Search Results (21,465)

Background: Fibroblast growth factor 23 (FGF23) and α-Klotho are key regulators of mineral metabolism and bone homeostasis; however, their combined diagnostic value in postmenopausal osteoporosis remains incompletely understood. This study investigated the associations of serum FGF23, α-Klotho, and the FGF23/α-Klotho ratio with bone mineral density (BMD), bone turnover markers, and their diagnostic performance for postmenopausal osteoporosis. Methods: This cross-sectional study included 165 women divided into three groups: premenopausal healthy controls (n = 55), postmenopausal non-osteoporotic women (n = 55), and postmenopausal women with osteoporosis (n = 55). Serum FGF23 and α-Klotho concentrations were measured by enzyme-linked immunosorbent assay. Bone mineral density was assessed by dual-energy X-ray absorptiometry. Correlation analyses, age- and BMI-adjusted partial correlations, multivariable linear and logistic regression analyses, receiver operating characteristic (ROC) analyses, and incremental diagnostic models were performed. Diagnostic ROC and incremental model analyses were restricted to postmenopausal women (n = 110). Results: Serum FGF23 concentrations and the FGF23/α-Klotho ratio increased progressively across the study groups, whereas α-Klotho levels decreased (all p < 0.001). FGF23 was inversely correlated with lumbar spine, femoral neck, and total hip BMD and T-scores (all p < 0.001), whereas α-Klotho demonstrated positive correlations with all BMD parameters (all p < 0.001). These associations remained significant after adjustment for age and BMI. In multivariable linear regression analyses, the FGF23/α-Klotho ratio showed the strongest independent association with skeletal T-scores (standardized β = −0.379 to −0.404; all p < 0.001). Multivariable logistic regression identified lower 25-hydroxyvitamin D, higher parathyroid hormone, higher FGF23, and lower α-Klotho as independent factors associated with osteoporosis. In analyses restricted to postmenopausal women, the FGF23/α-Klotho ratio showed the highest numerical discriminative performance for osteoporosis (AUC = 0.832, 95% CI: 0.755–0.901), followed by α-Klotho (AUC = 0.793) and FGF23 (AUC = 0.697). The ratio significantly outperformed FGF23 alone (ΔAUC = 0.135, p = 0.001), whereas its performance did not differ significantly from that of α-Klotho (ΔAUC = 0.038, p = 0.270). Adding FGF23 and α-Klotho to age, BMI, and 25-hydroxyvitamin D increased the AUC from 0.743 to 0.882. Conclusions: Serum FGF23 and α-Klotho are independently associated with bone mineral density and are linked to bone turnover markers in postmenopausal women. The FGF23/α-Klotho ratio showed the highest numerical discriminative performance among the evaluated biomarkers, although its performance was not significantly different from that of α-Klotho alone. The combined assessment of FGF23 and α-Klotho provided additional discriminatory information beyond the measured clinical variables. Given the cross-sectional design and lack of external validation, these findings should be considered exploratory and require validation in prospective independent cohorts. Full article

Astragalus membranaceus (AM) has been reported to support immune function, but its epigenetic mechanism on immune restoration of cyclophosphamide (CTX)-induced immunosuppression remains unclear. To evaluate the recovery of immune function, we assessed the injury of splenic pathology, cytokines levels in serum, proportional changes in CD4⁺ and CD8⁺ T cells, and the recall response of Hspx-specific T cell. In addition, to define the underlying epigenetic regulatory mechanism, we measured the expression levels of DNA methyltransferases (Dnmt1, Dnmt3a and Dnmt3b) and the methylation status of the Carnitine palmitoyltransferase 1A (Cpt1a) gene. The results showed that the crude extract of AM repaired the immunosuppression induced by CTX. This is reflected in the alleviation of splenic pathological injury, the elevated proportions of CD4⁺ and CD8⁺ T cells, and the increased levels of serum IL-2 and IFN-γ. The crude extract of AM also enhanced the recall response of Hspx-specific CD8⁺ T cells; that is, the frequencies of the resulting IL-2⁺ and IFN-γ⁺ cells were significantly higher than those in the CTX + Vaccine group. All these results indicate that the adaptive immune response induced by the crude extract of AM is significantly enhanced. On the other hand, AM crude extract reversed the CTX-induced downregulation of Dnmt3a mRNA and restored CpG methylation of Cpt1a gene to a level comparable to the vaccine group at molecular level. Consistent with the elevated CpG methylation, CTX-induced upregulation of Cpt1a mRNA was also reduced. These findings reveal that AM extract enhances the antigen-specific functional recall responses of CD8⁺ T cells in immunosuppressed mice were associated with Cpt1a gene methylation, thereby establishing a translational link between traditional herbal medicine and modern epigenetics. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and chronic low-grade inflammation. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), the systemic immune-inflammation index (SII), and the systemic inflammation response index (SIRI) are important markers used to evaluate inflammatory status in T2DM. This study aimed to compare inflammatory and metabolic parameters between patients receiving metformin monotherapy and those receiving metformin plus sodium-glucose cotransporter-2 (SGLT-2) inhibitor combination therapy in patients with newly diagnosed T2DM. Methods: This prospective observational study included 64 treatment-naïve patients with newly diagnosed T2DM. Patients were divided into two groups according to treatment strategy: metformin monotherapy (n = 32) and metformin plus SGLT-2 inhibitor combination therapy (n = 32). TNF-α, IL-6, SII, systemic inflammation response index (SIRI), neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP), metabolic parameters, and insulin resistance-related indices were evaluated at baseline and after six months. Baseline-adjusted multiple linear regression analyses were performed to assess between-group differences at six months, adjusting for the corresponding baseline biomarker value, baseline HbA1c, age, and sex. Results: After six months of follow-up, significant reductions in TNF-α, IL-6, glycated hemoglobin (HbA1c), and fasting plasma glucose levels were observed in both groups (p < 0.001). In baseline-adjusted analyses, the treatment-group association was not statistically significant for TNF-α (B = −26.80, β = −0.15, p = 0.213), CRP (B = 0.06, β = 0.00, p = 0.977), SII (B = −36.94, β = −0.11, p = 0.441), or NLR (B = −0.20, β = −0.18, p = 0.207). In contrast, the treatment group was associated with a lower six-month IL-6 level (B = −37.87, β = −0.31, p = 0.038; 95% CI, −73.52 to −2.23) after adjustment for baseline IL-6, baseline HbA1c, age, and sex. Serum uric acid levels were lower in the metformin plus SGLT-2 inhibitor group than in the metformin monotherapy group at six months in the unadjusted comparison (p = 0.016). However, the adjusted treatment-group association between treatment group and six-month serum uric acid levels was not statistically significant (B = −0.51, β = −0.20, p = 0.065). Conclusions: In patients with newly diagnosed T2DM, both treatment groups showed significant reductions in TNF-α and IL-6 levels over six months. After adjustment for baseline biomarker levels, baseline HbA1c, age, and sex, no significant incremental association with treatment group was detected for TNF-α, CRP, SII, or NLR, whereas a significant adjusted association was observed for IL-6. Given the observational design and physician-directed treatment allocation, the observed IL-6 association should not be interpreted as evidence of a causal anti-inflammatory effect of SGLT-2 inhibitor therapy. Full article

Background/Objectives: Vitamin D deficiency is highly prevalent among children with obesity, but the mechanisms underlying the effectiveness of vitamin D supplementation remain poorly understood. This study examined the expression patterns of VDR-target genes across metabolically diverse tissues and compared these molecular measures with circulating serum 25-hydroxyvitamin D (25OHD), the current clinical marker of vitamin D status. We hypothesized that VDR-pathway gene expression would correlate within metabolically relevant tissues but would not be significantly associated with circulating serum 25OHD levels. Methods: A secondary analysis was performed on blood, intestinal, and visceral and subcutaneous adipose tissue (VAT and SAT, respectively) samples obtained from adolescents with obesity. Subject data included age, gender, race/ethnicity, and BMI. The tissues were analyzed via real-time qPCR to obtain quantitative levels of VDR-target gene expression, which included TLR4, THBD, and VDR in SAT and VAT and TRPV6, S100G, and VDR in intestinal tissue. Blood samples were analyzed for serum 25OHD. Results: Gene expression of THBD, VDR, and TLR4 in SAT and VAT significantly correlated with each other. In intestinal tissue, there was significant correlation between TRPV6, S100G, and VDR. No statistically significant associations were identified between the gene expression levels and serum 25OHD levels. Conclusions: VDR-target gene expression levels correlated with each other across diverse tissues but not with serum 25OHD levels. This discrepancy suggests that circulating 25OHD concentrations may not fully reflect vitamin D action. Full article

Hepcidin centrally regulates iron homeostasis and responds to inflammation, iron status, hypoxia, and erythropoietic signaling, yet circulating hepcidin in stable bronchiectasis is poorly characterized. We compared serum hepcidin between 61 patients with stable bronchiectasis and 39 controls without bronchiectasis and assessed associations with anemia, iron metabolism, systemic inflammation, severity, and phenotype. Hepcidin was lower in bronchiectasis (20.34 ± 7.85 vs. 28.34 ± 9.82 ng/mL; median, 20.31 [15.07–25.35] vs. 25.03 [21.00–34.66] ng/mL; p < 0.001). It showed no significant associations with anemia status or hematologic, iron metabolism, erythropoietic, or inflammatory indices. Exploratory analyses identified phenotype differences (p = 0.002); levels were lowest in chronic obstructive pulmonary disease–bronchiectasis (15.98 ± 6.52 ng/mL), compared with bronchiectasis alone (21.57 ± 6.71) and asthma–bronchiectasis (24.81 ± 9.00). Low hepcidin discriminated bronchiectasis from controls (AUC = 0.729; 95% bootstrap CI: 0.628–0.822); the ≤20.85 ng/mL cutoff yielded 59.0% sensitivity and 79.5% specificity. To our knowledge, this is the first human case–control evidence of reduced circulating hepcidin in stable bronchiectasis. The absence of significant associations with systemic inflammation or anemia/iron status, alongside phenotype differences, suggests that hepcidin may be a candidate biomarker of biological heterogeneity in bronchiectasis not reflected by routine markers. Full article

This study evaluated the effects of graded fermented grape seed (FGS) supplementation in breeding-pigeon diets on the growth performance, immune responses, and redox status of squabs. Forty-eight healthy pairs of Gray King breeding pigeons were randomly assigned to four treatments, with 12 cages per treatment. Breeding pigeons received the experimental diets beginning 7 d before the expected hatch date. The basal diet was supplemented with 0, 10, 20, or 30 kg FGS per 1000 kg of diet (CON, FGS10, FGS20, and FGS30, respectively), and each pair reared three squabs until 28 d of age. Growth performance, carcass traits, meat quality, serum biochemical parameters, immunoglobulins, inflammatory cytokines, and serum and hepatic redox indices were evaluated. FGS supplementation affected body weight at 14 d of age and average daily gain (ADG) from 14 to 21 d and from 14 to 28 d of age (p < 0.05), but did not affect body weight at 28 d of age. FGS30 reduced ADG from 14 to 21 and 14 to 28 d and increased relative carcass yields, immunoglobulin A, G, and M levels, interleukin-10, tumor necrosis factor-α, aspartate aminotransferase, low-density lipoprotein cholesterol, and serum and hepatic malondialdehyde levels, while decreasing hepatic superoxide dismutase and glutathione peroxidase activities. FGS20 and FGS30 increased breast muscle L* values and press loss. FGS20 showed numerical advantages in several production traits, but increased breast muscle press loss and did not improve hepatic redox status. Overall, FGS supplementation in breeding-pigeon diets resulted in stage-specific and dose-related responses. FGS30 may exceed the appropriate inclusion range. Based on the present data, none of the tested supplementation levels can be considered optimal, and the range of 10–20 kg FGS per 1000 kg basal diet requires further validation. Full article

Cuproptosis is a novel form of metabolism-associated cell death. Cervical cancer (CC) exhibits elevated serum copper levels and mitochondrial metabolic reprogramming, making cuproptosis-related genes (CRGs) potentially critical for prognosis prediction and therapeutic targeting. However, studies on CRGs in CC remain limited. This study aimed to construct prognostic and cancer staging models for CC using machine learning (ML) algorithms. Gene expression profiles of patients with CC were obtained from the TCGA and GEO databases. Five ML algorithms were employed to identify significant factors, including random forest (RF), support vector machine (SVM), Gaussian mixture model (GMM), Bayesian, and StepCox. A prognostic model was subsequently constructed using LASSO–Cox regression based on the selected genes. Concurrently, a cancer staging model was built using ML algorithms incorporating three distinct gene categories. Finally, qRT-PCR and Western blotting were conducted to validate the expression of signature genes at both the tissue and cellular levels. Additionally, CTD-based screening and in vitro functional assays were performed to evaluate the effects of DDP on CC cells. Through integrated bioinformatics and ML approaches, a prognostic model comprising nine CRGs was successfully established (GMM = 0.72). The derived risk score served as an independent prognostic indicator for CC (p < 0.001, 95% CI: 3.681 [1.785–7.591]). Calibration curves confirmed that the nomogram accurately predicted overall survival (OS) at 1, 3, and 5 years. Additionally, a cancer staging model was effectively constructed using the GMM algorithm (AUC = 0.74). DDP dose-dependently inhibited CC proliferation/migration and down-regulated CRG expression. In this study, we developed two different models—a cuproptosis-related prognostic model and a cancer staging model—that highlight promising biomarkers for predicting patient prognosis and cancer progression in patients with CC. Full article

Objectives: This study focuses on exploring the mechanism by which Schisandrin B (Sch B) regulates metabolic dysfunction-associated steatotic liver disease (MASLD) mice induced by a high-fat methionine–choline-deficient (MCD) diet through the activation of peroxisome proliferator-activated receptor γ (PPARγ). Methods: Male C57BL/6 mice were fed a high-fat MCD diet for 8 weeks to establish a mouse MASLD model, and the effects of Sch B on MASLD and the mechanisms were investigated. PPARγ overexpression (OE) was induced by adeno-associated virus (AAV) administration via intrahepatic portal vein injection in mice, and a negative control (NC-OE) was also established. Body weight; wet liver weight; hepatic index; serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β); and hepatic triglyceride (TG) levels were measured in the mice. The histopathology and lipid deposition were observed by hematoxylin and eosin (H&E) staining and Oil Red O staining, while the fibrosis was assessed using Masson staining. Western blot was employed to detect the expression levels of PPARγ, sterol regulatory element-binding protein 1c (SREBP-1c), carnitine palmitoyltransferase 1A (CPT1A), transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA), collagen type I (collagen I), Smad family members 2/3 (Smad2/3), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), and extracellular signal-regulated kinase 1/2 (ERK1/2), along with the phosphorylation activation status of these kinases. Results: It was confirmed that Sch B caused effects similar to those induced by PPARγ overexpression, reducing the hepatic index, AST, and ALT levels while alleviating lipid accumulation and fibrosis; and upregulating PPARγ and CPT1A while inhibiting SREBP-1c; and the phosphorylation of the TGF-β/Smad and MAPK pathways were involved in the mechanisms. Conclusions: Sch B can alleviate high-fat MCD-induced MASLD by activating PPARγ in mice. Full article

Toxoplasma gondii infection is relevant to animal production, food safety, and public health, but current epidemiological data for small ruminants in northeastern Portugal are limited. This cross-sectional study estimated seroprevalence and investigated factors associated with seropositivity in 2678 animals from 149 flocks sampled between May 2022 and December 2024. Serum samples were tested using an indirect enzyme-linked immunosorbent assay, and associated factors were evaluated using mixed-effects logistic regression with flock as a random effect. The overall true seroprevalence was estimated at 21.5% (apparent seroprevalence: 21.6%). At the flock level, 83.9% (125/149) of the sampled flocks were seropositive. True seroprevalence was higher in sheep than in goats (23.4% versus 14.4%), and seropositivity was detected in all surveyed municipalities. In the multivariable model, higher odds of seropositivity were observed in sheep (adjusted odds ratio 1.74), adult animals (2.78), non-native breeds (1.84), animals not kept in permanent housing (3.16), and animals from farms with cats (1.69). These findings indicate exposure throughout the surveyed area and associations with both host-related and farm-level characteristics. Strengthening farm biosecurity, limiting contamination of feed and water, and integrating animal health, environmental, and food safety measures may contribute to prevention within a One Health framework. Full article

The kidney biopsy is the cornerstone of prognostication in lupus nephritis, yet which features predict renal outcome—and which kind—remains incompletely defined. This narrative review relates eight histological axes to two families of renal outcome defined a priori: soft outcomes (renal flare/relapse and response/remission) and hard outcomes (doubling of serum creatinine, sustained decline in estimated glomerular filtration rate, and end-stage kidney disease; death is considered a competing, patient-level outcome). The axes span the ISN/RPS classification and its 2018 revision, individual glomerular and tubulointerstitial lesions, NIH activity and chronicity indices, lupus podocytopathy, lupus vasculopathy, antiphospholipid-antibody nephropathy, thrombotic microangiopathy and repeat biopsy. Across them, a consistent asymmetry emerges, although it is often not reproducible between studies. Chronicity—especially tubulointerstitial damage—predicts hard outcomes, whereas the activity index as a whole predicts response and flare. Cellular crescents and fibrinoid necrosis, active lesions that can signal hard outcomes, are the exceptions. Whether chronicity adds to baseline kidney function remains unsettled. Several prognostically important entities lie outside the proliferative classification; immune-deposit burden is largely diagnostic; and repeat histology adds information beyond the baseline biopsy. A recurring caveat is the therapeutic era, which modifies the very lesions scored. Full article

Background: Shenling Baizhu Powder (SLBZP) is a traditional Chinese medicine formula used to treat diarrhea. This study investigated its therapeutic effects and potential mechanisms in mice with fatigue- and high-fat diet-induced diarrhea, focusing on gut microbiota, bile acid metabolism, and farnesoid X receptor (FXR)-related signaling. Methods: Male Kunming mice were used to establish a model of diarrhea, followed by treatment with SLBZP. Fecal moisture content, serum levels of diamine oxidase and liver enzymes, and intestinal and hepatic histopathological changes were assessed. Small-intestinal microbiota composition, bile acid profiles in colonic contents, and FXR-related signaling in the ileum and liver were further analyzed. Results: SLBZP significantly reduced fecal moisture content. It also modulated the small-intestinal microbiota, with a significant increase in Faecalibaculum. In colonic contents, SLBZP reduced total bile acid levels, increased the secondary-to-primary bile acid ratio, and altered multiple bile acid species. These changes were accompanied by increased ileal FXR expression and changes in downstream regulators involved in hepatic bile acid synthesis. Correlation analysis further showed associations of selected bacterial taxa and FXR protein expression with colonic bile acid profiles. Conclusions: SLBZP alleviates diarrhea induced by fatigue combined with a high-fat diet in mice. Its effects may involve coordinated modulation of the gut microbiota, bile acid homeostasis, and FXR-related signaling, providing experimental support for the pharmacological basis of this traditional formula in diet-related diarrhea. Full article

The study aimed to investigate the effects of Bacillus amyloliquefaciens TL106 (TL106) on growth performance, antioxidant capacity, immune function, and intestinal microbiota in Danzhou chickens. A total of 384 healthy female Danzhou chicks were randomly assigned to a control group (CON) and three experimental groups (Ba1, Ba2, Ba3), receiving basal diets supplemented with TL106 at 5 × 10⁷, 5 × 10⁸, and 5 × 10⁹ CFU/kg, respectively, for 55 d (divided into early [1–35 d] and later [36–55 d] phases). While no significant growth improvement was observed in the early phase, average daily feed intake (ADFI) and final body weight (BW) increased, and the feed-to-gain ratio (F/G) was significantly reduced (p < 0.05) during the later phase in Ba2 and Ba3, especially in Ba3. At d 55, TL106 supplementation significantly elevated serum IgM content (p < 0.001) and total superoxide dismutase (T-SOD) activity (p < 0.05), reduced malondialdehyde (MDA) content (p < 0.01), and enhanced albumin (ALB) levels (p < 0.05). The Ba3 group also improved the villus height-to-crypt depth ratios (VH/CD) of the ileum and duodenum (p < 0.05). Microbial analysis indicated that abundances of Bacteroidota and Firmicutes increased while Proteobacteria and butyrate-producing Faecalibacterium were enriched in the TL106 groups compared to CON. Cecal butyrate concentrations rose dose-dependently (p < 0.05), with most of the key parameters—including final BW, ADFI, F/G, serum ALB, IgM, T-SOD, GSH-Px, MDA (d 55), duodenal and ileal VH/CD, and cecal butyric, propionic, and valeric acids—showing significant quadratic responses (p < 0.05). The results demonstrated that TL106 in diets enhanced growth performance and intestinal health in Danzhou chickens by modulating immunity, antioxidant responses, and microbiota, with 5.0 × 10⁸ CFU/kg appearing to be the most effective dose among those tested under the conditions of this study. Full article

Background/Objectives: Serum cancer antigen 15.3 (CA 15.3) is frequently measured in advanced breast cancer, but its prognostic significance after adjusting for established clinical factors remains incompletely characterized in Latin American populations. We evaluated the association of baseline CA 15.3 with metastatic burden and overall survival (OS) in hormone receptor-positive/HER2-negative advanced breast cancer and descriptively explored baseline/follow-up patterns. Methods: We retrospectively evaluated 127 women treated at a Peruvian public oncology institution between 2018 and 2024, with CA 15.3 levels ≥32.4 U/mL being considered elevated. Baseline associations were assessed using multivariable logistic regression, and OS was evaluated using Kaplan–Meier estimates and Cox proportional hazards regression adjusted for age, ECOG performance status, de novo versus recurrent disease, luminal subtype, first-line treatment, number of metastatic sites, and metastatic site. Results: Baseline CA 15.3 was elevated in 41/127 patients (32.3%) and was independently associated with postmenopausal status (OR: 3.27; 95% CI, 1.33–9.03; p = 0.014) and ≥2 metastatic sites (OR: 2.72; 95% CI, 1.24–6.10; p = 0.013). Median OS was 55 months (95% CI, 43–78), while elevated baseline CA 15.3 was associated with shorter OS (41 vs. 65 months; log-rank p = 0.024) and remained independently associated with shorter OS after multivariable adjustment (adjusted HR: 3.42; 95% CI, 1.63–7.19; p = 0.001). Conclusions: Elevated baseline CA 15.3 was associated with greater metastatic burden and shorter OS, and baseline/follow-up patterns were exploratory because the sampling was not standardized. Thus, CA 15.3 should be interpreted as an adjunct to clinical and radiological assessment. Full article

Background: Cholangiocarcinoma (CCA) frequently recurs after curative-intent resection. Metabolic alterations and systemic inflammation may contribute to aggressive disease, but their combined prognostic relevance remains unclear. Methods: We retrospectively reanalyzed 88 patients with resected CCA and documented recurrence, including 37 with early and 51 with late recurrence. A metabolite-based risk score was developed from recurrence-associated serum metabolites identified previously. Model development and internal validation used all 88 patients, whereas analyses involving preoperative neutrophil-to-lymphocyte ratio (NLR), clinicopathological variables, and survival outcomes included 85 patients with complete clinical data. Performance was assessed using repeated nested cross-validation, bootstrap validation, discrimination, calibration, and survival analyses. Results: The 10-metabolite risk score (MRS-10) showed moderate internally validated discrimination for distinguishing early from late recurrence, with a pooled patient-level out-of-fold AUC of 0.828 (95% CI, 0.725–0.911), with limited calibration. High MRS was associated with shorter disease-free survival (DFS) and overall survival (OS) (both p < 0.001) and remained independently associated with DFS events (HR, 7.92; 95% CI, 3.94–15.92) and mortality (HR, 4.05; 95% CI, 2.08–7.89). High MRS was also associated with elevated NLR (p < 0.001). The combined MRS–NLR framework improved prognostic discrimination and stratified patients into groups with stepwise differences in DFS and OS. Exploratory subgroup analyses showed broadly consistent adverse associations across selected clinicopathological strata. Conclusions: In this retrospective exploratory analysis, a metabolite-based risk score combined with preoperative NLR was associated with recurrence and survival outcomes in resected CCA. This metabolic–inflammatory framework may provide complementary prognostic information alongside conventional clinicopathological factors. However, the findings remain hypothesis-generating and require validation in larger independent cohorts before clinical application. Full article

Background: Optical neuropathy is a severe complication in patients with type 2 diabetes mellitus (T2DM) undergoing vitreoretinal surgeries. Early diagnostic indicators are critical to preventing irreversible vision loss. This study aimed to evaluate the alterations in blood serum amino acid profiles, with a specific focus on serine levels, and their potential clinical association with the severity of neuroretinal impairment. Methods: The clinical cohort included 28 patients aged 32 to 77 years with T2DM following vitreoretinal interventions. Visual field functional status was assessed using Humphrey automated perimetry, with mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI). Structural changes were quantified using optical coherence tomography (OCT) to measure peripapillary retinal nerve fiber layer (RNFL) thickness. Serum amino acid profiles were determined using an ion-exchange chromatography amino acid analyzer, alongside a reference group (n = 12). Results: All patients presented with moderate-to-severe visual field impairment. A profound decline in serum serine levels was observed in diabetic patients compared to the reference group (p < 0.001). The reduction in serine content closely mirrored both the degree of retinal sensitivity loss (MD and PSD values) and the number of thinned peripapillary RNFL sectors. Notably, the compensatory synthesis of serine via glycine cleavage appeared insufficient, as evidenced by a concomitant statistical decrease in glycine content (p < 0.05). No significant differences in serine levels were found between the subgroups when stratified strictly by age or isolated severity stages. Conclusions: It was demonstrated that the decline in serum serine levels in patients with T2DM following vitreoretinal interventions is significantly associated with the severity of optic neuropathy as assessed by optical coherence tomography (OCT). Consequently, serum serine may serve as a valuable dual biomarker, acting as a prognostic indicator for retinopathy progression and a predictive marker for early-stage neuropathy development. Full article