Alkaline Phosphatase Levels Research Articles

Zoledronate Therapy in Osteogenesis Imperfecta: Perspectives in Indonesia Tertiary Hospital.

Osteogenesis imperfecta (OI) is a rare disease with an estimated incidence of between 1/25,000 and 1/10,000 globally. The main treatment for OI is the administration of bisphosphonate drugs. Research on clinical, radiographic, and biochemical markers to monitor patients with OI treated with zoledronate can be challenging in countries in which patients have limited national health insurance. We aimed to examine patients with OI treated in Indonesia with a minimum follow-up period of 2 years. An observational study was conducted of all patients with OI treated with zoledronate between 2021 and 2023 at a tertiary hospital in Indonesia. We evaluated the paediatric quality of life (PedsQL), bone mineral density (BMD), and alkaline phosphatase (ALP) level before and after zoledronate treatment. To monitor safety, serum creatinine and calcium levels were also measured. Eleven boys (55%) and nine girls (45%), with an average age of 6.9 years (range, 4-17 years), were included. After 2 years of zoledronate treatment, the total PedsQL score increased from 66.7 to 76.9 (P=0.0001) and the mean lumbar and total body BMD increased from 0.467 and 0.501 to 0.599 g/cm2, and 0.626 g/cm2 (P=0.001), respectively. The ALP level decreased from 310.6 to 186.4 mg/mL (P=0.0001). Neither serum creatinine (P=0.586) nor calcium (P=0.53) levels changed from the pre-treatment to 2 years post-treatment time points. Zoledronate was safe and effective for the treatment of OI. There were significant improvements in the quality of life and BMD in patients with OI. The ALP level decreased, but serum creatinine and calcium levels were not affected by zoledronate.

Generalized Ketogenic Diet Induced Liver Impairment and Reduced Probiotics Abundance of Gut Microbiota in Rat

The ketogenic diet is becoming an assisted treatment to control weight, obesity, and even type 2 diabetes. However, there has been no scientific proof supporting that the ketogenic diet is absolutely safe and sustainable. In this study, Sprague–Dawley (SD) rats were fed different ratios of fat to carbohydrates under the same apparent metabolizable energy level to evaluate the effects of a ketogenic diet on healthy subjects. The results showed that the ketogenic diet could relatively sustain body weight and enhance the levels of serum alanine aminotransferase (ALT) and serum alkaline phosphatase (SAP), leading to more moderate lipoidosis and milder local non-specific inflammation in the liver compared with the high-carbohydrate diet. In addition, the abundance of probiotic strains such as Lactobacillus, Lactococcus, and Faecalitalea were reduced with the ketogenic diet in rats, while an abundance of pathogenic strains such as Anaerotruncus, Enterococcus, Rothia, and Enterorhabdus were increased with both the ketogenic diet and the high-carbohydrate diet. This study suggests that the ketogenic diet can lead to impairments of liver function and changed composition of the gut microbiota in rats, which to some extent indicates the danger of consuming a generalized ketogenic diet.

Clinical Impact of High-dose Esomeprazole-amoxicillin Dual Therapy as Rescue Treatment for Helicobacter pylori Infection: A Prospective, Multicenter, Randomized Trial.

This study aimed to compare the effectiveness and safety of high-dose dual therapy (HDDT) using esomeprazole and amoxicillin to furazolidone-based quadruple therapy (FBQT) in treating nonresponsive patients with Helicobacter pylori (H. pylori) infection. A total of 209 patients with H. pylori infection, who had previously received ineffective treatment and visited an outpatient clinic, were randomly assigned to either the HDDT or FBQT groups. All patients underwent a 14-day treatment regimen, and the success rates of H. pylori eradication and safety of the treatment regimens were assessed 4 weeks posttreatment. Following the 14-day treatment period, the intention-to-treat (ITT) analysis revealed eradication rates of 93.6% for HDDT and 86.9% for FBQT. In the per-protocol (PP) analysis, eradication rates were 94.5% for HDDT and 88.7% for FBQT. No significant difference in eradication rates was observed between the two groups. HDDT exhibited significantly lower rates of adverse reactions (9.1% in ITT and 9.2% in PP) compared with FBQT (58.6% in ITT and 59.8% in PP). Multivariate analysis identified interval time, alkaline phosphatase, and serum creatinine level as factors influencing the eradication rate. The area under the receiver operating curve of the interval time between the FBQT group and the HDDT group and the success of H. pylori eradication were 0.622 and 0.578, respectively. The optimal salvage treatment intervals were determined as 6 months for FBQT and 1 year for HDDT. HDDT using high-dose esomeprazole and amoxicillin demonstrated efficacy in treating H. pylori infection, with the added benefits of reduced side effects and improved medication compliance compared with FBQT. HDDT can be considered a rescue treatment option when other methods fail, with treatment intervals optimized accordingly.

Factors Associated With Infusion Reactions in Patients With Breast Cancer Receiving Trastuzumab.

Trastuzumab (TRA) is a key drug in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer treatment. Infusion reactions (IR) with TRA are frequently observed in practice. Although the efficacy of premedication has been previously reported, it remains uncommon. The probability of severe IR due to TRA is low; however, when it does occur, it is associated with patient discomfort and expenditure of medical resources. This study aimed to analyze the factors associated with the occurrence of IR in patients with breast cancer who received TRA. We retrospectively studied 204 patients who underwent TRA for breast cancer treatment between September 2008 and June 2023, identifying factors influencing the occurrence of IR at the time of TRA administration. A total of 182 patients were included in this study, and the incidence of IR was 25.8% (47/182 patients). Multiple logistic regression analysis showed that pertuzumab (PER) use, high alkaline phosphatase (ALP), and low high-density lipoprotein (HDL) cholesterol levels were associated with IR. IR should be considered when PER is combined with TRA. ALP and HDL cholesterol levels may be predictive markers of TRA-induced IR in patients with breast cancer.

Prevalence of chondrocalcinosis and calcium pyrophosphate deposition disease in a cohort of adult patients with low alkaline phosphatase levels and a positive versus negative genetic ALPL study.

To estimate the prevalence of chondrocalcinosis and calcium pyrophosphate dihydrate deposition disease (CPPD) in patients with low alkaline phosphatase (ALP) levels and a positive ALPL genetic study (+GT) for hypophosphatasia (HPP) compared to those with the same biochemical abnormality and a negative genetic test (-GT). As a secondary objective, to analyze the biochemical factors associated with its presence in subjects with ALPL variants. Seventy-eight subjects with persistently low ALP levels and ALPL genetic test were included. Baseline and 24-mo knee ultrasounds were performed in 42 + GT and 36 -GT subjects, in whom the fibrocartilage, hyaline cartilage of menisci, tendons, and synovial fluid were scanned to detect calcium pyrophosphate deposits. A MyLabTwice ultrasound machine (Esaote) with a multifrequency linear array transducer (4-13MHz) was used. A higher percentage of chondrocalcinosis was observed in the +GT group [9/42 (21.4%)] compared to the -GT group [2/36 (5.6%), p=.045)]. Two patients (4.76%), both in the +GT group, had arthritis secondary to CPPD. No new cases were identified at the 24-mo control. When comparing +GT patients with and without chondrocalcinosis, ALP levels were lower, and pyridoxal-5'-phosphate (PLP) and phosphate levels were higher in the former group (p<.05). Logistic regression analysis revealed that higher PLP levels are associated with the presence of chondrocalcinosis (OR: 1.1; 95% confidence interval, CI, 1.001-1.012). Chondrocalcinosis was a frequent ultrasonographic finding in HPP. Arthritis secondary to calcium pyrophosphate deposits, however, proved less prevalent. Genetic causes, such as HPP, should be considered when evaluating patients with chondrocalcinosis in clinical practice.

Assessment of clinical and laboratory parameters of oral сavity in patients with orthodontic systems

equipment (braces) on the biochemical parameters of oral fluid. Materials and methods. The study involved patients aged 18 to 22 years who are undergoing orthodontic treatment with a bracket system. Thegroup of examined persons was 25 people. The control group included 15 practically healthy people without braces. All patients underwent dental status assessment (Green – Vermillion hygiene index – simplified IG-Y; PMA inflammation index), laboratory examination of oral fluid before and after controlled oral hygiene. The biochemical analysis included determination of the acid-base balance in the oral fluid using a pH meter, assessment of free radical oxidation by chemiluminogram parameters by biochemiluminescence and by levels of molecular products of lipid peroxidation (diene and triene conjugates, Schiff bases), activity of the enzyme alkaline phosphatase, concentrations of total protein and lactate. Results and discussions. In patients undergoing orthodontic treatment with a bracket system, an insufficient level of oral hygiene and inflammatory manifestations in the gums of moderate severity were revealed. The level of the acid-base balance of the oral fluid before controlled hygiene was equal to 6.8±0.19, that is, below the range of normal pH values in the oral cavity. After hygiene, the pH of the oral fluid returned to the norm of 7.1±0.2. In patients with braces, activation of free radical oxidation and an increase in lipoperoxidation parameters – triene conjugates and Schiff bases, increased activity of alkaline phosphatase, total protein and lactate levels took place.Cоnclusion. After hygienic treatment of the oral cavity, the biochemical parameters did not differ statistically significantly from the control data.

The Effects of Traditional Asian Diet on Metabolism, Gut Microbiota, and Liver Tissue in NASH Rats

Traditional Asian Diets (AD) in rural areas have a significant risk of mortality due to cirrhosis and hepatocellular carcinoma as nonalcoholic fatty liver disease (NAFLD). This study aims to determine the relationship between AD and liver cancer cases using rat experimental animals Rattus norvegicus strain Wistar. The measured variables include metabolic parameters, gut microbiota profile, and liver histology. This study used 14 rats in two groups: Chow Diet (7 rats to CD) and AD (7 rats to AD), and were given the respective diets for 12 weeks. Enzyme-linked immunosorbent assay (ELISA) methods are used to analyze liver enzymes, lipid profiles, and blood sugar levels. The analysis of gut microbiota used variable region-specific 16S rRNA gene and V3-V4. Biopsy stained with Hematoxylin Eosin was used to study the histology of the liver. Moreover, it was analyzed utilizing NAS (NAFLD Activity Score). The result of this study indicated that reduce body weight the rats treated with AD significant different than treated with CD. Firmicutes, Lactobacillus reuteri, Prevotellaceae bacterium, Romboutsia ilealis, and Bacteroidota in AD greater than CD. Alzheimer's disease had notably higher levels of alkaline phosphatase compared to those diagnosed with Crohn's disease on individual diagnosis. Differences in total bilirubin, alanine transaminase, aspartate transaminase, blood sugar, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides were not significant. The NAS analysis indicated that the two groups comprised rats lacking non-alcoholic fatty liver disease. Despite the high caloric content of the Asian diet, it did not lead to significant changes in metabolic parameters and liver histology related to non-alcoholic steatohepatitis. This behavior can be ascribed to the advantageous influence of the gut microbiota.

Drivers of greenhouse gas emissions in agricultural soils: the effect of residue management and soil type

Developing successful mitigation strategies for greenhouse gases (GHGs) from crop residue returned to the soil can be difficult due to an incomplete understanding of factors controlling their magnitude and direction. Therefore, this study investigates the effects of varying levels of wheat residue (WR) and nutrient management on GHGs emissions (CO2, N2O, and CH4) across three soil types: Alfisol, Vertisol, and Inceptisol. A combination of laboratory-based measurements and a variety of data analysis techniques was used to assess the GHG responses under four levels of WR inputs (0, 5, 10, and 15 Mg/ha; WR0, WR5, WR10, and WR15) and three levels of nutrient (NP0: no nutrient, NP1: nutrients (N and P) were added to balance the residue C/nutrient stoichiometry of C/N/P= 100: 8.3: 2.0 to achieve 30% stabilization of added residue C input at 5 Mg/ha (R5), and NP2: 3 × NP1). The results of this study clearly showed that averaged across residue and nutrient input, Inceptisol showed negative N2O flux, suggesting consumption which was supported by its high legacy phosphorus (19.7 mg kg⁻1), elevated pH (8.49), and lower clay content (13%), which reduced microbial activity, as indicated by lower microbial biomass carbon (MBC) and alkaline phosphatase (Alk-P) levels. N2O emissions were more responsive to nutrient inputs, particularly in Vertisol under high WR (15 Mg/ha) input, while CH4 fluxes were significantly reduced under high residue inputs, especially in Vertisol and Inceptisol. Alfisol exhibited the highest total carbon mineralization and GWP, with cumulative GWP being 1.2 times higher than Vertisol and 1.4 times higher than Inceptisol across residue and nutrient input. The partial least square (PLS) regression revealed that anthropogenic factors significantly influenced CO2 and N2O fluxes more than CH4. The anthropogenic drivers contributed 62% and 44% of the variance explained for N2O and CH4 responses. Our study proves that different biogeochemical mechanisms operate simultaneously depending on the stoichiometry of residue C and nutrients influencing soil GHG responses. Our findings provide insight into the relative contribution of anthropogenic and natural drivers to agricultural GHG emissions, which are relevant for developing process-based models and addressing the broader challenge of climate change mitigation through crop residue management.

Characteristics of the proinflammatory response of monocytes/macrophages in patients with metabolic syndrome, exemplified by the production of IL-6 and MCP-1

Metabolic syndrome (MS) is one of the most common socially significant diseases. Around 1.9 billion people suffer from this disease, which places an enormous burden on healthcare systems around the world. This is particularly true in connection with concomitant diseases. With the progression of MS, disorders in the function of the immune system occur in the body, including those associated with mitochondrial dysfunction, leading to the development of chronic inflammation. In particular, there is an increase in the number of circulating monocytes actively recruited to inflamed adipose tissue, where there is non-specific proinflammatory activation of innate immune cells, which adopt an M1-like phenotype and become less sensitive to anti-inflammatory stimuli. This ultimately leads to a decrease in the functional activity of monocytes/macrophages and their immunoplasticity. The subject of the study was the venous blood of patients and the CD14+ monocytes/macrophages obtained from it by immunomagnetic separation. In our work, we focused on the search for significant relationships between markers of chronic inflammation and the formation of immune tolerance of monocytes/macrophages in patients with metabolic syndrome. Biochemical parameters, basal and LPS-stimulated production of proinflammatory cytokines (IL-6 and MCP-1) were investigated by culture of monocytes/macrophages in patients with metabolic syndrome. The evaluation of biochemical parameters in blood samples from MS patients and healthy donors revealed that the levels of ALAT, AST, GGT, alkaline phosphatase, uric acid, C-reactive protein, glucose and insulin were significantly higher in MS patients than in healthy donors. The levels of P-amylase and high-density lipoprotein were significantly lower than in the control group. Within the experimental model, repeated stimulation showed a decrease in cytokine production in response to LPS compared to the first stimulation on day 7. It was also found that the response to the primary stimulus was higher in cells from patients with a body mass index (BMI) 40 kg/m2, which could indirectly indicate the presence of a phenotype associated with chronic inflammation and consequently with reduced plasticity of the monocyte/macrophage immune response.

Toxicological assessment of the aqueous extract of Juniperus oxycedrus L. on acute and subacute toxicities in rats

Juniperus oxycedrus L. (J. oxycedrus) has a rich historical background in herbal remedies to treating digestive system abnormalities. However, no comprehensive evaluation of its potential toxic effects has been conducted. The current investigation aimed to evaluate the acute and subacute toxicity of an aqueous extract of J. oxycedrus (AEJO). AEJO was prepared by the conventional Moroccan methods by decoction the arial part of the plant. The acute and subacute toxicity tests were conducted in mice and rats, respectively. Acute toxicity tests showed that the extract was not toxic even at high doses of 5000 mg/kg. In the subacute study, no detectable indications of toxicity or mortality were observed and there were no notable deviations in food intake or water consumption among all rats. However, changes in body weight of animals treated with 1000 and 2000 mg/kg underwent a significant decrease. AEJO administration decreased platelet number, elevated levels of alanine aminotransferase and alkaline phosphatase, and reduced albumin levels. Histological examination revealed normal renal parenchyma despite increased creatinine. It also showed binucleation, and hepatocyte vacuolation. The results indicate that AEJO has considerable tolerance for consumption, but repeated use can affect hepatocytes and kidneys. Therefore, additional analyses, such as subchronic, chronic, and neurotoxic studies, are required before using this plant in clinical research.

Effect of different levels of turmeric (Curcuma longa) on productivity in broiler chickens

This research was conducted to evaluate the effect of different levels of turmeric powder on the performance, blood parameters, immunity, intestinal morphology, carcass characteristics, cecum microbial flora, fatty acid profile and sensory evaluation of breast meat of broiler chickens. A completely randomized design was used including four levels of turmeric powder (250, 500, 750 and 1000 mg/kg diet) and a control treatment (without turmeric), in 5 replications. The growth performance was measured periodically and at the end of the 42-day period, three chickens from each experimental unit were killed for carcass examination. In order to check blood parameters at the end of the course, blood samples were taken from three chickens from each experimental unit. To check the immunity of broiler chickens, the weight percentage of immune glands was also evaluated. To measure the morphology of the cecum, one chicken from each experimental unit was killed to check the desired traits. The results of the experiment showed that different levels of turmeric had a significant effect on performance, carcass characteristics, blood parameters, immunity, intestinal morphology, cecal microbial flora, fatty acid profile, and the sensory evaluation of breast meat (P&lt;0.05). The results of the experiment showed body weight, feed intake and feed conversion ratio (FCR) at the end of the period were significant in the treatments that received turmeric powder (P&lt;0.05). Survival percentage, produced body weight per square meter, and final profit was also significant (P&lt;0.05). Relative weight of abdominal fat, villus height and villus height/ crypt depth of the small intestine were significant in the treatments receiving turmeric powder (P&lt;0.05). By adding turmeric powder to the diet of broiler chickens, the microbial population of the cecum also became significant (P&lt;0.05). The concentration levels of uric acid, total cholesterol, glucose, HDL, albumin and liver enzymes alkaline phosphatase and ALT were significant in the birdsreceiving turmeric powder (P&lt;0.05). Turmeric powder in the diet of broilers also had a significant effect on chondroitinic acid, linoleic acid and total polyathenoids (P&lt;0.05). Turmeric powder was significant on the lactobacilli microbial population (P&lt;0.05). The results of this experiment showed that fat content, juicyness, crispyness, chewability, elasticity, mouthfeel and general acceptance were significantly improved (P&lt;0.05). In this research, the treatment receiving 500 mg of turmeric powder per kg had the greatest effect on the measured characteristics of broiler chickens. It can be concluded that the addition of the powder of these medicinal and aromatic plants to the diet of broiler chickens has beneficial effects on the carcass characteristics and meat quality. Keywords: fatty acid, blood plasma, abdominal cavity, triglyceride, feed conversion ratio, Curcuma longa

Clinical Outcome Patterns of Use of Radium-223 in Patients with Metastatic Castration-Resistant Prostate Cancer

Introduction: Radium-223 dichloride (radium-223) is a bone-targeting radioisotope therapy that aids in the survival of patients with metastatic castration-resistant prostate cancer (mCRPC) to bones. This study aimed to describe the clinical characteristics and outcomes of patients with mCRPC treated with radium-223 in a real-world setting. Methods: This was a retrospective study of patients with mCRPC treated with radium-223 between 2016 and 2020 at the London Health Sciences Centre in London, Canada. The baseline characteristics between the patients receiving 1–3 and 4–6 treatment cycles were compared using a two-sample t-test and Chi-square test. ANOVA was used to determine if there was a difference in each diagnostic variable per treatment cycle. Kaplan–Meier curves were generated to estimate progression-free survival (PFS) and overall survival in the patients treated with different numbers of cycles. Results: Fifty eligible patients were identified. The median age was 71 years (IQR: 66–76). Most patients (62%) received radium-223 beyond the third-line treatment. The mean number of radium-223 treatments was four. While 60% of the patients received 4–6 injections, 40% received 1–3 injections. Fifty-eight percent (58%) of the patients demonstrated a clinical benefit, with the remainder expressing either disease progression (28%) or stable disease (10%). The patients treated with 4–6 cycles had a delay to disease progression compared to those given 1–3 cycles of radium-223 (F5,35 = 10.52, p &lt; 0.001). A higher alkaline phosphatase level prior to treatment was associated with a longer PFS (z33 = 2.362, p = 0.018). Treatment-related hospitalization for skeletal-related events was noted in 8% of the patients, and 14% required treatment discontinuation due to hematologic toxicity. Conclusions: This study confirms the safety of radium-223 in patients with mCRPC in a real-world setting. The radium-223 treatment was associated with a clinical benefit in the majority of the patients, particularly in those with higher pre-treatment serum alkaline phosphatase levels. Further studies to identify the predictive biomarkers are warranted to better guide the contemporary use of radium-223.

Effects of i-PRF, A-PRF+, and EMD on Osteogenic Potential of Osteoblasts on Titanium.

The study evaluates three biologically active substances with known bone-inductive potential on previously decontaminated titanium (Ti) discs. Rough and smooth Ti surfaces were contaminated with a multispecies biofilm and cleaned with a chitosan brush. Discs were treated either with injectable-platelet-rich fibrin (i-PRF), advanced platelet-rich fibrin (A-PRF+), or enamel matrix derivatives (EMDs) before osteoblast seeding. Biocompatibility, adhesion, migration, and gene expression of runt-related transcription factor 2 (RUNX2), collagen Type I Alpha 2 (COL1a2), alkaline phosphatase (ALP), osteocalcin (OC), and osteonectin (ON) were performed. All the tested biologic agents similarly increased cell viability. Specifically, osteoblasts seeded over i-PRF and EMD-treated surfaces showed improvement in adhesion and migration and significantly increased ALP, OC, ON, RUNX-2, and COL1a2 mRNA levels up to 2.8 fold (p < 0.05) with no differences between Ti surfaces. i-PRF and EMD possess beneficial bioactive properties that enhance tissue healing and promote regeneration on thoroughly sterilized surfaces. Biologically active materials may hold the potential to influence the process of implant re-osseointegration, which warrants more research since sterilization of the affected surfaces under clinical conditions is still not reliably possible and remains one of the greatest challenges.

Engineering Budesonide Microparticles for Enhancing Pulmonary Targeting: Validation through In Vivo Investigations

AbstractThe study aimed to develop and evaluate budesonide inhalation micro‐suspension to target inflammation in the lower trachea and bronchi. Initially, the slurry phase is prepared by dispersing the drug (0.25 and 0.5 mg ml−1) in the Water for Injection with polysorbate 80. The slurry is mixed with the aqueous phase comprising other excipients. The mixture is further subjected to the treatment with homogenizer. The prepared formulations are subjected to various physio‐chemical analysis like description, density, pH, osmolality, viscosity, shelf life, impurities, assay, particle size, etc. Andersen cascade impactor is used to estimate the aerodynamic performance. In vivo analysis is initiated with the induction of Asthma in Sprague Dawley rats by ovalbumin challenge intranasally and the treatment is given with the aid of a nebulizer. Lastly, the biochemical estimations are carried out in blood and bronchoalveolar lavage fluid (BALF). The lungs are also subjected to morphological and histological evaluations. The physio‐chemical and analytical examination indicated a stable formulation that is compliant with the standard guidelines. The D90 value of the test formulation is ≤4.5 µm. Cascade impactor evaluation estimated almost, 2–10% higher amount of budesonide reaching the target region as compared to the marketed product. Test formulation attenuated the manifestation of ovalbumin‐induced asthma through suppression of inflammatory cell count in blood and BALF, and modulation of Lactate dehydrogenase and Alkaline Phosphatase levels which is further confirmed by histopathological analysis. The formulated budesonide micro‐suspension demonstrated stability, safety, and efficient delivery to the target site.

Exploring the Potential Antidiabetic Effects of Alkannin (A Naphthoquinone Compound): In Vivo and In Silico Studies

Background It is estimated that the plant has been utilized in India’s traditional medical system for close to 2,500 years. Alkanin is a key active component in Boraginaceae medicinal plant roots. Many scientists are interested in this tiny molecule due to its biological potential. Purpose To examine the hypoglycemic effects of alkannin (a naphthoquinone pigment). Methods Initially, we determined the dosage of alkannin by conducting an acute oral toxicity study per Organisation for Economic Co-operation and Development guidelines. Subsequently, streptozocin was used to induce diabetes in mice, and we chose several parameters such as body weight, food and water intake, blood glucose level, and biochemical estimation for the in vivo evaluation. The enhanced pharmacokinetic features of alkannin, such as its better cytochromes P450 metabolism profiles and higher intestinal absorption as compared to glimepiride, were validated by in silico investigations utilizing Swiss ADME (Absorption, Distribution, Metabolism, and Excretion) and AutoDock Vina. Results In particular, blood glucose levels and body weight in the alkannin-treated group drastically decreased to 138 ± 1.45 mg/dL and 27.9±0.54 g, respectively, as compared with the diabetic-treated group. Moreover, alkaline phosphatase levels dropped to 57.26 ± 3.05 U/L in the alkannin group, suggesting enhanced liver and kidney functions. Creatinine levels also decreased from 1.44 ± 0.10 mg/dL to 0.92 ± 0.09 mg/dL, and serum glutamic oxaloacetic transaminase/aspartate aminotransferase levels decreased from 64.16 ± 3.14 U/L to 47.85 ± 2.01 U/L. Additionally, diabetic controls maintained cholesterol levels between 102.1 ± 11.46 mg/dL and 93.53 ± 2.61 mg/dL. With a considerable binding score of –9.2 kcal/mol for alkannin, molecular docking demonstrated a high degree of binding efficiency and robust interaction with biological targets. The docking results revealed that alkannin exhibits drug-like properties. In addition, it satisfies the lead likeness requirement and has a lower synthetic accessibility score compared to glimepiride. Conclusion The results revealed the promising characteristics and positive outcomes of alkannin, underscoring its potential as a viable candidate for further investigation and prospective advancement as a treatment drug for diabetes.

Effects of Increasing Oral Deoxynivalenol Gavage on Growth Performance, Blood Biochemistry, Metabolism, Histology, and Microbiome in Rats.

Mycotoxin-contaminated feed or food can affect physiological responses and cause illnesses in humans and animals. In this study, we evaluated the effects of deoxynivalenol (DON) toxicity on the growth performance, blood biochemistry, histology, microbiome, and metabolism of rats fed with different toxin concentrations. After 1 week of acclimatization, seven-week-old male rats received 0.9% saline as a control, 0.02 mg/kg DON as T1, and 0.2 mg/kg DON as T2 via oral gavage for 4 weeks. The final body weight of the T2 group was significantly lower than that of the control and T1; however, the average daily gain, feed intake, and feed conversion ratio did not differ. Fibrosis and apoptosis were observed in various tissues as DON concentration increased. Creatinine and alkaline phosphatase levels were significantly lower in the DON-treated group than in the control. Firmicutes and Desulfobacterota phyla dominated the cecum, whereas those in the feces were Proteobacteria and Bacteroidetes. Metabolomic profiling showed phenylalanine, tyrosine, and tryptophan biosynthesis as the most prominent pathways. Overall, our results suggest that low-dose and short-term DON exposure can trigger several adverse effects in rats. Dietary toxicants in rats may explain the physiological effects associated with the metabolism commonly reported in animals.

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.

Wharton's jelly of the umbilical cord serves as a natural biomaterial to promote osteogenesis.

Various factors can contribute to bone damage or loss, presenting challenges for bone regeneration. Our study explores the potential clinical applications of two processed forms of Wharton's jelly of the human umbilical cord for treating bone loss. Wharton's jelly from fresh umbilical cords underwent two distinct processes: (1) frozen Wharton's jelly (WJF), preserved with cryoprotective agents, and (2) decellularized Wharton's jelly matrix (WJD), prepared only via lyophilization without cryoprotectants. Both WJD and WJF are rich in collagen, hyaluronan, and polysaccharide proteins. Notably, WJD exhibited a porous structure lacking nuclei from human umbilical cord mesenchymal stem cells, unlike WJF. In direct contact experiments, WJD stimulated osteoblast migration, enhanced osteoblast maturation, and promoted calcium deposition for bone formation when administered to cultured rat osteoblasts. Furthermore, in transwell co-culture experiments, both WJD and WJF increased the rat osteoblast expression of RUNX2 and OPN genes, elevated alkaline phosphatase levels, and enhanced extracellular calcium precipitation, indicating their role in osteoblast maturation and new bone formation. Hyaluronic acid, one of the ingredients from WJD and WJF, was identified as a key component triggering osteogenesis. In vivo experiments involved creating circular bone defects in the calvarias of rats, where WJD and WJF were separately implanted and monitored over five months using micro-computerized tomography. Our results demonstrated that both WJD and WJF enhanced angiogenesis, collagen formation, osteoblast maturation, and bone growth within the bone defects. In summary, WJD and WJF, natural biomaterials with biocompatibility and nontoxicity, act not only as effective scaffolds but also promote osteoblast adhesion and differentiation, and accelerate osteogenesis.

Assessment of disorders of metabolic process on the base of quantification of target proteins under aerogenic influence of aluminum oxide in children

Introduction. The study of the mechanisms of the occurrence of adverse events at the molecular level, followed by the study of biological processes at the cellular, tissue, and organ level, allows further investigating the mechanism of the toxic action of chemicals to predict the development of adverse effects in humans. The purpose of the study is to evaluate disturbances in the signal-transporter pathways of metabolic processes on the base of the quantification of identified target proteins under aerogenic exposure to aluminum oxide in children. Materials and methods. Using the methods of chemical-analytical, statistical, proteomic, biochemical, histological research, and bioinformation analysis, the adverse effects were assessed in 4–7 years children and Wistar rats exposed to aerogenic and inhalation exposure to aluminum oxide (Al2O3). A comparative analysis of the results obtained in the experiment and natural conditions was carried out. Results. In children under conditions of long-term aerogenic exposure to Al2O3 at the level of 0.1–1.0 RfC, the urine concentration of the studied substance was found to be up to 2 times higher than the average comparison value and the reference value. In the experiment with chronic inhalation of Al2O3 at a dose equivalent to the real one, the aluminum urine content in rats was 3.5 times higher than the control value. Comparative analysis of proteomic maps in children revealed 23 significantly different protein spots, 8 of which had a relationship between intensity changes and an increase in Al urine concentration. In rats, 15 significantly different protein spots were found between the groups, 13 of which had a reliable relationship with the exposure marker. In natural and experimental studies, only two identical proteins were found: apolipoprotein A-I and transthyretin; increased levels of ALAT, ASAT and alkaline phosphatase, total and direct bilirubin, gamma-aminobutyric and glutamic acids, lipid hydroperoxide in the blood serum; increased MDA and decreased AOA in the blood plasma. Pathomorphological changes in the tissues of the brain, heart, and liver were confirmed in the experiment. Limitations. The research conducted allows drawing a conclusion about the effect of Al2O3 on the body only through the aerogenic route of entry. Conclusion. Based on the bioinformational analysis of the results obtained and assessment of the cause-and-effect relationships of the transformation of the proteomic profile of blood plasma under natural conditions, verified in the experiment, the leading molecular-cellular events in the development of adverse effects in the form of oxidation, imbalance of lipoprotein and neurotransmitter metabolism, and decreased neurogenesis activity were identified. Metabolic disorders are predicted in the tissues of the heart, blood vessels, liver, and brain under continued conditions of aerogenic exposure to Al2O3. The study of the cascade of events of adverse responses (from the molecular to the organ level) expands knowledge about the pathogenetic mechanisms of metabolic processes of dysregulation of signal-transporter pathways in the human body in response to the influence of a chemical factor, including Al2O3. This increases the effectiveness of early prediction of the occurrence of the disease and the development of targeted measures to prevent adverse consequences.

Transcriptome Analysis Reveals Immune and Antioxidant Defense Mechanisms in the Eriocheir japonica sinensis after Exposure to Ammonia.

As a key species in freshwater aquaculture, Eriocheir japonica sinensis was subjected to ammonia stress to assess its impact on the hepatopancreas. A total of 4007 differentially expressed genes (DEGs) were identified between control and treatment groups, comprising 1838 upregulated and 2169 downregulated genes. Following exposure to 300 mg/L of ammonia, the oxidative phosphorylation pathway was activated, while the lysosomal pathway was suppressed, thereby influencing immune functions. Thirteen DEGs from these pathways were further validated via qRT-PCR, revealing gene expression changes of one- to two-fold. Both acid phosphatase (ACP) and alkaline phosphatase (AKP) levels in the hepatopancreas and hemolymph initially increased and then decreased, indicating a disruption in immune functionality. Additionally, alanine transaminase (ALT) and triglyceride (TG) levels were measured, alongside catalase (CAT) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content, all of which showed an upward trend, signifying oxidative stress and tissue damage. These results offer critical insights into the antioxidant and immune mechanisms of E. j. sinensis in ammonia-enriched environments.