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Search Results (205)

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Keywords = U-13C-glucose

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16 pages, 1961 KiB  
Article
A Novel Glycosylated Ferulic Acid Conjugate: Synthesis, Antioxidative Neuroprotection Activities In Vitro, and Alleviation of Cerebral Ischemia–Reperfusion Injury (CIRI) In Vivo
by Jian Chen, Yongjun Yuan, Litao Tong, Manyou Yu, Yongqing Zhu, Qingqing Liu, Junling Deng, Fengzhang Wang, Zhuoya Xiang and Chen Xia
Antioxidants 2025, 14(8), 953; https://doi.org/10.3390/antiox14080953 (registering DOI) - 3 Aug 2025
Abstract
Antioxidative neuroprotection is effective at preventing ischemic stroke (IS). Ferulic acid (FA) offers benefits in the treatment of many diseases, mostly due to its antioxidant activities. In this study, a glycosylated ferulic acid conjugate (FA-Glu), with 1,2,3-triazole as a linker and bioisostere between [...] Read more.
Antioxidative neuroprotection is effective at preventing ischemic stroke (IS). Ferulic acid (FA) offers benefits in the treatment of many diseases, mostly due to its antioxidant activities. In this study, a glycosylated ferulic acid conjugate (FA-Glu), with 1,2,3-triazole as a linker and bioisostere between glucose at the C6 position and FA at the C4 position, was designed and synthesized. The hydrophilicity and chemical stability of FA-Glu were tested. FA-Glu’s protection against DNA oxidative cleavage was tested using pBR322 plasmid DNA under the Fenton reaction. The cytotoxicity of FA-Glu was examined via the PC12 cell and bEnd.3 cell tests. Antioxidative neuroprotection was evaluated, in vitro, via a H2O2-induced PC12 cell test, measuring cell viability and ROS levels. Antioxidative alleviation of cerebral ischemia–reperfusion injury (CIRI), in vivo, was evaluated using a rat middle cerebral artery occlusion (MCAO) model. The results indicated that FA-Glu was water-soluble (LogP −1.16 ± 0.01) and chemically stable. FA-Glu prevented pBR322 plasmid DNA cleavage induced via •OH radicals (SC% 88.00%). It was a non-toxic agent based on PC12 cell and bEnd.3 cell tests results. FA-Glu significantly protected against H2O2-induced oxidative damage in the PC12 cell (cell viability 88.12%, 100 μM) and inhibited excessive cell ROS generation (45.67% at 100 μM). FA-Glu significantly reduced the infarcted brain areas measured using TTC stain observation, quantification (FA-Glu 21.79%, FA 28.49%, I/R model 43.42%), and H&E stain histological observation. It sharply reduced the MDA level (3.26 nmol/mg protein) and significantly increased the GSH level (139.6 nmol/mg protein) and SOD level (265.19 U/mg protein). With superior performance to FA, FA-Glu is a safe agent with effective antioxidative DNA and neuronal protective actions and an ability to alleviate CIRI, which should help in the prevention of IS. Full article
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14 pages, 839 KiB  
Article
Biochemical Profile Variations Among Type 2 Diabetic Patients Stratified by Hemoglobin A1c Levels in a Saudi Cohort: A Retrospective Study
by Abdulrahman Alshalani, Nada AlAhmari, Hajar A. Amin, Abdullah Aljedai and Hamood AlSudais
J. Clin. Med. 2025, 14(15), 5324; https://doi.org/10.3390/jcm14155324 - 28 Jul 2025
Viewed by 332
Abstract
Background: The global increase in type 2 diabetes mellitus (T2DM) cases necessitates the need for early detection of metabolic changes. This study investigated variations in liver enzymes, renal markers, electrolytes, and lipid profiles among T2DM patients stratified by hemoglobin A1c (HbA1c) categories [...] Read more.
Background: The global increase in type 2 diabetes mellitus (T2DM) cases necessitates the need for early detection of metabolic changes. This study investigated variations in liver enzymes, renal markers, electrolytes, and lipid profiles among T2DM patients stratified by hemoglobin A1c (HbA1c) categories to support early identification and better management of diabetes-related complications. Methods: A retrospective observational study at King Khalid University Hospital (KKUH), Riyadh, included 621 adult patients diagnosed with T2DM categorized into four HbA1c groups: normal (<5.7%), prediabetes (5.7–6.4%), controlled diabetes (6.5–7.9%), and uncontrolled diabetes (≥8.0%). Biochemical parameters included the liver profile: alkaline phosphatase (ALP) and bilirubin, renal profile: creatinine, blood urea nitrogen (BUN), glucose, sodium, and chloride, and lipid profile: cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. Regression models identified predictors of ALP, cholesterol, and LDL. Results: ALP was higher in uncontrolled diabetes (89.0 U/L, Q1–Q3: 106.3–72.0) than in the prediabetes group (75.0 U/L, Q1–Q3: 96.8–62.3). Sodium and chloride were lower in uncontrolled diabetes (Na: 138.3 mmol/L, Q1–Q3: 140.3–136.4; Cl: 101.1 mmol/L, Q1–Q3: 102.9–99.4) compared to the normal group (Na: 139.5 mmol/L, Q1–Q3: 142.4–136.9; Cl: 103.5 mmol/L, Q1–Q3: 106.1–101.7). LDL was lower in uncontrolled diabetes (2.1 mmol/L, Q1–Q3: 2.8–1.7) than in the normal group (2.8 mmol/L, Q1–Q3: 3.7–2.2), while triglycerides were higher in patients with uncontrolled diabetes compared to the normal group (1.45 mmol/L, Q1–Q3: 2.02–1.11 vs. 1.26 mmol/L, Q1–Q3: 1.44–0.94). Regression models showed low explanatory power (R2 = 2.1–7.3%), with weight, age, and sex as significant predictors of select biochemical markers. Conclusions: The study observed biochemical variations across HbA1c categories in T2DM patients, likely reflecting insulin resistance. Monitoring these markers in conjunction with HbA1c can enhance early detection and improve the management of complications. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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18 pages, 1599 KiB  
Article
SGLT2 Inhibitors in MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) Associated with Sustained Hepatic Benefits, Besides the Cardiometabolic
by Mohamad Suki, Ashraf Imam, Johnny Amer, Yael Milgrom, Muhammad Massarwa, Wadi Hazou, Yariv Tiram, Ofer Perzon, Yousra Sharif, Joseph Sackran, Revital Alon, Nachum Lourie, Anat Hershko Klement, Safa Shibli, Tamer Safadi, Itamar Raz, Abed Khalaileh and Rifaat Safadi
Pharmaceuticals 2025, 18(8), 1118; https://doi.org/10.3390/ph18081118 - 26 Jul 2025
Viewed by 534
Abstract
Background and Aims: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown promise in metabolic dysfunction-associated steatotic liver disease (MASLD). This large real-world study aimed to evaluate the effects of SGLT2 inhibitors on MASLD patients’ clinical outcomes and liver-related complications over extended follow-up. Patients and [...] Read more.
Background and Aims: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown promise in metabolic dysfunction-associated steatotic liver disease (MASLD). This large real-world study aimed to evaluate the effects of SGLT2 inhibitors on MASLD patients’ clinical outcomes and liver-related complications over extended follow-up. Patients and Method: Data were sourced from TriNetX, a global health research platform with de-identified electronic medical records spanning 135 million patients across 112 healthcare organizations worldwide. We included MASLD adults diagnosed according to ICD9/10 criteria. Following propensity score matching based on 34 variables (demographics, comorbidities, laboratory tests and medication history), SGLT2 inhibitor-treated (n = 19,922) patients were compared with non-SGLT2 inhibitor (n = 19,922) cases. Exclusion criteria included baseline improved alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels > 4 upper normal limit (UNL), baseline advanced liver disease, liver transplant and cancer, past anticoagulation and non-MASLD etiologies. Assessed outcomes included survival, biochemical, hematologic, AFP, metabolic and cardiovascular parameters, progression to advanced liver disease (ALD), synthetic function, and metabolic markers over 1, 5, and 10 years. Results: Following matching, both cohorts were well-balanced across baseline characteristics. After one year, the SGLT2 inhibitor group demonstrated significantly reduced BMI (33.2 ± 6.2 vs. 34.1 ± 6.5 kg/m2, p < 0.001), improved ALT (40.3 ± 31.5 vs. 48.3 ± 41.2 U/L, p < 0.001), and better glycemic control (HbA1c 7.35 ± 1.51% vs. 7.93 ± 1.72%, p < 0.001). The SGLT2 inhibitor group showed higher 10-year survival rates (95.00% vs. 88.69%, p < 0.001), fewer cardiovascular events (10.19% vs. 11.80%, p < 0.001), and markedly reduced progression to advanced liver disease (6.90% vs. 14.15%, p < 0.001). These benefits were consistent across clinical, laboratory, and medication-defined ALD categories. Notably, rates of hepatic decompensation events were significantly lower with SGLT2 inhibitor therapy. Conclusions: In this large real-world cohort, SGLT2 inhibitor use in MASLD patients was associated with significantly improved long-term survival, cardiovascular, and liver-related outcomes over 10 years of follow-up. These benefits likely result from combined metabolic improvements, anti-inflammatory effects, and direct hepatoprotective mechanisms. SGLT2 inhibitors represent a promising therapeutic strategy for improving outcomes in MASLD. Full article
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17 pages, 8482 KiB  
Article
The Optimization of Culture Conditions for the Cellulase Production of a Thermostable Cellulose-Degrading Bacterial Strain and Its Application in Environmental Sewage Treatment
by Jiong Shen, Konglu Zhang, Yue Ren and Juan Zhang
Water 2025, 17(15), 2225; https://doi.org/10.3390/w17152225 - 25 Jul 2025
Viewed by 243
Abstract
A novel cellulose-degrading bacterial strain, D3-1, capable of degrading cellulose under medium- to high-temperature conditions, was isolated from soil samples and identified as Staphylococcus caprae through 16SrRNA gene sequencing. The strain’s cellulase production was optimized by controlling different factors, such as pH, temperature, [...] Read more.
A novel cellulose-degrading bacterial strain, D3-1, capable of degrading cellulose under medium- to high-temperature conditions, was isolated from soil samples and identified as Staphylococcus caprae through 16SrRNA gene sequencing. The strain’s cellulase production was optimized by controlling different factors, such as pH, temperature, incubation period, substrate concentration, nitrogen and carbon sources, and response surface methods. The results indicated that the optimal conditions for maximum cellulase activity were an incubation time of 91.7 h, a temperature of 41.8 °C, and a pH of 4.9, which resulted in a maximum cellulase activity of 16.67 U/mL, representing a 165% increase compared to pre-optimization levels. The above experiment showed that, when maize straw flour was utilized as a natural carbon source, strain D3-1 exhibited relatively high cellulase production. Furthermore, gas chromatography–mass spectrometry (GC-MS) analysis of products in the degradation liquid revealed the presence of primary sugars. The results indicated that, in the denitrification of simulated sewage, supplying maize straw flour degradation liquid (MSFDL) as the carbon source resulted in a carbon/nitrogen (C/N) ratio of 6:1 after a 24 h reaction with the denitrifying strain WH-01. The total nitrogen (TN) reduction was approximately 70 mg/L, which is equivalent to the removal efficiency observed in the glucose-fed denitrification process. Meanwhile, during a 4 h denitrification reaction in urban sewage without any denitrifying bacteria, but with MSFDL supplied as the carbon source, the TN removal efficiency reached 11 mg/L, which is approximately 70% of the efficiency of the glucose-fed denitrification process. Furthermore, experimental results revealed that strain D3-1 exhibits some capacity for nitrogen removal; when the cellulose-degrading strain D3-1 is combined with the denitrifying strain WH-01, the resulting TN removal rate surpasses that of a single denitrifying bacterium. In conclusion, as a carbon source in municipal sewage treatment, the degraded maize straw flour produced by strain D3-1 holds potential as a substitute for the glucose carbon source, and strain D3-1 has a synergistic effect with the denitrifying strain WH-01 on TN elimination. Thus, this research offers new insights and directions for advancement in environmental sewage treatment. Full article
(This article belongs to the Section Wastewater Treatment and Reuse)
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16 pages, 1638 KiB  
Systematic Review
Effect of Intermittent Fasting on Anthropometric Measurements, Metabolic Profile, and Hormones in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
by Yazan Ranneh, Mohammed Hamsho, Wijdan Shkorfu, Merve Terzi and Abdulmannan Fadel
Nutrients 2025, 17(15), 2436; https://doi.org/10.3390/nu17152436 - 25 Jul 2025
Viewed by 346
Abstract
Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by excess body weight, hyperandrogenism, hyperglycemia, and insulin resistance often resulting in hirsutism and infertility. Dietary strategies have been shown to ameliorate metabolic disturbances, hormonal imbalances, and inflammation associated with PCOS. Recent [...] Read more.
Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by excess body weight, hyperandrogenism, hyperglycemia, and insulin resistance often resulting in hirsutism and infertility. Dietary strategies have been shown to ameliorate metabolic disturbances, hormonal imbalances, and inflammation associated with PCOS. Recent evidence indicates that intermittent fasting (IF) could effectively enhance health outcomes and regulate circadian rhythm; however, its impact on PCOS remain unclear. Objective: Therefore, this systematic review and meta-analysis aims to examine the effect of IF on women diagnosed with PCOS. Methods: Comprehensive research was conducted across three major databases including PubMed, Scopus, and Web of Science without date restrictions. Meta-analysis was performed using Cochrane Review Manager Version 5.4 software. Results: Five studies fulfilled the inclusion criteria. IF significantly reduced body weight (MD = −4.25 kg, 95% CI: −7.71, −0.79; p = 0.02), BMI (MD = −2.05 kg/m2, 95% CI: −3.26, −0.85; p = 0.0008), fasting blood glucose (FBG; MD = −2.86 mg/dL, 95% CI: −4.83, −0.89; p = 0.004), fasting blood insulin (FBI; MD = −3.17 μU/mL, 95% CI: −5.18, −1.16; p = 0.002), insulin resistance (HOMA-IR; MD = −0.94, 95% CI: −1.39, −0.50; p < 0.0001), triglycerides (TG; MD = −40.71 mg/dL, 95% CI: −61.53, −19.90; p = 0.0001), dehydroepiandrosterone sulfate (DHEA-S; MD = −33.21 μg/dL, 95% CI: −57.29, −9.13; p = 0.007), free androgen index (FAI; MD = −1.61%, 95% CI: −2.76, −0.45; p = 0.006), and C-reactive protein (CRP; MD = −2.00 mg/L, 95% CI: −3.15, −0.85; p = 0.006), while increasing sex hormone-binding globulin (SHBG; SMD = 0.50, 95% CI: 0.22, 0.77; p = 0.004). No significant changes were observed in waist-to-hip ratio (WHR), total cholesterol (TC), LDL, HDL, total testosterone (TT), or anti-Mullerian hormone (AMH). Conclusions: IF represents a promising strategy for improving weight and metabolic, hormonal, and inflammatory profiles in women with PCOS. However, the existing evidence remains preliminary, necessitating further robust studies to substantiate these findings. Full article
(This article belongs to the Special Issue Nutrition and Female Reproduction: Benefits for Women or Offspring)
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27 pages, 3492 KiB  
Article
Amelioration of Metabolic Syndrome by Co-Administration of Lactobacillus johnsonii CRL1231 and Wheat Bran in Mice via Gut Microbiota and Metabolites Modulation
by Matias Russo, Antonela Marquez, Estefanía Andrada, Sebastián Torres, Arlette Santacruz, Roxana Medina and Paola Gauffin-Cano
Metabolites 2025, 15(7), 466; https://doi.org/10.3390/metabo15070466 - 9 Jul 2025
Viewed by 368
Abstract
Background/Objectives: Lactobacillus johnsonii CRL1231 (Lj CRL1231) is a strain with feruloyl esterase (FE) activity that enhances ferulic acid (FA) release from wheat bran (WB) and has potential as a probiotic for metabolic syndrome (MS). Given the potential health benefits of FA and [...] Read more.
Background/Objectives: Lactobacillus johnsonii CRL1231 (Lj CRL1231) is a strain with feruloyl esterase (FE) activity that enhances ferulic acid (FA) release from wheat bran (WB) and has potential as a probiotic for metabolic syndrome (MS). Given the potential health benefits of FA and its microbial metabolites, this study aimed to evaluate the therapeutic effect of Lj CRL1231 co-administered with WB in a mouse model of metabolic syndrome (MS) induced by a high-fat diet (HFD). Methods: Mice were divided into three groups and fed for 14 weeks as follows: the Control group (standard diet), the MS group (HFD+WB), and the MS+Lj group (HFD+WB and Lj CRL1231-dose 108 cells/day). Specifically, we analyzed the changes in the intestinal microbiota (IM), colonic FE activity, generation of FA-derived and fermentation metabolites, and metabolic and inflammatory parameters. Results: Improvements in the MS+Lj group compared to the MS group included the following: a—a 38% increase in colonic FE activity, leading to elevated levels of FA-derived metabolites (e.g., dihydroferulic, dihydroxyphenylpropionic, and hydroxyphenylpropionic acids); b—a significant shift in the IM composition, with a 3.4-fold decrease in Firmicutes and a 2.9-fold increase in Bacteroidetes; c—a decrease in harmful bacteria (Desulfovibrio) by 93%, and beneficial bacteria like Bifidobacterium increased significantly (6.58 log cells/g); d—a 33% increase in total SCFAs; e—a 26% reduction in the adiposity index; f—a 12% increase in HDL cholesterol and a 19% reduction in triglycerides; g—normalized glucose and insulin resulting in a 2-fold lower HOMA-IR index; h—an improved inflammatory profile by decreasing TNF-α, IFN-γ, and IL-6 (3-, 5-, and 2-fold, respectively) and increasing IL-10 by 2-fold; i—alleviation of liver damage by normalizing of transaminases AST (19.70 ± 2.97 U/L) and ALT (13.12 ± 0.88 U/L); j—evidence of reduced oxidative damage. Conclusions: The co-administration of L. johnsonii CRL1231 and WB exerts a synergistic effect in mitigating the features of MS in HFD-fed mice. This effect is mediated by modulation of the gut microbiota, increased release of bioactive FA-derived compounds, and restoration of metabolic and inflammatory homeostasis. This strategy represents a promising dietary approach for MS management through targeted microbiota–metabolite interactions. Full article
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19 pages, 2466 KiB  
Article
Agmatine Mitigates Diabetes-Related Memory Loss in Female Mice by Targeting I2/I3 Imidazoline Receptors and Enhancing Brain Antioxidant Defenses
by Luis E. Cobos-Puc and Hilda Aguayo-Morales
Antioxidants 2025, 14(7), 837; https://doi.org/10.3390/antiox14070837 - 8 Jul 2025
Viewed by 906
Abstract
Cognitive decline is a common complication of diabetes mellitus, driven in part by oxidative stress and impaired glucose–insulin homeostasis. This study examined the neuroprotective effects of agmatine (200 mg/kg intraperitoneally) in female BALB/c diabetic mice. Several receptor pathways were examined using commercially available [...] Read more.
Cognitive decline is a common complication of diabetes mellitus, driven in part by oxidative stress and impaired glucose–insulin homeostasis. This study examined the neuroprotective effects of agmatine (200 mg/kg intraperitoneally) in female BALB/c diabetic mice. Several receptor pathways were examined using commercially available antagonists. Behavioral performance was evaluated using the novel object recognition test. Metabolic parameters, such as glucose and insulin levels, as well as antioxidants, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), were measured in blood and brain tissue. The diabetic mice exhibited impaired recognition memory (discrimination index = 0.08), hyperglycemia (24.3 mmol/L), decreased insulin levels (38.4 µU/mL), and diminished antioxidant defenses (CAT: 75.4 U/g tissue, SOD: 32.6 U/g tissue, and GSH: 8.3 mmol/g tissue). Agmatine treatment improved cognitive function and reversed the biochemical alterations. However, these effects were reduced when agmatine was co-administered with imidazoline I2/I3 receptor antagonists. Correlation analysis revealed that cognitive performance positively correlated with antioxidant enzyme levels and insulin levels and negatively correlated with glucose concentrations. Strong intercorrelations among CAT, SOD, and GSH levels suggest a coordinated antioxidant response. Overall, these results imply that agmatine’s neuroprotective effects are partially mediated by modulation of the oxidative balance and glucose–insulin regulation via imidazoline receptors. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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14 pages, 1177 KiB  
Article
Methylation of LINE-1 Retroelement in People with Type 1 Diabetes
by Andromachi Katsanou, Charilaos Kostoulas, Evangelos Liberopoulos, Agathocles Tsatsoulis, Ioannis Georgiou and Stelios Tigas
Genes 2025, 16(7), 759; https://doi.org/10.3390/genes16070759 - 28 Jun 2025
Viewed by 422
Abstract
Introduction: Emerging research indicates that alterations in the methylation of retrotransposons may contribute to genomic instability and cellular aging in various autoimmune disorders and diabetes mellitus (DM). As relevant information for people with type 1 diabetes mellitus (PwT1D) is limited, we aimed to [...] Read more.
Introduction: Emerging research indicates that alterations in the methylation of retrotransposons may contribute to genomic instability and cellular aging in various autoimmune disorders and diabetes mellitus (DM). As relevant information for people with type 1 diabetes mellitus (PwT1D) is limited, we aimed to investigate long interspersed nuclear element-1 (LINE-1) methylation status in this population. Methods: DNA methylation levels and patterns of LINE-1 were examined in the peripheral blood of 35 PwT1D and 28 healthy controls (age- and sex-matched), by using the COmbined Bisulfite Restriction Analysis methodology (COBRA). Results: Total LINE-1 methylation rate (mC) was higher in PwT1D compared to controls [47.3% (46.6–47.8%) vs. 46.5% (44.7–47.3%), p < 0.05]. The partial LINE-1 methylation pattern (uCmC) was less frequently observed in patients vs. controls [28.4% (24.7–33.3%) vs. 33.1% (27.8–37.9%), p < 0.05]. Prevalence of other methylation patterns [partially methylated (mCuC), hypermethylated (mCmC) and hypomethylated (uCuC)] was similar in the two groups. Furthermore, levels of fasting glucose and glycated hemoglobin (HbA1c) were positively associated with total methylation (mC) [Spearman’s rho = 0.380, p = 0.002 and rho = 0.342, p = 0.006, respectively], but negatively associated with the partially methylated (uCmC) pattern [Spearman’s rho = −0.383, p = 0.002 and rho = −0.270, p = 0.033, respectively]. The LINE-1 (uCmC) methylation pattern was negatively associated with the age at diagnosis of T1D [Spearman’s rho = −0.341, p = 0.049], but positively associated with disease duration [Spearman’s rho = 0.388, p = 0.021]. Conclusions: PwT1D were found to have higher total LINE-1 methylation rate (mC) compared to healthy controls. The partial methylation pattern (uCmC) was less frequently observed in these patients and was negatively associated with the glycemic status and the age at diagnosis of T1D, while demonstrating a positive correlation with disease duration. Full article
(This article belongs to the Section Epigenomics)
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16 pages, 1122 KiB  
Article
Effect of r-Human Insulin (Humulin®) and Sugars on Escherichia coli K-12 Biofilm Formation
by Balbina J. Plotkin, Ira Sigar and Monika Konaklieva
Appl. Microbiol. 2025, 5(3), 58; https://doi.org/10.3390/applmicrobiol5030058 - 27 Jun 2025
Viewed by 218
Abstract
E. coli attaches to, and forms biofilms on various surfaces, including latex and polystyrene, contributing to nosocomial spread. E. coli responds to both exogenous and endogenous insulin, which induces behavioral changes. Human insulin, a quorum signal surrogate for microbial insulin, may affect the [...] Read more.
E. coli attaches to, and forms biofilms on various surfaces, including latex and polystyrene, contributing to nosocomial spread. E. coli responds to both exogenous and endogenous insulin, which induces behavioral changes. Human insulin, a quorum signal surrogate for microbial insulin, may affect the ability of E. coli to interact with latex and polystyrene in the presence of various sugars. E. coli ATCC 25923 was grown in peptone (1%) yeast nitrogen base broth to either the logarithmic or stationary growth phase. Adherence to latex was determined using 6 × 6 mm latex squares placed in a suspension of washed cells (103 CFU/mL; 30 min; 37 °C) in buffer containing insulin at 2, 20, and 200 µU/mL (Humulin® R; Lilly) with and without mannose, galactose, fructose, sorbose, arabinose, xylose, lactose, maltose, melibiose, glucose-6-phosphate, glucose-1-phosphate, and glucosamine at concentrations reported to affect behavioral response. Attachment levels to latex were determined by the press plate method. Biofilm levels were measured in a similar fashion but with overnight cultures in flat bottom uncoated polystyrene plates. Controls were media, insulin, sugar, or buffer alone. Glucose served as the positive control. Overall, the stationary phase cells’ adherence to latex was greater, regardless of the test condition, than was measured for the logarithmic phase cells. The effect of insulin on adherence to latex was insulin and sugar concentration dependent. The addition of insulin (200 µU/mL) resulted in a significantly (p < 0.05) increased adherence to latex and biofilm formation on polystyrene compared with sugar alone for 12 of the 13 sugars tested with stationary phase bacteria and 10 of the 13 sugars tested with logarithmic phase bacteria. Adherence in response to sorbose was the only sugar tested that was unaffected by insulin. These findings show that insulin enhances E. coli’s association with materials in common usage in medical environments in a nutrition-dependent manner. Full article
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22 pages, 3876 KiB  
Article
In Vivo PK-PD and Drug–Drug Interaction Study of Dorzagliatin for the Management of PI3Kα Inhibitor-Induced Hyperglycemia
by Guanqin Jin, Kewei Zheng, Shihuang Liu, Huan Yi, Wei Wei, Congjian Xu, Xiaoqiang Xiang and Yu Kang
Pharmaceuticals 2025, 18(6), 927; https://doi.org/10.3390/ph18060927 - 19 Jun 2025
Viewed by 486
Abstract
Objectives: The anticancer effects of PI3Kα inhibitors (PI3Ki) are constrained by their hyperglycemic side effects, while the efficacy of conventional hypoglycemic agents, such as insulin, metformin, and SGLT-2 inhibitors, in mitigating PI3Ki-induced hyperglycemia remains suboptimal. Dorzagliatin, a novel glucokinase activator, has been approved [...] Read more.
Objectives: The anticancer effects of PI3Kα inhibitors (PI3Ki) are constrained by their hyperglycemic side effects, while the efficacy of conventional hypoglycemic agents, such as insulin, metformin, and SGLT-2 inhibitors, in mitigating PI3Ki-induced hyperglycemia remains suboptimal. Dorzagliatin, a novel glucokinase activator, has been approved in China for the management of hyperglycemia, offering a promising alternative. This study aims to investigate the pharmacokinetic properties and potential mechanisms of drug interactions of dorzagliatin in the regulation of PI3K-induced hyperglycemia. Methods: Plasma concentrations of WX390, BYL719, and Dorz in mice were measured using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Pharmacokinetic (PK) parameters and PK/PD models were derived by using Phoenix WinNonlin 8.3.5 software. Blood glucose levels at various time points and tumor volume changes over a four-week period were assessed to explore the interactions when PI3Ki were combined with dorzagliatin. Results: The results indicated that, compared to the Dorz group, the combination groups (Dorz + BYL719, Dorz + WX390) exhibited increases in AUC0t of dorzagliatin by 41.65% and 20.25%, and in Cmax by 33.48% and 13.32%, respectively. In contrast, co-administration of these PI3Ki with dorzagliatin resulted in minimal increase in their plasma exposure. The combination therapy group (Dorz+BYL719) exhibited superior antitumor efficacy compared to the BYL719 group. Conclusions: Our findings indicate that the drug–drug interactions (DDIs) between dorzagliatin and multiple PI3Ki (including WX390 and BYL719) may partially account for the enhanced antitumor efficacy observed in the combination therapy group compared to PI3Ki monotherapy. This interaction may be explained by the inhibition of P-glycoprotein (P-gp) and the pharmacological mechanism of dorzagliatin regarding the activation of insulin regulation. Full article
(This article belongs to the Special Issue Mathematical Modeling in Drug Metabolism and Pharmacokinetics)
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21 pages, 3205 KiB  
Article
Click on Click: Click-Flavone Glycosides Encapsulated in Click-Functionalised Polymersomes for Glioblastoma Therapy
by Nuno M. Saraiva, Ana Alves, Ana Isabel Barbosa, Andreia Marinho, Salette Reis, Marta Correia-da-Silva and Paulo C. Costa
Pharmaceutics 2025, 17(6), 771; https://doi.org/10.3390/pharmaceutics17060771 - 12 Jun 2025
Viewed by 637
Abstract
In this study, three new 3,7-dihydroxyflavone (1) derivatives with different sugars were designed and synthesised by click chemistry. Click chemistry requires the previously modification of building blocks with azide and alkyne groups and therefore, the 3,7-dihydroxyflavone (1) was first [...] Read more.
In this study, three new 3,7-dihydroxyflavone (1) derivatives with different sugars were designed and synthesised by click chemistry. Click chemistry requires the previously modification of building blocks with azide and alkyne groups and therefore, the 3,7-dihydroxyflavone (1) was first converted in 3,7-(prop-2-yn-yloxy)flavone (2) and acetobromo-α-D-glucose (3) was converted into 2,3,4,6-tetra-O-acetyl-β-glucopyranosyl azide (4). Subsequently, a click reaction was performed via copper-catalysed cycloaddition (CuAAC) between 2 and 4, as well as between 2 and 2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranosyl (AG931) and, 2 and commercial 2-azidoethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl (AG358), resulting in three distinct disubstituted flavone glycosides (5a5c). Biological assays performed on L929 fibroblast cell lines and human glioblastoma astrocytoma U-251 cell lines indicated cytocompatibility with fibroblasts and reduced metabolic activity of GBM cells in the presence of compound 5b and 5c. To enhance therapeutic effect, improve local drug delivery, and overcome solubility issues of these high molecular weight compounds, the synthesised compounds were encapsulated in polymeric particles (polymersomes, PMs) composed of polylactic acid-polyethylene glycol (PEG-PLA) functionalized, once more by click chemistry, with 0.1 mol% transferrin mimetic (T7—HRPYIAH) peptide. The PMs were prepared by solvent displacement and exhibited stability over 100 days, encapsulation efficiency of 39–93%, and mean size diameters of 120–180 nm. The toxicity assays of the PMs on the U-251 cell line showed a significant decrease in metabolic activity, supporting the potential of this delivery system against GBM. Among the PMs tested, the flavone 5c-based PM demonstrated the highest efficacy. Full article
(This article belongs to the Special Issue Nano-Based Technology for Glioblastoma)
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12 pages, 709 KiB  
Article
Unlocking the Potential of Pomelo Albedo: A Novel Substrate for Alpha-Amylase Production Using Bacillus licheniformis
by Thi Ngoc Tran, Si-Chun Chen, Chien Thang Doan and San-Lang Wang
Fermentation 2025, 11(6), 336; https://doi.org/10.3390/fermentation11060336 - 11 Jun 2025
Cited by 1 | Viewed by 759
Abstract
The bioprocessing of agricultural wastes to produce microbial enzymes has become significant due to its benefits in reducing enzyme production costs and improving waste management. In this study, various substrates, including spent coffee grounds, coffee husks, coffee pulp, rice husks, rice bran, pomelo [...] Read more.
The bioprocessing of agricultural wastes to produce microbial enzymes has become significant due to its benefits in reducing enzyme production costs and improving waste management. In this study, various substrates, including spent coffee grounds, coffee husks, coffee pulp, rice husks, rice bran, pomelo albedo, pomelo flavedo, orange peel, banana peel, sugarcane bagasse, and starch, were used as organic nutrient sources for α-amylase biosynthesis by B. licheniformis TKU004. Among the tested substrates, pomelo albedo (3%, w/v) was the most suitable carbon source for amylase production, with a productivity of 80.645 U/mL. The purification process resulted in a 60 kDa amylase. The protein identification of B. licheniformis TKU004 amylase revealed a coverage rate of 39% with α-amylase from Bacillus subtilis 168. B. licheniformis TKU004 amylase exhibited optimal activity at 60 °C and pH = 7 and showed a high compatibility with EDTA (Ethylenediaminetetraacetic acid). HPLC (high-performance liquid chromatography) analysis demonstrated that B. licheniformis TKU004 amylase is an α-amylase with the final products of maltobiose, maltose, and glucose. Due to its important properties, such as tolerance to EDTA, B. licheniformis TKU 004 amylase may be valuable for industrial applications, especially in detergents and food processing. Full article
(This article belongs to the Special Issue Fermentation of Organic Waste for High-Value-Added Product Production)
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14 pages, 1425 KiB  
Article
Earthing as a Supportive Therapy for Post-Spinal Surgery Recovery
by Paweł Sokal, Maciej Broda, Magdalena Zając and Julia Sokal
J. Clin. Med. 2025, 14(11), 3844; https://doi.org/10.3390/jcm14113844 - 29 May 2025
Viewed by 553
Abstract
Background/Objectives: Spinal surgery often results in injury to the paraspinal muscles and postoperative pain, which is associated with an elevated inflammatory response and increased creatine kinase (CK) levels. Earthing, a practice involving direct or indirect contact with the Earth, facilitates the movement [...] Read more.
Background/Objectives: Spinal surgery often results in injury to the paraspinal muscles and postoperative pain, which is associated with an elevated inflammatory response and increased creatine kinase (CK) levels. Earthing, a practice involving direct or indirect contact with the Earth, facilitates the movement of electric charge between the body and the Earth, thereby stabilizing electrical potentials and influencing biochemical and bioelectrical processes. This study aimed to investigate the effects of earthing on postoperative pain and biochemical parameters. Materials and Methods: The study included an earthing group (EG) of 42 patients (18 females) who underwent spinal surgery and were earthed during nighttime postoperative rest. Blood samples were collected to measure serum concentrations of sodium, potassium, urea, glucose, C-reactive protein (CRP), alkaline phosphatase (ALP), calcium, phosphates, CK, iron, ferritin, and transferrin. These parameters were assessed on the day after surgery and the day following earthing. A control group (CG) of 42 patients (25 females) who underwent surgery for lumbar spondylosis did not receive earthing. Results: The median reduction in the EG was significantly greater than in the CG (for CK 45.0 and 20.0 U/L; for ALP 6.0 and 1.0; for transferrin 0.17 and 0.08, respectively). The median CRP difference in the EG was 0.05 mg/dL, significantly lower than in the CG, 17.2 mg/dL. The median reduction in pain intensity in VAS score was greater in the EG–2.0 compared to the CG-1.0, acknowledging a strong analgesic effect of earthing (p < 0.01). Conclusions: Earthing after spinal surgery seems to promote recovery by reducing inflammation and pain, and accelerating general healing, suggesting its potential as a supportive postoperative therapy. Full article
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15 pages, 2577 KiB  
Article
Expression and Characterization of L-Arabinose Isomerase and Its Enzymatic Recycling of the Expired Milk
by Zhou Chen, Yuhan Yan, Ziang Wu, Yanyin Song and Jiangqi Xu
Foods 2025, 14(11), 1873; https://doi.org/10.3390/foods14111873 - 25 May 2025
Cited by 2 | Viewed by 581
Abstract
As global milk production continues to rise, the disposal of expired milk contributes to environmental pollution and valuable resource wastage. This study presents the development of a novel L-arabinose isomerase, designated BmAIase12, and its application in the enzymatic recycling of expired milk. [...] Read more.
As global milk production continues to rise, the disposal of expired milk contributes to environmental pollution and valuable resource wastage. This study presents the development of a novel L-arabinose isomerase, designated BmAIase12, and its application in the enzymatic recycling of expired milk. BmAIase12 exhibited a specific activity of 10.7 U/mg and showed optimal performance at 50 °C and pH 7.0. Furthermore, it exhibited higher activity than most other L-arabinose isomerases. It converted D-galactose into D-tagatose with a high conversion ratio of 53.3% after 48 h at 50 °C. The conversion efficiency of expired milk to D-tagatose was recorded at 40.62%, resulting in a maximum tagatose yield of 1.625 g/L. This was accomplished through the incorporation of β-galactosidase (120 U/mL) and Saccharomyces cerevisiae (30 mg/mL) to hydrolyze lactose and metabolize glucose, followed by the addition of 3 U/mL of BmAIase12. Ultimately, following purification, the purity of tagatose was determined to be 98%, and the final yield was 29.8%. These results suggest that BmAIase12 may serve as a promising enzyme for D-tagatose production due to its high conversion yield. Full article
(This article belongs to the Section Food Biotechnology)
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11 pages, 658 KiB  
Article
Exploring the Prevalence and Risk Factors of MASLD in Patients with Newly Diagnosed Diabetes Mellitus: A Comprehensive Investigation
by Hatice Beyazal Polat, Mehmet Beyazal, Medeni Arpa, Bayram Kızılkaya, Teslime Ayaz, Ömer Lütfi Gündoğdu, Kamil Konur, Zehra Polat, Fatma Beyazal Çeliker and Halil Atasoy
J. Clin. Med. 2025, 14(10), 3513; https://doi.org/10.3390/jcm14103513 - 17 May 2025
Viewed by 586
Abstract
Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) represents a growing concern in the context of metabolic disorders, particularly among individuals diagnosed with type 2 diabetes mellitus (T2DM). This study aimed to investigate the prevalence of MASLD among newly diagnosed T2DM patients and identify [...] Read more.
Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) represents a growing concern in the context of metabolic disorders, particularly among individuals diagnosed with type 2 diabetes mellitus (T2DM). This study aimed to investigate the prevalence of MASLD among newly diagnosed T2DM patients and identify the risk factors for MASLD in this population. Methods: This prospective study included 128 patients with newly diagnosed T2DM between January 2022 and June 2023. Demographic, clinical, anthropometric (BMI, waist circumference), and laboratory data (glucose, HbA1c, lipid profile, ALT, AST, creatinine, platelet count) were collected. MASLD was diagnosed based on ultrasonographic evidence of hepatic steatosis with at least one cardiometabolic risk factor after excluding other causes. Linear regression models were used to determine independent predictors. Results: MASLD was detected in 80.4% of patients. Compared with the MASLD (−) group, the MASLD (+) group had significantly higher ALT (47.1 ± 23 U/L vs. 24.9 ± 8 U/L, p < 0.001) and non-HDL cholesterol (189 ± 57 mg/dL vs. 167 ± 28 mg/dL, p = 0.047). Spearman correlation showed positive associations of MASLD severity with waist circumference, LDL cholesterol, and platelet count. ALT and BMI were independently associated with MASLD in linear regression analysis. Conclusions: This study underscores the significant prevalence of MASLD in newly diagnosed T2DM patients, emphasizing the relevance of early detection in addressing this common comorbidity in the diabetic population. Full article
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