This study suggests insulin can promote MSC proliferation and differentiation and reduce FBS usage. Thus, this study provides a potential means of cultivating MSCs on a large scale for cultured meat production. Full article

Background: Chicken Primordial Germ Cells (PGCs) are one of the few germ cells that can be cultured for a long time in vitro, but challenges remain such as low culture efficiency and unclear roles of nutrient factors and signaling pathways. Method: In this study, protein kinase B (AKT) pathway activator insulin-like growth factor 1 (IGF-1) was screened for its ability to promote cell proliferation by transcriptome results using various inhibitors of pathway activation. The effects of IGF-1 on PGCs were evaluated through EdU assays, qRT-PCR, flow cytometry, and migration experiments. Results: This study systematically examined the effects of insulin and IGF-1 on the proliferation, cell cycle, ferroptosis, migration capacity, and establishment efficiency of PGCs. The findings demonstrated that IGF-1 exhibited comparable effects to insulin and could effectively replace insulin in PGC culture systems. Conclusions: The research results are expected to provide a solid theoretical basis for optimizing the chicken PGC cultivation system and promoting its practical application. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver dysfunction worldwide, characterized by hepatic steatosis that may progress to nonalcoholic steatohepatitis and cirrhosis. Owing to its strong association with metabolic disorders, current management focuses on weight reduction via lifestyle modifications. Recently, the very-low-calorie ketogenic diet (VLCKD) has emerged as a promising intervention due to its potential for rapid weight loss and reduction in liver fat. This review aims to evaluate the clinical evidence regarding the impact of ketogenic diets on hepatic steatosis. We conducted an extensive MEDLINE literature search in databases including PubMed, Scopus, and Web of Science up to December 2024. Studies assessing the effects of ketogenic or low-carbohydrate high-fat diets on liver fat, evaluated by imaging, histology, or biochemical markers, were included. The analysis indicates that ketogenic diets significantly reduce hepatic fat content and improve metabolic parameters, including insulin sensitivity and liver enzyme levels. Evidence further suggests that substituting saturated fats with unsaturated fats or replacing carbohydrates with proteins may enhance these benefits. However, considerable variability exists among studies and long-term data remain limited. Although short-term outcomes are encouraging, potential adverse effects such as dyslipidaemia, gastrointestinal disturbances, and transient ‘keto flu’ symptoms require careful clinical monitoring. Future research should focus on elucidating underlying mechanisms, optimizing dietary composition, and assessing long-term safety to establish ketogenic diets as a robust strategy for managing MASLD. Full article

Background: Estrogen plays a crucial role in adipose tissue homeostasis, influencing fat distribution, lipid metabolism, and insulin sensitivity. Through estrogen receptor (ER) activation, particularly ERα, estradiol (E2) regulates adipogenesis, inhibits adipocyte hypertrophy, and promotes insulin signaling. It enhances lipid oxidation, reduces lipogenesis, and suppresses pro-inflammatory cytokine production, thereby maintaining metabolic health. Primary ovarian insufficiency (POI), characterized by estrogen deficiency before the age of 40, disrupts this regulatory network, leading to adverse metabolic effects. Objetives: This review examines the effects of estrogen on adipose tissue, lipid metabolism, and carbohydrate metabolism, with a particular focus on clinical evidence in women with POI. Methods: A narrative review of the metabolic alterations associated with POI, emphasizing the molecular, biochemical, and metabolic mechanisms underlying estrogen deficiency, with a special focus on adipose tissue. Results: Women with POI exhibit increased visceral fat accumulation, reduced lean mass, and alterations in adipokine secretion, resembling the metabolic phenotype of postmenopausal women. The decline in estrogen levels contributes to central adiposity, impaired lipid metabolism, and insulin resistance, exacerbating the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). The loss of estrogenic regulation leads to enhanced lipolysis in visceral fat, raising free fatty acid flux to the liver, promoting hepatic steatosis, and worsening insulin resistance. Studies indicate that POI patients have significantly higher total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides compared to age-matched controls, reinforcing their heightened CVD risk. Reduced sex hormone-binding globulin (SHBG) levels increase free androgen availability, aggravating central fat deposition. These metabolic disturbances can potentially accelerate atherosclerosis and vascular aging, increasing morbidity and mortality in POI patients. Conclusions: Understanding the role of estrogen in adipose tissue and its disruption in POI highlights the importance of early intervention. Although the available evidence is limited and largely extrapolated from menopause studies, strategies such as hormone replacement therapy, lifestyle modifications, and lipid profile optimization are essential to mitigate metabolic consequences and improve long-term health outcomes in women with POI. Full article

Background: Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by the destruction of pancreatic β-cells, leading to absolute insulin deficiency. Despite advancements in insulin therapy and glucose monitoring, achieving optimal glycemic control remains a challenge. Emerging technologies and novel therapeutic strategies are transforming the landscape of T1D management, offering new opportunities for improved outcomes. Methods: This review synthesizes recent advancements in T1D treatment, focusing on innovations in continuous glucose monitoring (CGM), automated insulin delivery systems, smart insulin formulations, telemedicine, and artificial intelligence (AI). Additionally, we explore biomedical approaches such as stem cell therapy, gene editing, immunotherapy, gut microbiota modulation, nanomedicine-based interventions, and trace element-based therapies. Results: Advances in digital health, including CGM integration with hybrid closed-loop insulin pumps and AI-driven predictive analytics, have significantly improved real-time glucose management. AI and telemedicine have enhanced personalized diabetes care and patient engagement. Furthermore, regenerative medicine strategies, including β-cell replacement, CRISPR-based gene editing, and immunomodulatory therapies, hold potential for disease modification. Probiotics and microbiome-targeted therapies have demonstrated promising effects in maintaining metabolic homeostasis, while nanomedicine-based trace elements provide additional strategies to regulate insulin sensitivity and oxidative stress. Conclusions: The future of T1D management is shifting toward precision medicine and integrated technological solutions. While these advancements present promising therapeutic avenues, challenges such as long-term efficacy, safety, accessibility, and clinical validation must be addressed. A multidisciplinary approach, combining biomedical research, artificial intelligence, and nanotechnology, will be essential to translate these innovations into clinical practice, ultimately improving the quality of life for individuals with T1D. Full article