Sustained Calcium Research Articles

Designing Ferulic Acid-Functionalized Dual Protein Conjugates: Process-Induced Changes, Structural Interplays, and Sustainable Calcium Fortification

Designing Ferulic Acid-Functionalized Dual Protein Conjugates: Process-Induced Changes, Structural Interplays, and Sustainable Calcium Fortification

7082 Hypercalcemia Due To Tumoral Production Of Calcitriol By Seminoma In A Patient With Pre-existing Primary Hyperparathyroidism

Abstract Disclosure: E. Naous: None. A. Jain: None. M. ElNajjar: None. A. Sabet: None. Background: Malignant hypercalcemia due to seminoma is extremely rare and has been reported in association with tumoral parathyroid-related protein (PTHrP) and/or calcitriol production. We present a unique case of a patient with seminoma and paraneoplastic calcitriol-induced hypercalcemia with co-existing primary hyperparathyroidism. Case Presentation: A 67-year-old male patient presented in May 2023 with obstructive uropathy and was diagnosed with a metastatic left testicular seminomatous germ-cell tumor with involvement of retroperitoneal soft tissue. At the time of diagnosis, the patient exhibited severe hypercalcemia with an albumin-corrected serum calcium level 14.1 mg/dL [8.6-10.3], phosphorus 3.0 mg/dL [2.5-4.5], intact parathyroid hormone (PTH) 20 pg/ml [15-65], PTHrP <2 pmol/L, 25-hydroxyvitamin-D 32 ng/ml [>30], and normal serum protein electrophoresis. 1,25-hydroxyvitamin-D was elevated at 132 pg/mL [24.8-81.5]. Review of prior records showed that the patient had a history of mild, chronic hypercalcemia (albumin-corrected serum calcium 10.5 mg/dL in August 2021, stable in 2022). His calcium level increased to 11.8 mg/dl in March 2023 and 14.1 mg/dl on presentation in May 2023. Given history of chronic mild hypercalcemia and presentation with severe hypercalcemia and “inappropriately normal” intact PTH, he was initially considered to have hypercalcemia solely due to primary hyperparathyroidism, a condition where elevated calcitriol levels are expected. However, the patient’s hypercalcemia was out of proportion to his intact PTH level, raising concern that tumoral calcitriol was contributory. He underwent left orchiectomy in May 2023 and completed chemotherapy cycles, including bleomycin, etoposide, and cisplatin, in September 2023. For hypercalcemia, he received IV saline, 48 hours of SC calcitonin, and prednisone 20 mg daily for 1 week followed by a rapid taper in addition to cinacalcet 30 mg daily. His serum calcium normalized within 48 hours of prednisone treatment. The patient remained on cinacalcet for a month, and his calcium levels remained normal more than a month after cinacalcet discontinuation. Clinical lesson: Severe hypercalcemia may be multifactorial. Our patient exhibited incompletely suppressed intact PTH and low-normal serum phosphorus, consistent with primary hyperparathyroidism. However, the abrupt onset of severe hypercalcemia, disproportionate to intact PTH, in a patient with seminoma and elevated calcitriol, suggested paraneoplastic hypercalcemia. The rapid response to corticosteroids and cancer chemotherapy, along with sustained normal calcium levels post-cinacalcet discontinuation, supported this diagnosis. Despite primary hyperparathyroidism being common, its presence in patients with severe hypercalcemia and malignancy does not rule out the possibility of co-existing hypercalcemia of malignancy. Presentation: 6/2/2024

Reactive astrocytes generated from human iPSC are pro-inflammatory and display altered metabolism

Astrocytes are the most abundant type of glial cell in the central nervous system and they play pivotal roles in both normal health and disease. Their dysfunction is detrimental to many brain related pathologies. Under pathological conditions, such as Alzheimer's disease, astrocytes adopt an activated reactive phenotype which can contribute to disease progression. A prominent risk factor for many neurodegenerative diseases is neuroinflammation which is the purview of glial cells, such as astrocytes and microglia. Human in vitro models have the potential to reveal relevant disease specific mechanisms, through the study of individual cell types such as astrocytes or the addition of specific factors, such as those secreted by microglia. The aim of this study was to generate human cortical astrocytes, in order to assess their protein and gene expression, examine their reactivity profile in response to exposure to the microglial secreted factors IL-1α, TNFα and C1q and assess their functionality in terms of calcium signalling and metabolism. The successfully differentiated and stimulated reactive astrocytes display increased IL-6, RANTES and GM-CSF secretion, and increased expression of genes associated with reactivity including, IL-6, ICAM1, LCN2, C3 and SERPINA3. Functional assessment of these reactive astrocytes showed a delayed and sustained calcium response to ATP and a concomitant decrease in the expression of connexin–43. Furthermore, it was demonstrated these astrocytes had an increased glycolytic capacity with no effect on oxidative phosphorylation. These findings not only increase our understanding of astrocyte reactivity but also provides a functional platform for drug discovery.

A sustained calcium response mediated by IP3 receptor anchoring to the desmosome is essential for apoptotic cell elimination

Efficient elimination of apoptotic cells within epithelial cell sheets is crucial for preserving epithelial barrier integrity.1 It is well established that immediate neighbors of an apoptotic cell actively participate in its removal by enclosing it within a wall of actomyosin, pushing it out in a purse-string manner in a process called apical extrusion.2,3,4,5,6,7 Here, we found that sustained elevation of calcium ions in neighboring epithelial cells is necessary to generate the contractility required for apoptotic cell elimination. This phenomenon, which we call calcium response in effectors of apical extrusion (CaRE), highlights the disparate calcium dynamics within the epithelial sheet. Furthermore, we elucidate the essential role of desmosomes in CaRE. Specifically, we identify a subset of IP3 receptors within the endoplasmic reticulum that is recruited to the desmosome by K-Ras-induced actin-binding protein as the core component of this process. The interplay between these cellular structures heightens actomyosin contractility to drive apoptotic cell removal. Our findings underscore the physiological significance of integrating desmosomes with the endoplasmic reticulum in epithelial sheet homeostasis, shedding new light on cell-cell communication and tissue maintenance.

Performance of a multiphase bioactive socket plug with a barrier function for alveolar ridge preservation

The natural healing process of extraction socket and traditional socket plug material could not prevent buccal bone wall resorption and down growth of epithelium from the socket orifice. A multiphase bioactive socket plug (BP) is designed to overcome the natural healing process by maintaining the three-dimensional (3D) volume of extraction sockets, particularly in sockets with wall defects, and later provide sufficient alveolar bone volume for implant placement. The study aimed to fabricate and evaluate the physical, chemical, and biological performance of BP in vitro. The BP was fabricated through freeze-drying and layer-by-layer assembly, comprised of a base serving as a scaffold, a central portion for promoting bone regeneration, an upper buccal portion for maintaining alveolar socket dimension with a covering collagen membrane (Memb) on the top and upper buccal surface to prevent soft tissue infiltration. The BP as the experimental group and a pure collagen plug (CP) as the control group were investigated and compared. Radiograph, scanning electron microscopy, and energy-dispersive spectroscopy mapping confirmed that the four-part BP was successfully assembled and fabricated. Swelling rate analysis indicated that BP, CP, and Memb reached swelling equilibrium within 1 hour. BP exhibited a high remaining weight percentage in collagenase solution (68.81 ± 2.21% on day 90) and sustained calcium ion release, reaching the maximum 0.13 ± 0.04 mmol l−1 on day 14. In biological assays, BP exhibited excellent cell proliferation (The OD value increased from 0.02 on day 1 to 0.23 on day 21.). The BP group exhibited higher alkaline phosphatase activity and osteocalcin content than the CP group within 21 days. Memb and BP exhibited outstanding barrier function, as evidenced by Hematoxylin and eosin staining. In summary, the multiphase bioactive socket plug represents a promising scaffold for alveolar ridge preservation application.

Engineering an in vitro retinothalamic nerve model.

Understanding the retinogeniculate pathway in vitro can offer insights into its development and potential for future therapeutic applications. This study presents a Polydimethylsiloxane-based two-chamber system with axon guidance channels, designed to replicate unidirectional retinogeniculate signal transmission in vitro. Using embryonic rat retinas, we developed a model where retinal spheroids innervate thalamic targets through up to 6 mm long microfluidic channels. Using a combination of electrical stimulation and functional calcium imaging we assessed how channel length and electrical stimulation frequency affects thalamic target response. In the presented model we integrated up to 20 identical functional retinothalamic neural networks aligned on a single transparent microelectrode array, enhancing the robustness and quality of recorded functional data. We found that network integrity depends on channel length, with 0.5-2 mm channels maintaining over 90% morphological and 50% functional integrity. A reduced network integrity was recorded in longer channels. The results indicate a notable reduction in forward spike propagation in channels longer than 4 mm. Additionally, spike conduction fidelity decreased with increasing channel length. Yet, stimulation-induced thalamic target activity remained unaffected by channel length. Finally, the study found that a sustained thalamic calcium response could be elicited with stimulation frequencies up to 31 Hz, with higher frequencies leading to transient responses. In conclusion, this study presents a high-throughput platform that demonstrates how channel length affects retina to brain network formation and signal transmission in vitro.

Sustainable calcium oxide nanoparticles based on agroindustry waste for potential endodontics applications

Development of sustainable proposals in various areas has been crucial nowadays. Thus, this research evaluated a sustainable synthesis of calcium oxide nanoparticles (CaO NPs), using an agroindustry waste from eggshells to promote dentistry tissue regeneration with antimicrobial activity. Then, eggshells were loaded to heat treatment with two different temperatures (700 °C and 900 °C) for three times (7, 15 and 24 h). These CaO NPs were characterized using spectroscopies (UV Vis, FTIR, XRD) and morphological (ZP, SEM, TEM). Additionally, antimicrobial activity against Escherichia coli and Candida albicans, cell viability, protein adsorption and alkaline phosphatase activity were evaluated. The results showed that CaO NPs were produced in both temperatures, but in the slow heating (at 700 °C), Ca(OH)2 was still presented. Moreover, morphological analysis showed charges close to zero, indicating high agglomeration of nanoparticles proved by SEM images. The CaO NPs’ size were in the range of 10 and 25 nm at 900 °C and showing high clustering and porosity at 700 °C by TEM analysis, and the band gap, 2.82–5.77 eV. Additionally, XRD showed nanoparticles of CaO and Ca(OH)2 in both temperatures, although in the case of high heating, the presence of more CaO was perceived. The cell viability was great for biological proposals, mainly in the sample performed at high temperature (over 90 %). Furthermore, the antimicrobial activity showed incredible results against both microbials with low calcium nanoparticles tested (40 μg). Thus, this research demonstrated a sustainable way to reusability agroindustry waste for dentistry applications.

Functionalization of PCL-Based Fiber Scaffolds with Different Sources of Calcium and Phosphate and Odontogenic Potential on Human Dental Pulp Cells.

This study investigated the incorporation of sources of calcium, phosphate, or both into electrospun scaffolds and evaluated their bioactivity on human dental pulp cells (HDPCs). Additionally, scaffolds incorporated with calcium hydroxide (CH) were characterized for degradation, calcium release, and odontogenic differentiation by HDPCs. Polycaprolactone (PCL) was electrospun with or without 0.5% w/v of calcium hydroxide (PCL + CH), nano-hydroxyapatite (PCL + nHA), or β-glycerophosphate (PCL + βGP). SEM/EDS analysis confirmed fibrillar morphology and particle incorporation. HDPCs were cultured on the scaffolds to assess cell viability, adhesion, spreading, and mineralized matrix formation. PCL + CH was also evaluated for gene expression of odontogenic markers (RT-qPCR). Data were submitted to ANOVA and Student's t-test (α = 5%). Added CH increased fiber diameter and interfibrillar spacing, whereas βGP decreased both. PCL + CH and PCL + nHA improved HDPC viability, adhesion, and proliferation. Mineralization was increased eightfold with PCL + CH. Scaffolds containing CH gradually degraded over six months, with calcium release within the first 140 days. CH incorporation upregulated DSPP and DMP1 expression after 7 and 14 days. In conclusion, CH- and nHA-laden PCL fiber scaffolds were cytocompatible and promoted HDPC adhesion, proliferation, and mineralized matrix deposition. PCL + CH scaffolds exhibit a slow degradation profile, providing sustained calcium release and stimulating HDPCs to upregulate odontogenesis marker genes.

Fabrication and characterization of a bioactive composite scaffold based on polymeric collagen/gelatin/nano β-TCP for alveolar bone regeneration

One strategy to correct alveolar bone defects is use of bioactive bone substitutes to maintain the structure of defect site and facilitate cells and vessels' ingrowth. This study aimed to fabricate and characterize the freeze-dried bone regeneration scaffolds composed of polymeric Type I collagen, nano Beta-tricalcium phosphate (β-TCP), and gelatin. The stable structures of scaffolds were obtained by thermal crosslinking and EDC/NHS ((1-ethyl-3-(3-dimethylaminopropyl) carbodiimide)/(N-hydroxysuccinimide)) chemical crosslinking processes. Subsequently, the physicochemical and biological properties of the scaffolds were characterized and assessed. The results indicated the bioactive composite scaffolds containing 10% and 20% (w/v) nano β-TCP exhibited suitable porosity (84.45 ± 25.43 nm, and 94.51 ± 14.69 nm respectively), a rapid swelling property (reaching the maximum swelling rate at 1 h), excellent degradation resistance (residual mass percentage of scaffolds higher than 80% on day 90 in PBS and Type I collagenase solution respectively), and sustained calcium release capabilities. Moreover, they displayed outstanding biological properties, including superior cell viability, cell adhesion, and cell proliferation. Additionally, the scaffolds containing 10% and 20% (w/v) nano β-TCP could promote the osteogenic differentiation of MC3T3-E1. Therefore, the bioactive composite scaffolds containing 10% and 20% (w/v) nano β-TCP could be further studied for being used to treat alveolar bone defects in vivo.

A Multichannel Metabolic Pathway Interference Strategy for Complete Energy Depletion‐Mediated Cancer Therapy

AbstractHydrogen sulfide (H2S) is being progressively integrated as an emerging inhibitor of the electron transport chain in energy interference‐based tumor therapy. However, metabolic reprogramming in cancer cells causes both oxidative phosphorylation (OXPHOS) and glycolysis to occur simultaneously, which contributes to the ineffective therapeutic effect of blocking a single pathway. To achieve complete suppression of energy production, an inorganic H2S donor ZnS@ZIF‐8@CaP nanoparticle (ZSZC NP) carrying Ca and Zn is constructed for achieving simultaneous interference of OXPHOS and glycolysis. The core–shell ZSZC nanoparticles can break down in the tumor microenvironment. This leads to a sustained H2S release and calcium overload to disrupt the normal functioning of mitochondria by inhibiting the expression of cytochrome c and causing damage to mitochondrial membrane potential. Meanwhile, the presence of Zn2+ hinders the typical process of glycolysis by impeding the functioning of lactate dehydrogenase and glyceraldehyde‐3‐phosphate dehydrogenase. The synchronous interference of OXPHOS and glycolysis hampers the energy supply to cancer cells. Additionally, H2S and calcium overload can expedite tumor necrosis in vivo by inducing cellular acidification and calcification. Therefore, this energy‐blocking strategy will completely deplete the energy reserves of cancer cells and provide new insights for exploring bioenergetic inhibition as a treatment approach.

Sustained store-operated calcium entry utilizing activated chromatin state leads to instability in iTregs.

Thymus-originated tTregs and in vitro induced iTregs are subsets of regulatory T cells. While they share the capacity of immune suppression, their stabilities are different, with iTregs losing their phenotype upon stimulation or under inflammatory milieu. Epigenetic differences, particularly methylation state of Foxp3 CNS2 region, provide an explanation for this shift. Whether additional regulations, including cellular signaling, could directly lead phenotypical instability requires further analysis. Here, we show that upon TCR (T cell receptor) triggering, SOCE (store-operated calcium entry) and NFAT (nuclear factor of activated T cells) nuclear translocation are blunted in tTregs, yet fully operational in iTregs, similar to Tconvs. On the other hand, tTregs show minimal changes in their chromatin accessibility upon activation, in contrast to iTregs that demonstrate an activated chromatin state with highly accessible T cell activation and inflammation related genes. Assisted by several cofactors, NFAT driven by strong SOCE signaling in iTregs preferentially binds to primed-opened T helper (TH) genes, resulting in their activation normally observed only in Tconv activation, ultimately leads to instability. Conversely, suppression of SOCE in iTregs can partially rescue their phenotype. Thus, our study adds two new layers, cellular signaling and chromatin accessibility, of understanding in Treg stability, and may provide a path for better clinical applications of Treg cell therapy.

Sustained store-operated calcium entry utilizing activated chromatin state leads to instability in iTregs

Thymus-originated tTregs and in vitro induced iTregs are subsets of regulatory T cells. While they share the capacity of immune suppression, their stabilities are different, with iTregs losing their phenotype upon stimulation or under inflammatory milieu. Epigenetic differences, particularly methylation state of Foxp3 CNS2 region, provide an explanation for this shift. Whether additional regulations, including cellular signaling, could directly lead phenotypical instability requires further analysis. Here, we show that upon TCR (T cell receptor) triggering, SOCE (store-operated calcium entry) and NFAT (nuclear factor of activated T cells) nuclear translocation are blunted in tTregs, yet fully operational in iTregs, similar to Tconvs. On the other hand, tTregs show minimal changes in their chromatin accessibility upon activation, in contrast to iTregs that demonstrate an activated chromatin state with highly accessible T cell activation and inflammation related genes. Assisted by several cofactors, NFAT driven by strong SOCE signaling in iTregs preferentially binds to primed-opened T helper (TH) genes, resulting in their activation normally observed only in Tconv activation, ultimately leads to instability. Conversely, suppression of SOCE in iTregs can partially rescue their phenotype. Thus, our study adds two new layers, cellular signaling and chromatin accessibility, of understanding in Treg stability, and may provide a path for better clinical applications of Treg cell therapy.

Sheep bone valorization: Enhancing gastronomic sustainability through hydroxyapatite-enriched potato wedges

In pursuit of sustainability and resource optimization, the zero-waste theory has gained momentum across diverse sectors. The concept of "zero waste" integrates waste management strategies to minimize waste such as animal bones. This study aimed to prepare Calcined and Nano hydroxyapatite (HAp) from sheep bone as a valuable calcium source by using calcination (850 °C) and ultra-sonication methods. FTIR, particle size distribution (PSD), atomic absorption spectroscopy (AAS), laser-induced breakdown spectroscopy (LIBS), scanning transmission electron microscopy (STEM), and XRD techniques were used to characterize the resulting samples. FTIR spectra confirmed PO43− at 1027.43 and 1030.32 cm−1 in nano and calcined HAp respectively. AAS, UV, and PSD indicated 32.3 ± 0.11% calcium content and 18.86 ± 0.19% P, with 142 nm particle size in Nano-HAp; which significantly differed from calcined HAp. STEM confirmed morphological behavior. XRD crystalline behavior seemed highest at 460a.u., whereas LIBS-derived Ca/P ratio was 1.99 in Nano HAp. Notably, in-vitro findings measured the highest bioavailable calcium content in Nano HAp (46.6%) and Calcined HAp (42.1%). Further, HAp was used to develop and characterize fortified baked potato wedges with formulations; 0%, 0.22%, 0.44%, and 0.66%. Moisture (%) was measured within the range of 21.51 ± 0.11 to 34.83 ± 0.03. Nano-Bio-2 (0.44%) was the best formulation that could be a better choice to wipe out calcium deficiency for end-users. Moreover, principal component analysis (PCA) was applied to the physical and sensory attributes of the developed product. On account of eigenvalues, the total variation was recorded at 94.71. Hence, current work showcased the potential of utilizing sheep bone for sustainable calcium enrichment and offered insights into innovative food formulations.

β1 Adrenergic Receptor Autoantibodies and IgG Subclasses: Current Status and Unsolved Issues.

A wide range of anti-myocardial autoantibodies have been reported since the 1970s. Among them, autoantibodies against the β1-adrenergic receptor (β1AR-AAb) have been the most thoroughly investigated, especially in dilated cardiomyopathy (DCM). Β1AR-Aabs have agonist effects inducing desensitization of β1AR, cardiomyocyte apoptosis, and sustained calcium influx which lead to cardiac dysfunction and arrhythmias. Β1AR-Aab has been reported to be detected in approximately 40% of patients with DCM, and the presence of the antibody has been associated with worse clinical outcomes. The removal of anti-myocardial autoantibodies including β1AR-AAb by immunoadsorption is beneficial for the improvement of cardiac function for DCM patients. However, several studies have suggested that its efficacy depended on the removal of AAbs belonging to the IgG3 subclass, not total IgG. IgG subclasses differ in the structure of the Fc region, suggesting that the mechanism of action of β1AR-AAb differs depending on the IgG subclasses. Our previous clinical research demonstrated that the patients with β1AR-AAb better responded to β-blocker therapy, but the following studies found that its response also differed among IgG subclasses. Further studies are needed to elucidate the possible pathogenic role of IgG subclasses of β1AR-AAbs in DCM, and the broad spectrum of cardiovascular diseases including HF with preserved ejection fraction.

Suppressing Src-Mediated EGFR Signaling by Sustained Calcium Supply Targeting Triple-Negative Breast Cancer.

Src is emerging as a promising target in triple-negative breast cancer (TNBC) treatment because it activates survival signaling linked to the epidermal growth factor receptor. In this study, the effect of calcium supply on Src degradation was investigated to confirm underlying mechanisms and anticancer effects targeting TNBC. MDA-MB-231 cells, the TNBC cell line, were used. Calcium supply was feasible through lactate calcium salt (CaLac), and the applicable calcium concentration was decided by changes in the viability with different doses of CaLac. Expression of signaling molecules mediated by calcium-dependent Src degradation was observed by Western blot analysis and immunocytochemistry, and the recovery of the signaling molecules was confirmed following calpeptin treatment. The anticancer effect was investigated in the xenograft animal model. Significant suppression of Src was induced by calcium supply, followed by a successive decrease in the expression of epithelial growth factor receptor, RAS, extracellular signal-regulated kinase, and nuclear factor kappa B. Then, the suppression of cyclooxygenase-2 contributed to a significant deactivation of the prostaglandin E2 receptors. These results suggest that calcium supply has the potential to reduce the risk of TNBC. However, as this study is at an early stage to determine clinical applicability, close consideration is needed.

Pancreatic ductal adenocarcinoma induces neural injury that promotes a transcriptomic and functional repair signature by peripheral neuroglia.

Perineural invasion (PNI) is the phenomenon whereby cancer cells invade the space surrounding nerves. PNI occurs frequently in epithelial malignancies, but is especially characteristic of pancreatic ductal adenocarcinoma (PDAC). The presence of PNI portends an increased incidence of local recurrence, metastasis and poorer overall survival. While interactions between tumor cells and nerves have been investigated, the etiology and initiating cues for PNI development is not well understood. Here, we used digital spatial profiling to reveal changes in the transcriptome and to allow for a functional analysis of neural-supportive cell types present within the tumor-nerve microenvironment of PDAC during PNI. We found that hypertrophic tumor-associated nerves within PDAC express transcriptomic signals of nerve damage including programmed cell death, Schwann cell proliferation signaling pathways, as well as macrophage clearance of apoptotic cell debris by phagocytosis. Moreover, we identified that neural hypertrophic regions have increased local neuroglial cell proliferation which was tracked using EdU tumor labeling in KPC mice, as well as frequent TUNEL positivity, suggestive of a high turnover rate. Functional calcium imaging studies using human PDAC organotypic slices confirmed nerve bundles had neuronal activity, as well as contained NGFR+ cells with high sustained calcium levels, which are indicative of apoptosis. This study reveals a common gene expression pattern that characterizes solid tumor-induced damage to local nerves. These data provide new insights into the pathobiology of the tumor-nerve microenvironment during PDAC as well as other gastrointestinal cancers.

Purinergic Activation of Store-Operated Calcium Entry (SOCE) Regulates Cell Migration in Metastatic Ovarian Cancer Cells.

Store-operated calcium entry (SOCE) is an important process in calcium signaling. Its role in physiological and pathological events is well recognized. However, in cancerous systems, the importance of SOCE in relation to the degree of cancer aggressiveness, as well as its regulation by ligands such as purinergic molecules, are not well documented. This study aimed to characterize a differential effect of the P2Y2 receptor (promoted by UTP of 10 µM and inhibited by ARC118925XX of 1 µM) on intracellular calcium response between metastatic (SKOV-3) and non-metastatic (CAOV-3) ovarian cell lines in conditions of normal (1.5 mM) and zero extracellular calcium concentration. The sustained calcium influx observed exclusively in SKOV-3 cells was associated with the presence of SOCE (promoted by thapsigargin (74.81 ± 0.94 ΔF) and sensitive to 2-APB (20.60 ± 0.85 ΔF)), whereas its absence in CAOV-3 cells (26.2 ± 6.1 ΔF) was correlated with a low expression of ORAI1. The relevance of SOCE in metastatic SKOV-3 cells was further corroborated when 2-APB significantly inhibited (40.4 ± 2.8% of covered area) UTP-induced cell migration (54.6 ± 3.7% of covered area). In conclusion, our data suggest that SOCE activation elicited by the P2Y2 receptor is involved in the aggressiveness of ovarian cancer cells.

Exploring the sustainability of concrete with fly ash, recycled coarse aggregate and biomineralisation method by life cycle assessment

Fly ash (FA) and recycled coarse aggregate (RCA) have been extensively studied, aiming to improve the sustainability of concrete. The biomineralisation method has also been researched to enhance the performance of concrete. However, introducing FA and RCA may decrease the strength of concrete, and the biomineralisation method may create extra environmental impact (EI) due to the production of bacteria and corresponding chemical agents. It is hard to directly judge the influence of these methods on the sustainability of concrete. This paper proposes to explore the sustainability of concrete with FA, RCA, and biomineralisation methods by life cycle assessment. Six scenarios were established, and Six EI categories of the six scenarios were quantified. The quantified EI values considering their corresponding strength were obtained and compared. The results showed that: using FA decreased EI, using RCA showed a limited effect on decreasing EI, the biomineralisation method significantly decreased EI, and using the treated RCA increased EI due to its high consumption of chemical agents in the treating procedure. In summary, biomineralisation enhanced FA concrete performance is recommended to substitute traditional concrete widely after comprehensively comparing sustainability, workability, strength, and durability. Finding more sustainable calcium sources and nutrition can further improve its sustainability.

Elevation of Cytoplasmic Calcium Suppresses Microtentacle Formation and Function in Breast Tumor Cells.

Cytoskeletal remodeling in circulating tumor cells (CTCs) facilitates metastatic spread. Previous oncology studies examine sustained aberrant calcium (Ca2+) signaling and cytoskeletal remodeling scrutinizing long-term phenotypes such as tumorigenesis and metastasis. The significance of acute Ca2+ signaling in tumor cells that occur within seconds to minutes is overlooked. This study investigates rapid cytoplasmic Ca2+ elevation in suspended cells on actin and tubulin cytoskeletal rearrangements and the metastatic microtentacle (McTN) phenotype. The compounds Ionomycin and Thapsigargin acutely increase cytoplasmic Ca2+, suppressing McTNs in the metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-436. Functional decreases in McTN-mediated reattachment and cell clustering during the first 24 h of treatment are not attributed to cytotoxicity. Rapid cytoplasmic Ca2+ elevation was correlated to Ca2+-induced actin cortex contraction and rearrangement via myosin light chain 2 and cofilin activity, while the inhibition of actin polymerization with Latrunculin A reversed Ca2+-mediated McTN suppression. Preclinical and phase 1 and 2 clinical trial data have established Thapsigargin derivatives as cytotoxic anticancer agents. The results from this study suggest an alternative molecular mechanism by which these compounds act, and proof-of-principle Ca2+-modulating compounds can rapidly induce morphological changes in free-floating tumor cells to reduce metastatic phenotypes.

Green double crosslinked starch-alginate hydrogel regulated by sustained calcium ion-gluconolactone release for human motion monitoring

Ionically conductive hydrogels can be used to produce wearable devices because of their mechanical flexibility and intelligent sensing. However, utilizing petrochemical or synthetic materials via complex procedures remains a challenge to sustainability. Here we report a new simple strategy to fabricate a double network hydrogel from natural ingredients of corn starch and sodium alginate. Starch-alginate hydrogel exhibited porous microstructure and high strength which can be modulated by appropriate calcium ion concentration. Because of the hydrogen bond and ion crosslinking, the starch-alginate hydrogel could be restored to its original shape after being compressed, twisted and stretched. The hydrogel prepared with high amylose starch and sodium alginate with 0.4 % (W/V) calcium ion addition had the highest breaking strength (281.51 kPa) and toughness (61.61 kJ/m3) at 160 % strain. The third harmonic wave revealed the transition process between the formation and destruction of the hydrogel network structure. The conductive hydrogel can adhere to human skin to monitor different motions and vocal cord vibrations. Our research brings new inspiration to the design of environment-friendly wearable electronic devices which can be manufactured in large quantity at extremely low cost.