Search Results (380)

Tetrasubstituted dihydrothiophenes represent a class of heterocyclic compounds with significant potential in various fields, particularly in medicinal chemistry and materials science. In this work, we have developed an eco-friendly and efficient method for synthesizing such compounds, using porcine pancreatic lipase (PPL) as a biocatalyst to promote the cyclization reaction between β-ketothioamides and β-nitrostyrenes. Through this approach, sixteen tetrasubstituted dihydrothiophenes were successfully synthesized, and all of them achieved high yields, ranging from 80% to 96%. This research not only expands the application scope of lipase in organic synthesis, demonstrating its versatility beyond traditional hydrolytic reactions, but also provides a new environmentally friendly pathway for the production of tetrasubstituted dihydrothiophenes, which is of great significance for advancing related fields of chemical synthesis. Full article

Background: Although semaglutide (Ozempic^®) is being prescribed off-label to individuals with obesity, some concerns have arisen regarding its use, particularly regarding the risk of thyroid and pancreatic disorders. Therefore, it is crucial to screen patients’ medical and family disease histories, as well as certain clinical parameters, before initiating this treatment for obesity or weight management. However, there is limited research investigating whether pretreatment assessment is adopted in clinical practice. Method: This is a single-center retrospective study involving adults who were prescribed semaglutide for obesity or weight management. Demographic data, comorbid conditions, semaglutide-related lab work, and disease history assessments, including pancreatitis, thyroid abnormalities, oculopathy, neuropathy, and any family history of thyroid cancer, were evaluated and documented prior to treatment initiation. Results: In total, 715 patients were included in the study, with an average age of 40.2 ± 12.0 years, and 49.5% of participants were male. The average weight and BMI prior to using semaglutide were 99.8 ± 18.1 kg and 36.3 ± 8.3 kg/m², respectively, with predominantly overweight and obese individuals (collectively 91.3%). Approximately 69% of patients had 3–5 complications, with a high prevalence of cardiovascular and metabolic diseases before using semaglutide. Although HbA1c, serum creatinine, TSH, T3, T4, triglycerides, HDL, LDL, total cholesterol, and total bilirubin were monitored prior to semaglutide use, none of the patients’ pancreatic lipase, amylase, or calcitonin levels were measured. Although it is important to investigate all personal and family disease histories, including thyroid abnormalities, thyroid cancer, pancreatitis, retinopathy, eye problems, and neuropathy prior to semaglutide initiation, checks were only conducted in 1.8% of patients, despite 98.6% having at least one of the diseases assessed pretreatment. Conclusions: The current pretreatment assessment approach for patients prescribed semaglutide for weight reduction is underdeveloped, particularly with regard to assessing the influence of disease history on semaglutide use. This predisposes patients to a risk of severe clinical outcomes, including thyroid cancer, pancreatitis, and retinopathy. Full article

Background: Diabetes and cancer are two of the most life-threatening disorders affecting individuals of all ages worldwide. This study aimed to develop a novel Acrocomia aculeata (bocaiuva) fruit pulp oil-loaded nanoemulsion and evaluate its inhibitory effects on α-glucosidase and pancreatic lipase, as well as its antiglycant activity and cytotoxicity against cancer cells. Additionally, this study assessed the impact of both the oil and the nanoemulsion on blood cells. Methods: The pulp oil was extracted by cold pressing. The oil’s physicochemical properties were determined according to the AOAC and the Brazilian Pharmacopeia. The lipid profile was performed by GC-MS. The nanoemulsion was prepared by the phase inversion method using ultrasonic stirring for particle size reduction and for homogenization. Response Surface Methodology was used for optimizing nanoemulsion preparation. Enzyme inhibition tests were conducted using assay kits. Cytotoxicity in cancer cells was evaluated using the Sulforhodamine B assay. Results: Comprehensive physicochemical and chemical characterization of bocaiuva oil was performed, identifying oleic acid (71.25%) as the main component. The oil contains 23.04% saturated fatty acids, 73.79% monounsaturated acids, and 3.0% polyunsaturated fatty acids. The nanoemulsion (particle size 173.6 nm; zeta potential −14.10 mV) inhibited α-glucosidase (IC₅₀: 43.21 µg/mL) and pancreatic lipase (IC₅₀: 41.99 µg/mL), and revealed a potent antiglycation effect (oxidative IC₅0: 18.36 µg/mL; non-oxidative pathway IC₅₀: 16.33 µg/mL). The nanoemulsion demonstrated good cytotoxicity and selectivity against prostate cancer cells (IC₅₀: 19.13 µg/mL) and breast cancer cells (IC₅₀: 27.22 µg/mL), without inducing hemolysis, platelet aggregation, or anticoagulant effects. Conclusions: In this study, a comprehensive physical and chemical characterization of bocaiuva fruit pulp oil was conducted for the first time as a preliminary step toward its future standardization as an active ingredient in cosmetic and pharmaceutical formulations. The resulting nanoemulsion represents a novel alternative for managing diabetes and cancer. Although the nanoemulsion exhibited lower cytotoxicity compared to doxorubicin, it remains promising due to its composition of essential fatty acids, phenols, and carotenoids, which offer multiple health benefits. Further studies are needed to validate its efficacy and safety in clinical applications. Full article

Mussels are nutrient-rich but perishable, resulting in substantial resource loss. A protease-producing strain (Bacillus velezensis Z-1, Mytilus edulis) isolated from marine sludge was used to hydrolyze mussels, producing Y-1, a hydrolysate with antioxidant activity. In this study, ultrafiltration, gel chromatography, and LC-MS/MS were employed to isolate and identify bioactive peptides from the hydrolysate. The results revealed that the hydrolysate exhibited antioxidant activity, pancreatic cholesterol esterase inhibitory activity, pancreatic lipase inhibitory activity, and α-glucosidase inhibitory activity. Molecular docking using AutoDock Tools 1.5.6 was performed to analyze the interactions of peptides with CD38 and Keap1, leading to the identification of five potentially bioactive peptides: VPPFY, IMLFP, LPFLF, FLPF, and FPRIM. These peptides formed hydrogen bonds and hydrophobic interactions with CD38 and Keap1, demonstrating strong DPPH radical scavenging and superoxide anion radical scavenging capacities. This study highlights the multifunctional bioactive potential of these peptides, offering insights into their therapeutic applications. The findings provide a novel approach for the effective utilization of mussel resources and highlight their potential application value in the development of functional foods. Full article

Obesity and its associated complications, including oxidative stress, pose significant global health challenges. Natural products offer a promising avenue for developing novel therapeutic strategies. In this study, we investigated the potential of Panax japonicus (T. Nees) C.A. Meyer, a traditional medicinal plant known for its antioxidant and anti-obesity properties. A methanol extract of Panax japonicus and its fractions were evaluated for their in vitro antioxidant activities (tested using DPPH and reducing power assays), pancreatic lipase (PL) inhibitory capacities, and underlying mechanisms of action. The results indicated that the ethyl acetate fraction of P. japonicus (PJEA) exhibited the greatest potency, demonstrating strong antioxidant activity and significantly inhibiting digestive enzyme activity (pancreatic lipase). Mechanistic studies revealed that the PL inhibition was of a mixed type, combining both competitive and non-competitive mechanisms. Furthermore, PJEA demonstrated the ability to inhibit the differentiation of preadipocytes, primarily exerting its anti-adipogenic effects by downregulating the mRNA expression of PPARγ and the gene expression of C/EBPα. In addition, the extract suppressed the gene expression of FAS and ACC in adipose tissue. Isolation of the bioactive compounds from PJEA identified kaempferol 3-O-α-L-rhamnoside and catechin, which potentially contribute to the observed anti-obesity effects. Overall, this study highlights P. japonicus as a promising natural ingredient for scavenging free radicals and managing obesity, suggesting its potential for development into functional foods or therapeutic agents. Full article

Obesity is a chronic epidemic caused by abnormal fat metabolism. As a key digestive enzyme, pancreatic lipase (PL) is an important target for regulating fat metabolism. The inhibitory potential of 5,10,15,20-Tetrakis (4-aminophenyl) porphyrin (TAPP), 5,10,15,20-Tetrakis (4-hydroxyphenyl) porphyrin (THPP), meso-Tetra (4-carboxyphenyl) porphine (TCPP), Cu (II) meso-Tetra (4-carboxyphenyl) porphine (Cu-TCPP) on PL was studied by enzymatic kinetics, multi-spectral, and molecular simulation technology. THPP, TCPP, TAPP, and Cu-TCPP all had good PL inhibitory activity (IC₅₀ range: 97.49–248.70 μM) and were uncompetitive inhibitors. The order of inhibitory ability was: THPP > TCPP > TAPP > Cu-TCPP. The fluorescence quenching mechanism of THPP to PL was a mixed quenching dominated by static quenching, while TCPP, TAPP, and Cu-TCPP were static quenching. The binding of THPP, TCPP and TAPP to PL was mainly driven by hydrogen bonds and van der Waals forces, while Cu-TCPP was mainly driven by a hydrophobic interaction. Four porphyrin compounds changed the conformation of PL, affected the microenvironment of Tyr and Trp residues, and induced changes in the secondary structure of PL, thereby reducing the stability and catalytic activity of PL. Hydrogen bonds played an important role in the binding stability of THPP, TCPP, TAPP, and PL. Full article

A five-month-old female mixed-breed dog presented with a two-week history of polyuria, polydipsia, and vomiting. Clinical examination revealed poor body condition, growth retardation, pale oral mucous membranes, weak pulse, and prolonged capillary refill time. Laboratory findings included neutrophilic leukocytosis with a regenerative left shift, fasting hyperglycemia, elevated fructosamine, glycated hemoglobin, and β-hydroxybutyrate concentrations, while the acid–base balance remained normal. Canine-specific pancreatic lipase and trypsin-like immunoreactivity concentrations ruled out an underlying pancreatitis or exocrine pancreatic insufficiency, respectively. Urinalysis showed glycosuria and ketonuria. Supportive care included antibiotics and regular insulin administration. Abdominal ultrasonography identified a pancreatic cavity with a thick wall and mixed echogenic fluid. Ultrasound-guided drainage was performed without complications. Cytology confirmed a pancreatic abscess with pyogranulomatous inflammation, though the culture results were negative. The dog was discharged with intermediate-acting lente insulin. Follow-up ultrasonographic evaluations at 7, 14, and 21 days and 5 months post-drainage showed no recurrence. The diabetes remained well-controlled one year post-discharge. This case report describes the successful management of a dog with juvenile diabetes mellitus complicated by a pancreatic abscess, highlighting the effectiveness of percutaneous ultrasound-guided drainage combined with medical therapy. Full article

Background and Clinical Significance: Diabetic ketoacidosis (DKA) is a serious and potentially life-threatening condition, often triggered by infections or undiagnosed diabetes. Spontaneous pneumomediastinum (SPM) and pneumothorax are rare but recognized complications of DKA, possibly due to alveolar rupture from increased respiratory effort or vomiting. Sometimes, acute pancreatitis (AP) may further complicate DKA, but the co-occurrence of these three conditions remains exceptionally rare. Case Presentation: We describe the case of a 60-year-old woman without a known history of diabetes who arrived at the emergency department with abdominal pain, fatigue, vomiting, and altered mental status. Initial laboratory findings showed metabolic acidosis, hyperglycemia, and elevated anion gap, consistent with DKA. Imaging revealed spontaneous pneumomediastinum and subsequently a left-sided pneumothorax, without evidence of trauma or esophageal rupture. Epigastric pain, along with elevated serum lipase and CT findings, also confirmed acute pancreatitis. Despite the complexity of her condition, the patient responded well to supportive treatment, including oxygen therapy, fluid resuscitation, insulin infusion, and antibiotics. She was discharged in good condition after 28 days, with a confirmed diagnosis of type 2 diabetes, without further complications. Conclusions: This case highlights an unusual combination of DKA complicated by spontaneous pneumomediastinum, pneumothorax and acute pancreatitis in a previously undiagnosed diabetic patient. Because prompt intervention can lead to favorable outcomes even in complex, multisystem cases, early recognition of atypical DKA complications is critical in order to avoid misdiagnosis. Full article

The advancement of modern lifestyles has precipitated excessive consumption of energy-dense foods, driving the escalating global burden of lipid metabolism dysregulation-related pathologies—including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disorders—which collectively pose a formidable challenge to global public health systems. The almond hull, as a by-product of almond processing, is rich in polyphenolic compounds with demonstrated antioxidant, anti-inflammatory, and lipid-lowering potential, though its precise hypo-lipidemic mechanisms remain elusive. In this study, polyphenols were extracted from almond hulls using 50% ethanol with ultrasound-assisted extraction, followed by preliminary purification via solvent partitioning. The ethyl acetate fraction was analyzed by liquid chromatography–mass spectrometry (LC-MS). Network pharmacology and molecular docking were employed to investigate the interactions between key bioactive constituents (e.g., quercetin, baicalein, and kaempferol) and targets in lipid metabolism-related pathways. Molecular dynamics (MD) simulations further evaluated the stability of the lowest-energy complexes. Results revealed that the ethyl acetate fraction exhibited potent pancreatic lipase inhibitory activity (IC50 = 204.2 µg/mL). At 0.1 mg/mL after 24 h treatment, it significantly reduced free fatty acids (FFAs)-induced intracellular triglyceride accumulation (p < 0.01) and enhanced cellular antioxidant capacity. Network pharmacology and in vitro studies suggest almond hull extract modulates PI3K-AKT signaling and improves insulin resistance, demonstrating lipid-lowering effects. These findings support its potential in functional foods and pharmaceuticals, though further in vivo validation and mechanistic investigations are required. Full article

Background/Objectives: The increasing use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to a rise in immune-related adverse events (irAEs), including pancreatic injury. While current guidelines suggest that baseline monitoring of amylase and lipase levels is not necessary, it remains common in clinical settings, leading to confusion regarding their interpretation and management. This practice may lead to confusion, especially when patients exhibit isolated mild elevations of amylase and lipase, which may not always correlate with clinical pancreatitis. In contrast, significant elevations in these enzymes warrant further investigation, including imaging to assess the presence of pancreatitis. Methods: This review aims to provide a clearer framework for clinicians in managing ICI-induced pancreatic injury, promoting consistency in practice, and improving patient outcomes by reducing unnecessary interruptions to ICI therapy. Results: It is critical to distinguish between the severity of pancreatitis to guide management. Conclusions: Considering the expected rise in the use of immune ICIs, it is crucial to increase awareness about the potential for pancreatic injury associated with these treatments. Full article

Obesity represents a significant global public health issue, contributing to the rising prevalence of metabolic diseases. One treatment for obesity is orlistat, a drug that inhibits pancreatic lipase. It is widely used due to its efficacy in reducing dietary fat absorption. However, patient adherence to this drug is often hindered by its associated adverse effects. As a result, there is an increasing interest in exploring alternative therapeutic options derived from natural sources, such as plants and algae, particularly extracts and their bioactive compounds. These extracts and compounds have shown potential in inhibiting pancreatic lipase and other markers associated with obesity. Nevertheless, they also present certain limitations, including low bioavailability. In this context, combination therapy involving orlistat and these extracts or their compounds has emerged as a promising strategy. This approach aims to enhance the inhibition of pancreatic lipase and other obesity-related markers, thereby improving therapeutic outcomes and reducing adverse effects associated with treatment. The objective of this review is to analyze the available scientific evidence regarding the combined effects of orlistat and extracts or bioactive compounds in inhibiting various markers related to dyslipidemia and obesity, with the goal of proposing combination therapy as a safe and effective therapeutic option. Full article

This study aimed to investigate the effects of organic selenium-enriched yeast on the growth performance, muscle selenium deposition, and antioxidant capacity of juvenile Cherax quadricarinatus. Five experimental diets supplemented with 0.00 (control), 1.00, 2.00, 3.00, and 4.00 mg/kg of selenium-enriched yeast were fed to crayfish with an average initial body weight of (6.35 ± 1.66) g for 56 days. On days 0, 14, 28, 42, and 56 of the trial, 10 crayfish from each group were randomly sampled for body weight measurement. On day 28, the body weight of the crayfish fed diets containing 1.00, 2.00, 3.00, and 4.00 mg/kg selenium-enriched yeast was significantly higher (p < 0.05) than that of the control group. On day 56, the weight gain rate (WGR) and specific growth rate (SGR) of crayfish fed 1.00, 2.00, and 3.00 mg/kg selenium-enriched yeast were significantly elevated (p < 0.05) compared to those of the control group. Dietary selenium supplementation significantly enhanced muscle selenium deposition (p < 0.05), with deposition levels increasing proportionally to the supplementation levels within the same period. Selenium deposition initially increased, peaked at day 28 (significantly higher than the control), and then declined and stabilized. On day 42, the activities of pancreatic lipase (LPS), total superoxide dismutase (T-SOD), and acid phosphatase (ACP) in the hepatopancreas were significantly higher in the 3.00 and 4.00 mg/kg groups (p < 0.05). In comparison, trypsin activity was significantly increased in the 2.00 mg/kg and 3.00 mg/kg yeast selenium groups (p < 0.05). Alkaline phosphatase (AKP) activity was highly significantly elevated in the 2.00 mg/kg group (p < 0.01). On day 56, glutathione peroxidase (GSH-PX) activity in the hepatopancreas was considerably enhanced in all the selenium-supplemented groups (1.00–4.00) mg/kg (p < 0.05). In conclusion, the appropriate supplementation of selenium-enriched yeast promotes growth performance, enhances muscle selenium deposition, improves hepatopancreatic digestive enzyme activity, and strengthens antioxidant and immune capacities in Cherax quadricarinatus. Full article

Celiac disease (CD) is a chronic and immune-mediated disorder triggered by the ingestion of gluten in some genetically predisposed individuals. CD can be associated with extra-gastrointestinal manifestations and diseases affecting several organs. In this review, the aim is to analyze and discuss the pancreatic alterations and/or comorbidities that could arise in the context of pediatric CD. Exocrine pancreatic insufficiency (EPI) can be observed in a variable fraction (up to 30%) of children diagnosed with CD at the diagnosis; indeed, it usually resolves after the implementation of a gluten-free diet (GFD). The main pathophysiological mechanisms of EPI could be represented by the impaired pattern of gastrointestinal hormones in CD patients. Conversely, pancreatitis seems to be a very rare comorbidity in CD children, since very few cases have been described in children. Therefore, there is no evidence that pancreatitis (including autoimmune forms) represents a relevant comorbidity in pediatric CD. Type 1 diabetes mellitus (T1DM) is a well-known and frequent comorbidity in CD children. The main determinant of this epidemiological association is the common HLA-related predisposing background, even if other (non-HLA-related) genetic and environmental factors (viruses, gut microbiome, and others) are likely to be also implicated in the development of both these autoimmune diseases. T1DM children with concomitant CD may experience specific challenges in the adherence to GFD, which has no negative impact on the glycemic and, in general, metabolic control of diabetes, if it is properly implemented and followed up. Full article

Bee pollen is widely recognized for its health benefits, with its nutritional and bioactive properties varying by botanical origin. This study analyzed twelve bee pollen samples collected from six different apiaries in Uruguay during two seasons (spring and autumn) to determine their botanical composition; nutritional profile (protein, lipids, carbohydrates, dietary fiber, ash, and fatty acid profile); bioactive compound content (total phenols, vitamin C, tocopherols, and carotenoids); antioxidant activity (ABTS and ORAC); color; and ability to inhibit enzymes involved in carbohydrate and fat digestion. Among the samples collected in autumn, three were monofloral (one from Casuarina and two from Eucalyptus). The spring samples, however, were all multifloral, except for one monofloral Rapeseed sample. Monofloral samples had higher protein, fiber, tocopherol, and total phenol content, along with higher ABTS and ORAC values, but lower carotenoid levels. In contrast, autumn samples had lower protein and lipid content but higher fiber and vitamin C levels. The predominant fatty acids were palmitic, linolenic, linoleic, and oleic acids, with most samples showing a higher proportion of polyunsaturated fatty acids (40.7–57.9%). Compared to other food matrices, the α-glucosidase inhibition values of Uruguayan bee pollen are similar to those found in raw citrus pomace. This is the first report on bee pollen’s ability to inhibit pancreatic lipase in relation to its in vitro anti-obesity properties. Uruguayan bee pollen shows significant potential for combating metabolic syndrome, obesity, and type 2 diabetes. Full article

Background: Hepatitis B (HBV) and C (HCV) virus coinfections remain major contributors to liver-related morbidity and mortality among people living with HIV (PLWH). This study aimed to assess the prevalence of HBV and/or HCV coinfections in a Romanian HIV cohort and to evaluate their impact on immunological, virological, and liver function parameters under antiretroviral therapy (ART). Methods: We retrospectively analyzed 462 HIV-infected patients (2018–2021) from the National Institute of Infectious Diseases, Bucharest, stratified into four groups: HIV mono-infection (n = 176), HIV/HBV (n = 114), HIV/HCV (n = 97), and HIV/HBV/HCV (n = 75) coinfections. Immunological (CD4 count, CD8 count, and CD4/CD8 ratio), virological (HIV-1 RNA), and hepatic parameters (ALT, AST, GGT, bilirubin, amylase, and lipase) were compared. Results: No significant differences were observed between groups regarding the immune recovery (mean CD4 count p = 0.89, HIV-RNA suppression p = 0.78). However, liver and pancreatic parameters showed statistically significant deterioration in the coinfected groups. ALT (p < 0.001), GGT (p = 0.009), total bilirubin (p = 0.011), amylase (p = 0.010), and lipase (p < 0.001) were significantly higher in the triple-infection (HIV/HBV/HCV) group compared to HIV mono-infected patients. Coinfection was also associated with a longer duration of illness (p = 0.002) and therapy (p = 0.021) and with a higher number of ART regimens used (p = 0.013). Conclusions: While HIV suppression and immune recovery were not significantly impaired by HBV/HCV coinfections, liver and pancreatic injuries were significantly more prevalent and severe in coinfected patients. Regular monitoring of hepatic function and integrated management strategies are recommended to minimize liver-related complications in this population. Full article