Alkaline Phosphatase 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.

Effects of Vitamin D Supplementation and a Cafeteria Diet on Various Parameters in the Next Generation of Rats with Metabolic Syndrome.

Metabolic Syndrome (MetS) is an increasingly widespread public health problem worldwide. MetS is associated with a cafeteria diet characterized by high fat and high simple carbohydrates. A cafeteria diet significantly affects serum glucose, creatine, urea, triglyceride, cholesterol and MetS parameters such as ALT, AST and ALP. Due to its epigenetic effects, vitamin D is important in controlling MetS parameters and minimizing MetS findings in subsequent generations. In this study, the effect of weekly 0.3 mL (1.000 IU/week) vitamin D intervention on MetS parameters was investigated in parental rats developing high-fructose MetS and their offspring. Offspring of MetS rats receiving and not receiving vitamin D supplementation were divided into four different groups and exposed to a cafeteria diet and vitamin D supplementation for eight weeks. It was shown that parental rats in the intervention group had lower serum urea, glucose, creatine, total cholesterol, ALP, AST and ALT levels (p < 0.05). Serum urea, glucose, creatine, ALT, AST, ALP, triglyceride, total cholesterol levels and body weights were lower and HDL levels were higher in the offspring (p < 0.05). However, initial serum ALT and AST values were higher in the offspring of MetS parent rats receiving vitamin D supplementation and in the offspring of rats not receiving supplementation than in the offspring of supplemented parents. In conclusion, it was found that vitamin D supplementation improved MetS parameters in parent rats, positively affected MetS parameters in offspring rats despite an inadequate diet, and positively affected some MetS parameters by affecting epigenetic pathways in offspring born to MetS mothers.

Impact of Combining Bio-Inoculants along with Inorganic Fertilizers on Soil Biological Characteristics in Transplanted Rice (Oryza sativa L.) Crop

A field experiment was carried out during the Kharif season in the year 2022 to assess the impact of inorganic fertilizers along with Bio-inoculants on soil biological properties in rice (Oryza sativa L.). The experiment consists of seven treatments viz., T1 Control, T2 100% RDF (150, 60, 40 N2, P2O5, K2O kg ha-1), T3 80% RDF + 10 kg BGA ha-1 Soil application + PSB (Phosphate solubilizing bacteria) 3kg/ha, T4 60% RDF + 10kg BGA ha-1 Soil application + PSB, T5 80% RDF + 500kg Azolla ha-1 Soil application +PSB, T6 60% RDF + 500kg Azolla ha-1 Soil application +PSB and T7 10kg BGA ha-1 Soil application + 500kg Azolla ha-1 Soil application + PSB were comprised in Randomized Block Design with three replication. The incorporation of inorganics, Azolla PSB, and BGA (bio-inoculants) actively activated microbial activities, resulting in a greater increase in the populations of total bacteria, actinomycetes, and fungi was observed throughout all growth stages, regardless of the treatments applied, when compared to their initial densities. This phenomenon supports the notion of a stronger rhizosphere effect. This trend aligns with the rise in organic carbon content. Moreover, soil dehydrogenase, alkaline phosphatase activities, along with microbial biomass carbon, displayed an upward trend in tandem with the progressive growth phases of the rice plant.

Prognostic Impact of a Histologic Grading Scheme in Dogs Diagnosed With Rib Chondrosarcoma.

Data regarding the outcome of canine rib chondrosarcoma is sparse and varied. While grade of tumour is associated with outcome for canine appendicular chondrosarcoma, the association of grade with outcome for canine rib chondrosarcoma is unclear. This study aimed to correlate the grade of canine rib chondrosarcoma with median survival time. Retrospectively, cases of primary rib chondrosarcoma were identified, and tumours were graded based on a 3-tier adapted human grading scheme. Twenty-two patients were included in the survival analysis. The median survival time was 1427 days (range: 27-3354 days). This was not significantly different for patients with grade I versus II versus III (p = 0.82), grade I-II versus III (p = 0.34), or grade I versus II-III (p = 0.49). No variables assessed including age, weight, tumour location (cranial vs. caudal thorax; left vs. right hemithorax), tumour location on rib (proximal, middle, and distal), radiographic appearance (lytic, proliferative, or mixed), elevated serum alkaline phosphatase activity, grade, grade specific histologic features (matrix production, architecture, pleomorphism, cellularity, necrosis, and total score), adjunct therapy post-surgical excision, development of metastatic disease post-surgery, or local recurrence post-surgery were found to impact the risk of death due to chondrosarcoma. In this limited group of patients, the grading scheme reported here, and the other variables assessed did not appear to offer additional prognostic information. However, this data must be interpreted considering the small sample size and thus low statistical power. Additional studies are needed to determine the true impact of grade on outcome for canine rib chondrosarcomas.

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.

Chemical profiling, in-silico investigation and in vivo toxicity assessment of lacatomtom (a psychoactive mixture) on selected indices in albino wistar rats

aims: To evaluate the safety and identify the psychoactive constituent of a new psychoactive cocktail that is abused among African youths. background: The use of lacatomtom (LTT), a psychoactive mixture of tomtom (TT) candies with lacasera (LC) beverage, has recently increased among young Nigerians and Africans. There isn't much scientific study on the constituent and effects of this psychoactive substance. objective: To chemically-profile the mixture using GCMS analysis, and evaluate the effect of the constituent of neural targets. To evaluate the toxicological effects in albino rats. To identify neur method: Herein, LTT was chemically-profiled using GCMS analysis, and the toxicological effects were examined in albino rats. In vivo experiment consists of five groups of six rats each (group 2 - LTT ad libitum; groups 1, 3, &amp; 4 - TTT, TT, LC (1 mL) mg/mL kg/body weight once/day respectively, group 5 - distilled water ad libitum). Identified constituents were examined against human monoamine oxidase (hMOA) and human catechol O-methyltransferase (hCOMT) using in silico methods. result: Forty-seven chemical compounds were identified. Ad libitum intake of LTT elevated plasma alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatinine, total cholesterol, and LDL-cholesterol levels. The docked poses, binding scores, and interactions with amino acids informed the selection of (4-Methoxymethoxy-hex-5-ynylidene)-cyclohexane (MM) (-9.4 kcal/mol) and 3-(hydroxyphenylmethyl)-3,4-dimethyl-1-phenylpentan-2-one (HP) for hCOMT (-9.4 kcal/mol), while propionylcodeine (-10.1 kcal/mol) and HP (-8.9 kcal/mol) for hMOA. Top-docked compounds (TDC) demonstrated the potential to permeate the blood-brain barrier. TDC was predicted to be a positive substrate of the P-glycoprotein and presents inhibitory potential for cytochrome P450 descriptors. HP was mutagenic and could induce human hepatotoxicity and drug-induced liver injury, while propionylcodeine had human hepatotoxic prediction. conclusion: The present study, for the first time, confirmed the potential toxicity of lacatomtom to the liver, kidney, heart, and central nervous system supported by the identified top-docked compounds regarded as potential psychoactive constituents of hMOA and hCOMT. other: Nono

Garcinol enriched fraction of Garcinia morella (Gaertn.) Desr. fruit rind improves gut health and reduces the risk of nonalcoholic fatty liver disease by regulating PCK1/ACC/SREBP1/FASn pathway in a mouse model

Nonalcoholic fatty liver disease (NAFLD), a fast-emerging global burden, is an umbrella term for several liver manifestations that result in excessive accumulation of fat in the liver. NAFLD leads to gut microbiome dysbiosis, loss in gut epithelia, increased gut permeability, etc. The limited availability of registered drugs for NAFLD highlights the urgent need to focus on understanding its pathogenesis and discovering new treatments, including the potential exploration of herbal therapies for managing the condition. In this study, we evaluated the bioactive potential of garcinol enriched fraction from Garcinia morella fruit rind in preventing NAFLD-associated increased gut permeability. Administration of garcinol-enriched fraction (GEF) significantly reduced body weight, serum lipids (triglyceride and total cholesterol) levels, and enzymes (alkaline phosphatase and aspartate aminotransferase) responsible for liver dysfunction in high-fat diet (HFD)-fed C57BL/6 mice. GEF treatment also regulated the alteration in signaling pathways of lipid metabolism in HFD-fed mice by inhibiting the overexpression of genes involved in de novo lipogenesis. Mice treated with GEF had increased gut microbial diversity, reduced pathogenic bacteria, and increased Lactococcus and Streptococcaceae genera. Additionally, GEF treatment could increase the expression of intestinal tight junction proteins, which were otherwise decreased in HFD-fed mice, stipulating its protective effect in maintaining gut barrier integrity. Our study demonstrated that GEF treatment reduces obesity in mice and improves gut health by keeping junctions tight and maintaining a healthy gut microbiome.

Calcium Phosphate Loaded with Curcumin Prodrug and Selenium Is Bifunctional in Osteosarcoma Treatments

Although SeO32− ions have been loaded onto calcium phosphate to treat a wide range of cancers, the quest to promote bone tissue regeneration is still ongoing. Curcumin (cur), an herbal extraction, can selectively inhibit tumor cells and promote osteogenesis. In this study, SeO32− ions were co-precipitated in biomimetic calcium phosphate (Se@BioCaP), and modified curcumin prodrug (mcur) was adsorbed on diverse Se@BioCaP surfaces (mcur-Se@BioCaP-Ads). Co-precipitation yielded Se@BioCaP with a significantly higher Se content and exhibited a tailorable micro-/nanostructure. The favorable pH-responsive release of Se and mcur from mcur-Se@BioCaP-Ads showed a synergistic anticancer efficiency in OS cells, enhancing OS cell inhibition more than a single dose of them, which might be associated with ROS production in OS cells. In addition, increased alkaline phosphatase activity and calcium nodule formation in MC3T3-E1 pre-osteoblasts were also verified. These results suggest this novel mcur-Se@BioCaP-Ads has promising and widespread potential in OS treatments.

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.

Investigation of hematological, biochemical and coagulological markers, their diagnostic effectiveness in toxic hepatitis in patients with COVID‑19

This article discusses hematological, biochemical and coagulological markers for the diagnosis of toxic hepatitis in patients with COVID-19. The analysis of the effectiveness of these markers in a large sample of patients confirmed their importance for the early detection of toxic hepatitis b in patients with COVID-19. Blood parameters such as platelets, ALT, AST, bilirubin, as well as coagulograms and markers of protein metabolism (albumin) conducted among patients divided into control and experimental groups were analyzed. It was found that in patients with concomitant toxic hepatitis c COVID-19, the tendency of thrombocytopenia is most common in clinical blood analysis. Among the biochemical parameters of blood, liver markers increase (ALT, GGT, alkaline phosphatase, etc.). It should be noted that in 1/3 of patients, the activity of liver enzymes alanine aminotransferase and aspartate aminotransferase increases, which indicates a violation of liver function.The analysis of these data using ROC analysis showed high diagnostic accuracy of these markers in the detection of toxic hepatitis in patients with COVID-19. These studies may be important for more effective screening and further monitoring of appropriately selected treatment in such clinical situations and contributes to more effective management of this condition, leading to an improved prognosis of this disease. This study is important in the context of understanding the effects of COVID-19 on liver function.

Protective Effects of Lemna minor Linn. On Hepatic and Cognitive Impairments in Acetaminophen Induced Hepatic Encephalopathy in Rats

Aim: Lemna minor Linn., an aquatic plant, is a promising novel therapeutic agent that has been traditionally used in ethnobotanical practices as an ecofriendly supplement for the management of various ailments. This study involves the evaluation of ethanolic extract of Lemna minor Linn. against Paracetamol-induced Hepatic Encephalopathy using in vitro and in vivo Models. Methods: The acute oral toxicity study of the ethanolic extract of Lemna minor (EELM) was conducted following the OECD-425 guidelines over a 14-day period. A total of nine animals were used for this toxicity assessment. The EELM was tested in Paracetamol(PCM)-induced bioactivation animal model at two different dosages 200 and in comparison with silymarin as a standard compound. The In vivo experimental study was conducted using Sprague Dawley rats which was divided into 5 groups each group containing 6 animals so the total no of animals used in the study was 30 animals. The treatment groups included: normal control ( ), 100mg/kg silymarin (standard) and the EELM of two different doses of 200 and , p.o were administered to rats 10 hr before paracetamol ( ) treatment. Rats were orally administered their respective doses every day for total 30days. Paracetamol-induced oxidative liver damage disrupted normal levels of liver enzymes, total protein, and bilirubin, while also depleting antioxidant reserves. This oxidative stress was strongly associated with paracetamol toxicity, leading to a marked depletion of glutathione (GSH) and impairing both memory and cognitive function in the animals. Behavioral parameters are performed to evaluate the effect of drugs on cognitive behaviour of animals. Morris water maze test was performed to study how animals learn and remembers the spatial information relying on distal cues to locate the hidden platform in an opaque water. Additionally, elevated plus maze was performed to measures the anxious behaviour of rats, the criterion was tested based on the conflict between rats innate instincts to explore new environment and avoid open, well-lit areas. The potential protective effects of EELM was evaluated by measuring serum enzyme levels and antioxidants status in the liver and brain, further histopathological analysis was performed respectively. Results: The acute toxicity study did not report any mortality or toxicity signs in animals. PCM toxicity led to a statistically increase in the liver and body weight, along with brain water content. The PCM-intoxicated group exhibited a marked reduction in the level of superoxide dismutase (SOD) and glutathione (GSH) in the brain and liver, as well as an increase in lipid peroxidation and serum biomarkers (AST, ALT, ALP, and total bilirubin). EELM significantly ( ) reduced liver injury by inhibiting ALT, AST and ALP levels in serum. SOD, GSH and MDA liver content were significantly ( ) elevated by EELM, compared to PCM treated rats. Comparing the treatment and induced group, the treated group successfully recovered the activity of antioxidant levels and also been acknowledged for restored liver functioning by alleviating oxidative stress and also GSH level in brain was significantly increased by EELM and preserved the histology of brain, which was chronically produced over a period of 30 days. Conclusion: The findings of this investigation indicate the traditional use of Lemna minor in hepatoprotection and neuroprotection by regulating oxidative stress and mitigating reactive oxygen species (ROS). The insights gained from this research contribute to the development of novel therapeutic agents and paves the way for further studies on Lemna minor to enhance health outcomes, particularly in the management of neurodegenerative diseases.

Investigating the potential effect of Holothuria scabra extract on osteogenic differentiation in preosteoblast MC3T3-E1 cells

The present medical treatments of osteoporosis come with adverse effects. It leads to the exploration of natural products as safer alternative medical prevention and treatment. The sea cucumber, Holothuria scabra, has commercial significance in Asian countries with rising awareness of its properties as a functional food. This study aims to investigate the effects of the inner wall (IW) extract isolated from H. scabra on extracellular matrix maturation, mineralization, and osteogenic signaling pathways on MC3T3-E1 preosteoblasts. The IW showed the expression of several growth factors. Molecular docking revealed that H. scabra BMP2/4 binds specifically to mammal BMP2 type I receptor (BMPR-IA). After osteogenic induction, the viability of cells treated with IW extract was assessed and designated with treatment of 0.1, 0.5, 1, and 5 µg/ml of IW extract for 21 consecutive days. On days 14 and 21, treatments with IW extract at 1 and 5 µg/ml showed increased alkaline phosphatase (ALP) activity and calcium deposit levels in a dose-dependent manner compared to the control group. Moreover, the transcriptomic analysis of total RNA of cells treated with 5 µg/ml of IW extract exhibited upregulation of TGF-β, PI3K/Akt, MAPK, Wnt and PTH signaling pathways at days 14. This study suggests that IW extract from H. scabra exhibits the potential to enhance osteogenic differentiation and mineralization of MC3T3-E1 preosteoblasts through TGF-β, PI3K/Akt, MAPK, Wnt and PTH signaling pathways. Further investigation into the molecular mechanisms underlying the effect of IW extract on osteogenesis is crucial to support its application as a naturally derived supplement for prevention or treatment of osteoporosis.

Isolated Alkaline Phosphatase Elevation in Severe Osteoporosis Treatment: Implications of Teriparatide

Isolated Alkaline Phosphatase Elevation in Severe Osteoporosis Treatment: Implications of Teriparatide

The effect of resveratrol on the viability of rat bone marrow mesenchymal stem cells

Background and aimResveratrol is a plant polyphenol that has antioxidant properties. In this research, in order to better understand the role of resveratrol on bone, the effect of different doses of resveratrol on the viability, proliferation, differentiation and biochemical factors of rat bone marrow mesenchyme stem cells (MSCs) was investigated. MethodsTo evaluate the ability of proliferation and differentiation, the MSCs were cultured up to three passages and were placed in culture media without osteogenic stimulation. At first to investigation the proliferation ability, the viability was evaluated by MTT test and trypan blue staining with 7.5, 15 and 30 mg/L treatment doses after 12, 24 and 36 hours. Then, to investigation the differentiation ability, the effect of 7.5, 15, and 30 mg/L treatment doses was assessed on the viability, electrolyte levels, and the activity of LDH, AST, ALP and ALT enzymes in differentiated cells after 5, 10, 15, and 21 days. To investigation the differentiation ability, the effect of 7.5, 15, and 30 mg/L treatment doses was assessed on the viability, electrolyte levels, and the activity of Lactate dehydrogenase (LDH), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) enzymes in differentiated cells after 5, 10, 15, and 21 days. The data were analyzed by ANOVA and Tukey's test, and p<0.05 was considered as a significant level. ResultsThe obtained results showed that in mesenchyme cells, the level of viability does not change in low dose of resveratrol, however increase in the time followed by decrease in the activity of metabolic enzymes (ALP, ALT and AST P<0.5) and subsequently viability (p<0.05), and this trend was reversed with increasing resveratrol concentration (significant differences among 5 days and others). ConclusionThe effect of resveratrol depends on the type of cell and the treatment conditions, so it was shown in this study that the sensitivity of mesenchymal cells is higher than that of osteoblast cells. In addition, high doses of resveratrol had a positive effect on bone differentiation, so high doses of resveratrol can have a beneficial role on the health of mesenchymal cells and their differentiation into osteoblasts.

Multivariable models of outcomes with [177Lu]Lu-PSMA-617: analysis of the phase 3 VISION trial

[177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged life in patients with metastatic castration-resistant prostate cancer (mCRPC) in VISION (NCT03511664). However, distinguishing between patients likely and unlikely to respond remains a clinical challenge. We present the first multivariable models of outcomes with 177Lu-PSMA-617 built using data from VISION, a large prospective phase 3 clinical trial powered for overall survival. Adults with progressive post androgen receptor pathway inhibitor and taxane prostate-specific membrane antigen (PSMA)-positive mCRPC received 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC) or SoC alone. In this post hoc analysis, multivariable Cox proportional hazards models of overall survival (OS) and radiographic progression-free survival (rPFS), and a logistic regression model of prostate-specific antigen response (≥50% decline; PSA50) were constructed and evaluated using C-index or receiver operating characteristic (ROC) analyses with bootstrapping validation. Nomograms were constructed for visualisation. Patients were randomised between June 2018 and October 2019. Data from all 551 patients in the 177Lu-PSMA-617 arm were analysed in multivariable modelling. The OS nomogram (C-index, 0.73; 95% confidence interval [CI], 0.70-0.76) included whole-body maximum standardised uptake value (SUVmax), time since diagnosis, opioid analgesic use, aspartate aminotransferase, haemoglobin, lymphocyte count, presence of PSMA-positive lesions in lymph nodes, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and neutrophil count. The rPFS nomogram (C-index, 0.68; 0.65-0.72) included SUVmax, time since diagnosis, opioid analgesic use, lymphocyte count, presence of liver metastases by computed tomography, LDH, and ALP. The PSA50 nomogram (area under ROC curve, 0.72; 95% CI, 0.68-0.77) included SUVmax, lymphocyte count and ALP. Performances of the OS and rPFS models were maintained when they were reconstructed excluding SUVmax. These models of outcomes with 177Lu-PSMA-617 are the first built using prospective phase 3 data. They show that a combination of pretreatment laboratory, clinical, and imaging parameters, reflecting both patient and tumour status, influences outcomes. These models are important for aiding treatment selection, patient management, and clinical trial design. Novartis.

Catalpol Enhances Osteogenic Differentiation of Human Periodontal Stem Cells and Modulates Periodontal Tissue Remodeling in an Orthodontic Tooth Movement Rat Model.

This study examines the effects and mechanisms of catalpol (CAT) on the proliferation and osteogenic differentiation of cultured human periodontal ligament stem cells (hPDLSCs) in vitro and assesses the impact of CAT on periodontal remodeling in vivo using an orthodontic tooth movement (OTM) model in rats. hPDLSCs were cultured in a laboratory setting, and their proliferation and osteogenic differentiation were assessed using the Cell-counting Kit-8 (CCK-8), Alizarin Red Staining (ARS), quantitative calcium assay, alkaline phosphatase (ALP) staining and activity assay, and immunofluorescence assay. Additionally, the expression of collagen type 1 (COL-1), ALP, and runt-related transcription factor-2 (RUNX-2) was evaluated through qRT-PCR and Western blot analysis. To verify the function of the estrogen receptor-α (ER-α)-mediated phosphatidylinositol-3-kinase-protein kinase B (PI3K/AKT) pathway in this mechanism, LY294002 (a PI3K signaling pathway inhibitor) and the ER-α specific inhibitor methyl-piperidine-pyrazole (MPP) were used. The osteogenic markers ER-α, AKT, and p-AKT (phosphoprotein kinase B) were identified through Western blot analysis. Eighteen male Sprague-Dawley rats were assigned to two groups randomly: a CAT group receiving CAT and a control group receiving an equivalent volume of saline. Micro-computed tomography (micro-CT) analysis was employed to evaluate tooth movement and changes in alveolar bone structure. Morphological changes in the periodontal tissues between the roots were investigated using hematoxylin and eosin (HE) staining and tartaric-resistant acid phosphatase (TRAP) staining. The expression of COL-1, RUNX-2, and nuclear factor-κB (NF-κB) ligand (RANKL) was assessed through immunohistochemical staining (IHC) to evaluate periodontal tissue remodeling. Tests were analyzed using GraphPad Prism 8 software. Differences among more than two groups were analyzed by one-way or two-way analysis of variance (ANOVA) followed by the Tukey's test. Values of p < 0.05 were regarded as statistically significant. In vitro experiments demonstrated that 10μM CAT significantly promoted the proliferation, ALP activity, and calcium nodule formation of hPDLSCs, with a notable increase in the expression of COL-1, ALP, RUNX-2, ER-α, and p-AKT. The PI3K/AKT pathway was inhibited by LY294002, and further analysis using MPP suggested that ER-α mediated this effect. In vivo, experiments indicated that CAT enhanced the expression of COL-1 and RUNX-2 on the tension side of rat tooth roots, reduced the number of osteoclasts on the compression side, inhibited RANKL expression, and suppressed OTM. CAT can promote hPDLSCs proliferation and osteogenic differentiation in vitro through the ER-α/PI3K/AKT pathway and enhance periodontal tissue remodeling in vivo using OTM models. These findings suggest the potential for the clinical application of catalpol in preventing relapse following OTM.

Maternal and Cord Blood Levels of Metals and Fetal Liver Function

Exposure to metals during pregnancy has been associated with adverse birth outcomes, but its impact on fetal liver function remains poorly understood. This study for the first time aimed to investigate the association between maternal and umbilical cord blood Metals levels and umbilical liver enzymes. A comprehensive analysis was conducted on 450 mother-newborn pairs in 2022, measuring 13 Metals in serum samples from pregnant women during the third trimester and umbilical cord blood samples. Regression analyses were utilized to examine the relationship between levels of maternal and umbilical cord blood Metals and the levels of gamma-glutamyl transferase (GGT), umbilical alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). G-comp analyses evaluated the combined effect of metals exposure on umbilical liver enzymes. Elevated levels of certain Metals in cord blood and maternal samples were positively linked with increased umbilical GGT, ALP, ALT, and AST levels. Notably, zinc (Zn) levels in cord blood exhibited an inverse correlation with umbilical liver enzyme levels. Furthermore, g-comp analyses revealed significant positive associations between exposure to metals mixtures and umbilical liver enzyme levels. An increase of one quartile in the mixture of maternal and umbilical Metals was linked with 99.45 U/L (95% CI:37.72, 161.19, p < 0.01), 2.79 (95% CI: 0.92, 4.65, p < 0.01), and 87.17 (95% CI: 53.96, 120.38, p < 0.01) increase in ALP, ALT and GGT levels. Further examination of the weight of Metals revealed As, Cd, Ni, Pb, Hg and Cr with the highest positive effects and Zn with the highest negative effect in the mixture effect on the umbilical liver enzyme. In summary, our results underscore the potential influence of prenatal heavy metal exposure on fetal liver function.

Uniaxial static strain enhances osteogenic and angiogenic potential under hypoxic conditions in distraction osteogenesis

ObjectiveBone incision leads to interrupted and sluggish blood flow in the process of distraction osteogenesis (DO), creating a hypoxia (0–2% oxygen tension) at the center of the bone callus. This hypoxia is critical in the coupling of osteogenesis and angiogenesis during DO. This study aimed to investigate the effect of Uniaxial Static Strain (USS) on osteogenesis in osteoblasts under hypoxic conditions, with a focus on the expression of osteogenic markers and angiogenic factors.MethodsThe USS was made by a multi-unit tension compression device.Osteoblasts were subjected to 10% USS made under hypoxic conditions to mimic the process of DO in vitro. The cell proliferation, alkaline phosphatase (ALP) activity, mineralized nodule formation, and expression of osteogenic and angiogenic markers were evaluated by using a CCK-8 assay, alkaline phosphatase (ALP) staining, ALP activity assay, alizarin red S staining, qRT-PCR, Western blotting and ELISA.ResultsHypoxia inhibited osteoblast cell proliferation, ALP activity, mineralized nodule formation, and the expression of runt-related transcription factor 2 (Runx- 2), osteopontin(OPN), osteocalcin (OCN), collagen type I (Col1a1). Conversely, hypoxia upregulated the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF), which are associated with angiogenesis. However, the application of USS enhanced osteoblasts’ osteogenic capacity and upregulated angiogenic factors under hypoxic conditions.ConclusionUSS can enhance osteogenesis in osteoblasts under hypoxic conditions. Moreover, it may stimulate angiogenesis by promoting the expression of VEGF, which further contributes to bone formation. This finding provides important implications for understanding the mechanisms involved in bone regeneration and may have clinical applications in optimizing the effectiveness of DO techniques.

"The Association between Vitamin D Deficiency and Childhood Obesity and Its Impact on Children’s Serum Calcium, Alkaline Phosphatase, and Bone Age"

ObjectiveThe research aimed to investigate the Association between Vitamin D deficiency and childhood obesity and its Impact on children’s serum calcium, alkaline Phosphatase, and bone Age MethodsThe study analyzed clinical data from 159 school-aged children who underwent medical examinations. The children were divided into a 25-(OH)D3 deficiency group and a non-25-(OH)D3 deficiency group based on their serum 25-hydroxy Vitamin D3 levels. The two groups were compared regarding BMI, TC, TG, FBG, HbA1c, Ca, ALP, and bone age differences. ResultsIndividuals with a deficiency in 25-(OH)D3 exhibited higher levels of BMI, TC, TG, and ALP, and lower levels of Ca and bone age than those without the deficiency. These differences were statistically significant (P<0.05). Further analysis revealed a negative association between 25-(OH)D3 levelsa positive correlation between Ca and bone age, and a positive correlation with, BMI, TC, TG, and ALP. ConclusionThe deficiency of 25-(OH)D3 in school-aged children is linked to obesity and impacts bone growth. Monitoring vitamin D levels is crucial for clinical practitioners.

Structural and physicochemical properties of corn starch modified by phosphorylase b, hexokinase and alkaline phosphatase

To improve the functional properties of corn starch, phosphorylase b (PB), hexokinase (HK), and alkaline phosphatase (AP) were used to produce enzyme-modified starches (PBMS, HKMS, and APMS). The results showed that enzyme-modified starches had different phosphorus contents and degrees of substitution. The presence of PO bonds and P-O-C bonds further demonstrated that phosphate groups were grafted into starch. The proportions of monostarch phosphate in PBMS, HKMS, and APMS were 77.05 %, 79.33 % and 85.88 %, respectively. The introduction of phosphate groups affected the functional properties of starch. The swelling powers of PBMS, HKMS and APMS increased from 0.99 % to 12.86 %, 10.83 % and 5.95 %, respectively. Compared to native starch (1820 mPa·s), the peak viscosities of PBMS, HKMS and APMS increased to 2655, 2838, and 2021 mPa·s, respectively. Meanwhile, the introduction of phosphate groups endowed phosphorylated starch with better freeze-thaw stability, larger paste transparency, higher solubility, and slower retrogradation rate.