Search Results (168)

Weaning is one of the most stressful stages in pig production, especially for Iberian piglets, which grow more slowly than other cosmopolitan breeds and therefore, have a lower weaning weight when raised in intensive systems. Stress at weaning, caused by separation from the sow, dietary change, and regrouping with unfamiliar piglets, can negatively impact welfare, immune function, and performance. Pre-weaning socialization, which allows piglets from different litters to interact before weaning, has been proposed as a strategy to reduce aggression and facilitate the adaptation to the post-weaning period. However, its physiological effects in Iberian pigs remain largely unknown. In this study, 8 Iberian sows and their litters were assigned to either a control group (CTRL) or a socialization group (SOC) where litters were mingled (socialized) two weeks before weaning. Salivary and serum biomarkers of stress, inflammation, immunity and metabolism were measured at weaning (pwD0) and 7 days post-weaning (pwD7), and growth performance was recorded until 60 days of age. Socialized piglets showed reduced salivary Adenosine Deaminase (ADA) activity at pwD0 and pwD7 and lower salivary chromogranin A (CgA) and serum Haptoglobin (Hp) levels at pwD7. In contrast, they presented higher concentrations in serum of high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, glucose, and urea at pwD7 compared to controls. Attending to the sex effect, Butyryl-cholinesterase (BChE) serum concentration was higher in males and urea, and creatinine were higher in females. Growth rates were higher in socialized piglets in the first two weeks post-weaning but lower thereafter. These findings may suggest that pre-weaning socialization could reduce the stress associated with early post-weaning in Iberian piglets, thus potentially improving welfare and adaptation during this period. Full article

Background/Objectives: Shift-working healthcare professionals are exposed to high psychophysiological demands associated with occupational stress, anxiety, and depressive symptoms. Salivary chromogranin A (sCgA) and secretory immunoglobulin A (sIgA) are non-invasive biomarkers reflecting sympathetic nervous system activation and mucosal immune function, respectively, and are increasingly used to assess biological stress responses. This study examined changes in these biomarkers and their associations with anxiety and depression. Methods: This cross-sectional comparative observational study was conducted among healthcare professionals working 12-h shifts (n = 95) and non-shift-working controls (n = 95) and included a within-shift pre-post assessment, with saliva samples collected before and after the work shift. Salivary biomarkers were determined using ELISA methods. Anxiety and depression were assessed using the State–Trait Anxiety Inventory and the Zung Self-Rating Depression Scale. Data were analyzed with t-tests, correlation, and multiple linear regression. Statistical analyses included between- and within-group comparisons, correlation analyses, and multiple linear regression models to examine independent associations between salivary biomarkers and psychological outcomes. Results: After a 12-h shift, healthcare professionals showed increased sCgA (3.82 ± 0.95 vs. 4.68 ± 1.02 ng/mL; p < 0.001) and decreased sIgA (165.3 ± 32.4 vs. 142.6 ± 29.8 mg/dL; p < 0.001). Psychological scores were higher in healthcare professionals than in controls (p < 0.001). Salivary sCgA correlated positively with anxiety and depression (r = 0.41 to 0.45), while sIgA correlated negatively (r = −0.29 to −0.36). Regression analysis confirmed occupational group (healthcare professionals vs. controls) as the strongest predictor, with independent contributions of sCgA and sIgA to psychological scores. Conclusions: A 12-h work shift in healthcare professionals leads to increased salivary chromogranin A, indicating sympathetic activation, and decreased secretory IgA, reflecting reduced mucosal immune activity. The combined assessment of sCgA and sIgA provides a sensitive and non-invasive approach for monitoring occupational stress and identifying early risks of anxiety and depressive symptoms among shift-working healthcare professionals. Full article

A 60-year-old woman with hypertension and hyperlipidemia was referred for an incidentally detected gastric subepithelial mass during screening endoscopy. Esophagogastroduodenoscopy revealed a 10 mm dimple in the antrum, and contrast-enhanced CT showed a 2.5 cm enhancing oval lesion. Laparoscopic partial gastrectomy with intraoperative endoscopic guidance was performed. Gross examination revealed a 3.0 × 2.0 × 1.0 cm pale, firm nodule. Histology showed small round cells arranged in nests and trabeculae within the muscularis propria, with numerous vessels and focal calcification. Immunohistochemistry was negative for CD117, HMB45, and chromogranin A, but demonstrated strong smooth muscle actin positivity, weak synaptophysin reactivity, and focal CD56 staining. The findings confirmed a gastric glomus tumor with neuroendocrine features. Smooth muscle actin immunostaining is essential to distinguish gastric glomus tumors from neuroendocrine tumors when biopsy material is limited, ensuring accurate diagnosis and appropriate management. Full article

Concurrent occurrence of two independent primary malignancies in a single dog is rare and presents diagnostic and surgical challenges. A 9-year-old neutered male Cocker Spaniel was diagnosed with adrenal pheochromocytoma and splenic diffuse large B-cell lymphoma. Abdominal imaging revealed two distinct masses. Surgical management included adrenalectomy, splenectomy, mesenteric lymphadenectomy, and excision of a small mass adherent to the portal vein adventitia. Histopathology confirmed two separate malignancies, with chromogranin A positivity supporting pheochromocytoma and CD20 positivity confirming B-cell lymphoma. No additional metastatic lesions were identified, and the portal vein-associated mass was considered an isolated lesion closely adherent to the vessel wall, with its exact pathogenesis remaining uncertain. To the authors’ knowledge, this represents the first veterinary report describing adrenal pheochromocytoma with portal vein involvement successfully managed by surgical removal. The patient recovered well and remained disease-free for three years without adjuvant therapy. This case emphasizes that, even in technically demanding situations, meticulous surgical planning and comprehensive oncologic assessment can achieve durable remission and inform future approaches to complex veterinary cancers. Full article

Background: Large-cell carcinoma (LCC) and large-cell neuroendocrine carcinoma (LCNEC) are kinds of rare lung tumors classified as distinct forms of non-small-cell lung cancer (NSCLC). They both differ in cellular morphology, neuroendocrine marker expression, and clinical outcomes. Thus, LCC and LCNEC exhibit different clinicopathological characteristics and survival outcomes. This study seeks to assess how clinicopathological and immunohistochemical features influence the need for adjuvant chemotherapy in individuals with early-stage, surgically resected LCC or LCNEC. Methods: This multicenter retrospective analysis included 79 patients who underwent surgical resection for large-cell carcinoma (LCC) or large-cell neuroendocrine carcinoma (LCNEC) between January 2008 and March 2025. We evaluated prognostic factors that influence survival in patients with LCC and LCNEC and assessed the effect of adjuvant chemotherapy on survival outcomes. Results: This study included 79 patients—39 diagnosed with LCC and 40 diagnosed with LCNEC. All patients were in stages I–III and received curative surgery. The median age was 61 years for LCC patients and 58.5 years for LCNEC patients. The median overall survival (mOS) was 80.1 months for patients with LCC and 34.2 months for those with LCNEC. Multivariate Cox regression analysis revealed that age (HR: 0.279), stage (HR: 0.198), and chromogranin A expression (HR: 0.088) were independent prognostic factors for overall survival in LCC patients. In LCNEC patients, stage (HR: 0.20), synaptophysin expression (HR: 0.30), type of surgery (HR: 0.31), and adjuvant chemotherapy (HR: 0.264) were identified as factors influencing overall survival. Adjuvant chemotherapy improved overall survival in LCNEC patients (67.0 vs. 17.8 months). Conclusions: Patients with LCNEC generally have poorer prognoses than those with LCC, exhibiting reduced overall survival periods. Disease stage is the most significant factor influencing overall survival for both groups. Notably, in LCNEC patients, adjuvant chemotherapy was found to independently improve survival outcomes regardless of stage. Full article

Background: Whether therapeutic albumin (ThHSA) can serve as a defense tool in Candida species (spp.) infections is still a matter of debate, although many physicians are in the habit of infusing ThHSA to restore the physiological concentration of endogenous human serum albumin (HSA). Given the need for innovative anti-Candida strategies, we assessed in vitro the role of ThHSA alone or in combination with voriconazole (VCZ) in combating Candida spp. growth and the role of bovine serum albumin (BSA)—used as a substitute for HSA—with two endogenous bovine antimicrobial peptides in combating C. albicans and other microbes. Results: The combination of ThHSA with VCZ enhanced the antifungal effect on C. albicans, sensitive C. tropicalis, sensitive C. glabrata, and C. lusitaniae. However, for resistant C. tropicalis, the combination of ThHSA with VCZ promoted yeast growth, and VCZ tended to suppress the antimicrobial effect of ThHSA on resistant C. glabrata. As to the possible transposition of ThHSA-type properties to BSA (as regards the growth inhibition of other pathogens), we tested combinations of BSA with two physiological chromogranin A-derived antimicrobial peptides (catestatin and cateslytin). BSA enhanced significantly the activity of catestatin (but not cateslytin) in combating C. albicans, A. fumigatus, and M. luteus, but was inactive against S. aureus and E. coli. Conclusions: Our experiments support the fact that albumins display intrinsic antimicrobial properties, with an unpredictable growth inhibitory effect on various microbes. ThHSA can thus be an adjunctive tool for more efficient care of some, though not all, infections. The interaction of BSA with catestatin and cateslytin is related to their structure, with BSA significantly enhancing the effect of catestatin but not that of cateslytin. Full article

Background: Prior research has reported increased expression of duodenal chromogranin-A (CgA), secreted by enteroendocrine cells (EECs), in association with pancreatic fibrosis. However, it remains unknown whether serum CgA levels are also elevated, and whether there is a different distribution pattern of EECs in pancreatic fibrosis and other dyspeptic causes. Aims: This study had three main objectives. First, to compare the serum CgA level between patients with pancreatic fibrosis and those with other dyspeptic conditions. Second, to analyze the distribution pattern of duodenal EECs. Third, to evaluate whether biopsy results varied depending on the specific location within the duodenum. Serum CgA levels were categorized into low and high groups based on a cutoff value of 50 ng/mL. Methods: This cross-sectional prospective case series included 15 patients, with 4 patients in the low CgA group and 11 in the high CgA group. Each participant underwent a serum CgA test, transabdominal ultrasonography, pancreatic elastography, and upper gastrointestinal endoscopy. During endoscopy, a single gastric biopsy and three duodenal biopsies from different locations were obtained. Results: Patients in the high CgA group were generally older (52–68 years) than those in the low CgA group (37–55 years), with a statistically significant difference (p < 0.01). The high CgA group exhibited a clustered and centralized pattern of EECs, whereas the low CgA group showed a more discrete pattern with fewer EECs (p < 0.01). All duodenal ulcer cases were found in the low CgA group, while three cases of pancreatic fibrosis and one case of chronic pancreatitis were identified in the high CgA group. In the high CgA group, five cases of functional dyspepsia showed a band-like EEC distribution pattern, whereas cases with pancreatic fibrosis demonstrated a more uniformly scattered EEC distribution (p < 0.01). Consistency among intra-individual duodenal biopsy results was high across different biopsy sites. Conclusions: Elevated serum CgA (>50 ng/mL) and specific duodenal EEC distribution patterns may serve as potential diagnostic indicators for pancreatic fibrosis or chronic pancreatitis. These characteristics could help differentiate these conditions from functional dyspepsia. Full article

Background and Clinical Significance: Mucinous tubular and spindle cell carcinoma (MTSCC) is an uncommon subtype of renal cell carcinoma, representing 1–4% of epithelial renal tumors. It usually shows a low-grade morphology and indolent behavior, although sarcomatoid variants with an aggressive course have been described. Because of its overlap with papillary renal cell carcinoma (papRCC), sarcomatoid RCC, mesenchymal tumors, and oncocytic neoplasms, diagnosis requires the integration of imaging, histopathology, and immunohistochemistry. Case Presentation: We report a 71-year-old female who presented with a three-month history of right-sided lumbar pain and intermittent hematuria. Her laboratory tests were unremarkable. Contrast-enhanced CT revealed a well-circumscribed nodular lesion in the mid-portion of the right kidney, measuring 50 × 47 × 52 mm. The patient underwent right nephrectomy. Macroscopic findings revealed an encapsulated, yellowish-gray nodule (5.2 × 5 × 4 cm) without renal pelvis invasion. Microscopically, the tumor consisted of cuboidal- to spindle-shaped cells arranged in cords and tubular structures within a mucinous stroma, with focal necrosis and foamy macrophages. Immunohistochemistry showed positivity for CK19, CK7, EMA, PAX8, and AMACR, with a Ki-67 index <10%, while CD117, RCC, CD10, and chromogranin were negative. Together, the low Ki-67 proliferation index, absence of invasion, and low-grade histological architecture confirmed MTSCC of low malignant potential. At a five-year follow-up, the patient remained disease-free. Conclusions: MTSCC is a rare renal neoplasm that can be diagnosed by integrating clinico-radiological, histopathological, and immunophenotypic features. Molecular profiling may further distinguish MTSCC from papRCC and identify aggressive variants. Surgical excision remains the cornerstone of management, supported by vigilant long-term follow-up. Full article

Introduction: Prolonged fasting induces histological and ultrastructural changes of the intestinal mucosa that may reduce absorption in malnourished patients with high risk of refeeding syndrome. Endocrine function of the intestinal mucosa may be affected by starvation with potential implications for nutritional support. Objective: The present study aims to evaluate the expression of gastrointestinal hormones in duodenal enteroendocrine cells (EECs) of patients after a long starvation period and to assess the changes in EEC hormonal expression after enteral refeeding in the same individuals. Methods: This was an observational prospective controlled study. Adult patients submitted to endoscopic gastrostomy (PEG) with an ingestion below 50% of daily needs for at least one month were enrolled. Duodenal biopsies were collected before gastrostomy (T0) and after 3–6 months of PEG feeding (T1). Biopsies underwent immunohistochemical analysis for chromogranin-A (CgA), neurotensin and incretin (GLP-1 and GIP) tissue expression. Normal duodenum biopsies were used as controls. Results: A total of 30 patients (16 men/14 women) aged 67.1 ± 13.5 years were included, and 14 patients completed follow-up at both periods (46.7%). Malnutrition was diagnosed in all patients according to GLIM criteria. T0 tissue expression defined by median stained area for CgA, GLP-1, and GIP were significantly higher in patients compared to controls (CgA: 1.04% vs. 0.41%; GLP-1: 0.17% vs. 0.03%; GIP: 0.19% vs. 0.03%) (p < 0.001) without differences for neurotensin (0.01%) (p = 0.96). T1 hormonal tissue expression was not significantly reduced after 3–6 months of enteral refeeding (p > 0.05). Conclusions: Prolonged fasting induces increased expression of incretins and chromogranin-A in the duodenum that probably reflect an adaptative response to maintain the anabolic insulin effect under nutritional deficiency. Hormonal expression does not normalize after PEG refeeding during a short period. Full article

Background: Small intestinal neuroendocrine tumors (SI-NETs) are the most common malignancies of the small bowel. Although typically well differentiated and slow-growing, they may exhibit aggressive behavior, especially when diagnosed at an advanced stage. Objective: To illustrate the diagnostic and therapeutic challenges of advanced SI-NETs through a rare case presentation and a narrative review of recent studies in the literature. Methods: A narrative literature review was conducted using the PubMed database to examine the incidence, risk factors, diagnostic modalities, and treatment strategies for advanced-stage SI-NETs. The search included studies published between January 2010 and June 2025 and focused on human subjects, using keywords such as “small intestinal neuroendocrine tumor”, “metastasis”, “tumor grade”, and “treatment”. Results: We report the case of a 68-year-old man who presented with bowel obstruction. Imaging and surgical exploration revealed a jejunoileal SI-NET with extensive liver and peritoneal metastases, mesenteric fibrosis, and ascites. Histopathology confirmed a well-differentiated grade 2 tumor (Ki-67: 3%) positive for chromogranin A and CD56. Despite a low proliferative index, the tumor demonstrated aggressive clinical behavior. The patient underwent emergency enterectomy with ileostomy and was referred for further evaluation, including somatostatin receptor imaging and consideration for peptide receptor radionuclide therapy (PRRT). Conclusions: This case highlights the potential for aggressive progression in well-differentiated SI-NETs with low Ki-67 indices. Histological grade alone may not predict clinical behavior. Early diagnosis, comprehensive staging, and individualized multidisciplinary management—guided by functional imaging and receptor profiling—are critical to improving outcomes in advanced SI-NETs. Full article

Pancreatic neuroendocrine tumors (pNETs) are rare malignancies, accounting for 1–2% of pancreatic cancers, with an incidence of ≤1 case per 100,000 individuals annually. Originating from pancreatic endocrine cells, pNETs display significant clinical and biological heterogeneity. Traditional classification based on proliferative grading does not fully capture the complex mechanisms involved, such as oxidative stress, mitochondrial dysfunction, and tumor-associated macrophage infiltration. Recent advances in molecular profiling have revealed key oncogenic drivers, including MEN1 (menin 1), DAXX (death domain–associated protein), ATRX (alpha thalassemia/mental retardation syndrome X-linked), CDKN1B (cyclin-dependent kinase inhibitor 1B) mutations, chromatin remodeling defects, and dysregulation of the mTOR pathway. Somatostatin receptors, particularly SSTR2, play a central role in tumor biology and serve as important prognostic markers, enabling the use of advanced diagnostic imaging (e.g., Gallium-68 DOTATATE PET/CT) and targeted therapies like somatostatin analogs and peptide receptor radionuclide therapy (PRRT). Established biomarkers such as Chromogranin A and the Ki-67 proliferation index remain vital for diagnosis and prognosis, while emerging markers, like circulating tumor DNA and microRNAs, show promise for enhancing disease monitoring and diagnostic accuracy. This review summarizes the molecular landscape of pNETs and highlights genomic, transcriptomic, proteomic, and epigenomic factors that support the identification of novel diagnostic, prognostic, and therapeutic biomarkers, ultimately advancing personalized treatment strategies. Full article

Enteroendocrine cells (EECs) are specialized secretory cells in the gut epithelium that differentiate from intestinal stem cells (ISCs). Mature EECs secrete incretin hormones that stimulate pancreatic insulin secretion and regulate appetite. Decreased EEC numbers and impaired secretion of the incretin glucagon-like peptide-1 (GLP1) have been implicated in obesity-associated metabolic complications. Gut microbial metabolites of dietary tryptophan (TRP) were recently shown to modulate ISC proliferation and differentiation. However, their specific effects on EEC differentiation are not known. We hypothesized that the gut microbial metabolites of dietary tryptophan counteract impaired GLP1 production and function in obesity by stimulating EEC differentiation from ISCs. We utilized complementary models of human and rat intestines to determine the effects of obesity or TRP metabolites on EEC differentiation. EEC differentiation was assessed by the EEC marker chromogranin A (CHGA) levels in the intestinal mucosa of normal versus obese rats. The effects of TRP metabolites on EEC differentiation were determined in human intestinal organoids treated with indole, a primary TRP metabolite, or the culture supernatant of Lactobacillus acidophilus grown in TRP media (LA-CS-TRP). Our results showed that the mRNA and protein levels of CHGA, the EEC marker, were significantly decreased (~60%) in the intestinal mucosa of high-fat-diet-induced obese rat intestines. The expression of the transcription factors that direct the ISC differentiation towards the EEC lineage was also decreased in obesity. In human organoids, treatment with indole or LA-CS-TRP significantly increased (more than 2-fold) CHGA levels, which were blocked by the aryl hydrocarbon receptor (AhR) antagonist CH-223191. Thus, the stimulation of EEC differentiation by colonic microbial metabolites highlights a novel therapeutic role of TRP metabolites in obesity and associated metabolic disorders. Full article

Background: Hypothermia, occurring when core temperature drops below 35 °C, can lead to death when the body’s heat loss exceeds its heat production. This study investigates two hypothermia-related deaths, exploring the utility of immunohistochemistry, specifically focusing on chromogranin A (CgA) as a potential diagnostic tool. The aim is to assess whether CgA expression in neuroendocrine tissues can be considered a reliable indicator of premortem stress response in fatal hypothermia cases. Case Presentation: In the first case, a 67-year-old man was found on a snowy road 24 h after his disappearance. The autopsy revealed cold-induced skin lesions, gastric hemorrhages, and cerebral and pulmonary edema. Positive CgA immunostaining was observed in the pancreatic islets and adrenal medulla. In the second case, a 49-year-old man was found dead in a wooded area with indications of suicide. Both cases were examined with attention to macroscopic findings and histological samples from major neuroendocrine organs. As in previous cases, CgA immunostaining was positive in the pancreatic islets and adrenal medulla. Staining intensity was moderate to strong, consistent with heightened neuroendocrine activity, supporting the hypothesis of systemic stress prior to death. Conclusions: Although CgA is a potentially valuable adjunct in hypothermia diagnosis, careful consideration of cadaveric preservation is emphasized, particularly when bodies are preserved before autopsy. Further studies with larger sample sizes are needed to confirm its diagnostic specificity and to distinguish true pathological patterns from postmortem artifacts. Full article

Anxiety and depression are highly prevalent mental health disorders often associated with dysregulation of neuroendocrine and immune systems, particularly the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic–adrenal–medullary (SAM) system. Recent research highlights the potential of salivary biomarkers to serve as non-invasive indicators for psychological distress. This narrative review synthesizes current evidence on key salivary biomarkers, cortisol, alpha-amylase (sAA), secretory immunoglobulin A (sIgA), chromogranin A (CgA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF), and salivary microRNAs (miRNAs), in relation to anxiety, depression, and stress. A comprehensive literature search (2010–2025) was conducted using multiple databases and relevant MeSH terms. The review reveals consistent associations between these salivary analytes and stress-related disorders, reflecting changes in neuroendocrine activity, immune response, and neuroplasticity. Cortisol and sAA mirror acute stress reactivity, while cytokines and CRP indicate chronic inflammation. BDNF and miRNAs provide insight into neuroplastic dysfunction and gene regulation. Despite promising results, limitations such as variability in sampling methods and biomarker specificity remain. In conclusion, salivary biomarkers offer a promising avenue for early detection, monitoring, and personalization of treatment in mood and anxiety disorders. Conclusions: Cortisol and alpha-amylase serve as the principal markers of acute stress response, whereas cytokines such as IL-6 and TNF-α, together with CRP, indicate chronic inflammation associated with extended emotional distress. Full article

Cancer during pregnancy is a rare but complex clinical scenario that affects approximately 0.1% of pregnant individuals and is associated with increased maternal morbidity. With the trend of delayed childbearing, the incidence of pregnancy-associated cancers is expected to rise. Neuroendocrine neoplasms (NENs), although rare in pregnancy, present unique diagnostic and therapeutic challenges due to their hormonal activity, histological diversity, and limited data on management in the gestational context. Objectives: This manuscript reviews the current evidence on the diagnosis, staging, and management of NENs during pregnancy, focusing on maternal–fetal safety, therapeutic limitations, and multidisciplinary care strategies. Methods: A comprehensive narrative review was conducted using relevant case reports, retrospective studies, clinical guidelines, and expert consensus documents addressing cancer in pregnancy and NEN-specific management. Results: Pregnancy complicates the evaluation and treatment of NENs due to overlapping symptoms, contraindications to standard imaging and systemic therapies, and unreliable biomarkers such as chromogranin A and 5-HIAA. Most systemic therapies for NENs, including somatostatin analogs, tyrosine kinase inhibitors, and peptide receptor radionuclide therapy, are contraindicated or lack safety data in pregnancy. Surgical interventions and supportive care require careful planning. Decisions regarding pregnancy continuation or termination must be individualized and supported by a multidisciplinary team. Conclusions: The management of NENs during pregnancy demands a highly individualized approach, coordinated among oncology, maternal–fetal medicine, and supportive care teams. Given the paucity of robust data, future research is essential to establish evidence-based guidelines and improve outcomes for both mother and fetus. Full article