Construction of the fluorescence sensing platform with a bifunctional Cu@MOF nanozyme for determination of alkaline phosphatase and its inhibitor.

In this work, a novel and sensitive fluorescence sensing system for alkaline phosphatase (ALP) was constructed using a bifunctional copper metal-organic framework (Cu@MOF) nanozyme, which had excellent oxidase-mimetic activity and fluorescence properties. Owing to the presence of 2-amino-1,4-benzenedicarboxylic acid (1,4-BDC-NH2) ligand, Cu@MOF displays excellent fluorescence performance at 444 nm. Additionally, Cu2+ endows the oxidase-like activity of Cu@MOF, which could trigger p-phenylenediamine (PPD) to be oxidized to a brown product (PPDox) and quench the photoluminescence of Cu@MOF through the inner filtration effect (IFE). As the preferential affinity of ATP for Cu2+, the catalytic activity of Cu@MOF was significantly reduced once ATP was added, thus PPD could not be oxidized and fluorescence was recovered. In the presence of ALP, ATP was hydrolyzed to adenosine and Pi, which allowed Cu@MOF to regain its catalytic activity and continued to catalyze the generation of PPDox. The fluorescence of Cu@MOF was therefore weakened once again. The ALP activity was directly proportional to the degree of decrease in fluorescence intensity. Thus, this novel fluorescence sensing strategy had a linear range of 0.5-60 U/L and the limit of detection was 0.14 U/L. The established sensing method could also be used to for ALP inhibitors screening, and achieved satisfactory results in determining the level of ALP activity in human serum.

Analysis of preoperative nutrition, immunity and inflammation correlation index on the prognosis of upper tract urothelial carcinoma surgical patients: a retrospective single center study.

BACKGROUND: SII, PNI, SIRI, AAPR, and LIPI are prognostic scores based on inflammation, nutrition, and immunity. The purpose of this study was to examine the prognostic value of the SII, PNI, SIRI, AAPR, and LIPI in patients with UTUC who underwent radical nephroureterectomy with bladder cuff excision. MATERIALS AND METHODS: Data of UTUC patients in Sichuan Provincial People's Hospital from January 2017 to December 2021 were collected. The optimal critical values of SII, PNI, SIRI, and AAPR were determined by ROC curve, and LIPI was stratified according to the dNLR and LDH. The Kaplan-Meier method was used to draw the survival curve, and Cox proportional hazard model was used to analyze the factors affecting the prognosis of UTUC patients. RESULTS: A total of 81 patients with UTUC were included in this study. The optimal truncation value of PNI, SII, SIRI and AAPR were determined to be 48.15, 596.4, 1.45 and 0.50, respectively. Univariate Cox proportional hazard regression showed that low PNI, high SII, high SIRI, low AAPR and poor LIPI group were effective predictors of postoperative prognosis of UTUC patients. Multivariate Cox proportional hazard regression showed that high SII was an independent risk factor for postoperative prognosis of UTUC patients. According to ROC curve, the prediction efficiency of fitting indexes of PNI, SII, SIRI, AAPR and LIPI is better than that of using them alone. CONCLUSIONS: The SII, PNI, SIRI, AAPR, and LIPI was a potential prognostic predictor in UTUC patients who underwent radical nephroureterectomy with bladder cuff excision.

Dissolved Organic Phosphorus Bond-Class Utilization by Synechococcus.

Dissolved organic phosphorus (DOP) contains compounds with phosphoester, phosphoanhydride, and phosphorus-carbon bonds. While DOP holds significant nutritional value for marine microorganisms, the bioavailability of each bond-class to the widespread cyanobacterium Synechococcus remains largely unknown. This study evaluates bond-class specific DOP utilization by Synechococcus strains from open and coastal oceans. Both strains exhibited comparable growth rates when provided phosphate, a phosphoanhydride (3-polyphosphate, 45-polyphosphate), or a DOP compound with both phosphoanhydride and phosphoester bonds (adenosine 5'-triphosphate). Growth rates on phosphoesters (glucose-6-phosphate, adenosine 5'-monophosphate, bis(4-methylumbelliferyl) phosphate) were variable, and neither strain grew on selected phosphorus-carbon compounds. Both strains hydrolyzed 3-polyphosphate, then adenosine 5'-triphosphate, and lastly adenosine 5'-monophosphate, exhibiting preferential enzymatic hydrolysis of phosphoanhydride bonds. The strains' exoproteomes contained phosphorus hydrolases, which combined with enhanced cell-free hydrolysis of 3-polyphosphate and adenosine 5'-triphosphate under phosphate deficiency, suggests active mineralization of phosphoanhydride bonds by these exoproteins. Synechococcus alkaline phosphatases presented broad substrate specificities, including activity towards the phosphoanhydride 3-polyphosphate, with varying affinities between strains. Collectively, these findings underscore the potentially significant role of compounds with phosphoanhydride bonds in Synechococcus phosphorus nutrition and highlight varied growth and enzymatic responses to molecular diversity within DOP bond-classes, thereby expanding our understanding of microbially-mediated DOP cycling in marine ecosystems.

Enzyme Cascade Amplification-Based Immunoassay Using Alkaline Phosphatase-Linked Single-Chain Variable Fragment Fusion Tracer and MnO2 Nanosheets for Detection of Deoxynivalenol in Corn Samples.

Deoxynivalenol (DON) is a common mycotoxin that contaminates cereals. Therefore, the development of sensitive and efficient detection methods for DON is essential to guarantee food safety and human health. In this study, an enzyme cascade amplification-based immunoassay (ECAIA) using a dual-functional alkaline phosphatase-linked single-chain fragment variable fusion tracer (scFv-ALP) and MnO2 nanosheets was established for DON detection. The scFv-ALP effectively catalyzes the hydrolysis of ascorbyl-2-phosphate (AAP) to produce ascorbic acid (AA). This AA subsequently interacts with MnO2 nanosheets to initiate a redox reaction that results in the loss of oxidizing properties of MnO2. In the absence of ALP, MnO2 nanosheets can oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to produce the blue oxidized product of TMB, which exhibits a signal at a wavelength of 650 nm for quantitative analysis. After optimization, the ECAIA had a limit of detection of 0.45 ng/mL and a linear range of 1.2-35.41 ng/mL. The ECAIA exhibited good accuracy in recovery experiments and high selectivity for DON. Moreover, the detection results of the actual corn samples correlated well with those from high-performance liquid chromatography. Overall, the proposed ECAIA based on the scFv-ALP and MnO2 nanosheets was demonstrated as a reliable tool for the detection of DON in corn samples.

Zinc Action in Vascular Calcification.

Although zinc's involvement in bone calcification is well-established, its role in vascular calcification, characterized by abnormal calcium and phosphorus deposition in soft tissues and a key aspect of various vascular diseases, including atherosclerosis, remains unclear. This review focuses on zinc's action in vascular smooth muscle cell (VSMC) calcification, including the vascular calcification mechanism. Accumulated research has indicated that zinc deficiency induces calcification in VSMCs and the aorta, primarily through apoptosis accompanied by a downregulation of smooth muscle cell markers. Moreover, zinc deficiency-induced vascular calcification operates independently of the action of alkaline phosphatase (ALP) activity, typically associated with osteogenic processes, but is partly regulated via inorganic phosphate transporter-1 (Pit-1). To date, research has shown that zinc regulates vascular calcification through a mechanism distinct from that of osteogenic calcification, providing insight into its dual effects on physiological and pathological calcification and thereby explaining the "zinc paradox," wherein zinc simultaneously increases osteoblastic calcification and decreases VSMC calcification.

Gastroprotective and microbiome-modulating effects of ubiquinol in rats with radiation-induced enteropathy.

Radiation enteritis is a frequently encountered issue for patients receiving radiotherapy and has a significant impact on cancer patients' quality of life. The gut microbiota plays a pivotal role in intestinal function, yet the impact of irradiation on gut microorganisms is not fully understood. This study explores the gastroprotective effect and gut microbiome-modulating potential of ubiquinol (Ubq), the reduced form of the powerful antioxidant CoQ-10. For this purpose, male albino rats were randomly assigned to four groups: Control, IRR (acute 7 Gy γ-radiation), Ubq_Post (Ubq for 7 days post-irradiation), and Ubq_Pre/Post (Ubq for 7 days pre and 7 days post-irradiation). The fecal microbiomes of all groups were profiled by 16S rRNA amplicon sequencing followed by bioinformatics and statistical analysis. Histopathological examination of intestinal tissue indicated severe damage in the irradiated group, which was mitigated by ubiquinol with enhanced regeneration, goblet cells, and intestinal alkaline phosphatase expression. Compared to the irradiated group, the Ubq-treated groups had a significant recovery of intestinal interleukin-1ß, caspase-3, nitric oxide metabolites, and thio-barbituric reactive substances to near-healthy levels. Ubq_Pre/Post group displayed elevated peroxisome proliferator-activated receptor (PPAR-γ) level, suggesting heightened benefits. Serum insulin reduction in irradiated rats improved post-Ubq treatment, with a possible anti-inflammatory effect on the pancreatic tissue. Fecal microbiota profiling revealed a dysbiosis state with a reduction of bacterial diversity post-irradiation, which was re-modulated in the Ubq treated groups to profiles that are indistinguishable from the control group. These findings underscore Ubq's gastroprotective effects against radiation-induced enteritis and its potential in restoring the gut microbiota's diversity and balance.

Alkaline Phosphatase: The Poor Man's iPTH - An Affordable Approach to Bone Health Assessment.

This review delves into relatively less discussed role of alkaline phosphatase (ALP) as an accessible alternative to intact parathyroid hormone (iPTH) in the context of bone health assessment, particularly focussing on its potential boon for underprivileged individuals with chronic kidney disease (CKD) in South Asia. The financial constraints faced by this demographic often hinder regular monitoring of iPTH levels. ALP emerges as a promising surrogate, offering a cost-effective and practical solution for bone health evaluation in resource-constrained settings.

Comparing the Soluble Form of Recombinant Human Insulin-like Growth Factor-1 (rhIGF-1) in Escherichia coli Using Thioredoxin as Fused and Co-expressed Protein.

INTRODUCTION: Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide with various physiological functions. Escherichia coli is one of the most desirable hosts for recombinant protein production, especially for human proteins whose post-translation modifications are not essential for their bioactivity, such as hIGF-1. OBJECTIVES: In this study, bacterial thioredoxin (Trx) was studied as a fused and non-fused protein to convert the insoluble form of recombinant human IGF-1 (rhIGF-1) to its soluble form in E. coli. METHODS: The rhIGF-1 was expressed in the E. coli Origami strain in the form of fused-Trx. It was co-expressed with Trx and then purified and quantified. In the next step, the biological activity of rhIGF-1 was evaluated by alkaline phosphatase (ALP) activity assay in human adipose-derived stem cells (hASCs) regarding the differentiation enhancement effect of IGF-1 through the osteogenic process. RESULTS: Results showed that Trx in both the fused and non-fused forms had a positive effect on the production of the soluble form of rhIGF-1. A significant increase in ALP activity in hASCs after rhIGF-1 treatment was observed, confirming protein bioactivity. CONCLUSION: It was strongly suggested that the overproduction of Trx could increase the solubility of co-expressed recombinant proteins by changing the redox state in E. coli cells.

Relationship between prostate-specific antigen, alkaline phosphatase levels, and time-to-tumor shrinkage: understanding the progression of prostate cancer in a longitudinal study.

BACKGROUND: This study delves into the complex interplay among prostate-specific antigen, alkaline phosphatase, and the temporal dynamics of tumor shrinkage in prostate cancer. By investigating the longitudinal trajectories and time-to-prostate cancer tumor shrinkage, we aim to untangle the intricate patterns of these biomarkers. This understanding is pivotal for gaining profound insights into the multifaceted aspects of prostate cancer progression. The joint model approach serves as a comprehensive framework, facilitating the elucidation of intricate interactions among these pivotal elements within the context of prostate cancer . METHODS: A new joint model under a shared parameters strategy is proposed for mixed bivariate longitudinal biomarkers and event time data, for obtaining accurate estimates in the presence of missing covariate data. The primary innovation of our model resides in its effective management of covariates with missing observations. Built upon established frameworks, our joint model extends its capabilities by integrating mixed longitudinal responses and accounting for missingness in covariates, thus confronting this particular challenge. We posit that these enhancements bolster the model's utility and dependability in real-world contexts characterized by prevalent missing data. The main objective of this research is to provide a model-based approach to get full information from prostate cancer data collected with patients' baseline characteristics ( Age , body mass index ( BMI ), GleasonScore , Grade , and Drug ) and two longitudinal endogenous covariates ( Platelets and Bilirubin ). RESULTS: The results reveal a clear association between prostate-specific antigen and alkaline phosphatase biomarkers in the context of time-to-prostate cancer tumor shrinkage. This underscores the interconnected dynamics of these key indicators in gauging disease progression. CONCLUSIONS: The analysis of the prostate cancer dataset, incorporating a joint evaluation of mixed longitudinal prostate-specific antigen and alkaline phosphatase biomarkers alongside tumor status, has provided valuable insights into disease progression. The results demonstrate the effectiveness of the proposed joint model, as evidenced by accurate estimates. The shared variables associated with both longitudinal biomarkers and event times consistently deviate from zero, highlighting the robustness and reliability of the model in capturing the complex dynamics of prostate cancer progression. This approach holds promise for enhancing our understanding and predictive capabilities in the clinical assessment of prostate cancer.

Progesterone regulates tissue non-specific alkaline phosphatase (TNSALP) expression and activity in ovine utero-placental tissues.

BACKGROUND: Tissue non-specific alkaline phosphatase (TNSALP; encoded by the ALPL gene) has a critical role in the postnatal regulation of phosphate homeostasis, yet how TNSALP activity and expression are regulated during pregnancy remain largely unknown. This study tested the hypothesis that progesterone (P4) and/or interferon tau (IFNT) regulate TNSALP activity during pregnancy in sheep. METHODS: In Exp. 1, ewes were bred and received daily intramuscular injections of either corn oil vehicle (CO) or 25 mg progesterone in CO (P4) for the first 8 days of pregnancy and were hysterectomized on either Day 9, 12, or 125 of gestation. In Exp. 2, ewes were fitted with intrauterine catheters on Day 7 of the estrous cycle and received daily intramuscular injections of 50 mg P4 in CO and/or 75 mg progesterone receptor antagonist (RU486) in CO from Days 8 to 15, and twice daily intrauterine injections of either control proteins (CX) or IFNT (25 µg/uterine horn/d) from Days 11 to 15 (treatment groups: P4 + CX; P4 + IFNT; RU486 + P4 + CX; and RU486 + P4 + IFNT) and were hysterectomized on Day 16. RESULTS: In Exp. 1, endometria from ewes administered P4 had greater expression of ALPL mRNA than ewes administered CO on Day 12. TNSALP activity appeared greater in the epithelia, stratum compactum stroma, and endothelium of the blood vessels in the endometrium and myometrium from ewes administered P4 than ewes administered CO on Day 12. On Day 125, TNSALP activity localized to uterine epithelial and endothelial cells, independent of P4 treatment. TNSALP activity in placentomes appeared greater in P4 treated ewes and was detected in endothelial cells and caruncular tissue in P4 treated but not CO treated ewes. In Exp. 2, endometrial homogenates from ewes administered RU486 + P4 + CX had lower TNSALP activity those for P4 + CX and P4 + IFNT ewes. Immunoreactive TNSALP protein appeared greater in the mid- and deep-glandular epithelia in RU486 + P4 + CX treated ewes as compared to the other treatment groups. Enzymatic activity appeared greater on the apical surface of the deep glandular epithelia in endometria from ewes treated with RU486 + P4 + CX compared to the other treatment groups. CONCLUSIONS: These results suggest that P4, but not IFNT, regulates the expression and activity of TNSALP in utero-placental tissues and has the potential to contribute to the regulation of phosphate availability that is critical for conceptus development during pregnancy.

Why are rare diseases underdiagnosed? A clinical management study on detection of primary biliary cholangitis in primary care.

Background: There are about 7,000 rare diseases that affect 10% of the world population. Primary biliary cholangitis, an autoimmune chronic liver disease of the interlobular bile ducts, is one of the most common causes of chronic cholestasis. However, it is a rare, often underdiagnosed and undertreated, disease which can lead to cirrhosis and liver failure. We aimed to assess the proportion of undetected primary biliary cholangitis patients in primary care through a clinical management process. Methods: We made two extractions of the clinical data concerning liver diseases, risk factors and laboratory tests from the databases of a sample of general practitioners, with a check and correction of mistakes. The clinical data of the patients without liver disease and major risk factors, and with serum Alkaline Phosphatase above the laboratory reference values, were re-evaluated by each general practitioner with an expert gastroenterologist. The patients with elevated Alkaline Phosphatase values and without evidence of intrahepatic or extrahepatic causes of cholestasis were considered suspected for primary biliary cholangitis and assessed for antimitochondrial antibodies test and specialist' s evaluation, according to present guidelines. Results: A total of 20,480 adults attending 14 general practitioners in the province of Brescia, Northern Italy, were included in the study. Nine patients had a prior primary biliary cholangitis diagnosis, with a prevalence of 43.9/100000. After excluding 2094 (10.2%) patient with liver diseases or other causes of cholestasis, 121 subjects with Alkaline Phosphatase above the reference values were re-evaluated by the general practitioners and gastroenterologist, and 27 patients without symptoms or signs of cholestasis were considered suspected for primary biliary cholangitis: 9 of them were tested for antimitochondrial antibodies, and three new primary biliary cholangitis cases were detected (+33%). Discussion and Conclusions: This study shows that there is a not negligible burden of undetected cases of adult rare diseases that can be diagnosed in primary care, through a disease management procedure, without modifying the routine clinical practice.

Ectonucleotidase inhibitors: targeting signaling pathways for therapeutic advancement-an in-depth review.

Ectonucleotidase inhibitors are a family of pharmacological drugs that, by selectively targeting ectonucleotidases, are essential in altering purinergic signaling pathways. The hydrolysis of extracellular nucleotides and nucleosides is carried out by these enzymes, which include ectonucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5'-nucleotidase (CD73). Ectonucleotidase inhibitors can prevent the conversion of ATP and ADP into adenosine by blocking these enzymes and reduce extracellular adenosine. These molecules are essential for purinergic signaling, which is associated with a variability of physiological and pathological processes. By modifying extracellular nucleotide metabolism and improving purinergic signaling regulation, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) inhibitors have the potential to improve cancer treatment, inflammatory management, and immune response modulation. Purinergic signaling is affected by CD73 inhibitors because they prevent AMP from being converted to adenosine. These inhibitors are useful in cancer therapy and immunotherapy because they may improve chemotherapy effectiveness and alter immune responses. Purinergic signaling is controlled by NTPDase inhibitors, which specifically target enzymes involved in extracellular nucleotide breakdown. These inhibitors show promise in reducing immunological responses, thrombosis, and inflammation, perhaps assisting in the treatment of cardiovascular and autoimmune illnesses. Alkaline phosphatase (ALP) inhibitors alter the function of enzymes involved in dephosphorylation reactions, which has an impact on a variety of biological processes. By altering the body's phosphate levels, these inhibitors may be used to treat diseases including hyperphosphatemia and certain bone problems. This article provides a guide for researchers and clinicians looking to leverage the remedial capability of ectonucleotidase inhibitors in a variety of illness scenarios by illuminating their processes, advantages, and difficulties.

Effects of microplastics on typical macrobenthos in sargassum ecosystems.

Recently, microplastics (MPs) have attracted extensive attention to their wide distribution and potential toxicity in ecosystems. However, there was a lack of research focused on MPs in seaweed bed ecosystems. This study investigated the distribution and toxicity of MPs in macrobenthos in Sargassum ecosystem. According to the in-situ investigation results, the abundance of MPs in the sediment was 0.9-2.3 items/g, the indoor microcosmic experiment was constructed. After exposure to MPs (0, 2, and 20 items/g) for 30 days, the abundance of MPs in macrobenthos exhibits a concentration-dependent increase. However, there was no significant bioaccumulation of MPs at the trophic level. The indoor toxicity test revealed that MPs induced oxidative stress and altered intestinal microflora composition in macrobenthos, even at actual environmental concentrations (2 items/g). It may result in a perturbation of the organism's homeostatic equilibrium. High-concentration (20 items/g) MPs had a greater impact on alkaline phosphatase (AKP) in Mollusks. The increase in AKP activity could be indicative of an adaptive mechanism in some macrobenthos while the decline in AKP activity might signal a decrease in their survival. These results elucidated the fate of MPs in ecosystem and the ecological risks of MPs to large benthic animals on model environmental conditions.

Impact of varying dissolved organic carbon load on sediment phosphorus release and its periodic mechanisms.

Phosphorus (P) release from sediment poses a severe challenge for eutrophication management in the aquatic environment. The dissolved organic carbon (DOC) concentrations in riverine ecosystems have shown an increasing trend due to intensified climate change and anthropogenic activities, while their impact on sediment P cycling remains unclear. To investigate the effects of different DOC loads on sediment P release and the underlying mechanisms, we conducted a two-month experiment in 15 plexiglass tanks, with five gradient-increasing target DOC concentrations set according to reality: control (S0), 5 mg/L (S5), 10 mg/L (S10), 15 mg/L (S15), and 20 mg/L (S20). The results demonstrated that: i) DOC enrichment promoted the sediment P mobilization and release, with the underlying mechanisms exhibited periodic characteristics. ii) reduced dissolved oxygen (DO) concentration and stimulated alkaline phosphatase activity (APA) were likely the primary and sustained facilitating mechanisms. While after the termination of DOC load, elevated pH level was also considered a contributing factor when chlorophyll a (Chl a) ranged between 5.9 µg/L and 7.7 µg/L iii) ultimate concentration of total P (TP) in the overlying water depended on DOC load. After DOC addition was terminated, decreased TP concentrations were observed when DOC concentration was in the range of 5-15 mg/L, which may be attributed to the direct uptake of P by phytoplankton counteracting the minor promotion of P release induced by anoxic conditions. However, when DOC concentrations exceeded 15-20 mg/L, there were notable increments in TP concentrations. Our findings provide further insight into the response mechanisms of sediment P release to the increasing organic C load in natural ecosystems. The impact of broader C forms or C loads on sediment P cycling needs to be fully elucidated and even quantified in future studies, especially through large-scale field investigations to further clarify the coupled roles between C and P.

Modified histological staining for the identification of arterial and venous segments of brain microvessels.

BACKGROUND: This study aimed to develop a modified histochemical staining technique to successfully identify arterial and venous segments of brain microvessels. NEW METHOD: Gelatin/red ink-alkaline phosphatase-oil red O (GIAO) staining was developed from the traditional gelatin-ink perfusion method. Oil red Chinese ink for brush writing and painting mixed with gelatin was used to label cerebral vascular lumens. Subsequently, alkaline phosphatase staining was used to label endothelial cells on the arterial segments of cerebral microvessels. Thereafter, the red ink color in vessel lumens was highlighted with oil red O staining. RESULTS: The arterial segments of the brain microvessels exhibited red lumens surrounded by dark blue walls, while the venous segments were bright red following GIAO staining. Meanwhile, the nerve fiber bundles were stained brownish-yellow, and the nuclei appeared light green under light microscope. After cerebral infarction, we used GIAO staining to determine angiogenesis features and detected notable vein proliferation inside the infarct core. Moreover, GIAO staining in conjunction with hematoxylin staining was performed to assess the infiltration of foamy macrophages. COMPARISON WITH EXISTING METHOD: Red Chinese ink enabled subsequent multiple color staining on brain section. Oil red O was introduced to improved the resolution and contrast between arterial and venous segments of microvessels. CONCLUSION: With excellent resolution, GIAO staining effectively distinguished arterial and venous segments of microvessels in both normal and ischemic brain tissue. GIAO staining, as described in the present study, will be useful for histological investigations of microvascular bed alterations in a variety of brain disorders.

Tumour burden score combined with albumin-to-alkaline phosphatase ratio predicts prognosis in patients with intrahepatic cholangiocarcinoma.

Tumour morphology (tumour burden score (TBS)) and liver function (albumin-to-alkaline phosphatase ratio (AAPR)) have been shown to correlate with outcomes in intrahepatic cholangiocarcinoma (ICC). This study aimed to evaluate the combined predictive effect of TBS and AAPR on survival outcomes in ICC patients. We conducted a retrospective analysis using a multicentre database of ICC patients who underwent curative surgery from 2011 to 2018. The Kaplan-Meier method was employed to examine the relationship between a new index (combining TBS and AAPR) and long-term outcomes. The predictive efficacy of this index was compared to other conventional indicators. A total of 560 patients were included in the study. Based on TBS and AAPR stratification, patients were classified into three groups. Kaplan-Meier curves demonstrated that 124 patients with low TBS and high AAPR had the best overall survival (OS) and recurrence-free survival (RFS), while 170 patients with high TBS and low AAPR had the worst outcomes (log-rank p < 0.001). Multivariate analyses identified the combined index as an independent predictor of OS and RFS. Furthermore, the index showed superior accuracy in predicting OS and RFS compared to other conventional indicators. Collectively, this study demonstrated that the combination of liver function and tumour morphology provides a synergistic effect in evaluating the prognosis of ICC patients. The novel index combining TBS and AAPR effectively stratified postoperative survival outcomes in ICC patients undergoing curative resection.

Predicting pathological complete response after neoadjuvant chemotherapy in breast cancer by clinicopathological indicators and ultrasound parameters using a nomogram.

The study explored the impact of pretreatment serum albumin-to-alkaline phosphatase ratio (AAPR) and changes in tumor blood supply on pathological complete response (pCR) in breast cancer (BC) patients following neoadjuvant chemotherapy (NACT). Additionally, a nomogram for predicting pCR was established and validated. The study included BC patients undergoing NACT at Yongchuan Hospital of Chongqing Medical University from January 2019 to October 2023. We analyzed the correlation between pCR and clinicopathological factors, as well as tumor ultrasound features, using chi-square or Fisher's exact test. We developed and validated a nomogram predicting pCR based on regression analysis results. The study included 176 BC patients. Logistic regression analysis identified AAPR [odds ratio (OR) 2.616, 95% confidence interval (CI) 1.140-5.998, P = 0.023], changes in tumor blood supply after two NACT cycles (OR 2.247, 95%CI 1.071-4.716, P = 0.032), tumor histological grade (OR 3.843, 95%CI 1.286-10.659, P = 0.010), and HER2 status (OR 2.776, 95%CI 1.057-7.240, P = 0.038) as independent predictors of pCR after NACT. The nomogram, based on AAPR, changes in tumor blood supply after two NACT cycles, tumor histological grade, and HER2 status, demonstrated a good predictive capability.

Circulating 25-hydroxycholecalciferol and calcium levels, and alkaline phosphatase activity among people living with and without human immunodeficiency virus and injecting drugs in kenya.

BACKGROUND: People who inject drugs (PWID) and living with the human immunodeficiency virus (PLHIV) are at higher risk of suffering marked derangements in micronutrient levels, leading to poor disease and treatment outcomes. Consequently, this can be monitored by measuring key biomarkers, such as total circulating (serum) 25-hydroxycholecalciferol (25(OH)D3), calcium, and alkaline phosphatase (ALP) for timely intervention. Therefore, circulating levels of 25(OH)D3 and calcium, and ALP activity were determined in PWID and are highly active anti-retroviral treatment (HAART)-experienced or -naive, along with those without HIV infection. METHODS: This cross-sectional study compared serum concentrations of 25(OH)D3, calcium, and ALP in Kenyan PLHIV and were HAART-naive (n = 30) or -experienced (n = 61), PWID and without HIV (n = 132). RESULTS: Circulating 25(OH)D3 levels were significantly different amongst the study groups (P < 0.001), and were significantly lower in the HAART-experienced (median, 17.3; IQR, 18.3 ng/ml; P < 0.001) and -naive participants (median, 21.7; IQR, 12.8 ng/ml; P = 0.015) relative to uninfected (median, 25.6; IQR, 6.8 ng/ml) PWID. In addition, the proportions of vitamin D deficiency (55.7%, 40.0%, and 17.4%) and insufficiency (31.1%, 53.3%, and 63.6%) compared to sufficiency (13.1%, 6.7%, and 18.9%; P < 0.001) were greater amongst HAART-experienced, -naive, and uninfected study groups, respectively. Likewise, serum total calcium concentrations were lower in the HAART-experienced relative to HIV-negative (P = 0.019) individuals. Serum ALP activity was also lower in the HAART-experienced in contrast to HIV-negative PWID (P = 0.048). Regression analysis indicated that predictors of circulating 25(OH)D3 were: age (ß = 0.287; R2 = 8.0%; P = 0.017) and serum ALP (ß = 0.283; R2 = 6.4%; P = 0.033) in the HAART-experienced PWID, and serum ALP (ß = 0.386; R2 = 14.5%; P < 0.001) in the HIV-negative PWID. CONCLUSION: This study suggests that HIV-1 infection and HAART, including injection substance use, decrease circulating 25(OH)D3, calcium and ALP activity. In addition, age and ALP activity are associated with low circulating vitamin D levels in HAART-experienced PWID. The results highlight the importance of incorporating vitamin D and calcium supplementation in treatment and rehabilitation protocols for PLHIV.

Would three BMPs at low concentration be better than one at high concentration? An experimental study with rat osteoprogenitor cells.

BACKGROUND: Bone morphogenetic proteins (BMPs) are used in clinical practice for stimulation of bone formation, but often evoke serious complications. Recent studies demonstrated that BMPs involved in early stages of bone formation are species specific. In cattle dominate BMP7, growth differentiation factor 5 (GDF5) and NEL-like protein 1 (NELL1) while in rats BMP2, BMP5 and BMP6. The purpose of the study was to compare the action of the species specific BMPs on the osteoprogenitor cells. Thus, rat osteoprogenitor cells were exposed to one BMP in a high dose and three of them at 1/3 of the former. MATERIALS AND METHODS: Isolated rat osteoprogenitor cells were treated in culture with different concentrations of BMP2, BMP5 and BMP6 or with lower concentration of combinations of these cytokines. Activity of alkaline phosphatase, calcium deposition and mRNA level for transcription factor SP7 (osterix) and tissue non-specific alkaline phosphatase (TNAP) served as indicators of BMPs effect. RESULTS: BMPs stimulated all studied parameters in comparison with control cultures, but no statistically significant differences were observed between the action of a large dose of one cytokine and a combination of cytokines given at lower concentrations. CONCLUSIONS: Three BMPs used in a low dose exert similar effect as the one used at high dose. Since the BMPs stimulate different receptors and activate different signaling pathways the use of the mixture of properly chosen BMPs at low concentration may give better results than the single one at high concentration and may avoid untoward effects.