This retrospective real-world cohort study evaluated the effectiveness and safety of recombinant human growth hormone therapy in Chinese children with Noonan syndrome, with a predefined comparison between short-acting growth hormone and long-acting growth hormone during the first 2 years of treatment. Twenty children with Noonan syndrome were included; 16 were boys, and the median age at recombinant human growth hormone initiation was 5.55 years. The baseline height standard deviation score was-3.01. During the first 2 years, 10 patients received short-acting growth hormone and 10 patients received long-acting growth hormone. The median height standard deviation score increased to-2.20 after 1 year and-1.84 after 2 years, with significant longitudinal improvement over time. The cumulative change in height standard deviation score did not differ significantly between short-acting growth hormone and long-acting growth hormone at year 1 (0.58 vs. 0.71) or year 2 (1.01 vs. 1.30). First-year growth velocity was comparable between groups, whereas the apparent second-year difference was no longer significant after excluding short-acting growth hormone-treated patients who entered puberty and received adjunctive therapy. Among 16 patients with PTPN11 variants, the median cumulative change in height standard deviation score was 1.20 and 56.3% achieved an HtSDS of above-2 standard deviation score at the last follow-up. No diabetes mellitus, malignancy, new cardiovascular events, intracranial hypertension, or slipped capital femoral epiphysis occurred. Insulin-like growth factor-1 standard deviation score elevations were transient. Recombinant human growth hormone therapy was associated with sustained linear growth in children with Noonan syndrome, and short-acting growth hormone and long-acting growth hormone showed broadly comparable short-term efficacy under regular safety monitoring.

MicroRNAs (miRNAs) are key components in the interaction between lifestyle-related risk factors and cancer development. In particular, miR-1303 expression is deregulated in breast cancer tissues, with elevated levels associated with poor prognosis. We have previously shown that regular exercise reduces the expression of this miRNA in skeletal muscle. The present pilot study aimed to evaluate the impact of lifelong football training on circulating miR-1303 expression and miR-1303 modulation on proliferation, migration, and invasion pathways in human breast cancer MCF-7 cells.

Background: Growth hormone deficiency (GHD) may result from structural abnormalities or space-occupying lesions of the pituitary gland; therefore, pituitary magnetic resonance imaging (MRI) is routinely performed as part of the etiological assessment. The reported prevalence of incidentally detected pituitary neuroendocrine tumors (PitNETs) in pediatric patients with GHD ranges from 0.5% to 20.3% across studies. PitNETs are rare in childhood and account for approximately 2.7% of supratentorial pediatric tumors and 3.6-6% of surgically treated PitNETs. Insulin-like growth factor-1 (IGF-I), a mitogenic agent elevated during recombinant human growth hormone (rhGH) therapy, has raised theoretical concerns regarding tumor growth stimulation. Objective: To evaluate longitudinal changes in tumor size of nonfunctional PiNETs, in patients with pre-existing PitNETs receiving rhGH therapy compared with untreated controls. Methods: This single-center retrospective cohort study included 15 GHD patients with PitNETs detected before rhGH initiation and 30 control patients with nonfunctional incidental PitNETs who did not receive rhGH therapy. Radiological follow-up was performed at baseline and at 6, 12, 18, 24, and 36 months. Results: No significant longitudinal changes in PitNETs width or length were observed in either group. One rhGH-treated patient underwent PitNET excision. Indications for pituitary imaging in the control group were predominantly central precocious puberty, headache, central hypothyroidism, and short stature. Conclusion: RhGH therapy was not associated with significant progression of nonfunctional PitNETs during a 36-month follow-up, supporting its safety when accompanied by regular radiological surveillance.

Male infertility refers to the inability of a male partner to contribute to pregnancy after 12 months or more of regular unprotected intercourse. It is frequently associated with impaired spermatogenesis, and many cases cannot be completely explained by genetic, inflammatory, endocrine, or environmental factors. Trimethylamine N-oxide (TMAO) is generated when gut bacteria convert dietary choline, L-carnitine, and betaine into trimethylamine (TMA), which is oxidized in the liver mainly by flavin-containing monooxygenase 3 (FMO3). This focused review evaluates current evidence on TMAO and impaired spermatogenesis within the gut-testis axis. The rationale is biologically plausible because sperm motility depends on coordinated glycolytic and mitochondrial energy metabolism, whereas Leydig cell steroidogenesis depends on mitochondrial cholesterol transport and redox balance. Human observational studies associate TMAO with asthenozoospermia and Leydig cell-related markers, particularly insulin-like peptide 3 (INSL3), while mouse studies suggest testicular injury and reduced spermatogenesis after TMAO-related exposure. The Hippo/Yes-associated protein (YAP)-mitochondria-steroidogenic acute regulatory protein (StAR) axis has been proposed as one possible mechanism, but direct reproductive tract exposure, blood-testis barrier kinetics, and human validation remain unresolved. Overall, TMAO should be considered as a candidate metabolic mediator and not a proven causal factor or therapeutic target in male infertility.

Initial management of diabetic ketoacidosis (DKA) often involves administration of regular insulin, and the transition from regular to intermediate or long-acting insulin can be challenging. While some guidelines exist for this, recent developments in the field have altered the diabetes treatment landscape. The objective of this study was to describe insulin prescribing practices of small animal specialists for patients with DKA and to explore the factors influencing the selection of insulin type and dose. An electronic survey involving two clinical case scenarios was distributed to diplomates of American College of Veterinary Internal Medicine (ACVIM) and American College of Veterinary Emergency and Critical Care (ACVECC) in Spring 2025. For the canine case, 76/162 participants (47%) selected insulin lente (Vetsulin® or Caninsulin), with 74/162 (46%) selecting insulin lente administered twice daily (BID). The median dose for insulin lente BID was 0.43 U/kg/injection (range, 0.05-1.29 U/kg/injection). 62 out of 162 respondents (38%) selected insulin NPH (Humulin®-N, Novolin®-N) BID at a median dose of 0.43 U/kg/injection (range, 0.11-2.15 U/kg/injection). For the feline case, 120/151 participants (79%) selected insulin glargine 100 U/ml, with 118/151 (78%) selecting insulin glargine BID. The median dose for insulin glargine BID was 0.17 U/kg/injection (range, 0.04-1.87 U/kg/injection). The survey data describe current prescribing practices and clinical decision-making. As options for novel insulins and diabetic therapies expand, additional studies focused on outcomes related to clinical control, cost efficacy, and quality-of-life for pet and owner are needed.

Low adiponectin levels may contribute to insulin resistance. This first-in-human study evaluated adiponectin receptor agonist (PEG)-BHD1028 in subjects with insulin resistance. Adults with BMI ≥ 27 kg/m2, HOMA-IR ≥ 1.8, and HbA1c < 6.5% received subcutaneous injections of (PEG)-BHD1028 or placebo in single-ascending dose (SAD) cohorts (4, 8, 16, 32, and 64 μg/kg) and multiple-ascending dose (MAD) cohorts for 28 days (8, 16, and 32 μg/kg QD). Each cohort had eight subjects, with two on placebo. Area under the curve (AUC) was obtained for insulin c-peptide, insulin, and glucose in a mixed meal tolerance test (MMTT) at Day -1 and Day 28. Body weight, triglycerides, and inflammatory markers were measured at regular intervals. Changes were analyzed by the Kruskal-Wallis test (for MMTT) and generalized estimating equations (GEEs). The MAD cohort mean age was 49 years, with a body mass index of 32, baseline HOMA-IR 3.8, and 42% female. Mild gastrointestinal adverse events occurred on (PEG)-BHD1028 (50%) and placebo (33%) without discontinuations. Drug exposure was proportional to dose. Insulin c-peptide AUC changes were +25% on placebo and -63%, + 24%, and + 2% on (PEG)-BHD1028 8, 16, and 32 μg/kg doses (p < 0.001). Reductions in insulin (p = 0.116) were also observed, with the greatest percentage change on 8 μg/kg. There were no consistent differences between groups in body weight, triglycerides, and inflammatory markers. Adiponectin agonist (PEG)-BHD1028 was well-tolerated with dose-related increases in exposure. Observed effects on insulin c-peptide and insulin during the MMTT support further development.

Pancreatic islets undergo coordinated cellular remodeling during obesity-induced insulin resistance. However, longitudinal changes across endocrine and non-endocrine compartments remain largely unexplored. We present a comprehensive high-resolution atlas using longitudinal single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on islets from C57BL/6 mice subjected to high-fat diet (HFD) feeding for 8, 16, and 24 weeks, along with age-matched controls on regular chow (RC). We mapped dynamic changes in islet cell composition and transcriptional states. Trajectory inference indicated diversification of beta-cell programs into adaptive and inflammatory states under HFD. Progression of insulin resistance induced shrinkage and transcriptional remodeling of glucagon-secreting alpha-cells, marked by upregulation of genes related to intracellular transport and oxidative stress, accompanied by the emergence of a polyhormonal alpha-cell subpopulation. Similarly, we identified delta-cell subpopulations exhibiting beta-like transcriptional signatures and polyhormonal identity under nutritional stress, suggesting adaptive delta-cell plasticity that may partially compensate for beta-cell loss during insulin resistance. The islet microenvironment exhibited robust expansion of proinflammatory M1 macrophages, reaching a plateau by 16 weeks of HFD, indicating niche saturation. Cell-cell communication analyses revealed disruption of key signaling pathways within endocrine and between endocrine and non-endocrine cells under HFD conditions. Notably, CCL27a-chemokine receptor signaling between beta-cells and M1 macrophages was significantly reduced in HFD islets, likely driven by reduced Ccl27a expression and chromatin accessibility in a distinct beta cell subpopulation, which we further validated using INS-1 cells exposed to HFD-like conditions. Comparative analysis with scRNA seq of human islets confirmed conserved stress signatures. Furthermore, genetic variants at the CCL27 locus were associated with increased T2D risk and HOMA-IR in human populations, establishing a novel link between beta-cell stress and systemic inflammation. This resource provides a hierarchical framework for understanding islet failure and identifies potential therapeutic nodes for type 2 diabetes.

MODY (Maturity-Onset Diabetes of the Young) is characterized by autosomal dominant mode of inheritance, early onset of diabetes in the absence of autoimmunity directed to pancreatic β-cells, impaired insulin secretory capacity, however, maintained over time, and extra-pancreatic manifestations in some patients. Its prevalence has been estimated 0.6% to 6.5% of all diabetes in Europe and the USA. Pathogenic variants in the genes encoding glucokinase or transcription factors HNF1A or HNF4A are responsible for the majority of cases of monogenic forms of diabetes referred to as MODY. The objective of the French National Diagnosis and Care Protocol (PNDS, Protocole National de Diagnostic et de Soins) dedicated to GCK-MODY (formerly MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1) is to provide to health professionals a guide for optimal management and care of patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Thorough analysis of personal and family history, clinical examination and biochemical testing are key to raise the diagnosis, which has to be confirmed by molecular analysis. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. Overall, the management of patients with MODY requires the collaboration of several health care providers.