Expression analysis of zinc-metabolizing enzymes in the saliva as a new method of evaluating zinc content in the body: two case reports and a review of the literature.

BACKGROUND: The activity level of alkaline phosphatase, a zinc-requiring enzyme in the serum, is used to indicate zinc nutritional status; however, it does not correlate with serum zinc levels or subjective symptoms of taste disorder in many cases. Hence, this study focused on the total activity of alkaline phosphatase, a zinc-requiring enzyme. The total alkaline phosphatasa activity level in the saliva was measured before and after zinc supplementation, and the results were compared with serum zinc levels. CASE PRESENTATION: This study included patients with hypozincemia, specifically a patient with zinc-deficient taste disorder (patient 1: a 69-year-old Japanese woman) and a patient with glossodynia with zinc deficiency (patient 2: an 82-year-old Japanese woman). Saliva samples were collected, and blood tests were performed before and after zinc supplementation. Subjective symptoms and serum zinc levels were simultaneously evaluated. Zinc supplementation was performed using zinc acetate hydrate or Polaprezinc. CONCLUSIONS: Total alkaline phosphatase activity levels were found to be associated with serum zinc levels and subjective symptoms. A further study with a higher number of patients is necessary to confirm whether total alkaline phosphatase activity levels more accurately reflect the amounts of zinc in the body than serum zinc levels.

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case-control study.

Vitamin D deficiency during infancy has been associated with increased bone turnover rate and bone mineral loss. However, few studies have examined bone turnover markers (BTMs) for both bone formation and resorption in infants with vitamin D deficiency. Here, we analyzed serum concentrations of 25OHD, intact parathormone (iPTH), and BTMs including total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and serum type I collagen N-telopeptide (NTx) as well as basic clinical characteristics of 456 infants (626 samples) aged less than 12 mo born at Saitama City Hospital, Japan (latitude 35.9° North) between January 2021 and December 2022. One hundred sixteen infants (147 samples) were classified as having vitamin D deficiency (25OHD < 12.0 ng/mL), and 340 infants (479 samples) had sufficient vitamin D levels (25OHD ≥ 12.0 ng/mL). In addition to 25OHD and ALP, both TRACP-5b and sNTx were measured in 331 infants (418 samples), while 90 infants (105 samples) had only TRACP-5b measured and 101 infants (103 samples) had only sNTx measured. Statistical comparison of 104 subjects each in the vitamin D deficiency and sufficiency groups after matching for the background characteristics revealed that the vitamin D deficiency group had significantly higher levels of ALP and iPTH compared with the sufficiency group (P = <.0001, .0012, respectively). However, no significant differences were found in TRACP-5b and NTx levels between the 2 groups (P = .19, .08, respectively). Our findings suggest discordant responses between bone formation and resorption markers in subclinical vitamin D deficiency during infancy.

Albumin-to-alkaline phosphatase ratio may be a better predictor of survival than sclerostin, dickkopf-1, osteopontin, osteoprotegerin and osteocalcin.

Objectives: The value of biochemical markers of bone turnover (BTMs) in predicting survival and disease remains unclear. In a prospective study we evaluated the novel biomarkers for bone turnover sclerostin, dickkopf-1 (DKK-1), osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC), as well as a traditional biomarker, alkaline phosphatase (ALP) in relation to risk of mortality, cardiovascular events and fractures. Participants: and Methods:Routine blood tests and serum BTMs, including ALP, were analyzed in patients with hip fracture n = 97, stroke n = 71 and healthy volunteers n = 83 (mean age 86, 83 and 77, respectively), followed for 7 years. Hazard Ratios (HR) were calculated for mortality, cardiovascular events and fractures in relation to these biomarkers. After adding the albumin-to-ALP ratio (AAPR) a post hoc analysis was performed. Results: 120 participants died during the study. In the entire group of patients and volunteers (n = 251) higher AAPR (HR 0.28, 95 % CI 0.14-0.59, p < 0.001) was associated with decreased mortality. OPN and OPG were associated with mortality risk only in the univariate statistical analysis. HR for high AAPR in relation to new cardiovascular events was borderline significant (HR 0.29, 95 % CI 0.08-1.06, p = 0.061). None of the examined biomarkers were associated with new fractures, nor with an increased risk of a new cardiovascular event. Conclusions: AAPR may be a better predictor of mortality than the more novel BTMs, and higher AAPR could be associated with longer life expectancy. Further studies should determine the clinical usefulness of AAPR as a biomarker of mortality and cardiovascular disease.

Biochemical Examination of Plasma Ghrelin Levels in Individuals Afflicted With Chronic Periodontal Disease: A Comparative Study.

OBJECTIVE: This study intended to assess plasma ghrelin levels in individuals with chronic periodontitis and analyze potential associations with bone turnover indicators, serum cytokines, and periodontal parameters. MATERIAL AND METHODS: The research contained 80 patients each with 40 individuals with periodontally healthy controls (C) (28 males, 12 females) and 40 chronic periodontitis (CP) patients (29 males, 11 females). The blood samples were analyzed for soluble receptor activator nuclear factor kappa B ligand (sRANKL), interleukin-1 beta (IL-1ß), total and acylated ghrelin, tumor necrosis factor-alpha (TNF-α), osteocalcin (OSC) and alkaline phosphatase (ALP), and periodontal parameters were recorded. RESULTS: The CP group had considerably higher plasma concentrations of both acylated and total ghrelin than the C group (p<0.05). Gender-based investigation showed substantial differences only among men in both groups (p<0.05). Hence, no significant modifications were identified in serum sRANKL, TNFα, and ALP levels between the groups. However, there was a notable difference in serum OSC and IL-1ß levels in the CP group (p<0.05). Furthermore, total ghrelin/acylated ghrelin and total ghrelin/ALP revealed positive correlations. No significant association was found between symptoms and ghrelin levels. CONCLUSION: The study findings indicate elevated levels of ghrelin and acylated ghrelin in male CP patients.

Bioactivity of human dental pulp-derived stem cells with boron-controlled S-PRG filler eluate by anion exchange.

Surface pre-reacted glass-ionomer (S-PRG) filler is a bioactive glass filler capable of releasing various ions. A culture medium to which was added an S-PRG filler eluate rich in boron was reported to enhance alkaline phosphatase (ALP) activity in human dental pulp-derived stem cells (hDPSC). To clarify the role of boron eluted from S-PRG fillers, the modified S-PRG filler eluate with different boron concentrations was prepared by using an anion exchange material. Therefore, elemental mapping analysis of anion exchange material, adsorption ratio, hDPSCs proliferation and ALP activity were evaluated. For statistical analysis, Kruskal-Wallis test was used, with statistical significance determined at p<0.05. ALP activity enhancement was not observed in hDPSC cultured in the medium that contained the S-PRG filler eluate from which boron had been removed. The result suggested the possibility that an S-PRG filler eluate with controlled boron release could be useful for the development of novel dental materials.

Increasing Natural Killer Cell Activity of Mineral Nanomaterial ALP1018 in Healthy Adults: A Randomized, Double-Blind, Placebo Comparative Clinical Trial.

This randomized, double-blind, placebo comparative clinical trial aimed to determine the immune-enhancing effects and safety of a nanomaterial with iron and zinc (ALP1018) in healthy adults. Participants who met the inclusion criteria were recruited for this study (n = 80) and randomly assigned to either the test group (n = 40), which was given Alp1018 in capsule form, or the placebo group (n = 40), which was given crystal cellulose capsules of identical appearance, weight, and flavor for 8 weeks. Compared to baseline, natural killer (NK) cell activity (%) increased in the test group after 8 weeks, although there were no changes in the placebo group. Furthermore, in the subgroup analysis of Coronavirus disease 2019 (COVID-19) affected participants, significantly increased NK cell activity was observed in the test group at 4 (p < 0.05) and 8 weeks (p < 0.05). No significant differences were observed in cytokine levels between the two groups. ALP1018 supplementation appeared to enhance immune function by improving NK cell activity without adverse effects in healthy adults.

A Case of Hypophosphatasia With Normal Alkaline Phosphatase Levels.

Background/Objective: Hypophosphatasia (HPP) is a rare disease associated with low serum alkaline phosphatase (ALP) activity. Here, we present a case of a patient with normal serum ALP levels diagnosed with HPP. Case Report: A 36-year-old woman presented with progressive fatigue, weakness, and joint pain. She had been evaluated in the past for genetic disorders due to these symptoms and was found to have a history of several total ALP levels within normal limits but elevated vitamin B6 levels. She also reported having loose teeth and "gray gums" during her childhood. Bone-specific ALP was tested for suspicion of HPP and returned at 4.4 µ/L (reference range, 5.3-19.5 µg/L), which prompted genetic testing. Genetic testing confirmed a positive pathogenetic variant of the ALPL gene, the c.542C>T (p.Ser181Leu) variant. She started asfotase alfa treatment to improve her symptoms. Discussion: HPP was diagnosed based on clinical suspicion supported by laboratory findings, which can cause it to be underdiagnosed or misdiagnosed. Current literature reports that a low total ALP level is the main biochemical marker of HPP and the only level needed to diagnose the disease. However, bone-specific ALP, a common marker used for bone turnover, has not been required to be tested. Conclusion: This case highlights a patient with normal total ALP, but low bone-specific ALP diagnosed with HPP confirmed by genetic testing. This case warrants future investigation into the diagnostic approach to HPP and the diagnostic utility between ALP and bone-specific ALP.

Association between blood markers and the progression of osseointegration in percutaneous prostheses patients-A pilot study.

Patients implanted with osseointegrated (OI) prosthetic systems have reported vastly improved upper and lower extremity prosthetic function compared with their previous experience with socket-suspension systems. However, OI systems have been associated with superficial and deep-bone infections and implant loosening due, in part, to a failure of the osseointegration process. Although monitoring the osseointegration using circulating biomarkers has clinical relevance for understanding the progression of osseointegration with these devices, it has yet to be established. Ten patients were enrolled in this study. Blood samples were collected at pre-selected times, starting before implantation surgery, and continuing to 12 months after the second surgery. Bone formation markers, bone resorption markers, and circulating amino acids were measured from blood samples. A linear mixed model was generated for each marker, incorporating patient ID and age with the normalized marker value as the response variable. Post hoc comparisons were made between 1 week before Stage 1 Surgery and all subsequent time points for each marker, followed by multiple testing corrections. Serial radiographic imaging of the residual limb containing the implant was obtained during follow-up, and the cortical index (CI) was calculated for the bone at the porous region of the device. Two markers of bone formation, specifically bone-specific alkaline phosphatase (Bone-ALP) and amino-terminal propeptide of type I procollagen (PINP), exhibited significant increases when compared with the baseline levels of unloaded residual bone prior to the initial surgery, and they subsequently returned to their baseline levels by the 12-month mark. Patients who experienced clinically robust osseointegration experienced increased cortical bone thickness at the porous coated region of the device. A medium correlation was observed between Bone-ALP and the porous CI values up to PoS2-M1 (p = .056), while no correlation was observed for PINP. An increase in bone formation markers and the lack of change observed in bone resorption markers likely reflect increased cortical bone formation induced by the end-loading design of the Utah OI device used in this study. A more extensive study is required to validate the correlation observed between Bone-ALP and porous CI values.

Evaluation of the genotoxicity, cytotoxicity, and bioactivity of calcium silicate-based cements.

BACKGROUND: As calcium silicate-based cements (CSCs) have found success in various vital pulp therapy applications, several new CSC products have emerged. This study aimed to assess the genotoxicity, cytotoxicity, and bioactivity of four CSCs by comparing the newly introduced materials Bio MTA+ and MTA Cem with previously studied materials, Biodentine and NeoMTA. METHODS: Genotoxicity was evaluated using the micronucleus (MN) assay in human peripheral blood lymphocyte cells, measuring MN frequency and nuclear division index (NDI). Cytotoxicity was assessed in human dental pulp stem cells through the Water-Soluble Tetrazolium Salt-1 (WST-1) colorimetric assay. Bioactivity was determined by ELISA, measuring the levels of angiogenic and odontogenic markers (BMP-2, FGF-2, VEGF, and ALP). Statistical analyses included ANOVA, Dunnet and Sidak tests, and Wald chi-square test. (p < .05). RESULTS: The MN frequency in the groups was significantly lower than that in the positive control group (tetraconazole) (p < .05). NDI values decreased with increasing concentration (p < .05). Bio MTA+ and NeoMTA showed decreased cell viability at all concentrations in 7-day cultures (p < .01). All materials increased BMP-2, FGF-2, and VEGF levels, with Biodentine and NeoMTA showing the highest levels of BMP-2 and FGF-2 on day 7. Biodentine displayed the highest VEGF levels on day 7. Biodentine and NeoMTA groups exhibited significantly higher ALP activity than the Bio MTA+ and MTA Cem groups by day 7. CONCLUSION: Bio MTA+ and MTA Cem demonstrated no genotoxic or cytotoxic effects. Moreover, this study revealed bioactive potentials of Bio MTA+ and MTA Cem by enhancing the expression of angiogenic and osteogenic growth factors.

A novel index to predict postoperative hypocalcemia in primary hyperparathyroidism.

BAKGROUND: Vitamin D (Vit D) deficiency is common in patients with hyperparathyroidism, but the importance of replacement before surgery is controversial. It can be predicted that hypocalcemia risk will be higher in patients with high bone turnover. AIM: In this study, the effect of preoperative ALP/Vit D ratio on postoperative hypocalcemia was investigated. METHODS: Among the primary hyperparathyroidism cases who were operated between 2015 and 2022, 158 patients with complete data were included in the study. Preoperative laboratory results, radiological images, and pathology reports of the patients were evaluated retrospectively. The cross-sectional value of the ALP/Vit D value predicting hypocalcemia was calculated. The effect of these parameters on postoperative hypocalcemia was investigated. RESULTS: The mean age of our patients was 54 (21-81 years). When factors affecting postoperative hypocalcemia were evaluated by univariable analysis, Vit D deficiency and insufficiency (p < 0.001), ALP (p < 0.001), ALP/Vit D ratio (p < 0.001), and T score (p = 0.026) found to be factors affecting postoperative hypocalcemia. In multivariate analysis, the ALP/Vit D ratio was found to be an independent variable in predicting hypocalcemia. It was found that hypocalcemia was 45 times more common in patients with ALP/Vit D > 6.34 (p < 0.001). ALP/Vit D ratio predicts patients who will develop postoperative hypocalcemia with 87.2% sensitivity and 87.1% specificity. CONCLUSIONS: Vit D deficiency increases the risk of postoperative hypocalcemia, but it is not sufficient alone to predict it. The risk increases more in patients with high bone turnover. The preoperative ALP/Vit D ratio is the strongest predictor of postoperative hypocalcemia risk.

Selenomethionine, a Trace Element, Increases Osteoblastic Activity of hFOB 1.19 Cells (an In Vitro Study).

Osteoporosis and resulting fractures affect a significant group of people in the world. It has been shown in many studies that selenium has positive effects on bone metabolism. Based on this information, the aim of this study is to investigate whether bone differentiation will start in a shorter time by applying selenomethionine (SeMet) to hFOB cells.First, hFOB 1.19 cells were cultured. Safe doses of SeMet were determined by MTT and LDH tests. Ossification levels were determined by alizarin red staining and measurement of alkaline phosphatase enzyme levels. The results were analyzed with statistical tests.It was observed that SeMet increased cell viability at concentrations of 10, 25, 50, 100, and 200 µM in 24 h. At these concentrations, cell viability increased above the control, the viabilities were as follows: 109.4%, 104.9%, 104.3%, 103.15%, and 100.27%. High doses of SeMet significantly reduce cell viability. According to Alizarin red staining, SeMet increases the amount of calcium deposits in hFOB cells in a dose-dependent manner. In the experimental groups, the highest ALP enzyme was determined in the 7-day SeMet application. The most effective dose was measured as 15 µM.It was determined that SeMet, which is found as a trace element in living things in nature, increases the viability of hFOB cells, which are osteoblast cell precursors, and increases osteoblastic differentiation and osteoblastic activity in these cells. Our results are at a level that sheds light on an important problem in public health.

Zinc Deficiency Promotes Calcification in Vascular Smooth Muscle Cells Independent of Alkaline Phosphatase Action and Partly Impacted by Pit1 Upregulation.

Inorganic phosphate (Pi) is a critical determinant of calcification, and its concentration is regulated by alkaline phosphatase (ALP) and Pit1. ALP is a key regulator of osteogenic calcification and acts by modulating local inorganic phosphate (Pi) concentrations through hydrolyzing pyrophosphate in the extracellular matrix (ECM). Pit1, a sodium-dependent phosphate transporter, regulates calcification via facilitating phosphate uptake within the cells. To investigate whether zinc differentially regulates osteoblastic and vascular calcifications, we examined ALP activity and Pit1 in osteoblastic and vascular smooth muscle cells (VSMCs). Our findings demonstrate that calcification in osteoblastic MC3T3-E1 cells is decreased via diminished ALP action under zinc deficiency. In contrast, zinc-deficiency-induced calcification in VSMCs is independent of ALP action, as demonstrated by very weak ALP activity and expression in calcified VSMCs. In zinc-deficient A7r5 VSMC, P accumulation increased with increasing Na phosphate concentration (3-7 mM) but not with ß-GP treatment, which requires ALP activity to generate Pi. Ca deposition also increased with Na phosphate in a dose-dependent manner; in contrast, ß-GP did not affect Ca deposition. In osteoblastic cells, Pit1 expression was not affected by zinc treatments. In contrast, Pit1 expression is highly upregulated in A7r5 VSMC under zinc deficiency. Using phosphonoformic acid, a competitive inhibitor of Pit1, we showed that calcification is inhibited in both A7r5 and MC3T3-E1 cells, indicating a requirement for Pit1 in both calcifications. Moreover, the downregulation of VSMC markers under zinc deficiency was restored by blocking Pit1. Taken together, our results imply that zinc-deficiency-induced calcification in VSMC is independent of ALP action in contrast to osteoblastic calcification. Moreover, Pit1 expression in VSMCs is a target for zinc deficiency and may mediate the inhibition of VSMC marker expression under zinc deficiency.

In vitro and in vivo genotoxicity evaluation of ALP1018, a nanomineral food supplement.

The use of nano-based dietary supplements is increasing around the world, as nanotechnology can help enhance nutrient bioavailability. ALP1018 is a newly developed iron-zinc complex supplement designed as a nanoformulation to improve the efficacy of iron and zinc supplementation. However, safety concerns have been raised, as there is no clear evaluation of ALP1018 toxicity. The goal of this study was to determine the potential mutagenicity and genotoxicity of ALP1018 through three standard screenings: the Ames test, which evaluates bacterial reverse mutations; the in vitro test of chromosomal aberration in Chinese hamster lung cells; and the in vivo micronucleus assay using ICR mice. ALP1018 showed no mutagenic effect, as no increase was observed in the presence or absence of metabolic activation (S9 mix) in revertant colonies on all the bacterial strains used in the Ames test. No structural chromosomal abnormalities were observed in the presence or absence of the S9 mix in mammalian cells used in the chromosomal aberration assay. In the micronucleus test, the frequency of micronucleated polychromatic erythrocytes was not significantly increased in mouse bone marrow cells. Based on these findings, we can conclude that ALP1018 is safe to use and has no mutagenic or genotoxic potential.

Rapidly derived equimolar Ca: P phasic bioactive glass infused flexible gelatin multi-functional scaffolds - A promising tissue engineering.

The study aims to design and fabricate an ultra-easier multi-functional biomedical polymeric scaffold loaded with unique equimolar Ca:P phasic bioactive glass material (BG). Gelatin (G) - 45S5 bioactive glass (BG) scaffolds were synthesized via a simple laboratory refrigerator with higher biocompatibility and cytocompatibility. The results proved that BG has enhanced bio-mineralization of the scaffolds and results support that the G: BG (1:2) ratio is the more appropriate composition. Brunauer-Emmett-Teller (BET) study confirms the higher surface area for pure Gelatin and G: BG (1:2). Scanning Electron Microscopic images display the precipitation of hydroxycarbonate apatite layer over the scaffolds on immersing it in simulated body fluid. Alkaline phosphate activity proved that G: BG (1:2) scaffold could induce mitogenesis in MG-63 osteoblast cells, thus helping in hard tissue regeneration. Sirius red collagen deposition showed that higher content bioactive glass incorporated Gelatin polymeric scaffold G: BG (1:2) could induce rapid collagen secretion of NIH 3T3 fibroblast cell line that could help in soft tissue regeneration and earlier wound healing. The scaffolds were also tested for cell viability using NIH 3T3 fibroblast cell lines and MG 63 osteoblastic cell lines through methyl thiazolyl tetrazolium (MTT) assay. Thus, the study shows a scaffold of appropriate composition G: BG (1:2) can be a multifunctional material to regenerate hard and soft tissues.

Ratio-fluorescent and naked-eye visualized dual-channel sensing strategy for Cu2+ and alkaline phosphatase activity assay.

The levels of Cu2+ and alkaline phosphatase (ALP) are the important indicators of the developed stage of the relative diseases. Herein, a binary ratio-fluorescent and smartphone-assisted visual strategy basing on 4'-aminomethyl-4, 5', 8-trimethylpsoralen (AMT) and the oxidation of o-phenylenediamine was developed. Under the action of Cu2+, the fluorescent molecule, 3-diaminophenazine (DAP) formed which can act as a fluorescent acceptor of the ratio-fluorescent sensor. The emission spectrum of AMT overlapped with the excitation spectrum of DAP and, thus, it can act as the fluorescent donor of the ratio-fluorescent sensor. With the increasing concentration of Cu2+ and ALP, the fluorescent intensity of AMT decreased and the fluorescent intensity of DAP increased. The dual-emission reverse change ratio-fluorescent sensor realized the sensitive detection Cu2+ and ALP with the detection limits of 2 nM and 0.03 U/mL, respectively. In addition, the acceptable recoveries were obtained when the Cu2+ and ALP in spiked samples were detected. Furthermore, the relative activity of ALP was assessed by increasing the concentrations of the inhibitor Na3VO4 and IC50 of 25 µM was obtained. Importantly, the target concentration-dependent color change of DAP allowed us to utilize R/B ratio values to design the smartphone-assisting visual detection model of Cu2+ and ALP activity with the detection limits of 0.1 µM and 0.18 U/mL. This simple, flexible, dual-mode sensor strategy has a potential for disease diagnosis and drug screening.

Enzyme-Induced Shape-Shifting Peptide Nanocarrier Coloaded with Paclitaxel and Dipyridamole Inhibits Platelet Function and Tumor Metastasis.

Tumor-associated platelets can bind to tumor cells and protect circulating tumor cells from NK-mediated immune surveillance. Tumor-associated platelets secrete cytokines to induce the epithelial-mesenchymal transition (EMT) in tumor cells, which promotes tumor metastasis. Combining chemotherapeutic agents with antiplatelet drugs can reduce the occurrence of metastasis, but the systemic application of chemotherapeutic agents and antiplatelet drugs is prone to causing serious side effects. Therefore, delivering drugs to the tumor microthrombus site for long-lasting inhibition is a problem that needs to be addressed. Here, we show that small molecule peptide nanoparticles containing the Cys-Arg-Glu-Lys-Ala (CREKA) peptide can deliver the platelet inhibitor dipyridamole (DIP) and the chemotherapeutic drug paclitaxel (PTX) to tumor tissues, thereby inhibiting tumor-associated platelet function while killing tumor cells. The drug-loaded nanoparticles PD/Pep1 inhibited platelet-tumor cell interactions, were effectively taken up by tumor cells, and underwent morphological transformation induced by alkaline phosphatase (ALP) to prolong the retention time of the drugs. After intravenous injection, PD/Pep1 can target tumors and inhibit tumor metastasis. Thus, this small molecule peptide nanoformulation provides a simple strategy for efficient drug delivery and shows promise as a novel cancer therapy platform.

Study of Cervical Mucus Cytology and Serum Inflammatory Biomarkers in Preterm Labour Compared to Term Pregnancy Cases in a Tertiary Care Center of Western Uttar Pradesh (UP), India.

PURPOSE: The onset of labor prior to 37 weeks of gestation is preterm labor. Incidence ranges from 5% to 7% of live births in developed countries, but higher in developing countries (10-13%). Preterm birth is a major threat in perinatal health care, as well as a risk factor for neurological impairment and disability. Considering that infection is the major risk factor for preterm labor in rural areas, this study was performed to assess the cytological changes in the cervical mucus of normal-term and preterm labor cases. METHOD: A hospital-based cross-sectional observational study was conducted in the Department of Obstetrics and Gynecology at a tertiary care center in western Uttar Pradesh (UP), India. The sample size calculated was 90. The neutrophil-to-lymphocyte ratio (NLR) in cervical mucus, along with serum inflammatory biomarkers such as CRP and serum alkaline phosphatase, were compared in both groups. RESULT: The incidence of preterm labor increased with an increase in parity, and progression to preterm delivery is faster in the higher parity group. C-reactive protein (CRP) (p value = < 0.001) and serum alkaline phosphatases (taking 220IU/L as the cutoff value), as well as the NLR (p value < 0.001) in cervical mucus in preterm labor, are significantly higher than those in term labor cases, which can be used to predict preterm labor. CONCLUSIONS: Higher levels of serum alkaline phosphatase (> 220 IU/L) and CRP positivity can be used as prognostic markers. Using a cutoff value of 5 for the NLR in the cervical mucus of preterm labor patients proved to be a highly accurate predictor (82.2%) for preterm labor diagnosis.

Plasma Markers for Therapy Response Monitoring in Patients with Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy.

BACKGROUND: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in plasma markers during PRRT can help identify patients with unfavorable outcomes. METHODS: A monocentric retrospective analysis of 141 patients with NET undergoing PRRT with [177Lu]Lu-DOTATOC was conducted. Changes in laboratory parameters were calculated by dividing the values determined immediately before each cycle of PRRT by the pretherapeutic value. Patients with low vs. high PFS were compared with the Wilcoxon rank-sum test. RESULTS: Progression, relapse, or death after PRRT was observed in 103/141 patients. Patients with low PFS showed a significant relative ALP increase before the third (p = 0.014) and fourth (p = 0.039) cycles of PRRT. Kaplan-Meier analysis revealed a median PFS of 24.3 months (95% CI, 20.7-27.8 months) in patients with decreasing ALP values (Δ > 10%) during treatment, 12.5 months (95% CI, 9.2-15.8 months) in patients with increasing ALP values (Δ > 10%), and 17.7 months (95% CI, 13.6-21.8 months) with stable ALP values (Δ ± 10%). CONCLUSIONS: Based on these exploratory data, a rise in plasma ALP might indicate disease progression and should be interpreted cautiously during therapy.

Do alkaline phosphatases have great potential in the diagnosis, prognosis, and treatment of tumors?

Alkaline phosphatase (ALP) is a group of enzymes that catalyze hydrolysis of phosphate esters at an alkaline pH, resulting in the generation of inorganic phosphate. These enzymes are widely distributed, and their activity is found in various tissues including bone, liver, intestine, and placenta. However, abnormalities in ALP expression and activity have been observed in certain types of cancer. In some cases, elevated serum levels of ALP are observed in patients with liver and bone metastasis. In other cases, increased levels of ALP have been observed in patients with pancreatic and lung cancer. On the other hand, low expression of ALP has also been associated with poor prognosis in patients with certain types of tumors, including colorectal cancer (CRC), breast cancer, and non-small cell lung cancer (NSCLC). In these cases, low ALP activity may be associated with decreased differentiation of cancer cells and increased cancer cell proliferation. Overall, the role of ALP in cancer is complex and context-dependent. This article reviews application progress of ALP in cancer, and we hypothesize that ALP might be a potential tumor biomarker, combined detection of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), bone-specific alkaline phosphatase (BSAP), carbohydrate antigen 19-9 (CA 19-9), lactate dehydrogenase (LDH) and ALP isozymes levels can be used for more accurate diagnosis of a particular tumor. Further research is needed to better understand the mechanisms underlying ALP dysregulation in cancer and to identify potential therapeutic targets.

PDZ and LIM Domain-Encoding Genes: Their Role in Cancer Development.

PDZ-LIM family proteins (PDLIMs) are a kind of scaffolding proteins that contain PDZ and LIM interaction domains. As protein-protein interacting molecules, PDZ and LIM domains function as scaffolds to bind to a variety of proteins. The PDLIMs are composed of evolutionarily conserved proteins found throughout different species. They can participate in cell signal transduction by mediating the interaction of signal molecules. They are involved in many important physiological processes, such as cell differentiation, proliferation, migration, and the maintenance of cellular structural integrity. Studies have shown that dysregulation of the PDLIMs leads to tumor formation and development. In this paper, we review and integrate the current knowledge on PDLIMs. The structure and function of the PDZ and LIM structural domains and the role of the PDLIMs in tumor development are described.