Tissue Calcium Research Articles

Endoplasmic Reticulum Stress in Myometrial Smooth Muscle Cells and Spontaneous Contraction Changes in the Uterus of Dehydroepiandrosterone-induced Polycystic Ovary Syndrome Rats.

Myometrial changes in polycystic ovary syndrome (PCOS) are poorly investigated. Thus, we aimed to investigate endoplasmic reticulum (ER) stress in myometrial smooth muscle cells and changes in spontaneous uterine contraction in PCOS. Twenty-one female Sprague-Dawley rats (21 days old) were divided into control (n = 7), vehicle (n = 7) and PCOS (n = 7) groups. While the control group was not injected subcutaneously, the vehicle group was injected subcutaneously with sesame oil (0.2 ml/day) for 20 consecutive days. The PCOS group was injected subcutaneously with dehydroepiandrosterone (6 mg/100 g/day dissolved in 0.2 ml sesame oil) for 20 consecutive days. Blood samples were collected for the measurement of follicle stimulating-hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) and glucose-regulated protein 78 (GRP78). The mRNA expression of GRP78 in the uterine tissue samples was analysed by quantitative real-time polymerase chain reaction. GRP78 protein expression was assessed by immunohistochemistry. Myometrial smooth muscle cells were examined by transmission electron microscopy. Uterine contractions were evaluated with isolated organ bath experiments. In the PCOS group, T and LH levels increased significantly, although FSH and E2 levels decreased, but this decrease was not statistically significant. Additionally, GRP78 levels increased significantly in the PCOS group. In the PCOS group, the mRNA level, immunostaining intensity of GRP78, and ER damage grade increased, but the uterine tissue calcium levels, and the frequency and amplitude of spontaneous uterine contractions decreased. The results indicated that increased ER stress in myometrial smooth muscle cells may play a causative role in the decreased spontaneous uterine contractions in PCOS.

Vitamin D3 alleviates the damage caused by high-fat and maintains lipid metabolism homeostasis in hepatopancreas by promoting fatty acid β-oxidation of Portunus trituberculatus

The purpose of present study was to evaluate the effects of vitamin D3 supplementation in high-fat diet on growth performance, calcium and phosphorus in tissue, immunity and lipid metabolism, and to explore whether adding vitamin D3 to high-fat diet can alleviate the adverse effects of high-fat diet on swimming crab (Portunus trituberculatus). The three experimental diets were normal fat diet (NFD, 9.35 % fat, 45.53 % protein), high fat diet (HFD, 14.69 % fat, 44.93 % protein) and high fat diet supplemented with 0.47 mg/kg VD3 (HFD+VD), respectively. A total of 108 healthy swimming crabs with an initial body weight of 9.42±0.13 g were selected for an 8-week feeding trial. The results showed that crabs fed with HFD+VD diet exhibited significantly higher percent weight gain (PWG), specific growth rate (SGR), feed efficiency (FE) and molting rate (MR) compared to those fed with HFD diet (P < 0.05). It was observed from hepatopancreas crude lipid content, TG content and hepatopancreas sections that HFD caused hepatopancreatic cell damage and abnormal lipid accumulation (P < 0.05), however, there were no significant differences in hepatopancreas crude fat content, TG content and hepatopancreas section observation between HFD+VD group and NFD group (P > 0.05). Crabs fed HFD diets with or without VD3 significantly down-regulated the expression of genes related to fatty acid transport, such as fabp9 and lpr1 in hepatopancreas (P < 0.05), moreover, the expression of genes related to fatty acid β-oxidation (cpt2 and acox1) were significantly up-regulated and genes related to lipid synthesis (fas and 6pgd) were significantly down-regulated in the hepatopancreas of the crabs fed with HFD+VD diet compared to those fed with HFD diet (P < 0.05). In conclusion, the results of present study indicated that a high-fat diet can cause deformation and rupture of hepatopancreas cells through abnormal lipid accumulation, thereby causing associated inflammation, leading to large calcium and phosphorus deposits in hemolymph and muscle, however, high fat diet supplemented with vitamin VD3 mainly enhanced the β-oxidation of fatty acids, inhibited lipid synthesis, alleviated abnormal lipid accumulation, and thus maintained the balance of lipid metabolism in hepatopancreas cells and promoted growth performance and feed utilization for swimming crab.

Placental Element Content Assessed via Synchrotron-Based X-ray Fluorescence Microscopy Identifies Low Molybdenum Concentrations in Foetal Growth Restriction, Postdate Delivery and Stillbirth.

Placental health and foetal development are dependent upon element homeostasis. Analytical techniques such as mass spectroscopy can provide quantitative data on element concentrations in placental tissue but do not show spatial distribution or co-localisation of elements that may affect placental function. The present study used synchrotron-based X-ray fluorescence microscopy to elucidate element content and distribution in healthy and pathological placental tissue. The X-ray fluorescence microscopy (XFM) beamline at the Australian Synchrotron was used to image trace metal content of 19 placental sections from healthy term (n = 5, 37-39 weeks), foetal growth-restricted (n = 3, <32 weeks, birth weight <3rd centile), postdate (n = 7, >41 completed weeks), and stillbirth-complicated pregnancies (n = 4, 37-40 weeks). Samples were cryo-sectioned and freeze-dried. The concentration and distribution of fourteen elements were detected in all samples: arsenic, bromine, calcium, chlorine, copper, iron, molybdenum, phosphorous, potassium, rubidium, selenium, strontium, sulphur, and zinc. The elements zinc, calcium, phosphorous, and strontium were significantly increased in stillbirth placental tissue in comparison to healthy-term controls. Strontium, zinc, and calcium were found to co-localise in stillbirth tissue samples, and calcium and strontium concentrations were correlated in all placental groups. Molybdenum was significantly decreased in stillbirth, foetal growth-restricted, and postdate placental tissue in comparison to healthy-term samples (p < 0.0001). Synchrotron-based XFM reveals elemental distribution within biological samples such as the placenta, allowing for the co-localisation of metal deposits that may have a pathological role. Our pilot study further indicates low concentrations of placental molybdenum in pregnancies complicated by foetal growth restriction, postdate delivery, and stillbirth.

Andrographis paniculata Ethanolic Extract Improved Doxorubicin-induced Cardiac Inflammation, Alterations in Liver Function Parameters and Anemia

Background: Doxorubicin (DOX), an efficacious chemotherapy drug is compromised by cardiotoxicity, myelosuppression, and hepatotoxicity. Due to the limited success of current treatments for DOX toxicity, there is a pressing need to explore alternative medical interventions, particularly from plant sources. This study was conducted to investigate the potential protective effect of ethanolic extract of Andrographis paniculata leaves (EEAP) against DOX-induced cardiac inflammation, liver toxicity, and anemia.Materials and methods: Sprague-Dawley rats were intraperitoneally injected with DOX at a total dose of 16 mg/kgBW. EEAP was administered orally for 4 weeks at doses of 125, 250, and 500 mg/kgBW/day according to the assigned treatment groups. The mRNA expression levels of interleukin-1β (IL-1β) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) in the heart tissue, along with the concentrations of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and calcium level were examined. Additionally, the hematological parameters (including hematocrit, hemoglobin and red blood cells (RBCs)), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels in blood were also analyzed.Results: EEAP dose-dependently decreased the mRNA expressions of IL-1β (p&lt;0.05), tended to decrease mRNA expression of NLRP3 and the concentrations of NFκB and calcium in heart tissue compared with the DOX-only group. Additionally, EEAP dose-dependently decreased ALP values (p&lt;0.0001) and tended to improve hematological parameters, as well as AST and MDA levels in serum.Conclusion: This extract may prevent DOX-induced cardiac inflammation, anemia, and hepatotoxicity. However, further studies are needed to confirm these findings, including the efficacy profile of the extract in cancer rats treated with DOX.Keywords: doxorubicin, Andrographis paniculata, inflammation, anemia, hepatotoxicity, herbal medicine

Methionine supplementation regulates eggshell quality and uterine transcriptome in late-stage broiler breeders

This study aimed to compare the effects of dietary methionine (Met) and 2-hydroxy-4-(methylthio)-butanoate (HMTBA) on the eggshell quality of broiler breeder hens and elucidate the mechanism of Met in improving eggshell quality from the perspectives of eggshell microstructure and shell gland physiological function. A total of 720 WOD188 broiler breeder hens at 40 wk old were assigned to 3 groups, with 8 replicates per group and 30 birds per replicate. Over 7 weeks, birds were fed a basal diet or the same diet supplemented with 0.15% Met or 0.17% HMTBA. Our findings revealed significant improvements in the Met group for egg shape index, shell thickness, breaking strength, and fracture toughness (P < 0.05), whereas the HMTBA group showed no significant improvements (P > 0.05). Met supplementation increased calcium and phosphorus levels in both serum and shell gland tissue (P < 0.05), and enhanced Ca2+ ATPase activity in shell gland tissue (P < 0.05). Histomorphological changes included enhanced mucosal fold dimensions and increased epithelial height in the shell gland (P < 0.05). Met also improved eggshell ultrastructure, resulting in a thicker effective layer and broader mammillae with fewer type B structures (P < 0.05). The mRNA levels for genes regulating eggshell ultrastructure, such as OC-116, CALB1, and ITM2C, were significantly upregulated in the Met group (P < 0.05). Transcriptome analysis identified 248 differentially upregulated genes in the Met group, primarily linked to the non-canonical Wnt/Ca2+ signaling pathway, crucial for calcium ion transport and cellular proliferation. This research highlights that Met supplementation improves eggshell quality by enhancing calcium transport and cellular proliferation in uterine function, particularly through the modulation of WNT11 and CALB1, influencing calcium deposition and ultrastructural development.

Impact and accumulation of calcium on soft-shell mud crab Scylla paramamosain in recirculating aquaculture system

Soft-shell crabs are highly valued for their commercial significance and culinary appeal. To enhance production of soft-shell crabs, careful attention should be paid to the water calcium concentration in their culture. This study investigated the influences of different levels of calcium concentrations on the molting and growth of mud crab (Scylla paramamosain) within a meticulously controlled recirculating aquaculture system (RAS). We established three distinct water calcium concentration gradients (200, 300, and 450 mg/L) to comprehensively assess feeding habits, molting patterns, growth, and tissue calcium levels of mud crab. Initially, we observed a gradual reduction in water calcium concentrations with increments of crab molting events in RAS. Throughout one molting cycle, the feeding incidence of the crabs remained consistently high from 4 days to 37 days post-molt, irrespective of different calcium concentrations. Nonetheless, high water calcium levels (300 and 450 mg/L) significantly shortened molt intervals and accelerated exoskeletal calcification. Specifically, the molt intervals were 52.30 ± 2.72 d, 41.65 ± 5.24 d, and 37.70 ± 3.02 d, while the carapace hardening durations were 21.51 ± 4.33 h, 17.23 ± 3.38 h, and 13.46 ± 2.76 h at water calcium concentrations of 200, 300, and 450 mg/L, respectively. Moreover, elevated calcium concentrations also significantly enhanced weight gain of the mud crab during molting. Noteworthy, regardless of fluctuations in water calcium concentration, the condition factor of the molting crabs was approximately 63%, which could be an indicator of crab selection in soft-shell crab cultivation. Furthermore, the dynamic changes in calcium concentrations were disparate among different tissues in the post-molt stage. Gill and exoskeleton tissues exhibited an upward trend in calcium concentrations, while hemolymph and hepatopancreas tissues displayed distinct patterns of decrease followed by increase. Gill and exoskeleton tissues were identified as primary sites for calcium absorption and utilization, evidenced by a positive correlation between high calcium concentrations and increased calcium content in these tissues at 6 h and 3 d post-molt. Overall, our findings provide practical evidence for optimizing aquaculture management strategies through adjustments in water calcium concentration, thus to enhance production efficiency and profitability in soft-shell mud crab aquaculture.

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.

Lipoprotein(a)'s Role in Atherosclerosis and Aortic Stenosis: A Contemporary Literature Review.

Lipoprotein(a), or Lp(a), is a distinctive lipoprotein particle linked to various cardiovascular diseases, notably atherosclerosis and aortic stenosis. Much like plasminogen, Lp(a) hinders normal fibrinolysis, leading to increased thrombosis and slower clearance of fibrin debris. It also causes inflammation, oxidative stress, and endothelial dysfunction, contributing to the formation of atherosclerotic lesions. Epidemiological studies have consistently shown that even slight increases in Lp(a) levels correlate with a heightened risk of cardiovascular events. Furthermore, Lp(a) plays a role in aortic stenosis by binding to leaflet valves, accumulating within them, and triggering calcium deposition and nodule formation. These calcium deposits gradually narrow the arteries, impeding blood flow. By raising inflammation and oxidative stress in the valve, Lp(a) accelerates tissue damage and calcium deposition. Traditional lipid-lowering therapies have limited efficacy in reducing Lp(a) levels. However, new treatments using RNA interference and antisense oligonucleotides to decrease Lp(a) production in the liver offer promising prospects for mitigating the risks and managing atherosclerosis and aortic stenosis associated with high Lp(a) levels. As Lp(a) screening becomes more common in healthcare, physicians will be better equipped to assess patients' risk levels and provide tailored treatments. This review aims to examine the role of Lp(a) in the development of aortic stenosis and atherosclerosis.

#289 Lipocalin-2 promotes cardiovascular calcification in chronic kidney disease by upregulating STAT3/NCOA4-mediated ferritinophagy and ferroptosis

Abstract Background and Aims Cardiovascular calcification (CVC) is a common complication of chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality without any effective therapies. To date, the underlying mechanism of CKD-CVC has not been elucidated. Recent studies suggest that ferroptosis is a novel programmed cell death that may play a role in the process of CKD-CVC, but the mechanism is largely unclear. Ferritinophagy is an important inducer of ferroptosis that is regulated by nuclear receptor coactivator 4 (NCOA4). However, the relationship between ferritinophagy and CKD-CVC has not been explored. Lipocalin-2 (LCN2) is an iron-trafficking protein that has been associated with both osteogenesis and ferroptosis, but the exact role and molecular mechanism of LCN2 in CKD-CVC needs to be explored. Method A cross-sectional clinical study was utilized to examine the association between LCN2 expression and CKD-CVC in serum and calcified radial arteries of CKD patients. LCN2 knockout mice, their wild type littermates and mice infected with VSMCs-targeted adeno-associated virus encoding LCN2 gene or negative control gene were all fed by the high adenine and phosphate diet to induce CKD-CVC.VSMCs transfected with LCN2-overexpressing lentivirus, LCN2-shRNA lentivirus or LCN2 siRNA and recombinant LCN2 stimulated VSMCs were treated under the condition of calcifying medium to investigate the role of LCN2 in CKD-CVC in vitro. Cardiovascular calcification was evaluated by Von-kossa staining and tissue calcium content assay. VSMCs calcification were checked by the Alizarin Red Staining and cellular calcium content assay. Cellular reactive oxygen species (ROS) were measured by the DCFDA assay. Lipid peroxidation was measured by the fluorescence of the fatty acid analog C11-BODIPY581/591 probe. Intracellular labile ferrous iron levels were measured by fluorescence of Phen Green SK probe and ferro-orange probe. Transmission electron microscopy was also used to examine mitochondrial change of ferroptosis. Results The cross-sectional study identified that LCN2 levels in serum and radial arteries were significantly increased as the severity of CKD-CVC increased. High adenine and phosphate diet intake provokes renal fibrosis and cardiovascular calcification in vivo. In vitro, five-days high phosphate sodium stimulation induced calcium deposition and osteoblastic trans differentiation of VSMCs. Meanwhile, high phosphate also increased the levels of ferroptosis in VSMCs as evidenced by decreased cell viability, iron and ROS accumulation, upregulated PTGS2 and MDA levels, reduced glutathione peroxidase 4 (GPX4) levels and significantly mitochondrial damage in VSMCs. Intriguingly, calcium deposition in VSMCs could be reversed by the ferroptosis inhibitor ferrostatin-1. LCN2 expression was significantly upregulated both in the aorta of mice and calcified VSMCs. Compared with WT mice, deletion of LCN2 inhibited cardiovascular calcification whereas VSMC-targeted LCN2 overexpression aggravated CKD-CVC. Consistently, LCN2 knockdown also alleviated calcium deposition of VSMCs. Meanwhile, inhibition of ferroptosis were observed after LCN2 silencing as evidenced by decreased ferrous and lipid oxidation while increased levels of GPX4. Mechanically, we demonstrated high phosphate increased the protein level of NCOA4 and downregulated FTH1, which was reversed by depletion of LCN2. Knockdown of NCOA4 partly alleviated the ferritin reduction, ferroptosis, and calcification in VSMCs, indicating that NCOA4-mediated ferritinophagy was required for VSMCs calcification. Furthermore, we found that the recombinant LCN2 treatment significantly upregulated phosphorylated STAT3. STAT3 signaling inhibitor abolished the recombinant LCN2 induced NCOA4 upregulation and calcification in VSMCs. Conclusion Our findings indicate that the pro-calcific effect of high phosphate is due to VSMCs ferroptosis mediated by LCN2 upregulation. LCN2 silencing alleviates CKD-CVC by suppressing the STAT3/ NCOA4/FTH1 signaling mediated ferritinophagy. LCN2 could serve as a candidate therapeutic strategy for CKD-CVC.

Direct red blood cell effect on thrombosis is dependent on the interaction of tissue factor and calcium with membrane phosphatidylserine.

Prior literature has implicated red blood cells (RBCs) in the initiation of thrombosis and suggests that posttransfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine (PS) is a prothrombotic phospholipid present within the RBC cell membrane. We hypothesized that RBC aggregation is dependent on the interaction between RBC membrane bound (exposed) PS, extracellular calcium, and tissue factor. Human whole blood (WB) was separated into components, including RBCs and platelet-rich plasma (PRP). Whole blood, PRP, and RBCs underwent impedance aggregometry utilizing arachidonic acid (AA), ADP, collagen, calcium, and tissue factor (TF)-based agonists. Red blood cells then underwent impedance aggregometry utilizing combined calcium and TF agonists. Red blood cells were pretreated with Annexin V, a known PS blocking agent, and underwent impedance aggregometry with combined calcium and TF agonists to determine if the mechanism of calcium/TF-induced RBC aggregability is dependent on PS. Red blood cells treated with calcium, TF, calcium+TF, and pre-treated with Annexin V followed by calcium+TF were perfused through an in vitro model of pulmonary microcirculatory flow. Red blood cell aggregation was significantly higher than that of WB and PRP when utilizing a TF agonist, an effect unique to TF. The combination of calcium and TF demonstrated significantly higher RBC aggregation than either agonist alone. Pretreatment with Annexin V resulted in a significantly reduced aggregability of RBC following treatment with TF + calcium. Red blood cells aged to 42 days did not exhibit significant change in aggregation. Exposure to calcium and TF significantly reduced time to thrombosis of RBCs perfused through a pulmonary microcirculatory model. Treatment with both TF and calcium synergistically induces RBC aggregation. Phosphatidylserine appears to play an integral role in the TF/calcium-based, age-independent RBC aggregation response. Red blood cells treated with TF + calcium exhibit more rapid thrombus formation in an in vitro model of pulmonary microcirculatory perfusion.

Initial agronomic benefits of enhanced weathering using basalt: A study of spring oat in a temperate climate.

Addressing soil nutrient degradation and global warming requires novel solutions. Enhanced weathering using crushed basalt rock is a promising dual-action strategy that can enhance soil health and sequester carbon dioxide. This study examines the short-term effects of basalt amendment on spring oat (Avena sativa L.) during the 2022 growing season in NE England. The experimental design consisted of four blocks with control and basalt-amended plots, and two cultivation types within each treatment, laid out in a split plot design. Basalt (18.86 tonnes ha-1) was incorporated into the soil during seeding. Tissue, grain and soil samples were collected for yield, nutrient, and pH analysis. Basalt amendment led to significantly higher yields, averaging 20.5% and 9.3% increases in direct drill and ploughed plots, respectively. Soil pH was significantly higher 256 days after rock application across cultivation types (direct drill: on average 6.47 vs. 6.76 and ploughed: on average 6.69 vs. 6.89, for control and basalt-amended plots, respectively), likely due to rapidly dissolving minerals in the applied basalt, such as calcite. Indications of growing season differences in soil pH are observed through direct measurement of lower manganese and iron uptake in plants grown on basalt-amended soil. Higher grain and tissue potassium, and tissue calcium uptake were observed in basalt-treated crops. Notably, no accumulation of potentially toxic elements (arsenic, cadmium, chromium, nickel) was detected in the grain, indicating that crops grown using this basaltic feedstock are safe for consumption. This study indicates that basalt amendments can improve agronomic performance in sandy clay-loam agricultural soil under temperate climate conditions. These findings offer valuable insights for producers in temperate regions who are considering using such amendments, demonstrating the potential for improved crop yields and environmental benefits while ensuring crop safety.

Reduction in Placental Metal and Metalloid in Preeclampsia: A Case-Control Study.

Preeclampsia is a primary placental disorder, with impaired placental vascularization leading to uteroplacental hypoperfusion. We aimed to investigate differences in metal and metalloid content between the placentas of women with preeclampsia and healthy controls. This was a case-control study in 63 women with preeclampsia and 113 healthy women. Clinical data were obtained from medical records. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the placental metals and metalloids content. Compared with healthy control subjects, preeclampsia was associated with a significantly lower concentration of essential elements (magnesium, calcium, iron, copper, zinc, and selenium) in the placental tissue. After multivariable adjustment, an interquartile range (IQR) increase in selenium concentration was associated with a reduced risk of preeclampsia with an OR of 0.50 (95% CI: 0.33-0.77). The joint effects of multiple selected metals and metalloids were associated with a reduced risk of preeclampsia. The lower placental magnesium, chromium, iron, zinc, and selenium concentrations of preeclampsia cases indicate a potential link to its pathogenesis. It also provides an intriguing avenue for future research in revealing the underlying mechanisms and potential intervention strategies for preeclampsia.

Serum and tissue metallome of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) patients have late presentation at the time of diagnosis and a poor prognosis. Metal dyshomeostasis is known to play a role in cancer progression. However, the blood and tissue metallome of PDAC patients has not been assessed. This study aimed to determine the levels of essential and toxic metals in the serum and pancreatic tissue from PDAC patients. Serum samples were obtained from PDAC patients before surgical resection. Tissue (tumor and adjacent normal pancreas) were obtained from the surgically resected specimen. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis was performed to quantify the levels of 10 essential and 3 toxic metals in these samples. Statistical analysis was performed to identify dysregulated metals in PDAC and their role as potential diagnostic and prognostic biomarkers. Significantly decreased serum levels of magnesium, potassium, calcium, iron, zinc, selenium, arsenic, and mercury and increased levels of molybdenum were shown to be associated with PDAC. There were significantly decreased levels of zinc, manganese and molybdenum, and increased levels of calcium and selenium in the pancreatic tumor tissue compared with the adjacent normal pancreas. Notably, lower serum levels of calcium, iron, and selenium, and higher levels of manganese, were significantly associated with a poor prognosis (i.e., overall survival) in PDAC patients. In conclusion, this is the first study to comprehensively assess the serum and tissue metallome of PDAC patients. It identified the association of metals with PDAC diagnosis and prognosis.

Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities.

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43- and ionized calcium (Ca2+). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.

Correction to: Nd: YAG laser irradiation consequences on calcium and magnesium in human dental tissues

Correction to: Nd: YAG laser irradiation consequences on calcium and magnesium in human dental tissues

The effects of dietary cadmium on growth, antioxidant defence system and feed evaluation performance of rainbow trout (Oncorhynchus mykiss)

The present study was carried out to determine the effect of dietary cadmium exposure on growth performance, changes in manganese, zinc, copper, calcium, magnesium, iron, selenium, and cadmium metals in liver and muscle tissue, liver antioxidant enzymes, and the histology of the fish. Rainbow trout (Oncorhynchus mykiss) with weights of 39.45 ±1.13 g was used in the experiment conducted in 2 groups and three replicates. The Control group was fed a cadmium-free diet, and the Cadmium group was fed a diet containing 5.03 µg/kg of cadmium twice a day until satiation. It was determined that cadmium intake through the diet affected growth rate and the feed evaluation performance negatively. In fish exposed to cadmium, manganese, zinc, copper, calcium, magnesium, iron, selenium, superoxide dismutase, catalase and glutathione peroxidase values in both muscle and liver tissues were significantly (p&lt;0.05) decreased, whereas cadmium levels in muscle and liver and malondialdehyde levels in liver were significantly (p&lt;0.05) increased. The histopathological examination of the liver revealed that cadmium caused liver damage. These results showed that rainbow trout exposed to dietary cadmium were highly sensitive to the metal, and the decreased levels of metals such as copper, zinc, manganese, and selenium in the liver tissue, which are involved in the antioxidant defence system, can be considered an indicator of the weakening of the antioxidant defence system.

A review on calcinosis cutis

Calcinosis, marked by hydroxyapatite, calcium, and phosphate deposits in skin and subcutaneous tissues, is common in individuals with various physiological conditions, soft tissue ailments, and autoimmune disorders. Researchers categorize and analyze these occurrences, shedding light on their pathophysiology. They also review scientific evidence regarding non- pharmacologic and pharmacodynamic treatments. Calcinosis cutis involves the accumulation of insoluble calcium ions in the epidermis and subcutaneous tissue, classified into dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis subgroups. Dysplastic deposits result from cellular damage, while metastatic calcification stems from irregular potassium and phosphorous metabolism. Undiagnosed calcification occurs independently of tissue destruction or underlying disease. Autoimmune syndrome-induced epidermal calcification is a rare therapy-related effect. Calciphylaxis, primarily affecting the vascular system, is introduced, with disturbances in calcium and phosphorus biotransformation and congenital hypothyroidism as contributing factors.

The Utility of Invengenx® Bovine Patch for Right Ventricular Outflow Tract (RVOT) Reconstruction and Augmentation in the Surgical Management of Tetralogy of Fallot (TOF): A Contemporary Study and Review of the Literature.

Background and objective Complex congenital heart diseases (CHDs), such as the tetralogy of Fallot (TOF), often warrant reconstruction and augmentation of the right ventricular outflow tract (RVOT). This procedure requires the use of both synthetic and natural materials. However, finding the ideal material for tissue implants can be challenging. Biological materials often face issues such as tissue degeneration, calcium deposition, antigenicity, rejection, shrinkage, and fibrosis. These issues can lead to complications such as stenosis and insufficiency, potentially requiring early reoperations. In light of this, this study aimed toinvestigate the effectiveness of the Invengenx® bovine patch for RVOT reconstruction and augmentation. Methods This was a retrospective observational studyconducted among eight children who underwent TOF correction cardiac surgery. Their demographic and clinical characteristics, intraoperative findings, and postoperative follow-up results at six months were collected from the hospital patient database. Results There were no deaths or complications in this study. We observed a significant reduction in the gradient across the pulmonary valve and the outflow tract at six months post-procedure. The analysis demonstrated that the Invengenx® bovine patch was successful and did not lead to any complications. Conclusions This study demonstrates the safety and efficacy of this engineered bovine pericardial patch (Invengenx®) as a cardiovascular substitute for surgical repair of both simple and more complex congenital cardiac defects.

FRI116 Inhibition Of Mitochondrial Fission And Restoration Of Mitochondrial Function Attenuates Vascular Calcification

Abstract Disclosure: S. Kwon: None. M. Kim: None. S. Zerwa: None. S. Kim: None. B. Jueun: None. J. Jeon: None. I. Lee: None. Objectives: Vascular calcification is associated with cardiovascular disease mortality, especially in patients with diabetes mellitus and chronic kidney disease. One of proposed mechanisms for development of vascular calcification suggested mitochondrial dysfunction of vascular smooth muscle cells (VMSCs), especially excessive mitochondrial fission that led to apoptosis and tissue calcium deposit formation. In existing literature, Vitamin B1 inhibited mitochondrial fission and improved mitochondrial function. This study investigated whether inhibiting mitochondrial fission prevents vascular calcification in vitro and in vivo by using inorganic phosphate and cholecalciferol-induced vascular calcification models, respectively. Methods: VMSCs from thoracic aorta of 4-week-old rats were treated by 2.6mM inorganic phosphate and 2mM calcium chloride to induce calcification. 6-week-old male C57BL/6J mice were given vitamin B1 analogue solution or water with daily oral gavage for 13 days, then aortic calcification was induced by subcutaneous injection of 5.5×10-5 IU/kg cholecalciferol for 3 days before sacrifice. Cells and tissues were stained for calcium deposition, (van Kossa stain), apoptosis (TUNEL) and mitochondrial morphology (Mitotracker). Western blotting and quantitative real-time PCR were used to assess calcification pathways and mitochondrial function. Tissue calcium content, normalized with total protein contents, was measured to quantify the extent of calcification. Mitochondrial oxygen consumption ratio (OCR) and mitochondrial membrane potential (JC-1 dye staining) were assessed to analyze quantified mitochondrial function. Results: Calcium deposition in both in vivo and in vitro models were alleviated by vitamin B1 analogue through inhibition of mitochondrial fission and restoration of mitochondrial function. In addition, vitamin B1 analogue downregulated expression of genes related to calcification and osteogenesis, such as bone morphogenic protein 2, osteocalcin, osteopontin, and runt-related transcription factor 2. Conclusion: Prevention of mitochondrial dysfunction in VSMCs may be a viable therapeutic strategy for treatment of vascular calcification. Presentation: Friday, June 16, 2023

Radial and vertical variation of wood nutrients in Bornean tropical forest trees

AbstractNitrogen, phosphorus, potassium, calcium, and magnesium concentrations in woody tissue are poorly documented, but are necessary for understanding whole‐tree nutrient use and storage. Here, we report how wood macronutrient concentrations vary radially and along the length of a tree for 10 tropical tree species in Sabah, Malaysia. Bark nutrient concentrations were consistently high: 2.9–13.7 times greater than heartwood depending on the nutrient. In contrast, within the wood both the radial (sapwood vs. heartwood) and vertical (trunk bottom vs. trunk middle) variation was modest. Higher concentrations in sapwood relative to heartwood provide empirical support for wood nutrient resorption during sapwood senescence. Dipterocarp species showed resorption rates of 25.3 ± 7.1% (nitrogen), 62.7 ± 11.9% (phosphorus), and 56.2 ± 12.5% (potassium), respectively, while non‐dipterocarp species showed no evidence of nutrient resorption in wood. This suggests that while dipterocarps have lower wood nutrient concentrations, this family is able to compensate for this by using wood nutrient resorption as an efficient nutrient conservation mechanism. In contrast to other nutrients, calcium and magnesium tended to accumulate in heartwood. Wood density (WD) showed little vertical variation along the trunk. Across the species (WD range of 0.33 to 0.94 mg/cm3), WD was negatively correlated with wood P and K concentration and positively correlated with wood Ca concentration. As our study showed exceptionally high nutrient concentrations in the bark, debarking and leaving the bark of the harvested trees on site during logging operations could substantially contribute to maintaining nutrients within forest ecosystems.