Group G2 Research Articles

Standardisation of Curcuminoids into More Bioavailable form (CurcuminAura™) and Its Pharmacokinetics

Curcuminoids are naturally occurring phytocompound extracted from the turmeric rhizome Curcuma longa, a member of the ginger (Zingiberaceae) family. Through the development of a trademark product called Bio-Curcumin, this study seeks to increase the bioavailability and absorption of regular marketed curcumin by 95%. This finding has important implications for the academic and scientific community. The pharmacokinetic study of CurcuminAura™ and its innovation of biocurcuminoids is detailed in detail. Innovation of BioCurcuminoids and its Pharmacokinetic Study of CurcuminAura™ with regular curcuminoids is significantly described which is the need of the hour. This enhanced sunflower lecithin is an effective ingredient in the trademark product CurcuminAuraTM, which was created by Bio-Med Ingredients Pvt.Ltd. Its potency in the market can be increased by lecithin's capacity to efficiently encapsulate active substances, improve bioavailability, and increase absorption. Regular curcumin's weak solubility and poor absorption in its free form. Regular Curcumin due to its poor solubility and poor absorption in the free form in the gastrointestinal tract and its rapid biotransformation to inactive metabolites can greatly limit its utility as a health-promoting agent and dietary supplement. Hence to make it more readily available in the body. CurcuminovaTM is developed will enhance the properties of Curcumin making it more potent in the market. The Evaluation of the Comparative Pharmacokinetic Study of CurcuminAuraTM with Marketed Curcumin 95.0% was carried out through pre-clinical investigations in Sprague Dawley Rats via Oral Route which is the aim of this study with two groups in the study design, with four rats of each sex. Oral administration of CurcuminAuraTM and Curcumin 95.0% was administered to rats in the G1 and G3 groups, respectively. A dosage volume of 10 milliliters per kilogram of body weight was maintained for the oral route. After Dosage, under isofluorane,the blood samples were taken from the retroorbital sinuses after the dose was administered under varying periods of anaesthesia. Animals were split up into two sets for each group, and blood samples were taken at 30-, 2-, and 4-hour intervals. Samples were taken for analysis after being kept at -800C. Designed to increase the bioavailability of curcuminoids, CurcuminAuraTM is standardized to 60.9% total curcuminoids by HPLC, as opposed to marked conventional curcumin 95%. This has been confirmed by HPLC analysis. According to comparison studies, CurcuminAuraTM has a bioavailability that is 3.8 times greater than the reference standard. Additionally, in this study it is shown that the maximum absorption happens in the timeline 3 hrs after feeding the drug.

Abstract PR009: Application of Liquid Biopsy-RECIST (LB-RECIST) criteria to track metastatic colorectal cancer (mCRC) molecular response in first-line (1L) setting: Findings from the PLATFORM-B study

Abstract Introduction: Circulating tumor DNA (ctDNA) analysis is a minimally invasive and reproducible method to explore tumor molecular biology. Recently, Gouda et al. proposed the LB-RECIST criteria to monitor molecular response, validating them on a heterogeneous metastatic population. However, data on mCRC are lacking. Here, we report the first attempt to apply LB-RECIST in the multicenter prospective PLATFORM-B study, which enrolled 130 mCRC patients (pts) receiving 1L standard therapy, with ctDNA analysis performed at different time points. Materials and Methods: Baseline (BL) and week 8 (W8) plasma samples were analyzed using a targeted NGS-based approach (Ion S5 system). Changes in ctDNA detectability were assessed to determine molecular response as per qualitative LB-RECIST criteria: Group1 (G1, detectable ctDNA at BL and W8); Group2 (G2, detectable BL and undetectable W8); Group3 (G3, undetectable BL and detectable W8); Group4 (G4, undetectable at BL and W8). Changes in aggregate variant allele frequency (VAF) - the sum of all VAFs of the studied genes in a sample - were used to assess quantitative LB-RECIST responses: ctDNA Complete Response (CCR, clearance after initial detectability), Partial Response (CPR, decrease >10%), Stable Disease (CSD, no change or decrease <10%), Progressive Disease (CPD, increase >10% or new mutations), and Non-measurable Disease (CND, undetectable at BL and W8). Molecular results were correlated with clinical outcomes. Statistically significant differences were assessed across different groups using 2-sided P values with an α ≤ .05 level of significance. Results: Overall, 79 pts had paired BL and W8 samples. Quantitative LB-RECIST identified 32 CCR, 18 CND, 20 CPR, 8 CPD, and 1 CSD cases. Qualitative LB-RECIST found 22 G1, 32 G2, 7 G3, and 18 G4 cases. Radiological RECIST identified 6 CR, 47 PR, 21 SD, and 5 PD. CCR showed the highest survival rates: with a median follow-up of 25 months (mo) (range: 1–49), median progression-free survival (mPFS) was not reached (NR) and median overall survival (mOS) was 41.8 mo. The CND group had similar rates (mPFS NR; mOS 41.1 mo). CPR and CPD had the poorest outcomes: for CPR, mPFS was 12.7 and mOS 16.4 mo; for CPD, mPFS and mOS were 11.9 and 25.5 mo, respectively. In the G1, G2, G3, and G4 groups, mPFS was 11.9, NR, 14.2, and NR, respectively, while mOS was 16.4, 41.8, 33.4, and 41.1 mo. Kaplan-Meier analysis of the quantitative groups showed statistically significant differences (P < .0001) for both PFS and OS curves. The same level of significance was found in the qualitative groups. Conclusion: LB- RECIST can be a rapid and reproducible method to assess molecular response in mCRC. However, concerns remain. The CND group (23% of cases) showed survival rates similar to the CCR group, as observed also between G4 and G2. These data suggest that absence of ctDNA at W8 is the best surrogate for OS. Moreover, CPD had higher OS rates than CPR, but similar PFS. Further investigations in larger populations are needed to refine these criteria and improve molecular response stratification Citation Format: Valentino Martelli, Joana Vidal, Maria Concepción Fernández-Rodríguez, Pilar García-Alfonso, David Páez, Joan Gibert, Jennifer Linares, Annarita Sibilio, Vicente Alonso, Maria Teresa Cano, Cristina Santos, Gema Duran, Elena Élez, José Luis Manzano, Rocio Garcia-Carbonero, Reyes Ferreiro, Ferran Losa, Estela Pineda, Javier Sastre, Auxiliadora Gomez-España, Rodrigo Toledo, Fernando Rivera, Beatriz Bellosillo, Josep Tabernero, Ramon Ramon Salazar, Enrique Aranda, Clara Montagut. Application of Liquid Biopsy-RECIST (LB-RECIST) criteria to track metastatic colorectal cancer (mCRC) molecular response in first-line (1L) setting: Findings from the PLATFORM-B study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR009.

Effects of orthodontic wax and ora-aid on pain and discomfort at the beginning of orthodontic treatment.

Wounds may occur in the mouth during orthodontic treatment. Orthodontists use a variety of substances to eliminate the irritation. This randomized clinical trial aimed to examine the effect of orthodontic wax and ora-aid material on wound healing, the duration of staying in the mouth, and the effect on pain and to evaluate the effect on the patient's quality of life. The study included two hundred forty patients aged 11-14 years. At the end of 1 week, patients with no wound were determined as the control group G1(n:65), patients using Ormco orthodontic wax as G2(n:86), and patients using Ora-aid as G3(n:89). The patients were asked to fill out the questionnaire given to them five times in total, as T0 when the wound occurred, T1 after 24h, T2 after 48h, T3 after 96h, and T4 after 168h. The study's results demonstrated no significant differences in the level of pain between males and females. For all post-baseline time points, the Ora aid group had a lower VAS for pain when compared with the Ormco orthodontic wax group (P < 0.01). This study demonstrated that ora-aid effectively reduces the mucosal discomfort associated with orthodontic appliances, and this product may be a suitable alternative to traditional orthodontic wax material for dealing with oral mucosal injuries during orthodontic treatment. This product may be a suitable alternative to traditional orthodontic wax material for dealing with oral mucosal injuries during orthodontic treatment.

Effect of Age, Sex, Renal Impairment and Hepatic Impairment on the Safety, Pharmacokinetics and Pharmacodynamics of Asundexian.

Asundexian is a reversible and selective inhibitor of activated factor XI. It is currently under investigation for the prevention of secondary stroke in at-risk patients; these patients are often characterised by advanced age, impaired organ function and comorbidities. This article summarises results from three Phase I studies that investigated the effects of age and sex (study 1), chronic kidney disease including end-stage kidney disease (ESKD) on dialysis and dialysis-free days (study 2) and Child-Pugh A and B liver disease (study 3) on the safety, pharmacokinetics and pharmacodynamics of a single oral dose of asundexian 25mg. Study 1 was a multicentre, randomised, single-blind, placebo-controlled group-stratification design; study 2 was a single-centre, non-randomised, non-placebo-controlled, non-blinded group-stratification design; and study 3 had a non-randomised, non-blinded, non-placebo-controlled group-stratification design. Single doses of asundexian 25 mg were generally well tolerated in all three studies, with no asundexian-related bleeding events or treatment-emergent adverse events of special interest. Point estimates (geometric least squares [LS] means) (90% confidence intervals [CIs]) for the total asundexian area under the plasma concentration-time curve (AUC) for participants aged ≥65 to< 75 years versus ≥18 to <45 yearsand ≥75 to ≤80 years versus ≥18 to <45years were 1.257 (1.134-1.393) and 1.288 (1.158-1.433), respectively, and for females versus males, it was 1.084 (0.995-1.182). Point estimates (geometric LS means) (90% CIs) for unbound AUC in participants in estimated glomerular filtration rate (eGFR) categories G2 (60-89 mL/min/1.73 m2), G3 (30-59 mL/min/1.73 m2) and G4 (15-29 mL/min/1.73 m2) versus control were 1.003 (0.698-1.443), 0.791 (0.550-1.138) and 0.882 (0.606-1.285), respectively, and in participants with ESKD on dialysis-free day versus control was 0.597 (0.406-0.877). There was no effect of the dialysis procedure on the pharmacokinetics of asundexian. In participants deemed Child-Pugh class A and Child-Pugh class B, geometric LS means (90% CIs) for unbound AUC were 0.834 (0.597-1.164) and 1.143 (0.810-1.612), respectively, when compared to participants with normal liver function. Activated partial thromboplastin time (aPTT) was assessed as a pharmacodynamic variable of interest. Geometric mean maximum aPTT prolongation as a ratio to baseline after administration of asundexian 25 mg ranged from 1.45 to 1.55 in all age and sex groups, 1.49-1.59 in the control and eGFR G2 to G4 groups, 1.38-1.54 in the control and ESKD groups on dialysis and dialysis-free day and 1.38-1.89 in the healthy control and liver impairment groups. The effects of the investigated intrinsic factors on the exposure of asundexian were small and not considered clinically relevant. The impact of lower exposure in participants with ESKD requires further investigation. Pharmacodynamics were as expected. EudraCT 2022-000196-38 and 2020-000626-25.

Interleukin 37 Role in Diabetic Iraqi Patients: A comparison between patients treated with and without Insulin

Background: Diabetes Mellitus (DM) is defined as a metabolic disorder that is characterized by some clinical features, such as chronic hyperglycemia accompanied by impairment of carbohydrates metabolism, proteins, and lipids. However, relative or absolute insulin deficiency is associated with the high blood glucose levels, which is attributed to the β-cells dysfunction, insulin resistance or could be both. The anti-inflammatory cytokine interleukin-37 (IL-37) negatively regulates inflammation, therefore, reduces inflammation and alters metabolic pathways. It acts by suppressing inflammatory cytokines and chemokines, activation of IL-37 inhibits inflammation and obstructs the infiltration of pro-inflammatory cells, primarily neutrophils and eosinophils. Aim of Study: The estimation of IL 37 and other biochemical parameters in patients with Diabetes mellitus and study its role in the pathogenicity of the disease. Materials and methods: A case-control study design was adopted to study the relationship between Interleukin 37 and insulin treatment in Nasiriyah in the Diabetes and Endocrinology Specialized Center between December 2023 and January 2024. It was conducted on patients with Diabetes Mellitus type 2 (60 patients) divided into two groups (30 patients treated with Insulin injection) and (30 patient treated with oral tab only). On the other hand, 30 people were taken as a control group without Diabetes Mellitus.Result: Patients with diabetes mellitus have been noticed to have higher levels of IL-37 in comparison to the healthy control groups. In general, patients with diabetes mellitus have higher levels of IL-37 compared to three groups, G1, G2, and healthy control groups. Conclusion We demonstrated that serum levels concentration of IL 1b and IL 37 significantly increased in our patients also FBS, HbA1c, Insulin Resistance, HOMO IR, TG, cholesterol, and decrease C- peptide as compared to healthy individuals.

The effect of melatonin and probiotics on radiation-induced enteritis in experimental rat models

Radiotherapy plays an important role in the treatment of tumors, and enteritis is a common side effect of this therapy. The aim of present study was to evaluate the protective effect of melatonin and probiotics on radiation-induced intestinal tissue damage in rats. Histopathological, biochemical and microbiological samples were examined. Thirty-two Wistar Albino rats were randomly distributed into four groups: the control group, only radiotherapy (RT) group, radiotherapy plus melatonin (RT + MEL) groups and radiotherapy plus probiotics (RT + PROB) groups. The abdominal-pelvic region of the experimental rat was irradiated with in a single dose of 16 Gy. The melatonin was administered at a single dose of 50 mg/kg through intraperitoneal injection, 15 min before radiation exposure. The probiotic was administered orally every day to the rats for 5 days starting before radiotherapy. There was a statistically significant changes in histopathological (villus atrophy, mitotic activity, apoptotic index, goblet cell swelling, degenerative changes, atypia) and biochemical (oxidant and antioxidant status, IL-1β, IL-6 and TNF- α levels) parameters in the small intestine in the radiotherapy group G2 compared to the G1 control group (p < 0.05). However, a significant decrease was observed with the administration of probiotics and melatonin (p < 0.05). In addition, although positive bacterial growth was detected in the mesenteric lymph node of all rats in the radiotherapy group, there was no statistically significant difference between all groups (p > 0.05). Melatonin and probiotics were found to have a potent radioprotective effect against radiotherapy-induced acute small intestinal tissue damage. However, their superiority over each other was not observed.

Effect of Arabic Gum on Gentamicin Nephrotoxicity in Mice: A Pathological Study

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; To investigate the effect of Arabic gum on gentamycin nephrotoxicity in mice kidney.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; Forty (40) mice were divided into five groups, eight mice in each. Group one (G1) stands for the negative control group. The second one (G2) was injected with gentamycin only, while the third one (G3) was given an Arabic gum orally 10g/kg. The 4th group (G4) was injected with gentamycin for 8 days, and then followed by Arabic gum orally for 8 days. The fifth group (G5) was injected with gentamycin plus oral administration of Arabic gum at the same time. A scoring system (+1-+4) was used to grade the histological features in the kidneys.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; The results revealed a significant increase in body weight in G3 group only; this group presented a significant decrease in the level of both urea and creatinine. Group G2 showed a marked elevation in both serum urea and creatinine. Acute tubular necrosis (+4), in both G2 and G5. In G3, kidney sections presented mild cell swelling of the tubular epithelium in addition to the normal architectures (score +1), while G4 sections revealed tubular hyalin cast, expansion of glomerular tufts.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; The research indicates that gentamycin leads to kidney damage in mice. Arabic gum could be a treatment option although additional studies are required to determine the best dosing and timing, for optimal effectiveness.&amp;lt;/p&amp;gt;

Accurate and Safe Tumor Targeting of Orally-administered Salmonella typhimurium A1-R Leads to Regression of an Aggressive Fibrosarcoma in Nude Mice.

Salmonella typhimurium A1-R has been shown to target and inhibit many types of cancers in mouse models without continuous infection of normal tissue. The objective of the present study was to determine the effective dose of orally-administered Salmonella typhimurium A1-R, expressing-green fluorescent protein (GFP), on an HT1080 human-fibrosarcoma nude-mouse model. The HT1080-human- fibrosarcoma nude-mouse models were randomized into the following three groups: G1: untreated control; G2: Oral Salmonella typhimurium A1-R (5×107 colony forming units [CFU]/body, twice a week, 2 weeks); G3: Oral Salmonella typhimurium A1-R (3.3×108 CFU/body, twice a week, 2 weeks). Each group comprised five mice. Body weight and tumor volume were measured twice a week. The number of colonies of Salmonella typhimurium A1-R-GFP in excised tumors and excised livers in groups G2 and G3 were determined on day 3, day 7 and 14 by growth on agar plates. Tukey-Kramer analysis was used to examine the relationships between variables. Statistically-significant results are defined as those with p≤0.05. Salmonella typhimurium A1-R was administered orally at a dose of 3.3×108 CFU, which successfully regressed the HT1080 tumor in nude mice. However, this effect was not observed at a lower dose of 5×107 CFU. After administering Salmonella typhimurium A1-R at 3.3×108 CFU, tumors and liver tissues were harvested, homogenized, and cultured on days 3, 7 and 14. Resulting GFP-expressing Salmonella typhimurium A1-R colonies were then counted. The number of GFP-bacterial colonies derived from excised tumors at intervals of 3, 7, and 14 days increased over time post-administration of oral GFP-Salmonella typhimurium. Conversely, the number of GFP-Salmonella typhimurium A1-R colonies that could be grown from excised livers decreased over time, following oral administration of GFP-Salmonella typhimurium. Additionally, the GFP-bacterial colonies grown from the excised tumors were significantly larger than those grown from the excised livers. The present study showed that an aggressive fibrosarcoma could be regressed by orally-administered Salmonella typhimurium A1-R which accurately targeted tumors without continuous growth in normal organs. The present results suggested the potential of orally-administered Salmonella typhimurium A1-R as a probiotic to treat aggressive soft-tissue sarcoma.

Effects of high-dose glucose oxidase on broiler growth performance, antioxidant function, and intestinal microbiota in broilers.

Glucose oxidase (GOD) has been investigated as a potential additive for enhancing intestinal health and growth performance in poultry. However, limited research exists on the effects of ultra-high doses of GOD in practical poultry production. This study aimed to investigate the impact of high dietary GOD levels on broiler growth performance, antioxidant capacity, and intestinal microbiota. A total of 400 healthy, 1-day-old, slow-growing broiler chickens were randomly assigned to four treatment groups. The control group was fed a standard basal diet, while the other groups (G1, G2, and G3) were fed the basal diet supplemented with 4 U/g, 20 U/g, and 100 U/g of VTR GOD, respectively. The results showed that a dose of 100 U/g GOD significantly improved the final body weight and average daily feed intake (ADFI) (p < 0.05). Additionally, the G3 group exhibited a marked increase in glutathione peroxidase (GSH-Px) activity (p < 0.05), reflecting enhanced antioxidant function. Gut morphology remained intact across all groups, indicating no adverse effects on intestinal barrier integrity. Microbiota analysis revealed significant increases (p < 0.05) in Firmicutes and Verrucomicrobiota abundance at the phylum level in the GOD-supplemented groups. Moreover, GOD treatments significantly increased the abundance of Faecalibacterium, Mucispirllum, and CHKCI001 at the genus level. Metabolic function predictions suggested that high-dose GOD supplementation enriched carbohydrate metabolism, particularly starch and sucrose metabolism. Correlation analysis indicated that Faecalibacterium and CHCKI001 were two bacteria strongly influenced by GOD supplementation and were associated with enhanced growth performance and improved gut health. In conclusion, high-dose GOD supplementation had no adverse effects and demonstrated significant benefits, promoting both growth performance and gut health in broilers.

Therapeutic Efficacy of Eucalyptus Oil as Teat Dip in Subclinical Mastitis in Goats

Mastitis, an inflammation of the parenchyma of mammary gland, results in alterations to the chemical and physical composition of milk due to a variety of infectious and non-infectious causes. The present work was conducted in the Department of Veterinary Medicine, College of Veterinary Science and Animal Husbandry, Nanaji Deshmukh Veterinary Science University, Jabalpur, Madhya Pradesh (M.P.). A total of 256 lactating goats irrespective of age, breed, parity and stage of lactation belonging to both organized and unorganized sectors at Jabalpur were screened from “February 2024 to July 2024”. On the basis of modified California mastitis test (MCMT) score, out of 256 lactating goats, 98 goats were found positive for subclinical mastitis with overall occurrence as 38.28% on animal basis and 33.33% on udder halves basis. Therapeutic study on 24 milk samples positive for subclinical mastitis by MCMT was conducted and categorized into four treatment groups (G1, G2, G3 and G4), each group comprised of 6 goats. Six apparently healthy goats were selected as healthy control group (G5). Two different teat dips viz. Eucalyptus oil 98% + DMSO 2% BID for 14 days in groups G1 and G3 and 5% Povidone iodine BID for 14 days in groups G2 and G4 were used as teat dips, respectively. Moreover, goats of groups G3 and G4 were commonly treated with parenteral antibiotic amoxicillin sulbactam @10 mg/kg b.wt. I/M OD for 3 days. Significantly higher values of somatic cell count, standard plate count, pH, freezing point and significantly lower value of lactose were observed in subclinical mastitis affected goats. The mean density and mean water percentage values varied within normal physiological range. On the basis of restoration of milk parameters and standard plate count, the most effective therapy was elicited by Eucalyptus oil 98%+ DMSO 2% as teat dip in combination with antibiotic amoxicillin sulbactam (G3).

Effect of ionizing radiation on the shear bond strength of two different adhesive systems in primary teeth. in-vitro study

BackgroundRadiotherapy is a treatment modality used for head and neck cancer patients. It has a negative influence on bonding strength of adhesives. Little information is available about the effect of radiotherapy on bonding strength of adhesives in primary teeth. Therefore, this in vitro study aimed to detect the best adhesive system and ideal time to apply restorations in primary irradiated teeth regarding adhesive shear bond strength.MethodsDentin samples from primary teeth were randomly assigned to four groups based on restoration application time and radiation exposure, (G1: control, G2: preradiation, G3: 24 h postradiation, and G4: 6 months postradiation) with 20 samples per group. These groups were further divided into 2 subgroups according to the adhesive system used, with 10 samples per subgroup. (1) 3M™ Single Bond Universal Adhesive (SB), (2) 3M AdperSingle Bond 2 (AS). Samples were exposed to gamma radiation from a cobalt-60 machine. One shot of 60 Gy of radiation was delivered. Then samples were subjected to a shear bond strength test. The load was applied until failure and the maximum load was recorded. Numerical data are presented as mean and standard deviation values, then distributed according to Shapiro–Wilk test or Levene's test and analyzed via two-way ANOVA. The significance level was set at p < 0.05 for all tests. Statistical analysis was performed with R statistical analysis software version 4.4.1 for Windows (Team RC, R: A language and environment for statistical computing. R foundation for statistical computing, 2023).ResultsCompared with the AS subgroup, the SB subgroup presented significantly greater values (p < 0.001). For SB, there was no significant difference among the G1 and G4 groups (p > 0.001). However, there was a significant difference between G1, G2, and G3 (p < 0.001, P = 0.025, P = 0.265 ns respectively), and G3 presented the lowest values. For AS, there was no significant difference between groups G1 and G4 (p = < 0.001). Compared with the other groups, G3 presented a significant difference (p = 0.265 ns) and the lowest results.ConclusionRestorations performed 24 h after radiation had lower bond strength than those performed six months after radiation. Regardless of the adhesive system used, SB performed better than AS in terms of the shear bond strength.

Efficacy of Sodium Fluoride and Fluoridated Calcium Phosphate in Mitigating Dental Erosion on Human Enamel: An In Vitro Analysis.

With increasing prevalence of dental erosion, this study explores the protective role of traditional fluoride-based products and newer formulations on eroded enamel. To assess the protective effectiveness of casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF) and sodium fluoride (NaF) on human enamel against erosion using surface microhardness (SMH) and Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analyses. Ten extracted human third molars were sectioned to obtain 40 enamel sections and randomly assigned into four groups (n = 10) and treated as follows: G1 (Sound Enamel), G2 (Erosive Challenge), G3 (CPP-ACPF + Erosive Challenge), and G4 (NaF + Erosive Challenge). All samples were subjected to Vicker's SMH analysis, while changes in surface morphology and elemental composition were validated in few representative samples using FTIR and SEM, respectively. Paired samples test, Kruskal-Wallis test, and Tukey HSD test were performed using SPSS software version 23 setting P value < 0.05 as statistically significant. The mean SMH1 values for the experimental groups G3 and G4 were significantly higher (426.58VHN and 455.83VHN) when compared to G1 (P = 0.000) and G2 (P = 0.000). In SEM analysis, G2 showed eroded honeycomb appearance compared to the smooth homogenous surface of G1, while both G3 and G4 showed deposition of some precipitates. FTIR analysis revealed that in G3 and G4, a characteristic peak of phosphate vibrations between 528 and 823 cm-1 and carbonate bands at 845-932 cm-1 was observed. Both CPP-ACPF and NaF demonstrated a protective effect on enamel against erosive challenge by an orange juice-based beverage.

Grouper bone nano-calcium and substitution long-chain triglyceride (LCT) into medium-chain triglyceride (MCT) enhanced calcium bioavailability and rat’s bone density

BACKGROUND: The most effective strategy to prevent osteopenia or osteoporosis in the old life is to consume an adequate amount of calcium from childhood through adulthood. OBJECTIVE: This study compared the bioavailability of CaCO3 which is the standard non-dairy calcium supplementation with grouper bone nano-calcium (GBN) combined with various percentages of Long-Chain Triglyceride (LCT) into Medium-Chain Triglyceride (MCT) on calcium bioavailability and rat’s bones density. METHODS: This study was carried out during the rat’s growth period, from the weaning until the rats reached 16 weeks. Thirty-five weaned rats were separated into seven groups and fed varied feeds for 12 weeks. The seven groups of feed were (1) CCa: standard feed AIN-93G, (2) C0: standard calcium deficient feed (without calcium), (3) G0: GBN + MCT:LCT 0 : 100%, (4) G25: GBN + MCT:LCT 25 : 75%, (5) G50: GBN + MCT:LCT 50 : 50%, (6) G75: GBN + MCT:LCT 75 : 25%, and (7) G100: GBN + MCT:LCT 100 : 0%. Parameters observed were serum levels of calcium, phosphorus, and alkaline phosphatase, femur bone characteristics, bone microarchitecture by histomorphometry, micro computed-tomography (μCT), and mechanical strength. RESULTS: The CCa and G100 groups had the best dietary results based on all parameters. The G100 group was superior to CCa in calcium and phosphorus bioavailability, rat’s bone strength and density. CONCLUSIONS: G100: GBN + MCT:LCT 100 : 0% group feed beneficially affected the bioavailability of calcium, was letting he rat’s bones to develop properly, had high density, and been strong throughout the growth phase.

Clinicopathological correlations in 38 cases of gastroenteropancreatic high-grade neuroendocrine neoplasms.

Diagnosis and treatment of gastroenteropancreatic high-grade neuroendocrine neoplasms (GEP-HG-NENs), particularly G3 well-differentiated neuroendocrine tumours (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) relies on histopathological morphology, immunohistochemistry, and molecular biological markers, which are lacking especially in cases with ambiguous histomorphology. In this study to contribute to the development of more targeted treatment strategies, we examined various immunohistochemical and molecular biological markers and their association with clinicopathological features in GEP-HG-NENs. We included 38 patients with GEP-HG-NENs in this study, with their retrospective follow-up data. The expression of tumour protein p53 (TP53), RB transcriptional corepressor 1 (RB1), somatostatin receptor 2 (SSTR2), clusterin (CLU), and marker of proliferation Ki-67 (MKI67) was immunohistochemically analysed. KRAS proto-oncogene, GTPase (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E expression was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between immunohistochemical and molecular biological markers and clinicopathological characteristics were examined using a Cox risk regression model, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses. SSTR2, RB, TP53, and CLU expression differed between NET G3 and NECs, with variations among the NET G3 and small- and large-cell NEC (SCNEC and LCNEC, respectively) groups (p < 0.05). The median MKI67 proliferative index was approximately 40% and 70% in G3 NETs and NECs, respectively. The NET G3 group exhibited a median survival of 25 months, indicating a relatively better prognosis than that of the NECs group (median survival, 11 months). Both Kaplan-Meier survival analysis and the Cox risk regression model indicated a statistical correlation among treatment methods, CLU expression, and prognosis (p < 0.05). The BRAF V600E mutation rate was 32.4% in G3 NETs and SCNEC, demonstrating a significant difference between both types (p = 0.0086). Furthermore, ROC curve analysis highlighted the diagnostic significance of the positive expression of the immunohistochemical markers CLU, SSTR2, and RB in identifying NET G3. To guide more suitable treatment strategies, it is essential to develop and apply valuable and more targeted immunohistochemical and molecular pathological markers for a comprehensive analysis.

The efficiency of injectable P4 combined with the male effect on the pregnancy rate of boer goats in the off-season

Goats are seasonally polyestrous, which implies that the kid production is restricted to once a year. However, through estrous cycle manipulation, the production can be distributed throughout the year. Therefore, the present study aimed to estimate the reproductive viability of Boer female goats after administration of injectable P4, either combined with the male effect or independently, during the off-season in the southern region of Paraná. The outcomes evaluated in the study included the pregnancy rate, parturition rate, twin births, number of births, and concentration of births. The study was conducted in a beef goat farm, using 72 goats randomly assigned to three experimental groups. In the G1 group (n=22), females were stimulated by the male effect, in the G2 group (n=25), the animals received 75 mg of P4 intramuscularly at the beginning of the experiment, and in the G3 group (n=25), the goats received 75 mg of P4 intramuscularly at the beginning of the experiment combined with the male effect. The goats were in a breeding season of 60 days. The pregnancy rate, parturition rate, percentage of twin births, and the number of kids born per group were evaluated. The use of injectable P4 showed a similar pregnancy rate to the other groups, with a higher concentration of births in the G1 and G3 groups, both of which were subjected to the male effect (p&lt;0.05). Furthermore, more studies should be carried out using different P4 concentrations.

Genetic diversity and evolution of porcine hemagglutinating encephalomyelitis virus in Guangxi province of China during 2021-2024.

Porcine hemagglutinating encephalomyelitis virus (PHEV) is the only known porcine neurotropic coronavirus, which is prevalent worldwide at present. It is of great significance to understand the genetic and evolutionary characteristics of PHEV in order to perform effective measures for prevention and control of this disease. In this study, a total of 6,986 tissue samples and nasopharyngeal swabs were collected from different regions of Guangxi province in southern China during 2021-2024, and were tested for PHEV using a quadruplex RT-qPCR. The positivity rate of PHEV was 2.81% (196/6,986), of which tissue samples and nasopharyngeal swabs had 2.05% (87/4,246) and 3.98% (109/2,740) positivity rates, respectively. Fifty PHEV positive samples were selected for PCR amplification and gene sequencing. Sequence analysis revealed that the nucleotide homology and amino acid similarities of S, M, and N genes were 94.3%-99.3% and 92.3%-99.2%, 95.0%-99.7% and 94.7%-100.0%, 94.0%-99.5% and 93.5%-99.3%, respectively, indicating M and N genes were more conservative than S gene. Phylogenetic trees based on these three genes revealed that PHEV strains from different countries could be divided into two groups G1 and G2, and the PHEV strains from Guangxi province obtained in this study distributed in subgroups G1c and G2b. Bayesian analysis revealed that the population size of PHEV has been in a relatively stable state since its discovery until it expanded sharply around 2015, and still on the slow rise thereafter. S gene sequences analysis indicated that PHEV strains existed variation of mutation, and recombination. The results indicated that the prevalent PHEV strains in Guangxi province had complex evolutionary trajectories and high genetic diversity. To the best of our knowledge, this is the first report on the genetic and evolutionary characteristics of PHEV in southern China.

Glucose enhanced lignin accumulation in grapevine stems via promoting phenylpropanoid biosynthesis

BackgroundThe lignification of branches can promote the accumulation of nutrients, increase plant survival and resistance to biotic and abiotic stresses. As an important carbon source for plants, glucose is also the carbon skeleton for lignin synthesis. Grapevine is a perennial cash crop, and highly lignified branches are essential to ensure the growth of the grapevine plant and the development of the fruit.MethodsHere, ‘Red Globe’ grape (Vitis vinifera L.) plantlets were selected as the material and cultured with different concentrations of glucose: 0 g/L, 20 g/L, 40 g/L and 60 g/L glucose (G0, G20, G40 and G60). Among them, G0 group as control. Lignin, anthocyanins and glucose contents, plant height and microstructure were measured at each glucose concentration after 40-, 50-, and 60-day treatments. Transcriptome and metabolome were used to analyze the difference in genes and metabolites after 50 days of growth.ResultsAfter 50 days of cultivation, the lignin content in G40 group was the highest. And the xylem cells number also increased. To further, transcriptome and metabolome have identified a total of 3638 differentially expressed genes (DEGs) (including 245 TFs) and 510 differently accumulated metabolites (DAMs) in three comparison groups. In-depth joint analysis revealed that phenylpropanoid biosynthesis pathway significantly respond to exogenous glucose, and 37 DEGs were identified. Therefore, the phenylpropane biosynthesis pathway may be the key to exogenous glucose to increase lignin levels in grapes, with differential expression of genes being a top priority. These findings provide a new perspective for understanding the relationship between glucose and lignin in grape.Graphical

Pharmacodynamic and pharmacokinetic study of Shaoyao Gancao decoction for repairing intestinal barrier damage in ulcerative colitis

ObjectiveTo study the therapeutic effect and mechanism of Shaoyao Gancao Decoction (SGD) on ulcerative colitis (UC) mice based on the perspective of intestinal barrier, and this study provides a new consultation for the clinical application of SGD. MethodsThe chemical composition of SGD was characterized by HPLC. The UC mouse model was constructed by 3 % dextran sodium sulfate (DSS), which were randomly divided into the model group (DSS), the positive drug group (5-ASA), the Shaoyao group (SYD), Gancao group (GCD), and the Shaoyao Gancao Decoction group (SGD) at low, medium, and high dosages, respectively. The effects of each drug treatment group on UC were evaluated by the rate of body weight loss, disease activity index (DAI), colon length, spleen index, histopathological evaluations, and the levels of serum inflammatory factors (IL-1β, IL-6, IL-10, IL-21, and TNF-α). The goblet cell was observed by Alcian blue/periodic acid-Schiff (AB/PAS) straining, ELISA was used to detect the content of LPS in serum, and Western blot was used to detect the changes in the expression of tight junction proteins ZO-1, occludin, and the pathway proteins TLR4 and NF-κBp65 in the colonic tissues, to explore the protective effect of SGD on the intestinal barrier of UC mice. The vivo absorption process of the main active ingredients in the SG, SY and GC groups was determined by LC-MS. ResultsThe contents of albiflorin, paeoniflorin, liquiritin apioside, liquiritin and glycyrrhetinic acid were 6.1227 mg/g, 20.8993 mg/g, 4.0054 mg/g, 3.6140 mg/g and 8.2515 mg/g, respectively. Compared with DSS group, SGD reduced weight loss(P<0.01) and DAI scores(P<0.05), prevented colon shortening(P<0.01), and ameliorated histopathological damage of the colon in UC mice(P<0.01). SGD also protected the intestinal barrier to alleviate UC by significantly reducing serum LPS and inflammatory factor levels, altering the number of goblet cells, promoting tight junction proteins (ZO-1 and occludin) and decreasing the expression of TLR4 and NF-κB in colonic tissues. Pharmacokinetic results showed that there was no significant difference in Cmax, AUC0-t (μg/L.h) and Tmax of albiflorin and paeoniflorin between the SY and SG groups, the Tmax was within 1 h; the AUC0-t (μg/L.h) of liquiritin and glycyrrhizic acid were about 1.6 and 1.9 times higher in the SG group compared to the GC group, respectively. The Cmax, Tmax and AUC0-t (μg/L.h) of glycyrrhizinic acid were significantly reduced to 0.73, 0.68 and 0.68 times of that of the GC group. ConclusionSGD may have a therapeutic effect on DSS-induced UC mice by repairing the damaged intestinal barrier through the TLR4/NF-κB pathway. The combination of Shaoyao and Gancao increased the absorption of liquiritin and glycyrrhizic acid in vivo. The combination of Shaoyao and Gancao could promote the absorption of Gancao, and that the pairing of the two herbs could have a synergistic effect.

Coaxial Electrospun wound dressing integrated with Ag-doped hydroxyapatite for wound healing: Tetracycline delivery

The human body's natural defense against inflammation in wounds can sometimes be insufficient. Introducing a wound dressing with this capability could significantly enhance the healing process. This study aimed to create a PVP/PVA-based coaxial electrospun wound dressing integrated with tetracycline-loaded Ag-doped hydroxyapatite (Ag@iHA) in three concentrations [G1, G2, and G3]) with a focus on drug release and antibacterial activity. Nanoparticles were analyzed using DLS, Zeta potential, SEM, EDX, XRD, and FTIR. The final wound dressing was studied from the viewpoint of physicochemical properties biologically, and finally, it was assessed under an in vivo study (9 Wistar rats, six days). Drug release was measured at three pH (5.4, 7, and 9). The results showed a remarkable success in the integration of silver ion in the hydroxyapatite structure, with a 90–600 nm size. Increasing the content of hydroxyapatite improved the quality of nanofibers that were produced. The nanofibers had high hydrophilicity (<5˚) and swelling rates (70–118 %), which were wholly degraded after 14 days. The amount of the released drug was completely different at each pH and was higher in an alkaline environment, as seen in wounds. The survival percentage (>90 %) of L929 cells showed the biocompatibility of nanofibers. In the animal study, all groups reduced the growth of microorganisms, but the most efficacy belonged to the G3 group. In conclusion, this novel wound dressing has the potential to significantly accelerate the body's natural healing process by controlling the growth of microorganisms.

Assessing and predicting type 2 diabetes risk with triglyceride glucose-body mass index in the Chinese nondiabetic population-Data from long-term follow-up of Da Qing IGT and Diabetes Study.

We intended to characterize the superiority of triglyceride glucose-body mass index (TyG-BMI) in predicting type 2 diabetes mellitus (T2DM) compared with triglyceride glucose (TyG) and homeostatic model assessment for insulin resistance (HOMA-IR). A total of 699 nondiabetic participants in the Da Qing IGT and Diabetes Study were involved in the present analysis and classified according to the median of baseline TyG-BMI, namely the G1 (low TyG-BMI) and G2 (high TyG-BMI) groups. Information on developing diabetes was assessed from 1986 to 2020. During the 34-year follow-up, after adjustment for confounders, the G2 group had a higher risk of developing type 2 diabetes than the G1 group (hazard ratio [HR]: 1.92, 95% confidence interval [CI]: 1.51-2.45, p < 0.0001). Restricted cubic spline analyses showed that increased TyG-BMI was linearly related to higher risks of type 2 diabetes (p for non-linearity>0.05). Time-dependent receiver operator characteristics curves suggested that TyG-BMI exhibited higher predictive ability than TyG (6-year: area under the curve [AUC]TyG-BMI vs. AUCTyG, 0.78 vs. 0.70, p = 0.03; 34-year: AUCTyG-BMI vs. AUCTyG, 0.79 vs. 0.73, p = 0.04) and HOMA-IR (6-year: AUCTyG-BMI vs. AUCHOMA-IR, 0.78 vs. 0.70, p = 0.07; 34-year: AUCTyG-BMI vs. AUCHOMA-IR, 0.79 vs. 0.71, p = 0.04) in both short and long terms, and the thresholds of TyG-BMI to predict type 2 diabetes were relatively stable (195.24-208.41) over the 34-year follow-up. In this post hoc study, higher TyG-BMI was associated with an increased risk of type 2 diabetes and demonstrated better predictability than TyG and HOMA-IR, favoring the application of TyG-BMI as a potential tool for evaluating the risk of type 2 diabetes in clinical practice.