Hepatotoma is the leading type of primary liver cancer in adults and third cause of death in the world. Hydroxytyrosol is a natural phenol existing in olive (Olea europaea L.). Hydroxytyrosol is the chief ingredient of olive oil, which was early deemed to be the most robust antioxidant in olive oil. Hydroxytyrosol is known to inhibit various types of cancer by different methods. This study was aimed to delineate the action of hydroxytyrosol on viability and [Ca2+]i in HepG2 hepatoma cells. Fura-2 was used to detect [Ca2+]i, and WST-1 assays were applied to explore cell cytotoxicity. Hydroxytyrosol elicited [Ca2+]i raises. Eliminating external Ca2+ diminished the Ca2+ signal by 30%. Hydroxytyrosol-evoked Ca2+ influx was diminished by 20% by three inhibitors of store-operated Ca2+ channels and by a protein kinase C activator and an inhibitor. In the absence of Ca2+, thapsigargin eradicated hydroxytyrosol-provoked [Ca2+]i raises. Suppression of phospholipase C (PLC) with U73122, a PLC inhibitor, did not inhibit hydroxytyrosol-elicited [Ca2+]i raises. Hydroxytyrosol reduced cell viability. This cytotoxic action was not reversed by preincubation with BAPTA/AM, a cytosolic Ca2+ binder. In sum, in HepG2 hepatoma cells, hydroxytyrosol elicited [Ca2+]i raises by provoking PLC-unrelated discharge of Ca2+ from ER and Ca2+ influx through PKC-sensitive store-operated Ca2+ entry. In addition, hydroxytyrosol elicited Ca2+-dissociated cytotoxicity.

Gomisin A is a dietary lignan compound isolated from the fruit of Schisandra chinensis and has many pharmacological properties, including hepato-protective, anti-diabetic, and anti-oxidative activities. However, the benefit of gomisin A is still not well understood. The action of gomisin A is diverse. However, the effect of gomisin A on Ca2+ signaling in prostate cancer cells is unknown. Ca2+ is a pivotal second envoy that triggers and regulates cellular processes such as apoptosis, fertilization, energy transduction, secretion, and protein activation. The goal of this study was to explore the action of gomisin A on [Ca2+]i and cytotoxicity in PC3 prostate cancer cells. Gomisin A at 100–200 μM provoked [Ca2+]i raises. 20% of the response was reduced by removing external Ca2+. The Ca2+ influx provoked by gomisin A was suppressed by 20% by store-caused Ca2+ entry suppressors: econazole, SKF96365, nifedipine; also by phorbol 12-myristate 13 acetate and GF109203X. Without external Ca2+, gomisin A-caused [Ca2+]i raises were abolished by thapsigargin. In contrast, gomisin A suppressed the [Ca2+]i raises caused by thapsigargin. U73122 fell short to change gomisin A-caused [Ca2+]i responses. Gomisin A (20–100 μM) elicited cytotoxicity in a dose-associated fashion. Blockade of [Ca2+] elevations with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl failed to inhibit cytotoxicity of gomisin A. Collectively, gomisin A evoked [Ca2+]i raises and provoked cytotoxicity in a Ca2+-dissociated fashion in prostate cancer cells.

Esculetin is a derivative of coumarin, and is the dominant, vigorous component of the conventional Chinese medicine Cortex Fraxini . Recently, the molecular pathway study and clinical use of Cortex Fraxini and esculetin are becoming intensive. In vitro, esculetin has been shown to provoke apoptotic responses via mitochondrial routes and other cellular responses in diverse cell types. The action of esculetin on cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in prostate cells is unknown. [Ca 2+ ] i were assayed by applying fura-2, a fluorescent Ca 2+ -sensitive probe. WST-1 was used to measure cell death. Esculetin at doses of 25–100 µM provoked [Ca 2+ ] i raises. Removing external Ca 2+ decreased the response by 15%. Esculetin (100 µM) provoked Mn 2+ entry implying Ca 2+ influx. Esculetin-provoked Ca 2+ influx was suppressed by half by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate, PMA) and inhibitor (GF109203X); and by three inhibitors of store-operated Ca 2+ channels: nifedipine, econazole and SKF96365. In the absence of Ca 2+ , pretreatment with the endoplasmic reticulum (ER) Ca 2+ pump suppressor thapsigargin completely suppressed esculetin-provoked [Ca 2+ ] i raises. Suppression of phospholipase C (PLC) with U73122 eliminated esculetin-provoked [Ca 2+ ] i raises. Esculetin at 20–70 µM caused death of cells, which was not prevented by incubation with the Ca 2+ binder 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). In sum, in PC3 prostate cells, esculetin provoked [Ca 2+ ] i raises by provoking PLC-associated Ca 2+ discharge from ER and Ca 2+ influx via PKC-sensitive store-operated Ca 2+ influx. Additionally, esculetin provoked Ca 2+ -dissociated cell death.

Esculetin is derived from coumarin and is shown to be the main constituent of the Chinese herb Cortex Fraxini . The molecular paths underlying the action of esculetin are intensively studied. The outcome of esculetin on Ca 2+ concentration ([Ca 2+ ] i ) in prostate cells is unexplored. Fura-2 was used to detect Ca 2+ changes. Death was assessed by using WST-1. At doses of 25-100 mM, esculetin evoked [Ca 2+ ] i raises. This signal was lessened by 15% by exclusion of Ca 2+ . Esculetin (100 μM) induced Mn 2+ entry that implied Ca 2+ influx. Esculetin-evoked Ca 2+ influx was curbed by 50% by nifedipine (1 mM), econazole (0.5 mM) and SKF96365 (5 mM); phorbol 12-myristate 13 acetate (PMA; 1 nM; a protein kinase C [PKC] activator); and GF109203X (2 mM; a PKC inhibitor. In the absence of Ca 2+ , pretreatment with the endoplasmic reticulum (ER) Ca 2+ pump inhibitor thapsigargin (1 mM) eradicated esculetin-induced [Ca 2+ ] i raises. U73122, a phospholipase C (PLC) suppressor got rid of esculetin-caused [Ca 2+ ] i rises. Esculetin (20-70 mM) evoked death which was not restrained by treatment with the Ca 2+ binder BAPTA/AM. In summary, in PC3 cells, esculetin stimulated [Ca 2+ ] i raises by Ca 2+ influx through PKC-sensitive store-operated Ca 2+ entry and PLC-associated ER Ca 2+ discharging. Esculetin provoked Ca 2+ -independent cell death.

Tectorigenin, a traditional Chinese medicine, is isolated from the flower of plants such as Pueraria thomsonii Benth. It is an O-methylated isoflavone, a type of flavonoid. Previous studies have shown that tectorigenin evoked various physiological responses in different models, but the effect of tectorigenin on cytosolic-free Ca2+ levels ([Ca2+]i) and cytotoxicity in renal tubular cells is unknown. Our research explored if tectorigenin changed Ca2+ signal transduction and viability in Madin–Darby Canine Kidney (MDCK) renal tubular cells. [Ca2+]i in suspended cells were measured by applying the fluorescent Ca2+-sensitive probe fura-2. Viability was explored by using water-soluble tetrazolium-1 as a fluorescent dye. Tectorigenin at concentrations of 5–50 μM induced [Ca2+]i rises. Ca2+ removal reduced the signal by approximately 20%. Tectorigenin (50 μM) induced Mn2+ influx suggesting of Ca2+ entry. Tectorigenin-induced Ca2+ entry was inhibited by 10% by three inhibitors of store-operated Ca2+ channels, namely, nifedipine, econazole, and SKF96365. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin inhibited 83% of tectorigenin-evoked [Ca2+]i rises. Conversely, treatment with tectorigenin abolished thapsigargin-evoked [Ca2+]i rises. Inhibition of phospholipase C with U73122 inhibited 50% of tectorigenin-induced [Ca2+]i rises. Tectorigenin at concentrations between 10 and 60 μM killed cells in a concentration-dependent fashion. Chelation of cytosolic Ca2+ with 1,2-bis (2-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid/acetoxy methyl did not reverse tectorigenin's cytotoxicity. Our data suggest that, in MDCK cells, tectorigenin evoked [Ca2+]i rises and induced cell death that was not associated with [Ca2+]i rises. Therefore, tectorigenin may be a Ca2+-independent cytotoxic agent for kidney cells.

Thioridazine, belonging to first-generation antipsychotic drugs, is a prescription used to treat schizophrenia. However, the effect of thioridazine on intracellular Ca2+ concentration ([Ca2+]i) and viability in human liver cancer cells is unclear. This study examined whether thioridazine altered Ca2+ signaling and viability in HepG2 human hepatocellular carcinoma cells. Ca2+ concentrations in suspended cells were measured using the fluorescent Ca2+-sensitive dye fura-2. Cell viability was examined by WST-1 assay. Thioridazine at concentrations of 25–100 μM induced [Ca2+]i rises. Ca2+ removal reduced the signal by 20%. Thioridazine (100 μM) induced Mn2+ influx suggesting of Ca2+ entry. Thioridazine-induced Ca2+ entry was inhibited by 20% by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate) and inhibitor (GF109203X) and by three inhibitors of store-operated Ca2+ channels: nifedipine, econazole, and SKF96365. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) abolished thioridazine-evoked [Ca2+]i rises. On the other hand, thioridazine preincubation completely inhibited the [Ca2+]i rises induced by TG. Furthermore, U73122 totally suppressed the [Ca2+]i rises induced by thioridazine via inhibition of phospholipase C (PLC). Regarding cytotoxicity, at 30-80 μM, thioridazine reduced cell viability in a concentration-dependent fashion. This cytotoxicity was not prevented by preincubation with 1,2-bis (2-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM) (a Ca2+ chelator). To conclude, thioridazine caused concentration-dependent [Ca2+]i rises in HepG2 human hepatoma cells by inducing Ca2+ release from the endoplasmic reticulum via PLC-associated pathways and Ca2+ influx from extracellular medium through PKC-sensitive store-operated Ca2+ entry. In addition, thioridazine induced cytotoxicity in a Ca2+-independent manner.

Terfenadine, an antihistamine used for the treatment of allergic conditions, affected Ca2+-related physiological responses in various models. However, the effect of terfenadine on cytosolic free Ca2+ levels ([Ca2+](i)) and its related physiology in renal tubular cells is unknown. This study examined whether terfenadine altered Ca2+ signaling and caused cytotoxicity in Madin-Darby canine kidney (MDCK) renal tubular cells. The Ca2+-sensitive fluorescent dye fura-2 was used to measure [Ca2+](i). Cell viability was measured by the fluorescent reagent 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1) assay. Terfenadine at concentrations of 100-1000 mu M induced [Ca2+](i) rises concentration dependently. The response was reduced by approximately 35% by removing extracellular Ca2+. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) partly inhibited terfenadine-evoked [Ca2+](i) rises. Conversely, treatment with terfenadine abolished BHQ-evoked [Ca2+](i) rises. Inhibition of phospholipase C (PLC) with U73122 inhibited 95% of terfenadine-induced Ca2+ release. Terfenadine-induced Ca2+ entry was supported by Mn2+-caused quenching of fura-2 fluorescence. Terfenadine-induced Ca2+ entry was partly inhibited by an activator of protein kinase C (PKC), phorbol 12-myristate 13 acetate (PMA) and by three modulators of store-operated Ca2+ channels (nifedipine, econazole, and SKF96365). Terfenadine at 200-300 mu M decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in MDCK cells, terfenadine induced [Ca2+](i) rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Furthermore, terfenadine caused cell death that was not triggered by preceding [Ca2+](i) rises.

Chlorzoxazone is a skeletal muscle relaxant. However, the effect of chlorzoxazone on intracellular Ca2+ concentrations ([Ca2+]i) in oral cancer cells is unclear. This study examined whether chlorzoxazone altered Ca2+ signaling and cell viability in OC2 human oral cancer cells. [Ca2+]iin suspended cells was measured using the fluorescent Ca2+-sensitive dye fura-2. Cell viability was examined by water-soluble tetrazolium-1 assay. Chlorzoxazone (250–1000 μM) induced [Ca2+]irises in a concentration-dependent manner. Ca2+ removal reduced the signal by approximately 50%. Mn2+ has been shown to enter cells through similar mechanisms as Ca2+ but quenches fura-2 fluorescence at all excitation wavelengths. Chlorzoxazone (1000 μM) induced Mn2+ influx, suggesting that Ca2+ entry occurred. Chlorzoxazone-induced Ca2+ entry was inhibited by 20% by inhibitors of store-operated Ca2+ channels and protein kinase C (PKC) modulators. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) inhibited chlorzoxazone-evoked [Ca2+]irises by 88%. Conversely, treatment with chlorzoxazone-suppressed TG-evoked [Ca2+]irises 75%. Chlorzoxazone induced [Ca2+]irises by exclusively releasing Ca2+ from the endoplasmic reticulum. Inhibition of phospholipase C (PLC) with U73122 did not alter chlorzoxazone-induced [Ca2+]irises. PLC activity was not involved in chlorzoxazone-evoked [Ca2+]irises. Chlorzoxazone at 200–700 μM decreased cell viability, which was not reversed by pretreatment with Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl. In sum, in OC2 cells, chlorzoxazone induced [Ca2+]irises by evoking PLC-independent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Chlorzoxazone also caused Ca2+-independent cell death. Since [Ca2+]irises play a triggering or modulatory role in numerous cellular phenomena, the effect of chlorzoxazone on [Ca2+]iand cell viability should be taken into account in other in vitro studies.

Timolol is a medication used widely to treat glaucoma. Regarding Ca2+ signaling, timolol was shown to modulate Ca2+-related physiology in various cell types, however, the effect of timolol on Ca2+ homeostasis and cell viability has not been explored in human prostate cancer cells. The aim of this study was to explore the effect of timolol on intracellular Ca2+ concentrations ([Ca2+]i) and viability in PC3 human prostate cancer cells. Timolol at concentrations of 100-1000 μM induced [Ca2+]i rises. The Ca2+ signal in Ca2+-containing medium was reduced by removal of extracellular Ca2+ by approximately 75%. Timolol (1000 μM) induced Mn2+ influx suggesting of Ca2+ entry. Timolol-induced Ca2+ entry was partially inhibited by three inhibitors of store-operated Ca2+ channels: nifedipine, econoazole and SKF96365, and by a protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate [PMA]) or an inhibitor (GF109203X). In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished timolol-evoked [Ca2+]i rises. Conversely, treatment with timolol abolished thapsigargin-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 abolished timolol-induced [Ca2+]i rises. Timolol at concentrations between 200 and 600 μM killed cells in a concentration-dependent fashion. Chelation of cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not reverse cytotoxicity of timolol. Together, in PC3 cells, timolol induced [Ca2+]i rises by evoking Ca2+release from the endoplasmic reticulum in a PLC-dependent manner, and Ca2+ influx via PKC-regulated store-operated Ca2+ entry. Timolol also caused cell death that was not linked to preceding [Ca2+]i rises.

The aim of this study is to investigate the seasonal variations and source apportionment on atmospheric fine particulate matter (PM2.5) mass and associated trace element concentrations at a coastal area, in Chiayi County of southwestern Taiwan. Particle measurements were conducted in 2015. Twenty-three trace elements in PM2.5 were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Multiple approaches of the enrichment factor (EF) analysis and positive matrix fraction (PMF) model were used to identify potential sources of PM2.5-bound trace elements. Daily mean concentration of PM2.5 in cold season (25.41 μg m−3) was higher than that in hot season (13.10 μg m−3). The trace elements contributed 11.02 and 10.74% in total PM2.5 mass concentrations in cold season and hot season, respectively. The results of EF analysis confirmed that Sb, Mo, and Cd were the top three anthropogenic trace elements in the PM2.5; furthermore, carcinogenic elements (Cr, Ni, and As) and other trace elements (Na, K, V, Cu, Zn, Sr, Sn, Ba, and Pb) were attributable to anthropogenic emissions in both cold and hot seasons; however, highly enriched Li and Mn were observed only in cold season. The PMF model identified four main sources: iron and steel industry, soil and road dust, coal combustion, and traffic-related emission. Each of these sources has an annual mean contribution of 8.2, 27.5, 11.2, and 53.1%, respectively, to PM2.5. The relative dominance of each identified source varies with changing seasons. The highest contributions occurred in cold season for iron and steel industry (66.2%), in hot season for traffic-related emission (58.4%), soil and road dust (22.0%), and coal combustion (2.8%). These findings revealed that the PM2.5 mass concentration, PM2.5-bound trace element concentrations, and their contributions were various by seasons.

Captopril, an angiotensin-converting enzyme (ACE) inhibitor, induced different Ca²⁺ signaling responses in various cell models. However, the effect of captopril on Ca²⁺ homeostasis and cell viability in hepatoma cells is unknown. This study examined whether captopril altered Ca²⁺ homeostasis and viability in HepG2 human hepatoma cells. Intracellular Ca²⁺ concentrations in suspended cells were monitored by using the fluorescent Ca²⁺-sensitive dye fura-2. Cell viability was examined by using 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1). Captopril at concentrations of 500-3000 μM induced [Ca²⁺]i rises in a concentration-dependent manner. Ca²⁺ removal reduced the signal by approximately 15%. Mn²⁺ has been shown to enter cells through similar mechanisms as Ca²⁺ but quenches fura-2 fluorescence at all excitation wavelengths. Captopril (3000 μM)-induced Mn²⁺ influx indirectly suggested that captopril evoked Ca²⁺ entry. Captopril-induced Ca²⁺ entry was inhibited by 15% by a protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate, PMA) and an inhibitor (GF109203X) and three inhibitors of store-operated Ca²⁺ channels: nifedipine, econazole and SKF96365. In Ca²⁺-free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished captopril-evoked [Ca²⁺]i rises. Conversely, treatment with captopril abolished BHQ-evoked [Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122 inhibited 70% of captopril-induced [Ca²⁺]i rises. Captopril at concentrations between 150-550 μM killed cells in a concentration-dependent fashion. Chelation of cytosolic Ca²⁺ with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid/AM (BAPTA/AM) did not reverse captopril’s cytotoxicity. Together, in HepG2 human hepatoma cells, captopril induced [Ca²⁺]i rises and caused cell death that was not triggered by preceding [Ca²⁺]i rises.

Niflumic acid, a drug used for joint and muscular pain, affected Ca²⁺ signaling in differentmodels. However, the effect of niflumic acid on Ca²⁺ homeostasis and Ca²⁺-related physiologyin human osteosarcoma cells is unknown. This study examined the effect of niflumic acid oncytosolic free Ca²⁺ concentrations ([Ca²⁺]i) in MG63 human osteosarcoma cells. Intracellular Ca²⁺concentrations in suspended cells were monitored by using the fluorescent Ca²⁺-sensitive dye fura-2. Cell viability was examined by using 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1). In MG63 cells, niflumic acid atconcentrations of 250-750 μM evoked [Ca²⁺]i rises concentration-dependently. Niflumic acid-evokedCa²⁺ entry was confirmed by Mn²⁺-induced quenching of fura-2 fluorescence. This entrywas inhibited by nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol12-myristate 13 acetate (PMA), but was not affected by the PKC inhibitor GF109203X. In Ca²⁺-free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin (TG)inhibited niflumic acid-evoked [Ca²⁺]i rises. Conversely, treatment with niflumic acid abolished TG-evoked[Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122 also partly reduced niflumicacid-evoked [Ca²⁺]i rises. Niflumic acid killed cells at 200-500 μM in a concentration-dependentfashion. Chelating cytosolic Ca²⁺ with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid/AM (BAPTA/AM) did not reverse niflumic acid-induced cytotoxicity. Collectively, our data suggestthat in MG63 cells, niflumic acid induced [Ca²⁺]i rises by evoking PLC-dependent Ca²⁺ release fromthe endoplasmic reticulum, and Ca²⁺ entry via PKC-sensitive store-operated Ca²⁺ entry. Niflumicacid also induced Ca²⁺-independent cell death.

Objective Magnolol, a polyphenol compound from herbal medicines, was shown to alter physiology in various cell models. However, the effect of magnolol on Ca2+ homeostasis and its related physiology in oral cancer cells is unclear. This study examined whether magnolol altered Ca2+ signaling and cell viability in OC2 human oral cancer cells. Methods: Cytosolic Ca2+ concentrations ([Ca2+](i)) in suspended cells were measured by using the fluorescent Ca2+ -sensitive dye fura-2. Cell viability was examined by 4-[3-[4-lodopheny1]-2-4(4-nitropheny1)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1) assay. Results: Magnolol at concentrations of 20-100 mu M induced [Ca2+](i) rises. Ca2+ removal reduced the signal by approximately 50%. Magnolol (100 mu M) induced Mn2+ influx suggesting of Ca2+ entry. Magnolol-induced Ca2+ entry was partially suppressed by protein kinase C (PKC) regulators, and inhibitors of store-operated C-a2+ channels. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tertbutylhydroquinone (BHQ) abolished magnolol-evoked [Ca2+](i) rises. Conversely, treatment with magnolol abolished BHQ-evoked [Ca2+](i) rises. Inhibition of phospholipase C (PLC) with U73122 partially inhibited magnolol-induced [Ca2+](i) rises. Magnolol at 20-100 mu M decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Conclusions: Together, in OC2 cells, magnolol induced [Ca2+](i) rises by evoking partially PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca-2+ entry. Magnolol also caused Ca2+-independent cell death. Therefore, magnolol-induced cytotoxicity may not be involved in activation mechanisms associated with intracellular Ca2+ mobilization in oral cancer cells.

Tetramethylpyrazine (TMP) is a compound purified from herb. Its effect on Ca2+ concentrations ([Ca2+ ]i ) in renal cells is unclear. This study examined whether TMP altered Ca2+ signaling in Madin-Darby canine kidney (MDCK) cells. TMP at 100-800 μM induced [Ca2+ ]i rises, which were reduced by Ca2+ removal. TMP induced Mn2+ influx implicating Ca2+ entry. TMP-induced Ca2+ entry was inhibited by 30% by modulators of protein kinase C (PKC) and store-operated Ca2+ channels. Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) inhibited 93% of TMP-evoked [Ca2+ ]i rises. Treatment with TMP abolished BHQ-evoked [Ca2+ ]i rises. Inhibition of phospholipase C (PLC) abolished TMP-induced responses. TMP at 200-1000 μM decreased viability, which was not reversed by pretreatment with the Ca2+  chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. Together, in MDCK cells, TMP induced [Ca2+ ]i rises by evoking PLC-dependent Ca2+ release from endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. TMP also caused Ca2+ -independent cell death.

Ambient particulate matter (PM) can trigger adverse reactions in the respiratory system, but less is known about the effect of indoor PM. In this longitudinal study, we investigated the relationships between indoor PM and clinical parameters in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Indoor air quality (PM2.5 and PM10 levels) was monitored in the patients’ bedroom, kitchen, living room, and front door at baseline and every two months for one year. At each home visit, the patients were asked to complete spirometry and questionnaire testing. Exacerbations were assessed by chart review and questionnaires during home visits. Generalized estimating equation (GEE) analysis (n = 83) showed that the level of wheezing was significantly higher in patients whose living room and kitchen had abnormal (higher than ambient air quality standards in Taiwan) PM2.5 and PM10 levels. Patients who lived in houses with abnormal outdoor PM2.5 levels had higher COPD Assessment Test scores (physical domain), and those who lived in houses with abnormal PM10 levels in the living room and kitchen had higher London Chest Activity of Daily Living scores. Increased PM levels were associated with worse respiratory symptoms and increased risk of exacerbation in patients with moderate to very severe COPD.

This population-based study explored the effects of ambient fine particulate matter (PM2.5) on hospital emergency room visits (ERVs) for respiratory diseases (RDs) in Taiwan in 2012. Data on hospital ERVs for RDs and ambient PM2.5 levels in 2012 were obtained from the National Health Insurance Research database and the Environmental Protection Administration, respectively. The lag structure of relative risks (RRs) of hospital ERVs for RDs was estimated using the Quasi-Poisson generalized additive model. During the study period, the average daily number of hospital ERVs for RDs, chronic obstructive pulmonary disease (COPD), acute exacerbation chronic obstructive pulmonary disease (AECOPD), asthma, and pneumonia were 17, 15, 17, 17, and 17, respectively, and the mean 24-h average PM2.5 concentration was 27.8 mg/m(3). Increased hospital ERVs for RDs were significantly associated with PM2.5; moreover, geographic variation in PM2.5 hospital ERVs for RDs was observed. In terms of RRs for each 10 mg/m3 increase in PM2.5, Kao-Ping air quality zone (with districts: Kaohsiung and Pingdong) had the largest RRs associated with PM2.5; the RRs were 1.23 [95% confidence interval (CI) = 1.05-1.45] for AECOPD (at lag 0 -1 days), 1.07 (95% CI = 1.01-1.13) for asthma (at lag 0-1 days), and 1.07 (95% CI = 1.01-1.13) for pneumonia (at lag 0-1 days). On hot season, the RRs were 1.05 (95% CI = 1.01-1.08) for AECOPD (at lag 0 -3 days); moreover, on cold season, the RRs were 1.15 (95% CI = 1.03-1.28) for asthma (at lag 0-1 days) and 1.15 (95% CI = 1.03-1.28) for pneumonia (at lag 0-1 days). Overall, PM2.5 exposure had lag effects on hospital ERVs for RDs; elevated RRs started at 2-day (lag 0-1 days), and larger RR estimates were observed at longer lags. In summary, this study revealed an association between PM2.5 and hospital ERVs for RDs in Taiwan. (C) 2017 Turkish National Committee for Air Pollution Research and Control. Production and hosting by Elsevier B.V. All rights reserved.

Thymol is a phenolic compound that affects physiology in different cell models. However, whetherthymol affects Ca²⁺ homeostasis in prostate cancer cells is unknown. The action of this compound oncytosolic Ca²⁺ concentrations ([Ca²⁺]i) and viability in PC3 human prostate cancer cells was explored.The results show that thymol at concentrations of 100-1500 μM caused [Ca²⁺]i rises in a concentration-dependentmanner. Removal of extracellular Ca²⁺ reduced thymol’s effect by approximately 80%.Thymol-induced Ca²⁺ entry was confirmed by Mn²⁺ entry-induced quench of fura-2 fluorescence, and wasinhibited by approximately 30% by Ca²⁺ entry modulators (nifedipine, econazole, SKF96365), and theprotein kinase C (PKC) inhibitor GF109203X. In Ca²⁺-free medium, treatment with the endoplasmicreticulum Ca²⁺ pump inhibitor thapsigargin abolished thymol-induced [Ca²⁺]i rises. Treatment with thymolalso abolished thapsigargin-induced [Ca²⁺]i rises. Thymol-induced Ca²⁺ release from the endoplasmicreticulum was abolished by the phospholipase C (PLC) inhibitor U73122. Thymol at 100-900 μM decreasedcell viability, which was not reversed by pretreatment with the Ca²⁺ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in PC3 cells, thymolinduced [Ca²⁺]i rises by inducing PLC-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺entry via PKC-sensitive store-operated Ca²⁺ channels and other unknown channels. Thymol also inducedCa²⁺-dissociated cell death.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.

Methoxsalen is a natural compound found in many seed plants. The effect of methoxsalen on Ca²⁺-related physiology in human osteosarcoma is unclear. This study investigated the effect of methoxsalenon cytosolic free Ca²⁺ concentrations ([Ca²⁺]i) in MG63 human osteosarcoma cells. Methoxsalen induced[Ca²⁺]i rises concentration-dependently. Methoxsalen-induced Ca²⁺ entry was confirmed by Mn²⁺-inducedquench of fura-2 fluorescence. This Ca²⁺ entry was suppressed by nifedipine, econazole, and SKF96365.In Ca²⁺-free medium, incubation with the endoplasmic reticulum Ca²⁺ pump inhibitor 2,5-di-tert-butylhydroquinone(BHQ) inhibited methoxsalen-evoked [Ca²⁺]i rises by 96%. In contrast, incubationwith methoxsalen abolished BHQ-evoked [Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122abolished methoxsalen-induced [Ca²⁺]i rises. Methoxsalen was cytotoxic at 300-700 μM in a concentration-dependentfashion. Chelating cytosolic Ca²⁺ with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraaceticacid/acetoxymethyl ester (BAPTA/AM) did not prevent methoxsalen-induced cytotoxicity. Collectively, our data suggestthat in MG63 cells, methoxsalen induced [Ca²⁺]i rises by evoking PLC-dependent Ca²⁺ release from theendoplasmic reticulum, and Ca²⁺ entry via store-operated Ca²⁺ entry. Methoxsalen also induced Ca²⁺-disassociated cell death.