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Osteoporosis is an increasingly prevalent disease. The development of an osteoporosis-like experimental animal model is of great importance for the study of peri-implant osteogenesis in osteoporosis. The present authors aimed to establish a rapid modeling method of osteoporotic rabbits for implant-bone analysis and validate whether the models can affect the implant osseointegration. The present study included 29 female New Zealand rabbits (age: 5 to 6 months). Two rabbits were lost during anesthetization. Of the remaining 27 rabbits, 18 received an ovariectomy, with 9 receiving dexamethasone injections for 8 weeks (OVX+D group) and 9 receiving equivalent-volume saline injections (OVX group). As a control group, the remaining 9 rabbits were sham-operated and received an equivalent volume of normal saline (SHAM group). Then, serum biochemical markers of bone metabolism were detected and densitometric measurements were performed. Implants were then placed in the tibias of each rabbit. Bone samples (including implants) were obtained after 4, 8, and 12 weeks of healing and were subjected to histologic and histomorphometric analyses. The results showed that the OVX+D group experienced a 32% reduction in bone mineral density (BMD) from baseline. The BMD of the OVX+D group was significantly lower than that of the SHAM and OVX groups. Moreover, alkaline phosphatase (ALP) blood concentrations of in the OVX+D group were increased significantly. The osteoporotic rabbits exhibited marked decreases in osseointegration, characterized by slowed bone formation and decreased bone-to-implant contact (BIC). The combination of an ovariectomy and dexamethasone injections could experimentally induce osteoporosis in rabbits in the short term, which can be used as an appropriate animal model to study the osseointegration of implants under osteoporosis. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effects of a gluten-free diet on bone structure in children with celiac disease using fractal analysis on panoramic radiographs. Method and materials: A total of 49 patients with celiac disease aged 6 to 13 years, separated into two groups as previously and newly diagnosed, and a control group of 32 healthy individuals were evaluated. In previously and newly diagnosed patients with celiac disease, body mass index Z-scores were calculated, calcium, alkaline phosphatase, vitamin D3, and parathormone levels were measured, and bone mineral density Z-scores were obtained from dual energy x-ray absorptiometry. In all patients, the fractal dimensions of the right and left temporomandibular condyles were evaluated with the fractal analysis method on panoramic radiographs. Results: The mean values of serum biomarker levels and the body mass index and bone mineral density Z-scores for both celiac groups were within the normal reference range. No statistically significant difference was determined between right and left condyle fractal dimensions values in the three groups examined. In terms of both right and left condyle fractal dimensions values, there was a statistically significant difference between groups. The highest fractal dimensions values were determined in the previously diagnosed group. Conclusions: Differences in fractal dimensions values were observed among patients with celiac disease following the gluten-free diet. Utilizing fractal analysis on panoramic radiographs can prove valuable for dental practitioners in evaluating bone mineral density due to its cost-effect iveness, easy accessibility, and reduced radiation exposure for patients, enabling them to provide comprehensive oral health care and potential early interventions for patients with celiac disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of ultraviolet-C light (UVC) photofunctionalization treatment time on the biologic activity of airborne particle-abraded and acid-etched (SLA) titanium surfaces and to analyze its physical and chemical mechanisms. Materials and Methods: SLA titanium was treated with UVC light for different lengths of time (10 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 24 hours), and then changes to its surface characteristics were evaluated via electron microscope scanning, X-ray photoelectron spectroscopy (XPS), water contact angle measurement, and zeta potential measurement. The effect of UVC photofunctionalization on the biologic processes of SLA titanium surfaces was assessed by analyzing the bovine serum albumin adsorption, adhesion, proliferation, morphology, and alkaline phosphatase activity of MG-63 cells. Results: UVC irradiation did not change the topography of SLA titanium surfaces. As treatment times increased, the water contact angle decreased from 120 degrees to 0 degrees, and the hydrocarbon content decreased. Zeta potential testing showed increased surface potential of photofunctionalized titanium. In vitro testing showed that cell adhesion, proliferation, morphology, and alkaline phosphate (ALP) activity on titanium surfaces were significantly improved by UVC photofunctionalization. Conclusions: UVC photofunctionalization can improve the biologic activity of SLA titanium surfaces by removing hydrocarbons and increasing the surface potential of titanium. [ABSTRACT FROM AUTHOR]

BACKGROUND: Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD). METHODS: MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model. RESULTS: Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p

Creating interconnected macropores in calcium phosphate cement (CPC) is an effective strategy to promote its degradation and osteogenesis. However, little attention has been given to the osteogenic effect of the CPC scaffolds with pre-forming and in-situ forming interconnected macropores. Herein, two types of CPC scaffolds were prepared by infiltrating CPC pastes into 3D-printed polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) networks. Meanwhile, the sacrificial PCL network within CPC was dissolved to obtain the CPC scaffold with approximately 300 μm macropores, whereas the PLGA network was retained within the CPC to obtain the PLGA/CPC scaffold. The results indicated that the PLGA/CPC scaffold showed higher degradation rate and compressive strength compared to the CPC scaffold with pre-forming interconnected macropores. However, the proliferation rate and alkaline phosphatase activity of mouse bone mesenchymal stem cells cultured with the CPC scaffold were superior to those cultured with the PLGA/CPC scaffold. In addition, greater formation of new bone and material degradation in the CPC scaffold compared to the PLGA/CPC scaffold after implanted in the rabbit femoral defects. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. Three new drugs for AD based on monoclonal antibodies against the amyloid-β peptide (Aβ) have recently been approved because they favor the reduction of the burden of senile plaque in the AD patient's brain. Nonetheless, both drugs have very limited applicability and benefits and show several side effects. These limitations invite us to find alternative strategies for treating patients with AD. Here, we explored whether tissue-nonspecific alkaline phosphatase (TNAP), an ectoenzyme upregulated in the brain of AD patients and whose inhibition has beneficial effects on tau-induced pathology, is also efficient in reducing senile plaque burden. Methods: To evaluate whether TNAP may reduce cerebral senile plaque loading and Aβ-related toxicity, we use both pharmacological and genetic approaches. We analyze postmortem samples from human AD patients, APP/PS1 mice (a mouse model that mimics amyloid pathology observed in AD patients) treated or not with TNAP inhibitors, and the newly generated transgenic mouse line, TNAP-deficient APP/PS1 mice. Results: For the first time, we describe that genetic or pharmacological blockade of TNAP effectively reduces senile plaque burden by promoting its clearance, which leads to amelioration of cognitive impairment caused by Aβ-induced toxicity. These beneficial effects of TNAP inhibition occur concomitantly with higher microglial recruitment toward the senile plaque and increased microglial phagocytic capacity of Aβ by a mechanism involving metalloprotease-depending osteopontin processing. In addition, we also found that TNAP blockade favors LRP1-mediated transport of Aβ through the BBB. Conclusions: Here, we have shown that TNAP inhibition effectively reduces brain senile plaque burden and associated behavioral defects. Furthermore, given that we had previously reported that TNAP blockade also ameliorates Tau-induced neurotoxicity and increases lifespan of P301S tauopathy mouse model, we can state that TNAP blockade may be a novel and efficient therapy for treating patients with AD. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Material and Methods Results Conclusions 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. [ABSTRACT FROM AUTHOR]

The 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. [ABSTRACT FROM AUTHOR]

This study introduces an innovative approach for the real-time and efficient detection of alkaline phosphatase (ALP) activity, using a calcein fluorescence probe and leveraging the static quenching properties of calcein fluorescence by Ce3+ metal ions. In this method, calcein serves as the signal element, with its fluorescence effectively preserved through energy transfer or charge transfer when coordinated with Ce3+. Conversely, ALP catalyzes the phosphopeptide substrate to generate a substantial amount of Pi, preventing calcein fluorescence quenching due to the higher affinity between Pi and Ce3+ compared with that between calcein and Ce3+. The fluorescence intensity ratio (F-F0/F0) exhibited excellent linearity, facilitating sensitive ALP detection. The proposed ALP detection method covers a range from 0 to 1.4 mU/mL (R2 = 0.9942), with the limit of detection at 0.069 mU/mL (S/N = 3). Additionally, this method was successfully applied for detecting ALP in serum samples and studying its inhibitors. This research introduces a novel clinical diagnosis approach for ALP sensing while broadening the potential applications of calcein. [ABSTRACT FROM AUTHOR]

Abnormal liver blood tests and liver tumor burden are known prognostic factors in neuroendocrine neoplasms (NEN). However, the relationship between biochemical liver parameters and hepatic tumor load is largely unknown in NEN and in high‐grade NEN (G3) specifically. The primary objective of this study was to correlate the biochemical parameters and liver tumor volume of patients with neuroendocrine tumors grade 3 (NET G3) or neuroendocrine carcinomas (NEC). We wanted to investigate whether patients with NET G3 with extensive liver involvement had less severely elevated laboratory liver parameters than NEC patients. In total, 46 patients with NEN were included, 31 had NEC and 15 NET G3. All patients had distant metastatic disease, with liver metastases being the most common (n = 39). Both laboratory results and semiautomatic volumetric measurements of liver tumor burden were obtainable for 34 patients at baseline and 26 patients at follow‐up. Alkaline phosphatase (AP), gamma‐GT (gGT), and lactate dehydrogenase (LDH) increased significantly between the two time periods (p < .01). In a regression model, liver tumor burden significantly affected several blood parameters, for example, increasing AP, gGT, LDH, and aspartate aminotransferase (ASAT) by a factor of 1.02–1.04 per unit increase (1% tumor burden; all p < .001). AP, gGT, and LDH were significantly lower in NET G3 (factor of 0.43–0.68) than in NEC. Here, we found that liver chemistries changed over the NEN disease course, correlated with hepatic tumor burden, and differed by histologic subtype. The current data can potentially guide treatment decisions, for example, with regard to integration of liver‐directed therapies. [ABSTRACT FROM AUTHOR]

This study aimed to design sustained released biodegradable calcium carbonate nanoparticles loaded with chlorhexidine (CHX-loaded NPs) and to investigate the early osteogenic differentiation and antimicrobial effects on the important bacteria involved in infections of dental implants. The microemulsion method was used to prepare the calcium carbonate nanoparticles loaded with chlorhexidine. The prepared nanoparticles were characterized using conventional methods. The release pattern determination and the biodegradation test were performed for the prepared nanoparticles. For the early osteogenic differentiation test of the prepared nanoparticles, alkaline phosphatase (ALP) activity was detected in human dental pulp stem cells (HDPSCs). The antimicrobial effects of the nanoparticles were evaluated against Escherichia coli, Streptococcus mutans, Enterococcus faecalis, Staphylococcus aureus, and Pseudomonas aeruginosa. The sizes of free calcium carbonate nanoparticles and CHX-loaded NPs were 105 ± 1.63 and 118 ± 1.47 nm and their zeta potentials were − 27 and − 36, respectively. A 50% degradation of nanoparticles was achieved after 100 days. These nanoparticles showed a two-stage sustained release pattern in vitro. Microscopic images revealed that the morphology of free calcium carbonate nanoparticles primarily took on a spherical calcite form, while CHX-loaded NPs predominantly exhibited a cauliflower-like vaterite polymorph. The nanoparticles increased the activity of ALP in cells in two weeks significantly (p < 0.05). Antimicrobial and antibiofilm results showed an efficient effect of the prepared nanoparticle against the studied bacteria. Calcium carbonate nanoparticles are an efficient multifunctional vector for chlorhexidine and can be used as a bioactive antibacterial agent against various oral microorganisms to prevent implant infections. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AbstractCurrently, the combination of atezolizumab and bevacizumab (Atez/Bev) is recommended as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC). However, there is a lack of research on the levels of nutrient elements in advanced HCC patients receiving Atez/Bev treatment. In this study, data from 35 patients with advanced HCC and 37 healthy individuals of similar age and sex were included. The levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were significantly increased in patients with HCC. These levels returned to the reference range after three rounds of Atez/Bev treatment. Additionally, the levels of blood urea nitrogen and creatinine (Cr) increased after Atez/Bev treatment. In HCC patients, the levels of calcium (Ca), iron (Fe), and copper (Cu) were significantly higher, while the levels of sodium (Na), magnesium (Mg), and zinc (Zn) were significantly lower compared to healthy individuals. These changes were reversed after Atez/Bev treatment. In conclusion, our findings indicate that treatment with Atez/Bev influences the levels of Ca, Fe, Cu, Na, Mg, and Zn in patients with HCC. The alterations in these elements caused by Atez/Bev treatment require mechanistic research in the future. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Although turmeric is commonly ingested and well tolerated, there is increasing evidence that over‐the‐counter turmeric supplements can cause drug‐induced liver injury. We sought to thoroughly characterise clinicopathological features of patients for whom liver injury was attributed clinically to turmeric supplements.We identified 11 patients via retrospective pathology archive review: 10 females (91%) and one male, with a median age of 58 years (range = 37–66 years). Six patients (55%) were asymptomatic with abnormal liver function tests, while five patients (45%) presented with malaise and/or jaundice. Ten patients (91%) showed predominant transaminase abnormalities, while one exhibited predominant alkaline phosphatase elevation. Histologically, biopsies showed acute hepatitis (eight cases, 73%, including five pan‐lobular and three zone 3‐predominant inflammation), scattered lobular aggregates of histiocytes (two; 18%) and a chronic hepatitis pattern of injury (one; 9%). Mild bile duct injury was present in five biopsies (45%). All patients stopped ingesting turmeric supplements after presenting with liver injury, and four patients additionally received steroid therapy; liver function tests normalised in all patients. Roussel Uclaf causality assessment method (RUCAM) analysis estimated the likelihood of turmeric supplement‐associated liver injury to be probable (eight cases) and possible (three).Histological features in the ‘possible’ cases were consistent with drug‐induced injury, highlighting the added benefit of histological analysis relative to RUCAM analysis isolation. This study underscores the need to obtain a full history of over‐the‐counter medications and supplements when investigating aetiologies for liver injury, including supplements purportedly containing innocuous compounds such as turmeric. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Previous observational studies have identified correlations between liver enzyme levels and stroke risk. However, the strength and consistency of these associations vary. To comprehensively evaluate the relationship between liver enzymes and stroke risk, we conducted meta‐analyses complemented by Mendelian randomization (MR) analyses.Following the PRISMA guidelines, we performed meta‐analyses of prospective studies and conducted subgroup analyses stratified by sex and stroke subtype. Subsequently, adhering to the STROBE‐MR guidelines, we performed two‐sample bidirectional univariable MR (UVMR) and multivariable MR (MVMR) analyses using the largest genome‐wide association studies summary data. Finally, the single‐nucleotide polymorphisms associated with liver enzymes on sex differences underwent gene annotation, gene set enrichment, and tissue enrichment analyses.In the meta‐analyses of 17 prospective studies, we found the relative risks for serum γ‐glutamyl transferase (GGT) and alkaline phosphatase (ALP) were 1.23 (95% CI: 1.16–1.31) and 1.3 (95% CI: 1.19–1.43), respectively. Subgroup analyses revealed sex and stroke subtype differences in liver enzyme‐related stroke risk. Bidirectional UVMR analyses confirmed that elevated GGT, alanine aminotransferase, and aspartate aminotransferase levels were associated with increased stroke occurrence. The primary results from the MVMR analyses revealed that higher ALP levels significantly increased the risk of stroke and ischemic stroke. Gene set and tissue enrichment analyses supported genetic differences in liver enzymes across sexes.Our study provides evidence linking liver enzyme levels to stroke risk, suggesting liver enzymes as potential biomarkers for early identification of high‐risk individuals. Personalized, sex‐specific interventions targeting liver enzymes could offer new strategies for stroke prevention. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The aim of this study was to develop a population pharmacokinetics model for sugemalimab, a monoclonal antibody that targets programmed death‐ligand 1 (PD‐L1), using data from Phase I–III trials and to assess clinical factors affecting sugemalimab exposure.A nonlinear mixed‐effect modelling approach was employed to analyse pooled data from nine studies involving 1628 subjects to characterize the PopPK of sugemalimab. This investigation examined the influence of various covariates on sugemalimab pharmacokinetics (PK), encompassing demographics, baseline hepatic and renal function‐related covariates, and others (including anti‐drug antibody [ADA], combination treatment, Eastern Cooperative Oncology Group [ECOG] performance score, tumour burden and tumour type). Estimation accuracy and predictive ability of the final model were evaluated using various methods. The influence of covariates on sugemalimab exposure was assessed by simulation from the final model.A two‐compartment model with first‐order elimination and time‐varying clearance effectively described the PK of sugemalimab. Covariate analyses revealed significant relationships between sugemalimab clearance and body weight, albumin, gender, ADA, tumour burden and tumour type. The statistically significant covariates on central volume were body weight, albumin, gender and tumour type. No significant relationships were found in the final model for age, race, alanine aminotransferase, aspartate aminotransferase, creatinine, total bilirubin, alkaline phosphatase, combination treatment, creatinine clearance, ECOG, renal function or hepatic function. All significant covariates demonstrated less than a 20% effect on sugemalimab exposure.The PopPK model adequately described the pharmacokinetic profile of sugemalimab with no clinically meaningful impact observed on its exposure across all covariates. Dose adjustment does not appear to be necessary. [ABSTRACT FROM AUTHOR]

Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: In this study we have focused on biocompatibility and osteoinductive capacity analysis of self-manufactured single-phase (HAP) and two-phase (HAP and β-ТСР) bioactive ceramics with various chemical modifications (Fig. 1). Results: We demonstrate a reduction in solubility for all analyzed composite after the treatment with H2O and H2O2, accompanied by an enhancement in adsorption activity. This modification also resulted in an increase in micro- and macroporosity, along with a rise in the open porosity. Adipose-derived mesenchymal stromal cells demonstrated excellent cell adhesion and survival when cultured with these ceramics. Calcium phosphate ceramics (H-500, HT-500, and HT-1 series) stimulated alkaline phosphatase expression, promoted calcium deposition, and enhanced osteopontin expression in ADSCs, independently inducing osteogenesis without additional osteogenic stimuli. These findings underscore the promising potential of HAP-based bioceramics for bone regeneration/reconstruction. [ABSTRACT FROM AUTHOR]

Background: In this retrospective study, we aimed to identify key risk factors and establish an interpretable model for HCC with a diameter = 5 cm using Lasso regression for effective risk stratification and clinical decision-making. Methods: In this study, 843 patients with advanced hepatocellular carcinoma (HCC) and tumor diameter = 5 cm were included. Using Lasso regression to screen multiple characteristic variables, cox proportional hazard regression and random survival forest models (RSF) were established. By comparing the area under the curve (AUC), the optimal model was selected. The model was visualized, and the order of interpretable importance was determined. Finally, risk stratification was established to identify patients at high risk. Result: Lasso regression identified 8 factors as characteristic risk factors. Subsequent analysis revealed that the lasso-cox model had AUC values of 0.773, 0.758, and 0.799, while the lasso-RSF model had AUC values of 0.734, 0.695, and 0.741, respectively. Based on these results, the lasso-cox model was chosen as the superior model. Interpretability assessments using SHAP values indicated that the most significant characteristic risk factors, in descending order of importance, were tumor number, BCLC stage, alkaline phosphatase (ALP), ascites, albumin (ALB), and aspartate aminotransferase (AST). Additionally, through risk score stratification and subgroup analysis, it was observed that the median OS of the low-risk group was significantly better than that of the middle- and high-risk groups. Conclusion: We have developed an interpretable predictive model for middle and late HCC with tumor diameter = 5 cm using lasso-cox regression analysis. This model demonstrates excellent prediction performance and can be utilized for risk stratification. [ABSTRACT FROM AUTHOR]

Pulmonary coccidioidomycosis is a relatively common fungal disorder in dogs that have lived in or traveled to endemic regions and fluconazole is a common antifungal treatment. Liver enzymopathy can occur with fluconazole administration, but the frequency of occurrence nor potentially associative factors have been explored in dogs with pulmonary coccidioidomycosis. Therefore, our objectives were to describe the occurrence and magnitude of liver enzyme activity (LEA) elevation in dogs with pulmonary coccidioidomycosis during treatment with per os fluconazole and identify variables associated with liver enzymopathy. This was a retrospective observational study that analyzed serum biochemical data obtained from a separate prospective study that included 32 client-owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021. Per os fluconazole administration (median dosage: 16.2 mg/kg/day) was initiated after diagnosis and dogs were evaluated once every 3 months thereafter until remission or for a maximum of 12 months. Recorded biochemical parameters at each visit (including baseline) included alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). Magnitude of increased LEA was based on the fold increase above the upper limit of the reference interval and defined as mild (<5×), moderate (5-10×) or severe (>10×). Forty-seven percent (15/32) of dogs were documented to have elevations in one or more LEAs after initiation of fluconazole administration during the study period. Thirty-four percent and 25% of dogs had elevated ALP and ALT activities, respectively, at some point during treatment. Elevations in AST and GGT activities were rare. The magnitude of LEA elevation was mild in all cases. Logistic regression models did not identify associations between age, weight, sex, neutered status, prednisone administration, fluconazole dose or duration of treatment with the occurrence of liver enzymopathy. Approximately half of dogs with pulmonary coccidioidomycosis are expected to develop mild increases in activities of ALP and/or ALT with rare involvement of AST or GGT at some point during treatment with fluconazole up to 12 months. [ABSTRACT FROM AUTHOR]

Cutaneous-skeletal hypophosphatemia syndrome (CSHS) is a rare disorder characterized by the presence of melanocytic nevi, dysplastic cortical bony lesions, and fibroblast growth factor 23 (FGF23)-mediated hypophosphatemic rickets. Herein, we describe the diagnosis of an 8-year-old girl presenting with short stature, reduced lower limb mobility, and abnormal gait due to muscle weakness and constant pain in the legs. Biochemical parameters demonstrated hypophosphatemia, hyperphosphaturia, slight increase in parathyroid hormone (PTH), high levels of alkaline phosphatase, and elevated FGF23. Burosumab improved phosphate-wasting, serum phosphorus, alkaline phosphatase, and PTH, followed by a significant mineralization in vertebral bodies evidenced by radiographic assessment. Our report shows a long-term follow-up of CSHS with a notable improvement promoted by an anti-FGF23 therapy. [ABSTRACT FROM AUTHOR]

The design and development of fluorescent materials for detecting cancer-related enzymes are crucial for cancer diagnosis and treatment. Herein, we present a substituted rhodamine derivative for the chromogenic and fluorogenic detection of the cancer-relevant enzyme γ-glutamyltranspeptidase (GGT). Initially, the probe is non-chromic and non-emissive due to its spirolactam form, which hinders extensive electronic delocalization over broader pathway. However, selective enzymatic cleavage of the side-coupled group triggers spirolactam ring opening, resulting in electronic flow across the rhodamine skeleton, and reduces the band gap for low-energy electronic transitions. This transformation turns the reaction mixture from colorless to intense pink, with prominent UV and fluorescence bands. The sensor's selectivity was tested against various human enzymes, including urease, alkaline phosphatase, acetylcholinesterase, tyrosinase, and cyclooxygenase, and showed no response. Absorption and fluorescence titration analyses of the probe upon incremental addition of GGT into the probe solution revealed a consistent increase in both absorption and emission spectra, along with intensified pink coloration. The cellular toxicity of the receptor was evaluated using the MTT assay, and bioimaging analysis was performed on BHK-21 cells, which produced bright red fluorescence, demonstrating the probe's excellent cell penetration and digestion capabilities for intracellular analytical detection. Molecular docking results supported the fact that probe-4 made stable interactions with the GGT active site residues. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates predictive factors for distinguishing benign and malignant multifocal hepatic lesions in dogs using ultrasound, hematology, and serum biochemistry. The results show significant differences in hematological and blood chemical parameters, and ultrasonographic parameters. The hepatobiliary ultrasound score and lesion homogeneity show significant differences and high accuracy in predicting malignant multifocal liver lesions, making them effective parameters for screening in dogs. Multifocal hepatic lesions in dogs arise from various benign and malignant liver diseases. Diagnosing these lesions is challenging because clinical signs, hematological data, and serum biochemistry are not definitive indicators. Ultrasound is utilized as a diagnostic imaging tool to evaluate liver parenchyma and detect hepatic lesions. This study aims to investigate the predictive factors that differentiate between benign and malignant multifocal hepatic lesions by examining ultrasound characteristics, blood tests, and serum biochemistry. In total, 43 dogs with multifocal hepatic lesions were included in this study. All dogs were classified into benign hepatic diseases (n = 32) and malignant haptic diseases (n = 11). For all dogs, their liver characteristics, lesion characteristics, and hepatobiliary ultrasound score by ultrasound were evaluated and we collected individual clinicopathological data for analysis. The findings of the univariate analysis revealed significant differences in four hematological and blood chemical parameters (hematocrit, white blood cell count, aspartate transaminase (AST), and alkaline phosphatase (ALP)) and six ultrasonographic parameters (liver parenchymal echogenicity, lesion homogeneity, lesion echogenicity, maximum lesion dimension, average lesion dimension, and hepatobiliary ultrasound score). Using multivariate analysis, only two parameters, hepatobiliary ultrasound score and lesion homogeneity, showed significant differences (p-value < 0.001 and p-value = 0.011, respectively). Additionally, these parameters demonstrated high accuracy in predicting malignant multifocal liver lesions, with accuracy rates of 97.67% and 93.02%, respectively. Therefore, the hepatobiliary ultrasound score and lesion homogeneity are considered effective parameters for screening malignant multifocal liver lesions in dogs. [ABSTRACT FROM AUTHOR]

Simple Summary: Oleanolic acid is an organic natural compound, abundant in olive leaves, with various beneficial health effects in humans and animals. However, its in vivo efficacy is questioned given its low solubility, which hinders its bioavailability, that is, the capacity of a molecule to reach circulation. We investigated the digestibility and plasma concentration of oleanolic acid as an estimate of bioavailability in growing pigs. Because it is important to know the effects of oleanolic acid in the animal, growth, organ weights, digestibility of nutrients and plasma biochemical profile have been reported as well. Although there is a concern in the scientific community regarding the low bioavailability of oleanolic acid, in vivo data are lacking. We have demonstrated that, while digestibility of oleanolic acid was unexpectedly elevated, the appearance of the molecule in systemic blood was weak, probably indicating hepatic metabolism. No negative effects of oleanolic acid on growth or internal organs were observed. Oleanolic acid (OLA) has beneficial health effects in animals, but in vivo efficacy in monogastric animals is questioned due to its low bioavailability. To gain further insight on the nutritional effects of OLA it was administered as part of a diet. We investigated digestibility and plasma OLA in pigs and the associated influence on growth, organs, digestibility of nutrients and plasma biochemical profile. Twenty-four crossbred barrows (23.7 ± 1.0 kg BW) were assigned one of three treatments: Control (basal diet without OLA), OLA-1 (basal diet with 260 mg/free OLA) and OLA-2 (basal diet with 260 mg/kg cyclodextrin-OLA). Diets included chromium oxide to estimate digestibility. Blood samples were collected on day 14 for OLA analysis and feces on days 22–24 for determining digestibility. Pigs were slaughtered on day 31 (39.9 ± 2.43 kg BW) and their blood collected for analysis. Growth and organ weights were not affected (p > 0.05). OLA-1 decreased apparent total tract digestibility (ATTD) of energy (p < 0.05). OLA-2 increased ATTD of dry and organic matter compared with Control pigs (p < 0.05). OLA-1 increased plasma calcium and alkaline phosphatase (p < 0.05). Ileal digestibility of OLA was not affected (0.88), although OLA ATTD increased in OLA-1 compared to Control pigs (0.75 vs. 0.82; p < 0.05). OLA-1 and OLA-2 increased plasma OLA compared to Control pigs (p < 0.05 and p = 0.083). In conclusion, although the OLA was digested and absorbed, plasma concentration was low (4.29 µg/L), and pig growth, organs and plasma parameters were not affected. [ABSTRACT FROM AUTHOR]

Simple Summary: The European barracuda (Sphyraena sphyraena) is a wild fish species that is both commercially and ecologically valuable and is found in the Adriatic Sea. To better understand its distribution and physiology, this study examined the digestive enzymes in various parts of the barracuda's gastrointestinal system using histochemical analyses. This is the first known study to evaluate the activity of aminopeptidase, alkaline phosphatase, acid phosphatase, and non-specific esterase in the pyloric caeca and the anterior, middle, and posterior segments of the European barracuda's gastrointestinal tract. In this study, we examined the gastrointestinal tract of the European barracuda (Sphyraena sphyraena) living in the Adriatic Sea near Dubrovnik, Croatia. The study aimed to identify the presence and distribution of four digestive enzymes: alkaline phosphatase, aminopeptidase, acid phosphatase, and non-specific esterase. We found that alkaline phosphatase activity was present in the brush border of the enterocytes in all the investigated intestinal segments. The activity of the alkaline phosphatase was the strongest in the pyloric caeca but strong only in the basal part of the intestinal villi in the anterior and middle intestinal segments. In the posterior intestinal segment, alkaline phosphatase had strong activity along the entire villi. The activity of acid phosphatase was weak in all the investigated parts of the intestine, except in the posterior part, where it was moderate. Aminopeptidase was detected in the brush border of the intestinal epithelium, with stronger activity in the pyloric caeca and anterior part of the intestine and weaker activity posteriorly. The activity of the non-specific esterase was moderate in the pyloric caeca and anterior part of the intestine, while it was weak in the posterior segment and the lamina propria in all parts of the digestive tract. Weak acid phosphatase activity was observed only in the lamina propria of the posterior part of the intestine. This study is the first to evaluate the activity of digestive enzymes in the European barracuda. [ABSTRACT FROM AUTHOR]

Dermal papilla cells (DPCs) are located at the bottom of the hair follicle and play a critical role in hair growth, shape, and cycle. Epidermal growth factor receptor (EGFR) and Wnt/β-catenin signaling pathways are essential in promoting keratinocyte activation as well as hair follicle formation in DPCs. Piperonylic acid is a small molecule that induces EGFR activation in keratinocytes. However, the effects of piperonylic acid on DPCs in regard to the stimulation of hair growth have not been studied. In the present study, piperonylic acid was shown to activate the Wnt/β-catenin signaling pathway in addition to the EGFR signaling pathway in DPCs. Piperonylic acid suppressed DKK1 expression, which presumably promoted the accumulation of β-catenin in the nucleus. In addition, piperonylic acid promoted cyclin D upregulation and cell growth and increased the expression of alkaline phosphatase (ALP), a DPC marker. In a clinical study, the group that applied a formulation containing piperonylic acid had a significantly higher number of hairs per unit area than the placebo group. These results identify piperonylic acid as a promising new candidate for hair loss treatment. [ABSTRACT FROM AUTHOR]

Oxidative stress triggered by testicular torsion and detorsion in young males could negatively impact future fertility. Using a rat animal model for testicular IRI (tIRI), we aim to study the induction of autophagy (ATG) during testicular ischemia and tIRI and the role of oxidative-stress-induced c-Jun N-terminal Kinase (JNK) as a cytoprotective mechanism. Sixty male Sprague-Dawley rats were divided into five groups: sham, ischemia only, ischemia+SP600125 (a JNK inhibitor), tIRI only, and tIRI+SP600125. The tIRI rats underwent an ischemic injury for 1 h followed by 4 h of reperfusion, while ischemic rats were subjected to 1 h of ischemia only without reperfusion. Testicular-ischemia-induced Beclin 1 and LC3B expression was associated with decreased p62/SQSTM1 expression, increased ATP and alkaline phosphatase (AP) activity, and slightly impaired spermatogenesis. SP600125 treatment improved p62 expression and reduced the levels of Beclin 1 and LC3B but did not affect ATP or AP levels. The tIRI-induced apoptosis lowered the expression of the three ATG proteins and AP activity, activated caspase 3, and caused spermatogenic arrest. SP600125-inhibited JNK during tIRI restored sham levels to all investigated parameters. This study emphasizes the regulatory role of JNK in balancing autophagy and apoptosis during testicular oxidative injuries. [ABSTRACT FROM AUTHOR]

The article focuses on the molecular analysis of two-and-a-half-year-old twins diagnosed with odontohypophosphatasia due to a missense mutation in the alkaline phosphatase biomineralization associated (ALPL) gene. Topics discussed include the clinical presentation and diagnosis, identification of a novel heterozygous missense mutation (c.224G>A) in ALPL, and its predicted impact on tissue-nonspecific alkaline phosphatase (TNSALP) function.

Background: Nanofertilisers can enhance the efficiency of nutrient utilization in crop production. Nevertheless, it is unclear how soil microbial and enzyme activities are affected by the application of nanofertilisers to wheat inter‐root soil. Aims: The study aims to investigate the influences of nanocarbon (NC) and nano‐calcium carbonate (NCC) on soil enzyme activities and microbial community in the open field setting. Methods: The effects of nanofertilisers on soil wheat rhizosphere soil were studied through the evaluation of soil microbial quantity, enzyme activity, and microbial diversity. Results: The findings revealed that the combined utilization of nanofertilizers and compound fertilizers (CF) led to an augmentation in the diversity of the soil microbial community. When comparing the effects of 100% composite nanofertilizers (100% CF + 50% NC + 50% NCC) with the control (CK) (100% CF), it was observed that the activities of urease (EC 3.5.1.5), catalase (EC 1.11.1.6), alkaline phosphatase (EC 3.1.3.1), sucrase (EC.3.2.1.26), as well as the number of fungi, actinomycetes, and bacteria, increased by 22.4%, 7.7%, 17.8%, 9.3%, 35.9%, 27.7%, and 26.0%, respectively. Similarly, the employment of 70% composite nanofertilizers (70% CF + 35% NC + 35% NCC) also resulted in an enhancement of these aforementioned indicators. The magnitude of increase over the 100% CF was 19.0%, 6.6%, 13.6%, 6.2%, 26.8%, 21.3%, and 23.5%, respectively. Notably, there was no significant difference observed between 100% CF + 50% NC + 50 % NCC and 70% CF + 35% NC + 35% NCC within the 0–35 d after anthesis. Furthermore, both 100% CF + 50% NC + 50% NCC and 70% CF + 35% NC + 35% NCC contributed to an improvement in the species uniformity and operational taxonomic unit abundance of wheat rhizosphere microorganisms, while also increasing the abundance of Proteobacteria and Actinobacteria compared to the CK. The relative abundance of Bacteroidetes and Actinobacteria was found to be elevated in the nanomaterials‐treated groups, both at 0–7 d and 14–21 d after anthesis, and positively correlated with soil enzyme activities and soil microbial populations. Conclusions: These results indicate that the application of composite nanofertilizers can enhance the soil microenvironment in wheat fields, particularly under reduced fertilization conditions. [ABSTRACT FROM AUTHOR]

Fibrous dysplasia (FD), commonly known as Lichtenstein-Jaffe disease, is a benign fibro-osseous bone disease. Clinical symptoms often include bone pain, deformities, pathological fractures, or nerve compression. Fibrous dysplasia (FD) in the cranio-facial region presents major management concerns because to the risk of deformity, loss of function, and recurrence. The purpose of this study is to demonstrate a single institution's experience managing cranio-facial FD with zolendronic acid, as well as an extensive review of the available literature on the subject. This retrospective study was conducted in the Orthopedic Oncology unit of the Department of Surgical Oncology with a study duration between January 1, 2019, and January 1, 2022. There were seven patients with cranio-facial fibrous dysplasia in the current study. The effects of zolendronic acid were evaluated using clinical assessment, data, radiological findings, biochemical indicators. Furthermore, a comprehensive literature review was conducted in order to compile the current data of cranio-facial FD. The study included seven individuals (five men and two females), four with polyostotic FD and three with cranio-facial FD. The average follow-up duration was 18.75 months. The study found that all parameters improved: the mean VAS score increased from 7 to 1, mean serum calcium levels increased from 8.75 to 8.46 mg/dL, mean serum phosphorus levels increased from 4.46 to 4.17 mg/dL, and serum alkaline phosphatase levels increased from 152 to 93.25 IU/L.A comprehensive literature review was conducted using PubMed and Google Scholar with the following keywords: "Fibrous dysplasia," "Cranio-facial bones," "Bisphosphonate," and "Zolendronic acid." The search included 24 studies published between 2000 and 2022, incorporating all relevant studies available to date. Our study demonstrated the effectiveness of zolendronic acid in the treatment of cranio-facial fibrous dysplasia. Zolendronic acid offers potential as a feasible treatment options in treating cranio-facial FD, with possible advantages including alleviating symptoms, disease progression stabilisation, and morbidity reduction. However, multi-centre prospective randomised study with larger sample numbers and longer follow-up periods are needed in future. [ABSTRACT FROM AUTHOR]

One of the hallmarks of chronic kidney disease (CKD) is the development of vascular calcification. Inorganic pyrophosphate is a potent inhibitor of calcification, and previous studies have reported low plasma pyrophosphate levels in hemodialysis patients. A long-term mouse model of CKD-accelerated vascular calcification was developed to study pyrophosphate metabolism and to test whether oral pyrophosphate supplementation attenuates the propensity for arterial calcification. CKD was induced by repeated injections of aristolochic acid in wild-type and Abcc6-/- mice, which tend to develop vascular calcifications. CKD accelerated the development of vascular calcifications in Abcc6-/- mice, in the aorta and small renal arteries, and decreased circulating pyrophosphate levels. Oral pyrophosphate supplementation for 6 months attenuated CKD-induced vascular calcification in this model. These results show that oral pyrophosphate may be of interest in preventing vascular calcification in patients with CKD. Key messages: Chronic kidney disease accelerates the development of vascular calcification in pyrophosphate-deficient mice. Oral pyrophosphate supplementation for 6 months attenuates chronic kidney disease-induced vascular calcification in a mouse model. Oral pyrophosphate may be of interest in preventing vascular calcification in patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]

Drug-loaded non-resorbable polymeric nanoparticles (NPs) are proposed as an adjunctive treatment for pulp regenerative strategies. The present in vitro investigation aimed to evaluate the effectiveness of tideglusib-doped nanoparticles (TDg-NPs) in mitigating the adverse effects of bacterial lipopolysaccharide endotoxin (LPS) on the viability, morphology, migration, differentiation and mineralization potential of human dental pulp stem cells (hDPSCs). Cell viability, proliferation, and differentiation were assessed using a MTT assay, cell migration evaluation, cell cytoskeleton staining analysis, Alizarin Red S staining and expression of the odontogenic related genes by a real-time quantitative polymerase chain reaction (RT-qPCR) were also performed. Cells were tested both with and without stimulation with LPS at various time points. One-way ANOVA and Tukey's test were employed for statistical analysis (p < 0.05). Adequate cell viability was encountered in all groups and at every tested time point (24, 48, 72 and 168 h), without differences among the groups (p > 0.05). The analysis of cell cytoskeleton showed nuclear alteration in cultures with undoped NPs after LPS stimulation. These cells exhibited an in blue diffuse and multifocal appearance. Some nuclei looked fragmented and condensed. hDPSCs after LPS stimulation but in the presence of TDg-NPs exhibited less nuclei changes. LPS induced down-regulation of Alkaline phosphatase, Osteonectin and Collagen1 gene markers, after 21d. LPS half-reduced the cells production of calcium deposits in all groups (p < 0.05), except in the group with TDg-NPs (decrease about 10 %). LPS induced lower mineral deposition and cytoskeletal disorganization in hDPSCs. These effects were counteracted by TDg-NPs, enhancing osteogenic differentiation and mineralization. [Display omitted] • LPS induced in hDPSCs lower mineral deposition. • LPS produces in hDPSCs cytoskeletal disorganization. • Tideglusib counteracts LPS adverse effect on hDPSCs. • Tideglusib enhances mineralization ability of hDPSCs. [ABSTRACT FROM AUTHOR]

Cirrhosis is a prevalent, chronic condition with an asymptomatic compensated phase, in which patients may feel well, and a decompensated phase that begins with the onset of complications (eg hepatic encephalopathy, ascites, and/or variceal bleeding). Because patients with cirrhosis may appear healthy with normal liver enzymes, alkaline phosphatase, and serum bilirubin levels, awareness of clinical signals is important. For example, patients with thrombocytopenia should be evaluated for chronic liver disease and cirrhosis. Early recognition and management of cirrhosis-related complications (eg hepatic encephalopathy, ascites, and/or variceal bleeding) are important, given their association with hospitalization and poor prognosis (eg increased odds of short-term mortality). Hepatic encephalopathy can be the most subtle cirrhosis-related complication and associated cognitive impairment may be misdiagnosed. Because hepatic encephalopathy can be associated with hospital readmissions, reducing readmission rates after hepatic encephalopathy–related hospitalizations is critical. This includes incorporating ongoing therapy (eg rifaximin plus lactulose) in postdischarge management plans to reduce the risk of hepatic encephalopathy recurrence. Strategies that mitigate cirrhosis progression and prevent the development of cirrhosis-related complications are key to improving patient outcomes. [ABSTRACT FROM AUTHOR]

Recurrent primary biliary cholangitis (r PBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in r PBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with r PBC. A total of 332 patients with r PBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of r PBC was 58.0 years [IQR 53.2–62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation. During a median follow-up of 8.7 years [IQR 4.3–12.9] after r PBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at r PBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p < 0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p < 0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p < 0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival. Patients with r PBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC. One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis. [Display omitted] • Recurrent PBC (r PBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after LT. • Levels of alkaline phosphatase after 1 year of UDCA predict graft loss and mortality in patients with r PBC after LT. • Prognostic scores for UDCA-treated patients predict graft loss and mortality in patients with r PBC after LT. • Future studies to evaluate second-line treatments in patients with r PBC and incomplete response to UDCA are warranted. [ABSTRACT FROM AUTHOR]

Background and Purpose: Demand for new antidepressants has resulted in a re‐evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin‐containing "magic" mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects. Experimental Approach: We compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood–brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound. Key Results: In vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood–brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5‐HT2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5‐HT2A‐mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles. Conclusions and Implications: Collectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations. [ABSTRACT FROM AUTHOR]

[Display omitted] • Stocking density of Eisenia fetida could affect the green waste (GW) vermicomposting. • The optimum earthworm stocking density is 30 worms/kg (T3) for GW vermicomposting. • 30 worms/kg stocking increases the growth of earthworms and the NPK content. • T3 increased the OM degradation rate by 35 % relative to control (no earthworm). • PCA showed that earthworm growth was negatively correlated with lignocellulose. Appropriate stocking density plays an important role in ensuring the stability and improving the overall efficiency of the vermicomposting system. Although some studies have shown that earthworms can degrade lignocellulosic materials, relatively few studies have been conducted on the effect of earthworm stocking density on the degradation of a single green waste (GW) with high lignocellulosic content. Therefore, this study investigated the degradation effect of earthworms on GW at different stocking densities, and assessed the stability and maturity of the whole vermicomposting by comprehensively analysing the changes in physicochemical and biological properties of earthworms during vermicomposting, and by combining the growth of earthworms with a multi-dimensional assessment of the stability and maturity of the whole vermicomposting. In this study, six stocking densities (CK-T5) were set up, namely, no earthworms, 10, 20, 30, 40, and 50 worms/kg. The results showed that compared with the CK (without earthworms), when there were 30 earthworms per kg of GW (i.e. T3), the total nitrogen, total phosphorus, total potassium, organic matter decomposition, bacterial and fungal numbers, and germination index of earthworm compost products increased by 14 %, 29 %, 32 %, 35 %, 42 %, 94 %, and 125 %, respectively. T3 also enhanced the activities of cellulase and alkaline phosphatase. The results were further supported by principal component analysis. Finally, we conclude that when the stocking density of earthworms is appropriate (T3), it not only favours the growth of earthworms, but also positively affects the physicochemical properties of the vermicomposting process, which in turn significantly improves the biodegradation efficiency of GW. [ABSTRACT FROM AUTHOR]

Background: Infantile nephropathic cystinosis (INC) is a rare lysosomal storage disorder, mostly and often firstly affecting the kidneys, together with impaired disharmonious growth and rickets, eventually resulting in progressive chronic kidney disease (CKD). With the introduction of cysteamine therapy, most pediatric patients reach adulthood with no need for kidney replacement therapy. Still, detailed changes in INC patients' clinical and morphological presentation over the past decades have not yet been thoroughly investigated. Methods: Two groups with a respective total of 64 children with INC and 302 children with CKD, both treated conservatively and aged 2 to 18 years, were prospectively observed in the time span from 1998 to 2022 with 1186 combined annual clinical and morphological examinations clustered into two measurement periods (1998 to 2015 and ≥ 2016). Results: In INC patients, thoracic proportion indices remained markedly increased, whereas body fat stores remained decreased over the past 25 years (+ 1 vs. below ± 0 z-score, respectively). Their CKD peers presented with overall improved growth, general harmonization of body proportions, and improved body fat stores, while INC patients only presented with an isolated significant increase in leg length over time (∆0.36 z-score). eGFR adjusted for age did not significantly change over the past 25 years in both groups. Alkaline phosphatase (ALP) showed a significant decrease in CKD patients over time, while remaining above normal levels in INC patients. Conclusions: Disproportionate thoracic shape and impaired body fat stores remain the most characteristic morphological traits in INC patients over the past 25 years, while causal mechanisms remain unclear. [ABSTRACT FROM AUTHOR]

Platelet-rich fibrin (PRF) is a promising host-derived scaffold for regenerative endodontic treatment. This study investigated the effects of advanced PRF plus (A-PRF+) and injectable PRF (i-PRF) on the proliferation, migration, and differentiation of stem cells from apical papilla (SCAPs). A-PRF+ and i-PRF were prepared using a DUO Quattro centrifuge following a standard protocol. A-PRF+ and i-PRF extract were diluted in Dulbecco's modified Eagle's medium and Ham's F-12 medium (DMEM/F12) to produce the experimental culture medium. DMEM/F12 and DMEM/F12 supplemented with 10% foetal bovine serum (FBS) were used as the negative control (NC) and positive control (PC) media, respectively. The proliferative ability of SCAPs was assessed using a counting method (haemocytometer). The migration ability was examined using a scratch-wound assay. Alkaline phosphatase , bone sialoprotein , dentin matrix protein 1 , and dentin sialophosphoprotein expression were measured to determine the differentiation ability. The proliferation, migration, and differentiation of SCAPs in the A-PRF+ group were similar to those of the PC group. In the i-PRF group, the cell number was significantly (p < 0.01) lower than that of the A-PRF+ group on days 8 and 10; the percentage of the scratched area on days 1 and 2 was significantly higher than in the A-PRF+ group (p < 0.05). The mRNA expression levels of biomarkers in the i-PRF group were similar to those in the A-PRF+ group. Both A-PRF+ and i-PRF induce SCAPs proliferation, migration, and differentiation. However, A-PRF+ was superior in supporting the proliferation and migration of SCAPs. [ABSTRACT FROM AUTHOR]

Chemical screening of the octocoral Sarcophyton stellatum led to the isolation of a natural dihydrofuranocembranoid, 7 S ,8 R -dihydroxydeepoxysarcophytoxide (1). Single-crystal X-ray diffraction analysis was conducted to determine the absolute configuration of 1 , and its structure was confirm using two-dimensional NMR experiments and a literature review. Dihydrofuranocembranoid 1 actively enhanced alkaline phosphatase activity. [Display omitted] • 7 S ,8 R -Dihydroxydeepoxysarcophytoxide (1) was obtained from Sarcophyton stellatum. • The absolute configuration of cembranoid 1 was determined via X-ray analysis. • Dihydrofuranocembranoid 1 actively enhanced alkaline phosphatase activity. [ABSTRACT FROM AUTHOR]

Hypophosphatasia (HPP) is a rare, inherited metabolic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). Efzimfotase alfa (ALXN1850) is a second-generation TNSALP enzyme replacement therapy in development for HPP. This first-in-human open-label, dose-escalating phase 1 trial evaluated efzimfotase alfa safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. Fifteen adults (5/cohort) with HPP received efzimfotase alfa in doses of 15 mg (cohort 1), 45 mg (cohort 2), or 90 mg (cohort 3) as one intravenous (i.v.) dose followed by 3 weekly subcutaneous (s.c.) doses. The primary objective was to assess safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics of ALP substrates known to be biomarkers of disease (inorganic pyrophosphate [PPi] and pyridoxal 5′-phosphate [PLP]) and immunogenicity. Treatment-emergent adverse events (TEAEs) occurred in 12 (80%) participants. Eight (53%) participants had injection site reactions (ISRs), observed after 10 of 41 (24%) s.c. injections. Most ISR TEAEs were mild and resolved within 1–2 d. Peak and total exposures of efzimfotase alfa increased in a greater-than-dose proportional manner over the range of 15–90 mg after i.v. and s.c. dosing. The arithmetic mean elimination half-life was approximately 6 d; absolute bioavailability was 28.6%–36.8% over the s.c. dose range of 15–90 mg. Dose-dependent reductions in plasma concentrations of PPi and PLP relative to baseline reached nadir in the first week after i.v. dosing and were sustained for 3–4 wk after the last s.c. dose. Four (27%) participants tested positive for antidrug antibodies (ADAs), 3 of whom were ADA positive before the first dose of efzimfotase alfa. ADAs had no apparent effect on efzimfotase alfa pharmacokinetics/pharmacodynamics. No participants had neutralizing antibodies. Efzimfotase alfa demonstrated acceptable safety, tolerability, and pharmacokinetic profiles and was associated with sustained reductions in biomarkers of disease in adults with HPP, supporting further evaluation in adult and pediatric patients. Registration: ClinicalTrials.gov NCT04980248 (https://clinicaltrials.gov/study/NCT04980248). Lay Summary: Hypophosphatasia (HPP) is a rare metabolic disease caused by low activity of tissue nonspecific alkaline phosphatase (TNSALP), which is an enzyme involved in the formation and healing of bone and function of other body systems. People with HPP experience fractures, difficulty moving and walking, muscle weakness, pain, fatigue (tiredness), and teeth problems. Babies with HPP often have life-threatening breathing problems, craniosynostosis (early closure of skull bones), seizures that respond to treatment with vitamin B6, failure to thrive (inability to gain weight), and weak and abnormally shaped bones. Enzyme replacement therapy (ERT) for HPP was developed to supplement defective TNSALP with active enzyme, thus improving bone health and the symptoms of HPP. Asfotase alfa, the first ERT approved for the treatment of HPP, is given by subcutaneous injection either 3 or 6 times per week. Efzimfotase alfa is a second-generation ERT that is being developed for the treatment of HPP. Although similar to asfotase alfa, efzimfotase alfa has incorporated several changes that have the potential to require lower doses and reduce injection volume and dosing frequency, thereby potentially improving the treatment experience for patients. This first-in-human study investigated the safety, tolerability, pharmacokinetics (how a drug is absorbed into, distributed throughout, and removed from the body), pharmacodynamics (effects of the drug within the body), and immunogenicity (ability of a drug to provoke an undesirable immune response) of 4 injections of efzimfotase alfa when given by intravenous and subcutaneous routes of administration to adults with HPP. Our results showed that efzimfotase alfa has acceptable safety and pharmacokinetics and is effective for reducing biomarkers (measurable substances that reflect underlying disease) when given once weekly by subcutaneous injection, supporting further evaluation of efzimfotase alfa in planned clinical trials in adult and pediatric patients with HPP. [ABSTRACT FROM AUTHOR]

Objective: To estimate the levels of serum bioavailable vitamin D in children presenting with first episode nephrotic syndrome (FENS) at diagnosis and after 4 weeks of standard steroid therapy while the child is in remission, and compare the same with age-sex matched healthy controls. Methods: We included children aged 1 month to 12 years presenting as FENS and estimated the serum calcium, phosphorus, alkaline phosphatase, 25-hydroxy vitamin D [25(OH)D], parathormone, serum and urine vitamin D binding protein (VDBP) at diagnosis and after 4 weeks of standard steroid therapy while the child is in remission. We also included age-sex matched healthy controls for comparison. Bioavailable and free 25(OH)D were estimated at enrolment and at 4 weeks of therapy. Results: The mean (SD) 25(OH)D level (ng/mL) in children with FENS was 11.3 (6.1) at diagnosis and 13.6 (6.2) at 4 weeks follow-up, while the observed value in healthy controls was 16 (7) ng/mL. The median (IQR) serum VDBP level in FENS at enrolment was 223.0 (144, 305.5) µg/mL. There was significant correlation between serum VDBP and serum albumin levels (P = 0.04). At 4 weeks (remission), the median (IQR) VDBP levels increased to 554.5 (383, 644.75) µg/mL (P < 0.001). The median (IQR) free 25(OH)D levels (pg/mL) in children with FENS was 1.07 (0.8, 1.6) at enrolment and 0.53 (0.37, 0.86) at 4 weeks follow-up. The median (IQR) bioavailable vitamin D in FENS during proteinuria was 0.58 (0.4, 0.83) ng/ml, much lower as compared to controls 0.97 (0.85, 1.08) ng/mL (P < 0.001). On follow-up at 4 weeks of remission the median (IQR) bioavailable vitamin D levels increased to 0.87 (0.59, 1.42) ng/mL (P = 0.015). There was a very strong positive correlation between free vitamin D and bioavailable vitamin D (r = 0.9, P < 0.001); a strong negative correlation between serum VDBP and bioavailable vitamin D (r = − 0.69, P < 0.001). There was a positive correlation between 25 (OH)D and bioavailable vitamin D (r = 0.63, P < 0.001). Serum VDBP and serum albumin showed statistically significant positive correlation (r = 0.37, P < 0.05). Conclusion: Children with FENS are deficient in vitamin D. The free and bioavailable vitamin D levels are reduced in children with FENS during the proteinuric phase. Further studies to assess the association between bioavailable vitamin D and 25(OH)D with bone mineral density are needed in children with nephrotic syndrome to validate the utility of bioavailable vitamin D in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to investigate the role of miR‐146a‐5p in osteogenesis of hPDLSCs irradiated with low‐energy red LEDs. Methods: After irradiation with 5 J/cm2 red LED, miR‐146a‐5p expression was detected by real‐time quantitative polymerase chain reaction (RT‐qPCR), and osteogenic markers expression was determined by RT‐qPCR and Western blotting. Alkaline phosphatase (ALP) activity was assessed by ALP staining, and mineralization was assessed by Alizarin Red staining, respectively. Lentiviral vectors were designed to regulate miR‐146a‐5p expression. Dual‐luciferase reporter assay was performed to confirm the targeted relationship between miR‐146a‐5p and MAPK1. Short hairpin RNA (shRNA) was used to regulate MAPK1 expression. Results: RT‐qPCR and western blotting revealed that 5 J/cm2 irradiation elevated the levels of the osteogenic markers osterix (OSX) and bone sialoprotein (BSP) in hPDLSCs. miR‐146a‐5p is downregulated in hPDLSCs under the low‐energy red LED light irradiation. miR‐146a‐5p underexpression markedly promoted the osteogenic potential of hPDLSCs. miR‐146a‐5p targeted MAPK1. 5 J/cm2 red LED irradiation rescued the inhibitory effects of upregulated miR‐146a‐5p on osteogenic differentiation, and the positive influence of red LED irradiation could be reversed by downregulated MAPK1. Conclusion: These findings confirm that miR‐146a‐5p is involved in the effect of LED irradiation on the osteogenic differentiation of hPDLSCs by targeting MAPK1. Red LED irradiation may be a potential clinical adjunct therapy for periodontal regeneration. [ABSTRACT FROM AUTHOR]

Copyright of Current Research in Dental Sciences is the property of Ataturk University Coordinatorship of Scientific Journals and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Short beak and dwarfism syndrome (SBDS), characterised by growth retardation and short beak, is a contagious disease of ducks, caused by goose parvovirus (GPV). This study aimed to compare morphology and biochemistry data obtained from 4-week-old Pekin ducks naturally infected with parvovirus causing SBDS in healthy Pekin ducks of the same age. Materials and Methods: Forty Pekin ducks (twenty infected GPV and twenty clinically healthy controls) were examined. Measurement of the beak and metatarsus and histopathological examination were conducted, and blood morphological and biochemical analyses were performed for each individual. Results: Statistically significant increases in the SBDS group were observed in white blood cells (WBCs), alkaline phosphatase (ALP), and albumin levels, while decreases were noted in non-organic phosphorus, potassium, and amylase levels. ALP in the control group was 465.70 ± 161.49, while in the SBDS group it was 353.68 ± 79.97 (p ˂ 0.006). 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester (DGGR) lipase marker offered a refined gauge for pancreatic function, with established reference values for the healthy control group set at 14.95 ± 4.27 U/L. Conclusions: This study sheds light on the unique impact of GPV on the skeletal system of Pekin ducks, revealing significant insights into the mechanisms of SBDS without osteitis. Additionally, this work offers groundbreaking insights into the morphological and biochemical alterations in the blood during SBDS, establishing normative haematological and biochemical indices for Pekin ducks. It also introduces the DGGR lipase marker as a refined marker for pancreatic function for the healthy control group set at 14.95 ± 4.27 U/L. It highlights the role of ALP in ensuring proper bone growth and the need for ongoing research on its activity in the context of viral infections. [ABSTRACT FROM AUTHOR]

Sad and UNC84 domain 1 (SUN1) is a kind of nuclear envelope protein with established involvement in cellular processes, including nuclear motility and meiosis. SUN1 plays an intriguing role in human adipose‐derived stem cells (hASCs) differentiation; however, this role remains largely undefined. This study was undertaken to investigate the role of SUN1 in hASCs differentiation, as well as its underlying mechanisms. Employing siRNAs, we selectively downregulated SUN1 and CD36 expression. Microtubules were depolymerized using nocodazole, and PPARγ was activated using rosiglitazone. Western blotting was performed to quantify SUN1, PPARγ, α‐tubulin, CD36, OPN, and adiponectin protein expression levels. Alkaline phosphatase and Oil red O staining were used to assess osteogenesis and adipogenesis, respectively. Downregulated SUN1 expression increased osteogenesis and decreased adipogenesis in hASCs, concomitant with upregulated α‐tubulin expression and downregulated CD36 expression, alongside reduced nuclear localization of PPARγ. Microtubule depolymerization increased CD36 expression. Rescue experiments indicated that microtubule depolymerization counteracted the downregulated SUN1‐induced phenotypic changes. This study demonstrates that SUN1 influences the differentiation of hASCs towards osteogenic and adipogenic lineages, indicating its essential role in cell fate. [ABSTRACT FROM AUTHOR]

Copyright of West China Journal of Stomatology is the property of Sichuan University, West China College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aims Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement. Methods We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. Results Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18–66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAF N486_P490 (29.6%), BRAF V600E (18.5%), and MAP2K1 (14.8%). Outcomes After a median 40 months' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550–7.388, P  = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P  = .010) correlated with superior PFS versus chemotherapy. Conclusions In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy. [ABSTRACT FROM AUTHOR]

Reference intervals (RI) play a decisive role in the interpretation of medical laboratory results. An important step in the determination of RI is age- and sex specific partitioning, which is usually based on an empirical approach by graphical representation. In this study, we evaluate an automated machine learning approach. This study uses pediatric data from the CALIPER RI (Canadian Laboratory Initiative on Pediatric Reference Intervals) study. The calculation of potential partitions is carried out using a regression tree model included in the rpart package of the statistical programming language R. The Harris & Boyd method is used to compare the corresponding partitions suggested by rpart and CALIPER. For better comparability, the reference ranges of the partitions of both approaches are then calculated using reflimR. Most of the partitions suggested by rpart or CALIPER show sufficient heterogeneity among themselves to justify age- and/or sex-specific RI partitioning. With only few individual exceptions, both methods yield comparable results. The partitions of both approaches for albumin and γ-glutamyltransferase are very similar to each other. For creatinine rpart suggests a slightly earlier distinction between the sexes. Alkaline phosphatase shows the most pronounced differences. In addition to a considerable earlier sex split, rpart suggests different age intervals for both sexes, resulting in three partitions for females and four partitions for males. Our findings indicate that the automated analysis provided by rpart yields results that comparable to traditional methods. Nevertheless, the medical plausibility of the automatic suggestions needs to be validated by human experts. [ABSTRACT FROM AUTHOR]

Background and aim of study: Thyroidectomy and osteoarthritis have drawn more attention in last decades due to increase various local and systemic risk factors. This study is aimed to determine the association and impact between thyroidectomy and osteoarthritis by serological measurement of most specific related markers. Results: Measurement of thyroid markers showed the level of thyroid-stimulating hormone (TSH) was significantly increased, while parathyroid hormone (PTH), triiodothyronine (T3), and thyroxine (T4) levels were decreased in osteoarthritis subjected to thyroidectomy group (OTG) when compared to hyperthyroidism subjected to thyroidectomy group (TG), osteoarthritis group (OG), and healthy control group (CG). Detection the activity of bone markers showed the level of R-factor was significantly elevated concomitant with significant reduction in Dickkopf related protein 1 (DKK1), human hyaluronan-binding protein 2 (HABP2), osteocalcin (OC) in OG and OTG groups, while osteopontin (OPN) and procollagen I C-terminal propeptide (PICP) were significantly increased and decreased in TG and OTG. Furthermore, the level of S100 Calcium binding protein (S100CBP) showed significant decreased in patient's groups, while TG with OTG groups exhibited significant reduction in sclerostin (SOST) concentration. Regarding the inflammatory markers, the levels of interleukin-1 (IL-1) was increased in the OTG, while the level of interleukin-10 (IL-10) was increased in OG and TG groups, and reduced in OTG. While, the level of transforming growth factor-beta (TGF-β) was decreased in OG and TG associated with significant increases in tumor necrosis factor-alpha level (TNF-α) in OTG. Measurement of oxidant and antioxidant activity markers showed the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were significantly reduced in all patient's groups compared to control, except the level of CAT in TG, whereas, malondialdehyde (MDA) level was increased in OG and OTG patients. Furthermore, the levels of Alkaline phosphatase (ALP), C-Reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were increased in all patient groups compared to control, while fatty acid-binding protein (FABP) level was increased in OTG only. Conclusion: This unique study in Iraq is identified the interaction effect and impact of thyroidectomy to osteoarthritis according to the results that showed various changes and degree of correlation of study biomarkers in all patient groups, however more depth of specific quantitative and qualitative studies are required to support this association and the impact claim at molecular level. [ABSTRACT FROM AUTHOR]

Background: Evidence shows that the total flavonoids of Rhizoma Drynariae (TFRD) can improve bone mineral density (BMD). However, there is no evidence to summarize the improvement of biochemical indicators of bone metabolism (BIBM). Methods: The PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP Information Database (VIP) and SinoMed were searched from inception to 6 May 2024. The final included studies performed meta-analyses using RevMan 5.3. Results: Nine randomized controlled trials (RCTs) were ultimately included. The TFRD group had higher bone gla protein (BGP) and type I procollagen-N-propeptide (PINP) compared to theOther therapies (WMD: 5.11; 95% CI: 3.37, 6.84; p < 0.00001; WMD: 13.89; 95% CI: 11.81, 15.97; p < 0.00001). The tartrate-resistant acid phosphatase (TRACP) decreased significantly (WMD: -1.34; 95% CI: -1.62, -1.06; p < 0.00001). The alkaline phosphatase (ALP) increased significantly (WMD: 7.47; 95% CI: 6.29, 8.66; p < 0.00001). There were no significant differences in serum calcium (SC) or serum phosphorus (SP) levels between the TFRD and control groups (WMD: 0.08; 95% CI: -0.04, 0.20; p = 0.17; WMD: 0.02; 95% CI: -0.02, 0.05; p = 0.36). Conclusion: TFRD can stimulate bone formation and prevent bone resorption in osteoporosis (OP) patients, but it has no effect on SC and SP. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/. [ABSTRACT FROM AUTHOR]