Alkaline Phosphatase Levels Research Articles

The Impact of Sea Buckthorn (Hippophae rhamnoides L.) and Cornelian Cherry (Cornus mas L.) Plant Extracts on the Physiology of Gastrointestinal Tract Cell In Vitro Model in the Context of Metabolic Diseases

The aim of this study was to evaluate the impact of ethanol extracts from sea buckthorn and Cornelian cherry fruits and leaves on physiology of gastrointestinal tract cells. We used three cell lines relevant to the types of cells, which are exposed to bioactive compounds after oral administration, namely intestinal absorptive cells (Caco-2/HT-29 MTX model), hepatocytes (HepG2 cells) and immunocompetent cells (RAW 264.7 and P388D1 monocytes). The contents of antioxidant and bioactive polyphenols, such as cinnamic, caffeic and p-coumaric acids, rutin, myricetin, resveratrol, quercetin, apigenin and kaempferol, were assessed in the extracts using HPLC chromatography. The application of the extracts to Caco-2/HT-29-MTX cultures increased enterocyte differentiation markers (alkaline phosphatase and villin1 level) and goblet cell markers (mucins) over a fortnight. The extracts reduced lipid droplet size in hepatocytes challenged with hyperglycaemic glucose concentration, insulin and palmitate. Sea buckthorn leaf, fruit and Cornelian cherry leaf extracts blocked oxidative burst in the PMA-stimulated monocytes, while the sea buckthorn leaf and Cornelian cherry fruit extracts downregulated lipopolysaccharide-induced NO and IL-1β, respectively. The results indicate that the tested extracts modulate the behaviour of cells in the gastrointestinal tract in a beneficial way, especially regarding lipid accumulation and innate immunity actions.

Clinical features, treatment, and outcome of nivolumab-induced cholangitis

Background Cholangitis is an uncommon and severe adverse reaction of nivolumab with unclear clinical features. The purpose of this study was to investigate the clinicopathological features, imaging, and treatment of nivolumab-induced cholangitis. Methods Case reports, case series, and clinical studies of nivolumab-induced cholangitis were retrospectively analyzed by searching Chinese and English databases from January 1, 2017 to December 31, 2023. Results Thirty-eight patients entered the study. The median number of cycles of cholangitis onset was seven cycles after administration (range 1, 28) and the median time was 11 days (range 78, 390). Abdominal pain (42.1%) and fever (18.4%) were the most important initial symptoms. Some patients (15.8%) showed elevated liver enzymes without any clinical symptoms. The median alkaline phosphatase level was 1721 IU/L (range 126, 9118), and the median γ-glutamyltranspeptidase level was 829 IU/L (range 104, 3442). Anti-nuclear antibodies, anti-mitochondrial antibodies, and IgG4 typically show negative results. Imaging shows extrahepatic bile duct and intrahepatic bile duct dilation, hypertrophy, and stenosis. Liver biopsy and biliary tract biopsy mainly found CD8 inflammatory cell infiltration. Systemic steroids (84.2%) and ursodeoxycholic acid (UDCA) (34.2%) were administered, and 24 patients (63.2%) had poor to moderate response to steroids. Thirty-one patients (81.6%) improved and seven patients (18.4%) did not improve. Conclusions Clinicians must remain vigilant for patients experiencing cholestasis while on nivolumab and should assess for cholangitis and carry out appropriate imaging tests. Considering the excellent efficacy of UCDA in cholangitis, steroids combined with UDCA may be a viable treatment option in cases where steroids are ineffective for cholangitis.

Effect of viscosity of gelatin methacryloyl-based bioinks on bone cells

The viscosity of gelatin methacryloyl (GelMA)-based bioinks generates shear stresses throughout the printing process that can affect cell integrity, reduce cell viability, cause morphological changes, and alter cell functionality. This study systematically investigated the impact of the viscosity of GelMA-gelatin bioinks on osteoblast-like cells in 2D and 3D culture conditions. Three bioinks with low, medium, and high viscosity prepared by supplementing a 5% GelMA solution with different concentrations of gelatin were evaluated. Cell responses were studied in a 2D environment after printing and incubation in non-cross-linked bioinks that caused the gelatin and GelMA to dissolve and release cells for attachment to tissue culture plates. The increased viscosity of the bioinks significantly affected cell area and aspect ratio. Cells printed using the bioink with medium viscosity exhibited greater metabolic activity and proliferation rate than those printed using the high viscosity bioink and even the unprinted control cells. Additionally, cells printed using the bioink with high viscosity demonstrated notably elevated expression levels of alkaline phosphatase and bone morphogenetic protein-2 genes. In the 3D condition, the printed cell-laden hydrogels were photo-cross-linked prior to incubation. The medium viscosity bioink supported greater cell proliferation compared to the high viscosity bioink. However, there were no significant differences in the expression of osteogenic markers between the medium and high viscosity bioinks. Therefore, the choice between medium and high viscosity bioinks should be based on the desired outcomes and objectives of the bone tissue engineering application. Furthermore, the bioprinting procedure with the medium viscosity bioink was used as an automated technique for efficiently seeding cells onto 3D printed porous titanium scaffolds for bone tissue engineering purposes.

Altered Liver Enzyme Markers in Patients with Asymptomatic, and Mild Omicron Infection: A Retrospective Study.

The emergence of the SARS-CoV-2 Omicron variant has posed a significant global public health challenge. Elucidating the laboratory profiles of individuals infected with this variant is crucial for assessing organ damage. This study aimed to investigate the variations in liver function tests and their correlation with demographic characteristics and inflammatory markers in patients with early Omicron variant infections. A retrospective cohort study was conducted on 1133 mild or asymptomatic COVID-19 cases at Tianjin First Central Hospital. Data on age, gender, body mass index (BMI), and serum markers were collected and analyzed. Statistical analyses were performed using SPSS software, version 24.0. Abnormal liver function parameters, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TBIL), were observed in 314 (27.71%) patients. "Hepatocellular type" was identified in 56 (4.94%) patients, "cholestatic type" in 185 (16.33%) patients, and "mixed type" in 73 (6.44%) patients. In the mixed group, we observed a pronounced elevation in the levels of ALT, AST, and GGT. Moreover, the hepatocellular group exhibited a statistically significant increase in AST and ALT concentrations relative to both the normal and cholestatic groups. Notably, the cholestatic group demonstrated a substantial increment in ALP levels. Males had a significantly higher prevalence of "abnormal liver enzyme markers" compared to females. Patients with "abnormal liver enzyme markers" exhibited significantly decreased immunoglobulin G (IgG) levels and elevated levels of inflammatory markers, including procalcitonin (PCT), interleukin-6 (IL6), as well as C-reactive protein (CRP) compared to normal group. Logistic regression analysis revealed that male gender and PCT levels were significantly associated with the risk of abnormal liver enzyme markers. Patients in hepatocellular group were likely accompanied with high CRP levels, whereas those in the cholestatic type were associated with high IL6 levels. Early Omicron infection might cause liver stress response. Elevated liver enzyme marker levels were correlated with age, gender, inflammatory factors, and IgG.

Dysregulation of lncRNA TFAP2A-AS1 is involved in the pathogenesis of pulpitis by the regulation of microRNA-32-5p.

This study was designed to evaluate TFAP2A-AS1 expression in the dental pulp of teeth with or without pulpitis and to determine the function of TFAP2A-AS1 in pulp cells. GSE92681 was analyzed to filter out differentially expressed lncRNAs. Pulp samples from teeth with pulpitis and healthy teeth (control) were examined using real-time (RT) quantitative polymerase chain reaction (qPCR). Human dental pulp stem cells (hDPSCs) were cultured in a specific medium for osteogenic induction, or treated with lipopolysaccharide (LPS) to simulate inflammation. The viability and apoptosis of human DPSCs (hDPSCs) were determined by XTT assay and apoptosis detection kit. Inflammation was induced by LPS and assessed by measuring the expression and release of inflammatory cytokines after TFAP2A-AS1 knockdown. Osteogenic differentiation of hDPSCs was investigated by determining expression levels of osteogenic markers and alkaline phosphatase (ALP) activity after TFAP2A-AS1 overexpression. The downstream microRNA (miRNA) was predicted. Dual-luciferase reporter was used to confirm the binding between miR-32-5p and TFAP2A-AS1. The expression of TFAP2A-AS1 was evaluated in inflamed pulp using RT-qPCR. TFAP2A-AS1 had a discriminatory ability for healthy individuals and patients with pulpitis. The expression of TFAP2A-AS1 decreased upon the osteogenic differentiation of hDPSCs, and increased upon the LPS induction. TFAP2A-AS1 can reverse the osteogenic differentiation of hDPSCs, as evidenced by decreased levels of dentine sialophosphoprotein, dentin matrix protein-1, and ALP activity. TFAP2A-AS1 knockdown can promote cell proliferation of hDPSCs and relieve LPS-induced inflammation, as evidenced by decreased levels of TNF-α, IL-1β, and IL-6. miR-32-5p was identified as a downstream miRNA of TFAP2A-AS1. This study demonstrated the expression and potential function of TFAP2A-AS1 in the human dental pulp. TFAP2A-AS1 can inhibit odontogenic differentiation but promote inflammation in pulp cells.

Biochemical indices of patients with enteric fever and pancreatitis: A comparative cross-sectional study

ObjectiveEnteric fever (EF), a potentially fatal febrile illness, is prevalent in developing countries. Elevated levels of lipase and amylase in serum, typically associated with acute pancreatitis (AP), have been observed in patients with EF. The elevated enzymes in both conditions may lead to diagnostic confusion and care delays. This study aimed to determine biochemical indices that are peculiar to EF and AP. MethodsA cross-sectional comparative study was conducted at the Korle-Bu Teaching Hospital, Ghana. Volunteers were categorized into three groups: EF (n = 32), AP (n = 30) and healthy controls (n = 31). A standard questionnaire was used to collect socio-demographic and clinical information from the participants. Blood and stool samples were obtained, followed by biochemical analysis: total amylase, lipase, pancreatic amylase, serum elastase 1, hepatic enzymes, calcium, magnesium, phosphate, stool colour, stool pH, and stool fat presence. ResultsThe AP group displayed higher total amylase, lipase, elastase-1, alkaline phosphatase, aspartate aminotransferase, and gamma-glutamyl transferase levels compared to the EF and control groups (p < 0.05 respectively). Elastase 1 levels were found to be high in all AP participants, whereas no elevations were observed in the EF group. Positive associations were observed in the AP and EF groups for lipase vs total amylase (ρ = .543, p = 0.001; ρ = .543, p = 0.001 for both). ConclusionsElevated levels of total/pancreatic amylase and lipase were found to be indicative of a patient with AP and EF. Further, elastase-1 was found to be a good biomarker to distinguish between AP and EF.

Antibiotic-Polyphosphate Nanocomplexes: A Promising System for Effective Biofilm Eradication.

The eradication of bacterial biofilms poses an enormous challenge owing to the inherently low antibiotic susceptibility of the resident microbiota. The complexation of antibiotics with polyphosphate can substantially improve antimicrobial performance. Nanoparticular complexes of the model drug colistin and polyphosphate (CP-NPs) were developed and characterized in terms of their particle size and morphology, polydispersity index (PDI), zeta potential, and cytotoxicity. Enzyme-triggered monophosphate and colistin release from the CP-NPs was evaluated in the presence of alkaline phosphatase (AP). Subsequently, antimicrobial efficacy was assessed by inhibition experiments on planktonic cultures, as well as time-kill assays on biofilms formed by the model organism Micrococcus luteus. The CP-NPs exhibited a spherical morphology with particle sizes <200 nm, PDI <0.25, and negative zeta potential. They showed reduced cytotoxicity toward two human cell lines and significantly decreased hemotoxicity compared with native colistin. Release experiments with AP verified the enzymatic cleavage of polyphosphate and subsequent release of monophosphate and colistin from CP-NPs. Although CP-NPs were ineffective against planktonic M. luteus cultures, they showed major activity against bacterial biofilms, outperforming native colistin treatment. Strongly elevated AP levels in the biofilm state were identified as a potential key factor for the observed findings. Accordingly, polyphosphate-based nanocomplexes represent a promising tool to tackle bacterial biofilm.

Surgical decision-making: key factors influencing the shift from laparoscopic to open cholecystectomy

Background: Recognizing the preoperatively and intraoperatively factors can aid surgeons in making timely decisions to shift from laparoscopic cholecystectomy (LC) to open cholecystectomy (OC). This study aims to identify the main factors leading to LC conversion to OC among Iraqi patients. Methods: One-year prospective research was performed using cross-sectional design between 1st April, 2023, and 3oth March, 2024, at Alkalis General Public Hospital and Al Hayat Private Hospital, Diyala, Iraq. Pre and intraoperative data were collected from the planned LC surgeries including demographics, medical history, laboratory and Ultrasound findings. Descriptive and bivariate analysis was carried out to compare variables between patients undergoing LC and those requiring conversion to OC. Results: Out of 172 LC patients (mean age 48.28±12.62), 52.9% were female, 55.8% obese, 50.6% aged 49+, 23.3% diabetic, and 19.8% had emergency cholecystectomy; 15 (8.7%) required conversion to open surgery. The conversion group was mainly men (66.7% vs. 46.5%, P = 0.001) and older (73.3% vs. 48.4% aged 49+, P = 0.003). Obesity (60.0% vs. 55.4%, P = 0.005) and diabetes (53.3% vs. 20.4%, P &lt; 0.001) were more common. Public hospital referrals were higher (86.7% vs. 52.2%, P &lt; 0.001). Elevated total bilirubin, direct bilirubin, and alkaline phosphatase levels were significant predictors of conversion to OC. Adhesions in Calot's triangle (20.0% vs. 13.4%, P = 0.021) were more common in the conversion group, along with unclear anatomy, thick gallbladder wall, bleeding, stone and bile spillage, and cystic duct injury. Conclusion: In conclusion, out of 172 LC patients, 15 (8.7%) required conversion to open surgery, predominantly older men with higher obesity, diabetes, and elevated bilirubin and alkaline phosphatase levels, and more adhesions in Calot's triangle.

Impact of Hydroxyapatite Nanoparticles, Demineralized and Decellularized Bone Matrix on Tibia Fracture Healing: A Biochemical and Histological Study in Goats

At present, using bone grafts is the most successful surgical approach for repairing deficits in the bone structure. This study investigated into how goat tibial defect fracture healing was impacted by using hydroxyapatite (HA) or demineralized and decellularized bone matrix (dDBM) xenograft. Methodology: In this study, fifteen young goats were employed. Three groups (n=5) consisting of the control group, nano-group, and xeno-group were created from the animals. Bone drill was used to remove 2 mm from the tibia of the right hind limp in all animals. The hydroxyapatite nanoparticles (HA) in the Nano-group and the xenograft demineralized and decellularized bone matrix (dDBM) (obtained from sheep tibia) in the Xeno-group were used to fill the bone defect respectively, while the bone defect in the control group remained without treatment, and the surgical site was regularly closed. Blood serum was collected at the following intervals: postoperative, 14, 42, and 64 days for detection of alkaline phosphatase (ALP) and osteocalcin (OC) levels. At 64 days after surgery, all goats were euthanized and the healing was evaluated by specimen histological observation. Results: Biochemical examination in treated groups (Nano and Xeno groups) showed a statistically significant (P &lt; 0.05) increase in the level of ALP and OC. histopathological examination at 64 day post-operation, treated groups shows Completely grown woven bone and the fracture callus composed of mature fibro-osteoid mixture. In conclusion, We demonstrate that the healing process accelerated and the bone defect can be filled by using hydroxyapatite (HA), or dDBM, as a scaffold for the damaged tibia bone.

The Effect of Salmon Calcitonin Adjuvant Treatment for Lumbar Spine Fracture: A Prospective, Randomized, Controlled Trial.

The study aimed at analyzing the therapeutic effect of salmon calcitonin on patients with lumbar spine fracture after operation. Eighty-eight cases with lumbar spine fracture who underwent percutaneous vertebroplasty (PVP) in The Huichang People's Hospital from February 2020 to February 2023 were separated into two groups. The 44 cases in the control group were treated with calcium carbonate and Vitamin D3 tablets, on the basis, the salmon calcitonin was applied to treat the 44 cases in study group. The pain degree, bone metabolism index and matrix metalloproteinase levels were determined and compared between two groups. Lumbar function and daily living activity ability in two groups were evaluated, and adverse reactions during treatment were observed. The pain degree in study group was alleviated after treatment for 3 mo compared with the control group (p<0.05). The bone specific alkaline phosphatase (BALP) and osteocalcin (OC) levels were increased, while beta C-terminal cross-linked telopeptides of type I collagen (β-CTX) levels were decreased in study group after treatment for 3 mo compared with control group (p<0.05). After treatment for 3 mo, the serum matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) levels in study group were lower than those in control group (p<0.05). Three months after treatment, the Oswestry Disability Index (ODI) score was lower and Barthel Index (BI) score was higher in study group than those of control group (p<0.05). No severe adverse reactions were observed in both groups during treatment (p>0.05). Salmon calcitonin can relieve the pain degree, improve the levels of bone metabolism and matrix metalloproteinase, and improve the lumbar spine function and ability of daily living activity in patients with lumbar spine fracture.

Antibacterial Activity of Novel Agent N-2-Hydroxypropyl Trimethyl Ammonium Chloride Chitosan against Streptococcus mutans.

Dental caries (DC) is one of the most common oral diseases and is mainly caused by Streptococcus mutans (S. mutans). The use of antibiotics against S. mutans usually has side effects, including developing resistance. N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC), a natural product, has great potential utility in antibacterial agents owing to its low toxicity and good biocompatibility. Thus, the purpose of the present study was to explore the antimicrobial activity of N-2-HACC against S. mutans through the permeability of the cell wall, integrity of cell membrane, protein and nucleic acid synthesis, respiratory metabolism, and biofilm formation. Our results confirmed that the MIC of N-2-HACC against S. mutans was 0.625 mg/mL with a 90.01 ± 1.54% inhibition rate. SEM observed the formation of cavities on the surface of S. mutans after 12 h N-2-HACC treatment. The level of alkaline phosphatase (AKP) activity was higher in the N-2-HACC treatment group than in the control group, indicating that N-2-HACC can improve the permeability of the cell wall. Also, N-2-HACC treatment can destroy the cell membrane of S. mutans by increasing conductivity and absorbance at 260 nm, decreasing cell metabolic activity, and enhancing the fluorescence at 488 nm. Respiratory metabolism revealed that the activities of the Na+-K+-ATP enzyme, pyruvate kinase (PK), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were decreased after N-2-HACC treatment, revealing that N-2-HACC can inhibit glycolysis and the tricarboxylic acid cycle (TCA cycle) of S. mutans. Moreover, N-2-HACC can also decrease the contents of the nucleic acid and solution protein of S. mutans, interfere with biofilm formation, and decrease the mRNA expression level of biofilm formation-related genes. Therefore, these results verify that N-2-HACC has strong antibacterial activity against S. mutans, acting via cell membrane integrity damage, increasing the permeability of cell walls, interfering with bacterial protein and nucleic acid synthesis, perturbing glycolysis and the TCA cycle, and inhibiting biofilm formation. It is suggested that N-2-HACC may represent a new potential synthetically modified antibacterial material against S. mutans.

Peptidergic and adenosinergic drugs administration to comatose patients caused by alcohol consumption on early hospital period

Introduction. Medical care for patients diagnosed with the toxic effect of ethanol (according to ICD-10 code T51.0) it turns out to be in specialized toxicological centers or in emergency departments of multidisciplinary hospitals. The purpose of this study was to study the effectiveness of the drug моликсан® (molixаn) at different levels of medical care for patients diagnosed with the toxic effect of ethanol. Material and method. 128 patients were included in the study, of which 76 patients were taken to the emergency department of St. Petersburg State Medical Institution "Alexandrovskaya Hospital" and 52 patients were taken to the intensive care unit No. 11 of the St. Petersburg Scientific Research Institute of Emergency Medicine named after I.I. Dzhanelidze. All patients met the inclusion criteria: age 18–60 years; impaired consciousness of alcoholic genesis 21–30 points on the Glasgow–Pittsburgh coma scale (PBSS: Pittsburg Brain Stem Score, Kelsey S.F., et al. 1991); ethanol concentration in the blood is more than 2.5%. 72 patients were included in the моликсан® group, 56 patients in the Placebo group. Results. The use of the drug моликсан® has a positive effect on the dynamics of restoring the level of consciousness, which is reflected in higher values of the Glasgow–Pittsburgh scale after 1, 3 and 6 hours from the start of therapy (p&lt;0.01), reducing the period of stay of the patient in a coma from 150 [75; 178] minutes to 60 [50; 161.5] minutes (p&lt;0.05) and restoration of consciousness to a clear level after 3.5± 0.3 hours (p&lt;0.05).It was also revealed, that in the group of patients using моликсан®, normalization of heart rate (p&lt;0.05) and a decrease in the frequency and severity of tremor (p&lt;0.05) were noted. The hepatoprotective efficacy of моликсан® was shown, which manifested itself in a decrease in ALT, AST, GGTP, alkaline phosphatase, total and direct bilirubin (p&lt;0.001). Limitations. The clinical efficacy of моликсан® in the toxic effects of severe ethanol was carried out in patients with depression of consciousness and elevated levels of ALT, AST, GGTP, alkaline phosphatase, total and direct bilirubin, which indicated the presence of alcoholic hepatopathy. Conclusion. The conducted study showed the expediency of using моликсан® at a dosage of 3.0 mg/kg intravenously with the toxic effect of ethanol of moderate and severe severity of the disease.

Osteo-modulatory potential of biologically synthesized cis-resveratrol passivated gold nanoparticles

Resveratrol, a stilbene, particularly trans-isomer, shows significant osteogenic potential but experiences high instability and poor bioavailability. However, cis-isomer (cRes) is not explored yet due to its instability. Our study investigates the osteoinductive potential of cRes for the first time by stabilizing it onto the surface of gold nanoparticles. cRes capped GNPs (cRGNPs) presented no toxic effects on the MC3T3-E1 cells with increased levels of alkaline phosphatase and calcium deposition. The nanoparticles presented a 2.6-fold increase in cell number compared to the control. The pro-migratory effect of the cRGNPs was also significantly higher (97.21 ± 0.99 % migration) in 4 days. The osteoinductivity was further confirmed by enhanced expression of osteoblastic genes like RUNX2, OPN, OCN, BMP, OPG, and Col1A. The stability provided to cRes upon conjugating to GNPs allowed exploration of its potential in aiding proliferation, migration, and differentiation of the pre-osteoblasts, which will be beneficial in repairing bone defects.

Effect of Ginger Supplementation on Liver Enzymes: A Systematic Review and Meta-Analysis

Background: Ginger (Zingiber officinale), as one of the herbal medicines, has high antioxidant activity. It may have protective effects against hepatotoxicity. This study seeks to perform a systematic review and meta-analysis on the impact of ginger on liver enzymes. Methods: The present systematic review and meta-analysis study adhered to the guidelines outlined in the PRISMA 2020 statement. A comprehensive literature search was carried out in the Medline database (PubMed), Google Scholar, Embase, Scopus, Web of Science, and Cochrane Library until the conclusion of February 2021. All interventional animal studies were included. The selected studies were the ones that examined the impact of ginger on serum liver enzymes. Results: Out of 741 articles, 39 studies were incorporated into the systematic review and meta-analysis. The pooled results suggested that ginger significantly reduced alanine aminotransferase (ALT) (standardized mean difference (SMD): 2.52, 95% confidence interval (CI): 2.12 to 2.93), aspartate aminotransferase (AST) (SMD: 3.03, 95% CI: 2.48 to 3.58), and alkaline phosphatase (ALP) (SMD: 2.10, 95% CI: 1.60 to 2.60). Conclusion: Ginger has favorable effects on liver enzymes. It shows potential as a beneficial complementary therapy for higher levels of ALT, AST, and ALP because of its useful effects and negligible side effects.

Development of injectable microgel-based scaffolds via enzymatic cross-linking of hyaluronic acid-tyramine/gelatin-tyramine for potential bone tissue engineering

Currently, the healing of large bone defects relies on invasive surgeries and the transplantation of autologous bone. As a less invasive treatment option, the provision of microenvironments that promote the regeneration of defective bones holds great promise. Here, we developed hyaluronic acid (HA)/gelatin (Ge) microgel-based scaffolds to guide bone regeneration. To enable the formation of microgels by enzymatic cross-linking in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2), we modified the polymers with tyramine (TA). Spectrophotometry and proton nuclear magnetic resonance (1H NMR) spectroscopy analysis confirmed successful tyramine substitution on polymer backbones. To enable the formation of microgels by a water-in-oil emulsion approach, the HRP and H2O2 concentrations were tuned to achieve the gelation in a few seconds. By varying the stirring speed from 600 to 1000 rpm, spherical microgels were produced with an average size of 116 ± 8.7 and 68 ± 4.7 μm, respectively. The results showed that microgels were injectable through needles and showed good biocompatibility with the cultured human osteosarcoma cell line (MG-63). HA/Ge-TA microgels served as a promising substrate for MG-63 cells since they improved the alkaline phosphatase activity and level of calcium deposition. In summary, the developed HA/Ge-TA microgels are promising injectable microgel-based scaffolds in bone tissue engineering.

EFFECTS OF MANNAN-OLIGOSACCHARIDES ON GROWTH PERFORMANCE, SERUM BIOCHEMICAL INDICES, IMMUNE FUNCTION, AND INTESTINAL MORPHOLOGY IN FATTENING TAN SHEEP

This study examined the effects of dietary Mannan-Oligosaccharides (MOS) on growth performance, serum biochemical indices, immune function, and intestinal morphology in fattening Tan sheep. Twenty-eight four-month-old male Tan sheep were assigned to four groups and received a basal diet supplemented with 0%, 1%, 2%, or 3% MOS for 56 days following a 14-day adaptation period.Results indicated that MOS supplementation significantly increased average daily gain (ADG) in a dose-dependent manner (P ≤ 0.05). Serum biochemical analyses showed a linear and quadratic reduction in triglyceride (TG) levels, and a linear and quadratic increase in alkaline phosphatase (ALP) levels (P ≤ 0.05). Total cholesterol (TC) levels decreased linearly, whereas urea nitrogen (UN) levels increased linearly with higher MOS levels (P ≤ 0.05). Mannan-Oligosaccharides also enhanced total antioxidant capacity (T-AOC) and catalase (CAT) activity, with both parameters increasing linearly (P ≤ 0.05). Immune function was significantly improved, demonstrated by elevated levels of immunoglobulin A (IgA), interleukin-6 (IL-6), IL-10, and interferon-gamma (IFN-γ) (P ≤ 0.05). Additionally, 2% and 3% MOS groups showed increased immunoglobulin G (IgG) and tumor necrosis factor-alpha (TNF-α) levels (P ≤ 0.05). Linear increases were noted in serum IgG, IgA, IgM, IL-6, and TNF-α levels, while IL-10 and IFN-γ levels exhibited both linear and quadratic increases (P ≤ 0.05).Intestinal morphology analysis revealed significant improvements in jejunal villus height, crypt depth reduction, and the villus-to-crypt ratio, with these parameters showing both linear and quadratic changes in response to increasing MOS levels (P ≤ 0.05). In conclusion, 2% MOS supplementation is recommended for enhanced growth performance, metabolic health, immune function, and intestinal integrity in fattening Tan sheep. Keywords: Tan sheep; growth performance; antioxidant; immune function; intestinal morphology

The Potential of Enamel Matrix Derivative in Countering Bisphosphonate-Induced Effects in Osteoblasts.

The suppressive effect of bisphosphonates (BPs) on bone metabolism is considered to be a major cause of medication-related osteonecrosis of the jaw (MRONJ). Enamel matrix derivative (EMD) stimulates and activates growth factors, leading to the regeneration of periodontal tissues. In this study, we aimed to explore the potential of EMD in reversing the detrimental effects of BPs on human fetal osteoblasts (hFOBs) and osteosarcoma-derived immature osteoblasts (MG63s) by assessing cell viability, apoptosis, migration, gene expression, and protein synthesis. While the suppressive effect of zoledronate (Zol) on cell viability and migration was observed, the addition of EMD significantly mitigated this effect and enhanced cell viability and migration. Furthermore, an increased apoptosis rate induced by Zol was decreased with the addition of EMD. The decreased gene expression of alkaline phosphatase (ALP), osteocalcin (OC), and the receptor activator of nuclear factors kappa-B ligand (RANKL) caused by BP treatment was reversed by the co-addition of EMD to hFOB cells. This trend was also observed for ALP and bone sialoprotein (BSP) levels in MG63 cells. Furthermore, suppressed protein levels of OC, macrophage colony-stimulating factor (M-CSF), BSP, and type 1 collagen (COL1) were recovered following the addition of EMD. This finding suggests that EMD could mitigate the effects of BPs, resulting in the recovery of cell survival, migration, and gene and protein expression. However, the behavior of the osteoblasts was not fully restored, and further studies are necessary to confirm their effects at the cellular level and to assess their clinical usefulness in vivo for the prevention and treatment of MRONJ.

Resveratrol alleviates thiram-induced tibial dyschondroplasia by regulating BMP-2, RUNX-2 and HIF-1α expressions in broiler chickens

Tetramethylthiuram disulfide (thiram) is a pesticide and fungicide, widely used in agriculture, and is a recognized cause of tibial dyschondroplasia (TD), a skeletal abnormality in fast-growing broiler chickens. This study aimed to investigate the effect of resveratrol (RSV) against TD induced by thiram in broilers. A total of 240 broilers were evenly divided into three groups (n = 80) i.e., Control, TD and RSV. All groups received feed and water ad libitum, whereas the TD and RSV groups received standard diet with an addition of thiram (50 mg/kg of feed) from 4–7 days to induce TD. After the cessation of thiram on day 8, the RSV group was administered RSV at 400 mg/kg body weight orally from 8–18 days. Histopathological changes in tibia were assessed using hematoxylin and eosin (H&E) staining. In addition, the mRNA and protein expressions of targeted genes were analyzed using RT-qPCR, immunohistochemistry, and western blotting. Thiram feeding resulted in an increased growth plate (GP) width, decreased vascularization, irregular shaped chondrocytes with pyknotic nuclei, lameness, poor production performance, reduced levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), alkaline phosphatase (ALP) and elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA). The mRNA and protein expressions of BMP-2 and RUNX-2 were downregulated, whereas HIF-1α was upregulated in TD affected broilers (p < 0.05). RSV administration resulted in a significant increase in mRNA and protein levels of BMP-2 and RUNX-2 (p < 0.05) and a decrease in the levels of HIF-1α. In addition, RSV improved vascularization, angiogenesis, alleviated lameness, and enhanced production efficiency. Furthermore, it restored the GP width, serum biochemical levels and liver antioxidant enzymes. In conclusion, this study indicated that resveratrol mitigated the adverse effects of thiram toxicity in broiler chickens.

Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis

As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs) are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery of BPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolving and hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawley rats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkaline phosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls. Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVX controls and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. In the distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21 % in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. This proof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternative for weekly osteoporosis management.

A Comparative Study of Coagulation Profiles in Preeclamptic and Normotensive Patients in Relation to Maternal and Fetal Outcomes.

Background Hypertensive complications during pregnancy play a significant role in the increased rates of maternal and perinatal morbidity and mortality on a global scale. Preeclampsia is characterized by elevated blood pressure levels and the presence of protein in the urine and is associated with diverse hematological alterations, particularly impacting the coagulation cascade. The primary objective of this research was to conduct a comparative analysis of the coagulation profiles and pregnancy outcomes in women with preeclampsia versus those with normal blood pressure during pregnancy. Methods This was a prospective case-control study with 74 participants across two groups, conducted from September 2022 to May 2024. The participants were enrolled and divided into two groups, with 37 in the clinically diagnosed preeclampsia group and 37 in the normotensive group. Coagulation parameters including platelet count, bleeding time, clotting time, international normalized ratio (INR), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen levels, alkaline phosphatase (ALP) levels, D-dimer levels, and fibrin degradation products (FDP) levels were assessed. Maternal and neonatal outcomes were also compared. In our study, we comprehensively examined both maternal and neonatal outcomes in preeclampsia and normotensive groups. Maternal complications analyzed included mode of delivery, incidence of eclampsia, placental abruption, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, postpartum hemorrhage (PPH), and peripartum cardiomyopathy (PPCM). For neonatal outcomes, we assessed birth weight, appearance, pulse, grimace, activity, and respiration (APGAR) scores, and the duration of neonatal intensive care unit (NICU) stays. Results The results showed that mean platelet count was significantly lower in the preeclampsia group (151,503 ± 59,875/µL) compared to the normotensive group (245,405 ± 69,021/µL) (p < 0.0001). Bleeding time, INR, APTT, and PT showed significant elevation in the preeclampsia group, indicating a slower coagulation process. Fibrinogen levels, ALP levels, and D-dimer levels were significantly higher in the preeclampsia group (p < 0.0001). The preeclampsia group had a higher rate of cesarean sections (65% vs. 24%) and lower neonatal birth weights (mean 2.3 kg vs. 2.5 kg). APGAR scores were comparable between groups, but a higher number of neonates went to the NICU in the preeclampsia group (64.9% vs. 10.8%). The preeclampsia group also showed higher rates of low birth weight (27%), intrauterine growth restriction (27%), respiratory distress syndrome (10.8%), and asphyxia (5.4%). Conclusion Preeclampsia is associated with significant hematological changes, particularly in coagulation parameters, and adverse fetomaternal outcomes. Early identification and monitoring of these changes are crucial for timely intervention and improving maternal and neonatal health outcomes.