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Marine Drugs Oct 2023With rapid growth and high lipid contents, microalgae have become promising environmentally friendly candidates for renewable biodiesel and health supplements in our era...
With rapid growth and high lipid contents, microalgae have become promising environmentally friendly candidates for renewable biodiesel and health supplements in our era of global warming and energy depletion. Various pathways have been explored to enhance algal lipid production, especially gene editing. Previously, we found that the functional loss of PhoD-type alkaline phosphatase (AP), a phosphorus-stress indicator in phytoplankton, could lead to increased lipid contents in the model diatom , but how the AP mutation may change lipid composition remains unexplored. This study addresses the gap in the research and investigates the effects of PhoD-type AP mutation on the lipid composition and metabolic regulation in using transcriptomic and lipidomic analyses. We observed significantly modified lipid composition and elevated production of fatty acids, lysophosphatidylcholine, lysophosphatidylethanolamine, ceramide, phosphatidylinositol bisphosphate, and monogalactosylmonoacylglycerol after mutation. Meanwhile, genes involved in fatty acid biosynthesis were upregulated in mutant cells. Moreover, the mutant exhibited increased contents of ω-3 long-chain polyunsaturated fatty acid (LC-PUFA)-bound phospholipids, indicating that mutation could improve the potential bioavailability of PUFAs. Our findings indicate that AP mutation could influence cellular lipid synthesis and probably redirect carbon toward lipid production and further demonstrate that AP mutation is a promising approach for the development of high-value microalgal strains for biomedical and other applications.
Topics: Fatty Acids; Diatoms; Alkaline Phosphatase; Phospholipids; Fatty Acids, Unsaturated; Fatty Acids, Omega-3; Microalgae
PubMed: 37999384
DOI: 10.3390/md21110560 -
Paediatrics & Child Health Dec 2023Increasingly, laboratories flag low serum alkaline phosphatase (sALP) that are age-and sex-specific in paediatrics. The aim of this study was to report clinical...
OBJECTIVES
Increasingly, laboratories flag low serum alkaline phosphatase (sALP) that are age-and sex-specific in paediatrics. The aim of this study was to report clinical manifestations of paediatric patients with age-and sex-specific low sALP, thereby increasing awareness of its potential aetiologies.
METHODS
This retrospective Canadian tertiary care paediatric hospital study assessed all sALP of ambulatory patients aged less than 18 years from 2015 to 2017. The hospital used a Beckman Coulter AU assay to measure sALP and compared values to the Canadian age-and sex-specific reference intervals from CALIPER. All children who had at least one subnormal age-and sex-specific sALP were evaluated. A review of medical charts of included patients was performed and demographic characteristics, medical history and diagnosis were collected, and categorized under groups of medical disorders.
RESULTS
Of 11,874 included patients, 1,001 patients (9.2%) had low sALP. Of those, 48% (485/1,001) had transient low sALP activity and 9.6% (96/1,001) had persistently low sALP. Prolonged immobilization and inflammatory bowel disease represented the main aetiologies for persistently low sALP. Interestingly, 13.5% (13/96) of patients with persistently low sALP had no apparent aetiology.
CONCLUSIONS
Our results report aetiologies of low sALP in a Canadian paediatric population using age-and sex-specific Canadian reference ranges. This study highlights that healthcare providers should be aware that a low sALP may have clinical significance and should be repeated if warranted based on further clinical assessment.
PubMed: 38638542
DOI: 10.1093/pch/pxad031 -
PeerJ 2023Prostate cancer is the most common malignancy in men, and its incidence is increasing year by year. Some studies have shown that risk factors for prostate cancer are...
BACKGROUND
Prostate cancer is the most common malignancy in men, and its incidence is increasing year by year. Some studies have shown that risk factors for prostate cancer are related to insulin resistance. The triglyceride-glucose (TyG) index is a marker of insulin resistance. We investigated the validity of TyG index for predicting prostate cancer and the dose-response relationship in prostate cancer in relation to it.
OBJECTIVE
To investigate the risk factors of TyG index and prostate cancer prevalence.
METHODS
This study was screened from the First Affiliated Hospital of Xinjiang Medical University and included 767 people, including 136 prostate cancer patients in the case group and 631 healthy people in the control group. The relationship between TyG index and the risk of prostate cancer was analyzed by one-way logistic regression, adjusted for relevant factors, and multi-factor logistic regression analysis was performed to further investigate the risk factors affecting the prevalence of prostate cancer. ROC curves and Restricted Cubic Spline were established to determine the predictive value and dose-response relationship of TyG index in prostate cancer.
RESULTS
Blood potassium (OR = 0.056, 95% CI [0.021-0.148]), total cholesterol (OR = 1.07, 95% CI [0.792-1.444]) and education level (OR = 0.842, 95% CI [0.418-1.697]) were protective factors for prostate cancer, alkaline phosphatase, age, LDL, increased the risk of prostate cancer (OR = 1.016, 95% CI [1.006-1.026]) (OR = 139.253, 95% CI [18.523-1,046.893] (OR = 0.318, 95% CI [0.169-0.596]); TyG index also was a risk factor for prostate cancer, the risk increased with TyG levels,and persons in the TyGQ3 group (8.373-8.854 mg/dL) was 6.918 times (95% CI [2.275-21.043]) higher than in the Q1 group,in the TyGQ4 group (≥8.854) was 28.867 times of those in the Q1 group (95% CI [9.499-87.727]).
CONCLUSION
TyG index may be a more accurate and efficient predictor of prostate cancer.
Topics: Male; Humans; Retrospective Studies; Insulin Resistance; Prostatic Neoplasms; Alkaline Phosphatase; Glucose
PubMed: 37953784
DOI: 10.7717/peerj.16313 -
Kidney International Reports Apr 2024Secondary hyperparathyroidism (SHPT) increases the risk of fractures and cardiovascular (CV) disease in patients on hemodialysis (HD). The relationship between...
INTRODUCTION
Secondary hyperparathyroidism (SHPT) increases the risk of fractures and cardiovascular (CV) disease in patients on hemodialysis (HD). The relationship between parathyroid hormone (PTH) and outcomes has been inconsistent, possibly due to variable bone responsiveness to PTH. The KDIGO guideline suggests monitoring total alkaline phosphatase (ALP), but the role of ALP versus PTH in the management of mineral and bone disorder (MBD) is not clear.
METHODS
The analysis included 28,888 patients on HD in 9 countries in Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 3 to 7 (2005-2021). The primary exposures of interest were normalized ALP and PTH, which are raw values divided by facility upper normal limit, measured at study enrollment. Cox models were used to estimate hazard ratios of all-cause or CV mortality and any or hip fracture adjusted for potential confounders. Linear mixed models, adjusted for potential confounders, were employed to investigate the relationship between normalized ALP levels and patient characteristics.
RESULTS
Normalized PTH showed a J-shaped association with all-cause or CV mortality, and a weak linear association with fracture. In contrast, normalized ALP showed a strong association with all outcomes. Factors associated with higher ALP levels after controlling for PTH included Black race, longer dialysis vintage, diabetes mellitus, hypocalcemia, hypophosphatemia, elevated C-reactive protein (CRP), and the use of cinacalcet.
CONCLUSION
Total ALP is a more robust exposure of adverse outcomes than PTH in patients on HD. PTH responsiveness is affected by race, primary renal disease, comorbidities, and mineral metabolism and therapy. Our results indicate that it may be useful to evaluate target organ response, rather than PTH alone when considering the consequences of (SHPT).
PubMed: 38765600
DOI: 10.1016/j.ekir.2024.01.002 -
Journal of the American Heart... Feb 2024Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive and ultimately fatal cardiomyopathy. Biomarkers reflecting multiorgan dysfunction are of increasing...
BACKGROUND
Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive and ultimately fatal cardiomyopathy. Biomarkers reflecting multiorgan dysfunction are of increasing importance in patients with heart failure; however, their significance in ATTR-CA remains largely unknown. The aims of this study were to characterize the multifaceted nature of ATTR-CA using blood biomarkers and assess the association between blood biomarkers and prognosis.
METHODS AND RESULTS
This is a retrospective cohort study of 2566 consecutive patients diagnosed with ATTR-CA between 2007 and 2023. Anemia (39%), high urea (52%), hyperbilirubinemia (18%), increased alkaline phosphatase (16%), increased CRP (C-reactive protein; 27%), and increased troponin (98.2%) were common findings in the overall population, whereas hyponatremia (6%) and hypoalbuminemia (2%) were less common. These abnormalities were most common in patients with p.(V142I) hereditary ATTR-CA, and became more prevalent as the severity of cardiac disease increased. Multivariable Cox regression analysis demonstrated that anemia (hazard ratio [HR], 1.19 [95% CI, 1.04-1.37]; =0.01), high urea (HR, 1.23 [95% CI, 1.04-1.45]; =0.01), hyperbilirubinemia (HR, 1.32 [95% CI, 1.13-1.57; =0.001), increased alkaline phosphatase (HR, 1.20 [95% CI, 1.01-1.42; =0.04), hyponatremia (HR, 1.65 [95% CI, 1.28-2.11]; <0.001), and troponin-T >56 ng/L (HR, 1.72 [95% CI, 1.46-2.03]; <0.001) were all independently associated with mortality in the overall population. The association between biomarkers and mortality varied across the spectrum of genotypes and left ventricular ejection fraction, with anemia remining independently associated with mortality in p.(V142I) hereditary ATTR-CA (HR, 1.58 [95% CI, 1.17-2.12]; =0.003) and in a subgroup of the overall population with a left ventricular ejection fraction ≤40% (HR, 1.39 [95% CI, 1.08-1.81]; =0.01).
CONCLUSIONS
Cardiac and noncardiac biomarker abnormalities were common and reflect the complex and multifaceted nature of ATTR-CA, with a wide range of biomarkers remaining independently associated with mortality. Clinical trials are needed to investigate whether biomarker abnormalities represent modifiable risk factors that if specifically targeted could improve outcomes.
Topics: Humans; Prealbumin; Cardiomyopathies; Amyloid Neuropathies, Familial; Stroke Volume; Retrospective Studies; Alkaline Phosphatase; Hyponatremia; Ventricular Function, Left; Prognosis; Biomarkers; Anemia; Hyperbilirubinemia; Urea
PubMed: 38314569
DOI: 10.1161/JAHA.123.033094 -
BMC Nephrology Aug 2023To study the influencing factors for coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients and the relationship between CAC and bone metabolism...
BACKGROUND
To study the influencing factors for coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients and the relationship between CAC and bone metabolism markers and to attempt to find a reliable marker linking vascular calcification and bone metabolism in MHD patients.
METHODS
A total of 123 patients were enrolled. CAC was assessed by multislice spiral computed tomography (MSCT), and the CAC score (CACS) was evaluated using the Agaston method. Routine laboratory parameters, including triglycerides (TG), total cholesterol (TC), glucose (Glu), calcium (Ca), phosphorus (P), magnesium (Mg), etc., were measured. Serum markers of bone metabolism, such as alkaline phosphatase(ALP), calcitonin (CT), 25-hydroxy vitamin D [25-(OH)D], intact parathyroid hormone (iPTH), total type I procollagen amino-terminal peptide (tPINP), N-terminal mid-fragment of osteocalcin (N-MID OC), and β-type I collagen crosslinked carboxyl-terminal peptide (β-CTX), were also measured.
RESULTS
Among 123 MHD patients, 37 patients (30.08%) did not have CAC, and 86 patients (69.92%) had CAC, including 41 patients (47.67%) with mild calcification and 45 patients (52.33%) with moderate to severe calcification. Age, Body Mass Index(BMI), the prevalence of hypertension and diabetes mellitus, TC, Glu, P, and Ca×P in the calcification group were higher than those in the noncalcification group, whereas Mg, iPTH, tPINP, N-MID OC, and β-CTX were lower than those in the noncalcified group (P < 0.05). Compared with the mild calcification group (0
0.05). A logistic regression model was used to evaluate the influencing factors for CAC. The results showed that age, BMI, TC, Glu, P, and Ca×P were risk factors for CAC and its severity in MHD patients, whereas diabetes mellitus, Mg, and N-MID OC were protective factors for CAC in MHD patients. In addition, N-MID OC was a protective factor for the severity of CAC. After adjusting for the corresponding confounding factors, the results of the risk factors were consistent, and N-MID OC was still an independent protective factor for CAC and its severity. CONCLUSIONS
Elevated serum P and Ca×P were independent risk factors for CAC in MHD patients, and serum Mg may be an independent protective factor for CAC. CAC was closely related to abnormal bone metabolism and bone metabolic markers in MHD patients. Relatively low bone turnover can promote the occurrence and development of CAC. N-MID OC may be a reliable bone metabolic marker linking vascular calcification and bone metabolism in MHD patients.
Topics: Humans; Renal Dialysis; Coronary Artery Disease; Parathyroid Hormone; Vascular Calcification; Peptides; Alkaline Phosphatase
PubMed: 37582785
DOI: 10.1186/s12882-023-03286-z -
Journal of Clinical Medicine Apr 2024Hypophosphatasia is a rare genetic disease characterized by abnormal alkaline phosphatase activity and deficiency of bone and teeth mineralization. Hypophosphatasia is... (Review)
Review
Hypophosphatasia is a rare genetic disease characterized by abnormal alkaline phosphatase activity and deficiency of bone and teeth mineralization. Hypophosphatasia is well known in pediatrics with typical presentations in children, but mild forms can also be present in adults and are difficult to detect. We present the case of a 50-year-old woman referred for pain management, with a previous diagnosis of fibromyalgia. The association of clinical features (diffuse pain syndrome, early dental loosening, personal history of two fractures with osteoporosis, and family history of osteoporosis) with radiographic (heterotopic calcifications of the yellow and interspinous lumbar ligaments) and biological (low levels of total alkaline phosphatase) indices was suggestive of hypophosphatasia, which was confirmed by genetic analysis. We review and discuss the association between hypophosphatasia, musculoskeletal pain, and calcium pyrophosphate deposition and the importance of raising the diagnosis of adult-onset hypophosphatasia when facing these two rheumatologic entities.
PubMed: 38673536
DOI: 10.3390/jcm13082263 -
Cureus Sep 2023Voriconazole-induced periostitis (VIP) is an uncommon side effect typically seen in immunosuppressed patients requiring prolonged antifungal therapy. These patients can...
Voriconazole-induced periostitis (VIP) is an uncommon side effect typically seen in immunosuppressed patients requiring prolonged antifungal therapy. These patients can present with bone pain, fragility, and elevated alkaline phosphatase (ALP). We present a case of VIP in a 72-year-old immunocompromised female on antifungal therapy presenting with a comminuted intertrochanteric fracture after a ground-level fall. VIP, although rare, should be included as a differential diagnosis for patients presenting with bone pain and/or fractures with radiographic features of periostitis. This is particularly true when there is a history of or prior imaging suggesting a solid organ transplant. In these cases, a dedicated review of current medications noting long-term voriconazole use in the absence of underlying rheumatologic disease can result in a confident diagnosis.
PubMed: 37885496
DOI: 10.7759/cureus.45947 -
Nanomaterials (Basel, Switzerland) Jul 2023Alkaline phosphatase (ALP) is among the most studied enzymes by far, playing an important role in the metabolism of organisms and the regulation of protein activity....
Alkaline phosphatase (ALP) is among the most studied enzymes by far, playing an important role in the metabolism of organisms and the regulation of protein activity. Herein, a label-free composite nanoprobe is constructed by combining inorganic nanomaterials and aggregation-induced emission (AIE) molecule to achieve highly sensitive and selective detection of ALP. Negatively charged 9,10-bis [2-(6-sulfonatopropoxyl) naphthylethenyl] anthracene (BSNVA) molecule is synthesized, which has the AIE performance and can be assembled on the surface of amino-SiO nanoparticles through electrostatic interaction for fluorescence enhancement. MnO nanosheets are rich in negative charges, enabling them to be wrapped on the surface of the amino-SiO nanosphere to shield the positive charge on its surface, making it impossible for BSNVA to accumulate on the surface and then weakening the bio-fluorescence of the system. Furthermore, with catalyzed substrates induced by ALP, generating ascorbic acid and the redox reaction between ascorbic acid and MnO, the nanoprobe helps in realizing the high-sensitivity detection of ALP with a detection limit of 0.38 mU/mL. The proposed strategy requires no complex cleaning and modification processes and can overcome the quenching effect caused by the aggregation of traditional organic dyes, proving to be a simple, low-cost and "turn-on" fluorescent detection method for ALP.
PubMed: 37513149
DOI: 10.3390/nano13142138 -
International Journal of Pharmaceutics Apr 2024The study aimed to develop enzyme-degradable nanoparticles comprising polyphosphates and metal cations providing sustained release of the antibacterial drug ethacridine...
AIM
The study aimed to develop enzyme-degradable nanoparticles comprising polyphosphates and metal cations providing sustained release of the antibacterial drug ethacridine (ETH).
METHODS
Calcium polyphosphate (Ca-PP), zinc polyphosphate (Zn-PP) and iron polyphosphate nanoparticles (Fe-PP NPs) were prepared by co-precipitation of sodium polyphosphate with cations and ETH. Developed nanocarriers were characterized regarding particle size, PDI, zeta potential, encapsulation efficiency and drug loading. Toxicological profile of nanocarriers was assessed via hemolysis assay and cell viability on human blood erythrocytes and HEK-293 cells, respectively. The enzymatic degradation of NPs was evaluated in presence of alkaline phosphatase (ALP) monitoring the release of monophosphate, shift in zeta potential and particle size as well as drug release. The antibacterial efficacy against Escherichia coli was determined via microdilution assay.
RESULTS
NPs were obtained in a size range between 300 - 480 nm displaying negative zeta potential values. Encapsulation efficiency was in the range of 83.73 %- 95.99 %. Hemolysis assay underlined sufficient compatibility of NPs with blood cells, whereas drug and NPs showed a concentration dependent effect on HEK-293 cells viability. Ca- and Zn-PP NPs exhibited remarkable changes in zeta potential, particle size, monophosphate and drug release upon incubation with ALP, compared to Fe-PP NPs showing only minor differences. The released ETH from Ca- and Zn-PP nanocarriers retained the antibacterial activity against E. coli, whereas no antibacterial effect was observed with Fe-PP NPs.
CONCLUSION
Polyphosphate nanoparticles cross-linked with divalent cations and ETH hold promise for sustained drug delivery triggered by ALP for parental administration.
Topics: Humans; Pharmaceutical Preparations; Phosphoric Monoester Hydrolases; Drug Liberation; Hemolysis; Escherichia coli; HEK293 Cells; Nanoparticles; Anti-Bacterial Agents; Cations; Polyphosphates; Particle Size; Drug Carriers
PubMed: 38460768
DOI: 10.1016/j.ijpharm.2024.123983