Serum Alkaline Phosphatase Levels Research Articles

The relationship between maternal vitamin D levels and osteopenia development in preterm infants: A cross-sectional study

Background: Osteopenia of prematurity (OP) is characterized by reduced bone mineral content, and vitamin D deficiency may worsen OP by affecting bone metabolism. Objective: This study aimed to investigate the correlation between maternal vitamin D levels and biochemical markers related to OP. Materials and Methods: This analytical cross-sectional study, conducted at Shahid Sadoughi hospital, Yazd, Iran, from June 2022 to September 2023, included 49 pregnant women and their preterm infants. Based on the serum alkaline phosphatase and phosphorus levels of the infants at birth and 4 wk after birth, they were divided into osteopenic and non-osteopenic groups. Maternal and neonatal vitamin D and calcium levels were then compared between these groups. Results: The mean maternal vitamin D level was 24.9 ± 15.09 ng/ml, with 36% showing deficiency. 11 neonates at 4 wk exhibited osteopenia based on phosphorus and serum alkaline phosphatase levels. Those with osteopenia had significantly lower vitamin D (p = 0.032) and calcium levels compared to non-osteopenic neonates (p = 0.043), although maternal vitamin D mean was not a significant risk factor for OP (p = 0.313). Conclusion: The results suggest that maternal vitamin D levels do not have a significant association with the incidence of osteopenia in neonates, as the mean maternal vitamin D concentration was not identified as a risk factor for this condition. Therefore, it is recommended that future research should investigate alternative factors that may contribute to the development of osteopenia in preterm infants

Dietary supplementation of compound probiotics to improve performance, egg quality, biochemical parameters and intestinal morphology of laying hens.

The purpose of this study was to investigate the effects of dietary supplementation of compound probiotics on the performance, egg quality, biochemical parameters and intestinal morphology of laying hens. A total of 180 healthy 200-day-old Hyline Brown laying hens with similar initial laying rate (87.5% ± 0.2%) were randomly divided into the control group and the treatment group. Each group included 6 replicates and each replicate included 15 laying hens. The control group was provided a basal diet, while the treatment group received the basal diet supplemented with compound probiotics. The experiment lasted for 52 days. The study indicated the following outcomes: (1) The laying rate (LR) and average egg weight (AEW) of laying hens in the treatment group were significantly higher than those of the control group (p < 0.05), whereas the feed-to-egg ratio (F/E) was significantly lower (p < 0.05); (2) The yolk weight (YW), egg shape index (ESI) and albumen height (AH) were significantly higher (p < 0.05), whereas the eggshell percentage (EP) was significantly lower (p < 0.05) after the dietary supplementation of compound probiotics; (3) The treatment group significantly decreased in total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), immunoglobulin A (IgA), and immunoglobulin G (IgG) levels in serum compared to the CON group (p < 0.05). Additionally, serum levels of total protein (TP), globulin (GLB), albumin (ALB), high-density lipoprotein (HDL), alkaline phosphatase (ALP), and total antioxidant capacity (T-AOC) were significantly higher in the treatment group (p < 0.05); (4) The supplementation of compound probiotics to laying hen diets led to a significant reduction in crypt depth (CD) and the ratio of villus height to crypt depth (V/C) in the jejunum compared to the CON group (p < 0.05). In conclusion, the supplementation of compound probiotics can regulate the body metabolism and improve the intestinal morphology, thus enhancing the antioxidant capacity and immune function of the body, which in turn improves the performance and egg quality of laying hens.

Pretreatment administration of hydro-ethanolic extract of Syzygium aromaticum prevents thioacetamide-induced liver injury in rat

IntroductionLiver injury is an important problem in healthcare. Thioacetamide (TAA)-induced liver injury is an established model in experimental research for assessing the impact of various toxins and pharmaceuticals on the liver. TAA induces its harmful effects by the production of oxidative biomolecules. Oxidative stress subsequently alters liver function, resulting in alterations in the enzymatic activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Syzygium aromaticum has significant antioxidant and anti-inflammatory properties and has been utilised in traditional medicine for liver diseases. Therefore, this study evaluated the hepatoprotective effect of the hydro-ethanolic extract of Syzygium aromaticum (HESA) against TAA-induced liver injury.Material and methodsHepatotoxicity was induced with intraperitoneal administration of TAA (150 mg/kg body weight, 3 days per week for 4 weeks) in Wistar rats. The pretreatment with HESA was conducted at three doses of 50, 150, and 300 mg/kg body weight, administered orally, starting 4 weeks before TAA administration and continued for 8 weeks. The activities of serum AST, ALT, and ALP, as well as liver superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and malondialdehyde (MDA), were assessed. Histopathological analyses were conducted using hematoxylin and eosin (H&E) staining.ResultsThe findings showed that HESA pretreatment significantly lowered TAA-induced oxidative stress. Additionally, TAA significantly increased AST, ALT, and ALP serum levels, whereas HESA significantly recovered the corresponding values. H&E staining also showed that TAA-induced structural liver damage was characterised by central vein dilatation, and necrosis, and apoptosis in adjacent cells. The histopathological findings of the TAA group were partially recovered in the pretreatment extract groups.ConclusionThe results of this study support the antioxidant and anti-inflammatory properties of Syzygium aromaticum against TAA-induced liver injury.

Integrated Analysis of Transcriptome and Metabolome in the Brain After Cold Stress of Red Tilapia During Overwintering.

Cold stress during overwintering is considered a bottleneck problem limiting the development of the red tilapia (Oreochromis spp.) industry, and the regulation mechanism is currently not well understood. In this study, the fish (initial weight: 72.71 ± 1.32 g) were divided into the cold stress group (cold) and the control (normal) group. In the control group, the water temperature was maintained at 20 °C, which is basically consistent with the overwintering water temperature in greenhouses of local areas. In the cold group, the water temperature decreased from 20 °C to 8 °C by 2 °C per day during the experiment. At the end of the experiment, the levels of fish serum urea nitrogen, glucose, norepinephrine, alkaline phosphatase, total bilirubin, and total cholesterol in the cold group changed significantly compared with that in the control group (P < 0.05). Then transcriptome sequencing and LC-MS metabolome of brain tissue were further employed to obtain the mRNA and metabolite datasets. We found that the FoxO signaling pathway and ABC transporters played an important role by transcriptome-metabolome association analysis. In the FoxO signaling pathway, the differentially expressed genes were related to cell cycle regulation, apoptosis and immune-regulation, and oxidative stress resistance and DNA repair. In the ABC transporters pathway, the ATP-binding cassette (ABC) subfamily abca, abcb, and abcc gene expression levels, and the deoxycytidine, L-lysine, L-glutamic acid, L-threonine, ornithine, and uridine metabolite contents changed. Our results suggested that the cold stress may promote apoptosis through regulation of the FoxO signaling pathway. The ABC transporters may respond to cold stress by regulating amino acid metabolism. The results provided a comprehensive understanding of fish cold stress during overwintering, which will facilitate the breeding of new cold-resistant varieties of red tilapia in the future.

The Effect of Combined Exercises with and Without Blood Flow Restriction and Vitamin D Supplementation on Serum Levels of Alkaline Phosphatase in Elderly Women: A Randomized Clinical Trial Study

The Effect of Combined Exercises with and Without Blood Flow Restriction and Vitamin D Supplementation on Serum Levels of Alkaline Phosphatase in Elderly Women: A Randomized Clinical Trial Study

A simplified ratiometric fluorescent sensing strategy for enhanced detection of alkaline phosphatase employing Prussian blue nanozymes and commercially available chromogen

The traditional nanozymes-based ratiometric fluorescence sensing platforms usually necessitate the supplementary addition of fluorescent probes, therefore greatly restricting its convenient and broad application. In this study, a highly sensitive and selective ratiometric fluorescence platform for alkaline phosphatase (ALP) detection was established, only employing Prussian blue (PB) nanozymes and a commercially available chromogen of o-phenylenediamine (OPD). PB nanozymes with remarkable peroxidase-like (POD-like) activity can effectively catalyze OPD chromogen to yield 2,3-diaminophenazine (OPDox) with an intense yellow fluorescence at 573 nm emission peak. Target ALP can facilitate ascorbic acid 2-phosphate (AAP) dephosphorylation to generate phosphate and ascorbic acid (AA). Significantly, both these two resultant hydrolysis products could effectively decrease the OPDox generation via a dual-path based inhibition on the PB nanozymes POD-like activity. On the other hand, the generated dehydroascorbic acid (DHAA) from AA oxidation would exclusively react with OPD chromogen to yield 3-(dihydroxyethyl)furo[3,4-b]quinoxaline-1-one (DFQ) with a strong blue fluorescent signal at 434 nm, which further providing a significant enhancement on the sensing selectivity of ALP detection. As a result, an increased yellow fluorescence of OPDox and decreased blue fluorescence of DFQ could be clearly observed with different ALP addition. A robust linear relationship between the fluorescence ratio of F434/F573 and ALP activity ranging from 0.25 U/L to 6 U/L was obtained, with a low detection limit of 0.112 U/L. This proposed method demonstrates high sensitivity, excellent selectivity, cost-effectiveness, and operational simplicity, yet enabling an effective detection of ALP levels in human serum.

Association of serum alkaline phosphatase levels with bone mineral density, osteoporosis prevalence, and mortality in US adults with osteoporosis: evidence from NHANES 2005-2018.

The evidence regarding the association between serum T-ALP, BMD and osteoporosis prevalence in general population is incomplete, and limited evidence is available concerning its association with mortality among individuals with osteoporosis. The study investigated the association of serum T-ALP with BMD and osteoporosis prevalence in the general population, and examined its association with mortality in individuals with osteoporosis. All participants were adults from the NHANES (2005-2018), and mortality data were obtained from the National Death Index up to December 31, 2019. Firstly, the association of serum T-ALP with BMD and osteoporosis risk was assessed using linear regression model, subgroup analysis, analysis of covariance and weighted logistic regression model, respectively. Secondly, survival analysis including Kaplan-Meier curves, Cox proportional hazards models, and restricted cubic spline regression models were utilized to analyze the relationship between serum T-ALP levels and mortality risk. The study included 13,724 participants aged 18 to 85years, and 944 were diagnosed with osteoporosis, among whom 221 died during a median of 133months follow-up. Totally, elevated serum T-ALP was significantly associated with low BMD in femoral neck and lumbar spine, and the results exhibited consistency across diverse age, genders, races, and BMI subgroups. Moreover, for each 1 SD increase in T-ALP, there was a 0.5% increase in the prevalence of osteoporosis [OR (95%CI): 1.005 (1.005, 1.005), p < 0.001]. Among individuals with osteoporosis, for every 1 SD increase in T-ALP, the all-cause mortality increased by 0.4% [HR (95%CI):1.004 (1.002, 1.006), p < 0.001]. Meanwhile, comparing participants with highest serum T-ALP levels (> 79IU/L) to those with lowest levels (< 53IU/L) further raised the prevalence of osteoporosis [OR (95%CI):1.292 (1.021, 1.636), p = 0.033] and all-cause mortality [HR (95% CI):1.232 (1.041, 1.459), p = 0.015]. Based on a representative sample of US adults, elevated serum T-ALP levels were found to be significantly associated with both reduced BMD and an increased risk of osteoporosis across all participants, as well as with a higher all-cause mortality in individuals with osteoporosis.

Associations between serum levels of liver function biomarkers and all-cause and cause-specific mortality: a prospective cohort study

BackgroundThe liver plays critical roles in human health. Circulating level of liver function biomarkers may associate with the long-term and short-term mortality in general population.MethodsWe used data from US National Health and Nutrition Examination Survey 1988–94 and 1999–2014. People aged ≥ 20 years with measured serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), total bilirubin (TB), and albumin (ALB) at baseline were included. All-cause and cause-specific mortality was identified from the National Death Index through 31 December 2015. Additive Cox regression models were applied to assess the correlation patterns between the serum level of these analytes and mortality risk.ResultsA total of 44,508 participants were included; among them, 9,721 deaths occurred during a mean follow-up of 12.5 years. A “J-shaped” correlation was found between serum levels of ALT, AST, and TB and all-cause mortality. The risk of mortality monotonically increased with increasing GGT and ALP levels when their levels exceeded the valley points. A “L-shaped” correlation was found between the serum level of ALB and all-cause mortality. The correlation patterns were comparable among deaths from different causes and were consistent in subgroup and sensitivity analyses. While the integration of all six liver function biomarkers did not yield an optimal predictive performance for mortality (area under ROC curve = 0.706), it demonstrated a significantly better performance compared to any single biomarker..ConclusionCirculating liver function biomarkers showed diverse nonlinear correlations with mortality and may be utilized as part of a screening process to help identify individuals who may be at elevated risk of mortality.

A case study of hypophosphatasia: An underdiagnosed bone disorder characterized by low alkaline phosphatase.

Hypophosphatasia (HPP) is a rare genetic metabolic bone disorder that is underdiagnosed. Although there are many forms of this disease, based on age of onset, symptoms, and severity, HPP is characterized by low serum alkaline phosphatase levels, bone fractures, and dental complications. Diagnosis of HPP is made from clinical, laboratory, and radiologic findings. Genetic testing for an ALPL gene variant responsible for causing HPP confirms a molecular diagnosis. Distinguishing HPP from other more common bone disorders, such as osteoporosis, is important as the treatment for these diseases differs greatly. Although there is no known cure for HPP, treatment should be holistic and multidisciplinary.

Application of alkaline phosphatase-to-hemoglobin and lactate dehydrogenase-to-hemoglobin ratios as novel noninvasive indices for predicting severe acute pancreatitis in patients.

Preventing the progression of acute pancreatitis (AP) to severe acute pancreatitis (SAP) is crucial for AP patients. The use of clinical parameters in laboratory facilities for predicting SAP can be rapid, efficient, and cost-effective. This study aimed to investigate the predictive and prognostic value of collected clinical detection parameters, such as serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels, and their ratios, such as ALP-to-hemoglobin (Hb) and LDH-to-Hb ratios, for the prediction of SAP occurrence, complications, and mortality. In all, 50 healthy controls (CON), 455 patients with mild acute pancreatitis (MAP), 127 patients with moderately severe acute pancreatitis (MSAP), and 93 patients with SAP were included in the study. Thirty clinical parameters were collected, measured, compared, and analyzed. The ratios of ALP/Hb and LDH/Hb were subsequently calculated and evaluated with respect to gender and age and whether they could predict SAP occurrence, complications, and mortality. The results revealed that 15 parameters were significant for the prediction of AP. Furthermore, the following 6 indicators are associated with the occurrence of SAP: ALP, ALP/Hb, LDH, LDH/Hb, CRP, and blood glucose. Among these parameters, the predictive abilities of ALP/Hb and LDH/Hb for SAP were most effective. However, they fail to differentiate between MAP and MSAP or gender in SAP patients. Positive correlations were only observed between the levels of these indicators and age at onset of SAP. In addition, receiver operating characteristic (ROC) curves were generated to predict SAP incidence rates, complications, and mortality. The area under the curve (AUC) values for the ALP/Hb ratio ranged from 0.7097 to 0.7837, whereas those for the LDH/Hb ratio ranged from 0.5043 to 0.7778. These findings suggest that ALP and LDH alone or in combination with Hb possess unique predictive characteristics that may serve as independent factors for predicting SAP occurrence, complications, and mortality; of these, the ALP/Hb ratio is especially predictive of SAP mortality.

Comparison of Efficacy of Romosozumab With Denosumab and Risedronate in Patients Newly Initiating Glucocorticoid Therapy

Abstract Context Wnt/β-catenin signaling pathway is one of the pathogenic mechanisms of glucocorticoid-induced osteoporosis (GIOP). We previously reported the potential of inhibiting sclerostin as a treatment for GIOP. Objective To compare the efficacy of romosozumab (ROMO), a monoclonal antibody against sclerostin, with existing therapy for GIOP. Methods Patients with rheumatic diseases who had not previously received treatment for osteoporosis and were newly treated with prednisolone 15 mg/day or more were randomly assigned to receive ROMO, denosumab (DMAb), or bisphosphonates (BP). After the initiation of glucocorticoid therapy, we measured the bone mineral density (BMD) of the lumbar spine, femoral neck, and total hip every 6 months and bone turnover markers every 3 months for 12 months. Results Eleven patients were assigned to the ROMO group, 14 to the DMAb group, and 14 to the BP group. The median [25th to 75th percentile] percent change in lumbar spine BMD from baseline at 12 months was the greatest in the ROMO group (ROMO: 8.6 [3.1-12.4]%, DMAb: 3.3 [1.5-6.2]%, BP: −0.4 [−3.4-1.1]%). Among bone formation markers, serum levels of bone alkaline phosphatase were slightly elevated in the ROMO group, whereas those of N-terminal propeptide of type I procollagen and osteocalcin decreased in all 3 groups; however, these changes were smaller in the ROMO group. Serum levels of bone resorption markers and a urine bone quality marker decreased in all groups. Conclusion Treatment with ROMO significantly increased lumbar spine BMD in glucocorticoid-treated patients, suggesting that ROMO is effective for GIOP. Clinical trial number UMIN000037239

The correlation of Alkaline Phosphatase, lactate dehydrogenase, C-Reactive protein, erythrocyte sedimentation rate, and apparent diffusion coefficient values with Enneking staging and osteosarcoma subtypes

Apparent diffusion coefficient (ADC) values obtained from Magnetic Resonance Imaging (MRI) have shown potential as predictors of osteosarcoma staging and subtype, along with laboratory results for alkaline phosphatase (ALP), lactate dehydrogenase (LDH), c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). However, studies investigating this correlation are still relatively limited. These tests may be an alternative for osteosarcoma staging and subtyping, especially in low-resource settings. This study aims to investigate the correlation between the ADC value and laboratory findings with the staging and subtype of osteosarcoma. This retrospective study analyzed data from osteosarcoma patients from August 2021 to August 2023, including serum levels of ALP, LDH, CRP, ESR, and ADC values from MRI. A study of 39 osteosarcoma patients found that most were male (61.5%), with an average age of 19. The distal femur was the most common tumor location (33.3%), and osteosarcoma chondroblast type was the predominant subtype (30.8%). Enneking stage IIB was the most prevalent (79.5%). ALP, LDH, CRP, and ESR biomarkers significantly correlated with Enneking staging (p&lt;0.05). However, no correlations were found between these biomarkers and osteosarcoma subtype (p&gt;0.1). Additionally, no significant correlations were observed between the mean ADC and Enneking staging (p=0.061) or osteosarcoma subtype (p=0.084). ALP, LDH, CRP, and ESR levels have a strong and significant correlation to the staging of Enneking osteosarcoma. However, the mean ADC values on MRI do not have a significant correlation to the osteosarcoma subtype based on histopathology.

The Impact of a Ketogenic Diet on Late-Stage Pancreatic Carcinogenesis in Mice: Efficacy and Safety Studies.

High-fat diets (HFDs) have been associated with an increased risk of pancreatic cancer. In contrast, ketogenic diets (KDs) have been shown to display anti-tumor characteristics. The objective of this work was to evaluate the efficacy of a KD on late-stage pancreatic carcinogenesis in a genetically modified mouse model of pancreatic cancer [LSL-KrasG12D/+; Ptf1-Cre (KC) mice], as well as its liver safety, and to compare it to that of an HFD. Six-month-old female and male KC mice were randomly allocated to either a control diet (CD) (%kcal: 20% fat, 15% protein, 65% carbohydrates), an HFD (%kcal: 40% fat, 15% protein, 45% carbohydrate) or a KD (%kcal: 84% fat, 15% protein, 1% carbohydrate) and fed these diets for 6 months. HFD-fed, but not KD-fed, mice showed a 15% increase in body weight, plus elevated serum insulin (2.4-fold increase) and leptin (2.9-fold increase) levels, compared to CD-fed mice. At the pancreas level, no differences in pancreatic cancer incidence rates were observed among the diet groups. Regarding the liver safety profile, the HFD-fed mice had higher serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), when compared to the CD and KD groups. In addition, upon histologic examination, an HFD, but not a KD, showed a ~2-fold increase in both macro- and microsteatosis, as well as 35% and 32% higher levels of TLR4 and NF-κB activation, respectively, compared to CD-fed mice. In summary, although a KD intervention alone did not prevent pancreatic carcinogenesis, our data suggests that a KD modulates insulin signaling and hepatic lipid metabolism, highlighting its beneficial effects on healthspan and liver function when compared to an HFD.

Correlation Between Vitamin D Deficiency and Calcium, Phosphorus, Alkaline Phosphatase in Preterm Libyan Infants: Case-Control study

Vitamin D plays a vital role in regulating calcium and phosphorus levels and in bone mineralization. Vitamin D deficiency is a widespread issue contributing to metabolic bone disease in preterm infants. This study aimed to evaluate the biochemical parameters associated with varying levels of vitamin D deficiency. Serum samples were collected from preterm infants at the Neonatal Intensive Care Unit of Althawra Hospital Center, Al Beyda, Libya, from Feb-July 2019. The study included two groups: 62 preterm infants and a control group of 34 full-term infants. Serum levels of calcium, phosphorus, alkaline phosphatase, and 25OH-Vitamin D were measured using enzyme immunoassays and standard method. The study involved 62 preterm neonates, with a median gestational age of 32 weeks (range 28-36) and median birth weight of 1960 gm (range 900-2800 gm). The median levels recorded were calcium at 8.7 mg/dl (p=0.000), phosphorus at 4.1 mg/dl (p=0.584), ALP at 458 U/L (p=0.008), and vitamin D at 13.6 ng/ml. The prevalence of varying degrees of vitamin D deficiency was noted: very severe (9.7% &lt; 5 ng/ml), severe (19.4% 5-10 ng/ml), and overall deficiency (45% 10-20 ng/ml), and suboptimal (25.8% 20-30 ng/ml). Comparing preterm infants to the control group revealed statistically significant differences across all parameters (Vitamin D p=0.000, Ca p=0.007, PO4 p=0.036, and ALP p=0.000). All preterm infants exhibited inadequate vitamin D levels, and there was an inverse relationship between the biochemical parameters and vitamin D deficiency. Notably, the elevated ALP level could serve as a crucial marker for diagnosing vitamin D deficiency in clinical settings.

The circulatory levels and bone expression of MIR21, 34a, 155 and their target genes in a section of Egyptian Population

Bone tissue is constantly regenerated and repaired through a finely balanced process known as bone remodeling. Many miRNAs act as regulators of the signaling pathways involved in bone metabolic processes to maintain tissue homeostasis. This study aimed to assess the circulating levels of MIR21, MIR34a, and MIR155 in human serum and their bone expression, and the expression of bone turnover-related genes which can reflect the bone quality. This prospective study was conducted on 60 patients (30 males and 30 females) indicated for surgical interventions for neural decompression +/- fixation. Relative quantification of expression of MIR21, miR34a, and MIR155 and bone related genes was assayed using PCR. The serum levels of osteocalcin and Serum Bone Alkaline Phosphatase (sBAP) were assayed using a human ELISA kit. The main finding of the present work was the strong positive association between the circulating levels of only miR21 and MIR155 and their bone expression in the population under study and with bone markers and target genes Also, a positive association was found between both bone expression and circulating MIR21 levels with age and sBAP. These results suggest that the circulating levels of these microRNAs as early markers for the predication of bone quality.

Primary biliary cholangitis: Personalizing second-line therapies.

Primary biliary cholangitis (PBC) is an enigmatic, autoimmune disease targeting the small intralobular bile ducts resulting in cholestasis and potentially progression to biliary cirrhosis. Primarily affecting middle-aged women, the diagnosis of PBC is typically straightforward, with most patients presenting with cholestatic liver tests and the highly specific antimitochondrial antibody. For decades, the foundational treatment of PBC has been ursodeoxycholic acid, which delays disease progression in most patients but has no impact on PBC symptoms. Large cohort studies of patients with PBC have established the benefit of maximizing the reduction in serum alkaline phosphatase levels with ursodeoxycholic acid and the need to add second-line agents in patients who do not achieve an adequate response. Advances in the understanding of bile acid physiology have led to the development of new agents that improve cholestasis in patients with PBC and are predicted to reduce the risk of disease progression. Obeticholic acid, the first second-line therapy to be approved for PBC, significantly improves liver biochemistries and has been associated with improved long-term clinical outcomes but is limited by its propensity to induce pruritus. Elafibranor and seladelpar are peroxisome proliferator-activated receptor agonists recently approved for use in patients with PBC, whereas bezafibrate and fenofibrate are available as off-label therapies. They also have shown biochemical improvements among patients with an inadequate response to ursodeoxycholic acid but may improve symptoms of pruritus. Herein, we review the patient features to consider when deciding whether a second-line agent is indicated and which agent to consider for a truly personalized approach to PBC patient care.

Hard-to-treat autoimmune hepatitis and primary biliary cholangitis: The dawn of a new era of pharmacological treatment.

Patients with hard-to-treat autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC) are defined a posteriori as those who do not show a sufficient response or are intolerant to pharmacological treatments, thus not achieving biochemical surrogate endpoints that are associated with long-term liver-related-event-free survival. The absence of a recently harmonized definition of 'complete biochemical response within 6 months (CBR≤6M)', which is defined as the normalization of serum transaminase and IgG levels below the upper limit of normal (ULN) at ≤6 months after treatment initiation is regarded as hard-to-treat AIH. The implementation of CBR≤6M, in turn, has been facilitating clinical trials, e.g., between azathioprine and mycophenolate mofetil, to reconsider appropriate first-line steroid sparing agents, leading to a reduction in the number of hard-to-treat AIH cases. Regarding PBC, one of the disseminated definitions of hard-to-treat patients is the absence of POISE criteria, which are evaluated at 12 months with serum alkaline phosphatase and bilirubin levels, after the introduction of ursodeoxycholic acid. Hard-to-treat PBC not meeting the POISE criteria has very recently been the target population for the U.S. FDA-approved second-line drugs, elafibranor and seladelpar. In future pharmacological treatment of AIH and PBC, the primary objective for AIH is likely to focus on lowering the number of hard-to-treat patients with personalized steroid sparing treatment regimens. A challenging goal in PBC treatment is the further optimization of treatment surrogate endpoints, even to the stricter ALP normalization, with which an indication of second- or later-line drugs might be expanded, but could ultimately lengthen patients' long-term survival.

Levamisole Ameliorates Rheumatoid Arthritis by Downregulating the PI3K/Akt Pathway in SD Rats.

Background/Objectives: Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease characterized by a protracted course, high rates of morbidity, and disability yet lacks effective therapeutic modalities. Levamisole (LVM), an immunomodulatory drug, has been clinically reported for its potential in RA treatment, while its therapeutic mechanism toward RA remains to be elucidated. Hence, this study provides theoretical support for the application of LVM in the treatment of RA. Methods: This study employed male Sprague-Dawley (SD) rats to construct the adjuvant-induced arthritis (AIA) model, administering LVM orally (5 mg/kg, 15 mg/kg, and 45 mg/kg) for 25 days. An evaluation of LVM's therapeutic effects on RA was conducted through arthritis index scores, paw pad thickness, paw volume, hematoxylin and eosin (H&E) staining, 3D microcomputed tomography (micro-CT) scans, serum levels of pro-/anti-inflammatory cytokines, and serum biochemical indicators. Western blotting and immunohistochemistry staining were utilized to measure the expression levels of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) proteins in synovial and ankle joint tissues. Results: Treatment with the median dose of LVM (15 mg/kg, M-LVM) significantly reduced the arthritis index (p < 0.01), paw pad thickness (p < 0.001), and paw volume (p < 0.01) without affecting body weight. Additionally, M-LVM alleviated inflammatory lesions in the synovium and ankle joints and also normalized serum levels of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β). The Model group exhibited significant increases in serum levels of alkaline phosphatase (ALP) (p < 0.01), creatine kinase (CK) (p < 0.05), and glucose (GLU) (p < 0.001) compared with the Control group; however, M-LVM effectively regulated these parameters to normal levels. Western blotting and immunohistochemistry staining revealed that PI3K-/Akt-related proteins were highly expressed in the synovial and ankle joint tissues of rats in the Model group, while treatment with M-LVM significantly reduced the expression of these proteins. Furthermore, histological examination of major organs (heart, liver, lungs, kidneys, and thymus) showed no significant pathological changes, with the exception of the spleen, where M-LVM ameliorated splenic lesions. Conclusions: We demonstrate that LVM at an optimal dose substantially relieves synovitis and bone erosion in AIA rats by inhibiting the PI3K/Akt signaling pathway.

Therapeutic Effectiveness of Prunus dulcis for Nephroprotective and Hepatoprotective in Albino Mice

Background: Nephrotoxicity caused by GM is a complicated occurrence that results in a variety of structural and functional changes, including lesions in the glomerular region and proximal tubule damage, which leads to sudden kidney failure. The production of reactive oxygen species (ROS) has also been linked to GM. Acute hepatic impairments caused by medication might lead to rapid deterioration of liver function. Objective: The purpose of this study was to evaluate the suspension of nuts of Prunus dulcis at a lower dose (800 mg/kg, b.w.) and a higher dose (1600 mg/kg, b.w.) for nephroprotective and hepatoprotective activities. Materials and Methods: Drug-induced nephrotoxicity and drug-induced hepatotoxicity models were used to evaluate the nephroprotective and hepatoprotective activity using albino mice. A histopathological study was also performed. Results: Suspension of nuts Prunus dulcis exhibited significant nephroprotective and hepatoprotective activity. Suspension of nuts from Prunus dulcis at a higher dose (1600 mg/kg b.w.) showed higher nephroprotective and hepatoprotective activity compared to the lower dose (800 mg/kg). The nephroprotective activity was evident by decreased serum creatinine, uric acid, serum urea, and BUN, which were confirmed by histological study. The hepatoprotective effect was confirmed by significantly decreased serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, and total bilirubin levels in treated groups, which were further confirmed by histopathological study. Conclusion: The result suggests that Prunus dulcis possesses nephroprotective and hepatoprotective activities.

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

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