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Candida albicans has the capacity to neutralize acidic growth environments by releasing ammonia derived from the catabolism of amino acids. The molecular components underlying alkalization and its physiological significance remain poorly understood. Here, we present an integrative model with the cytosolic NAD+-dependent glutamate dehydrogenase (Gdh2) as the principal ammonia-generating component. We show that alkalization is dependent on the SPS-sensor-regulated transcription factor STP2 and the proline-responsive activator Put3. These factors function in parallel to derepress GDH2 and the two proline catabolic enzymes PUT1 and PUT2. Consistently, a double mutant lacking STP2 and PUT3 exhibits a severe alkalization defect that nearly phenocopies that of a gdh2-/- strain. Alkalization is dependent on mitochondrial activity and in wild-type cells occurs as long as the conditions permit respiratory growth. Strikingly, Gdh2 levels decrease and cells transiently extrude glutamate as the environment becomes more alkaline. Together, these processes constitute a rudimentary regulatory system that counters and limits the negative effects associated with ammonia generation. These findings align with Gdh2 being dispensable for virulence, and based on a whole human blood virulence assay, the same is true for C. glabrata and C. auris. Using a transwell co-culture system, we observed that the growth and proliferation of Lactobacillus crispatus, a common component of the acidic vaginal microenvironment and a potent antagonist of C. albicans, is unaffected by fungal-induced alkalization. Consequently, although Candida spp. can alkalinize their growth environments, other fungal-associated processes are more critical in promoting dysbiosis and virulent fungal growth.
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Aminoácidos , Candida albicans , Femenino , Humanos , Candida albicans/metabolismo , Aminoácidos/metabolismo , Amoníaco/metabolismo , Candida/metabolismo , Prolina/metabolismo , Candida glabrata/metabolismoRESUMEN
Malaria tropica, caused by the parasite Plasmodium falciparum (P. falciparum), remains one of the greatest public health burdens for humankind. Due to its pivotal role in parasite survival, the energy metabolism of P. falciparum is an interesting target for drug design. To this end, analysis of the central metabolite adenosine triphosphate (ATP) is of great interest. So far, only cell-disruptive or intensiometric ATP assays have been available in this system, with various drawbacks for mechanistic interpretation and partly inconsistent results. To address this, we have established fluorescent probes, based on Förster resonance energy transfer (FRET) and known as ATeam, for use in blood-stage parasites. ATeams are capable of measuring MgATP2- levels in a ratiometric manner, thereby facilitating in cellulo measurements of ATP dynamics in real-time using fluorescence microscopy and plate reader detection and overcoming many of the obstacles of established ATP analysis methods. Additionally, we established a superfolder variant of the ratiometric pH sensor pHluorin (sfpHluorin) in P. falciparum to monitor pH homeostasis and control for pH fluctuations, which may affect ATeam measurements. We characterized recombinant ATeam and sfpHluorin protein in vitro and stably integrated the sensors into the genome of the P. falciparum NF54attB cell line. Using these new tools, we found distinct sensor response patterns caused by several different drug classes. Arylamino alcohols increased and redox cyclers decreased ATP; doxycycline caused first-cycle cytosol alkalization; and 4-aminoquinolines caused aberrant proteolysis. Our results open up a completely new perspective on drugs' mode of action, with possible implications for target identification and drug development.
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Adenosina Trifosfato , Antimaláricos , Transferencia Resonante de Energía de Fluorescencia , Plasmodium falciparum , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/metabolismo , Plasmodium falciparum/genética , Adenosina Trifosfato/metabolismo , Antimaláricos/farmacología , Transferencia Resonante de Energía de Fluorescencia/métodos , Colorantes Fluorescentes/química , Humanos , Quinina/farmacología , Doxiciclina/farmacología , Artemisininas/farmacología , Cloroquina/farmacología , Concentración de Iones de HidrógenoRESUMEN
PURPOSE: The consumption of alkaline water, water with an average pH of 8 to 10, has been steadily increasing globally as proponents claim it to be a healthier alternative to regular water. Urinary alkalinization therapy is frequently prescribed in patients with uric acid and cystine urolithiasis, and as such we analyzed commercially available alkaline waters to assess their potential to increase urinary pH. MATERIALS AND METHODS: Five commercially available alkaline water brands (Essentia, Smart Water Alkaline, Great Value Hydrate Alkaline Water, Body Armor SportWater, and Perfect Hydration) underwent anion chromatography and direct chemical measurements to determine the mineral contents of each product. The alkaline content of each bottle of water was then compared to that of potassium citrate (the gold standard for urinary alkalinization) as well as to other beverages and supplements used to augment urinary citrate and/or the urine pH. RESULTS: The pH levels of the bottled alkaline water ranged from 9.69 to 10.15. Electrolyte content was minimal, and the physiologic alkali content was below 1 mEq/L for all brands of alkaline water. The alkali content of alkaline water is minimal when compared to common stone treatment alternatives such as potassium citrate. In addition, several organic beverages, synthetic beverages, and other supplements contain more alkali content than alkaline water, and can achieve the AUA and European Association of Urology alkali recommendation of 30 to 60 mEq per day with ≤ 3 servings/d. CONCLUSIONS: Commercially available alkaline water has negligible alkali content and thus provides no added benefit over tap water for patients with uric acid and cystine urolithiasis.
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Ácido Úrico , Urolitiasis , Humanos , Cistina , Citrato de Potasio/uso terapéutico , Urolitiasis/terapia , ÁlcalisRESUMEN
Electrochemical alkalization of (Cu-S)n metal-organic framework (MOF) and graphene oxide ((Cu-S)n MOF/GO) composite yields a new CuO/(Cu-S)n MOF/RGO (reduced GO) composite with porous morphology on screen printed carbon electrode (SPCE) which facilitated the electron transfer properties in electrochemical quercetin (QUE) detection. A selective QUE detection ability has been demonstrated by the constructed electrochemical sensor (CuO/(Cu-S)n MOF/RGO/SPCE), which also has a broad dynamic range of 0.5 to 115 µM in pH 3 by differential pulse voltammetry. The detection limit is 0.083 µM (S/N = 3). In this study, it was observed that the real samples contained 0.34 mg mL-1 and 27.7 µg g-1 QUE in wine and onion, respectively.
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Producing stable nitrite is a necessity for anaerobic ammonium oxidation (anammox) but remains a huge challenge. Here, we describe the design and operation of a hydrogenotrophic denitratation system that stably reduced >90% nitrate to nitrite under self-alkaline conditions of pH up to 10.80. Manually lowering the pH to a range of 9.00-10.00 dramatically decreased the nitrate-to-nitrite transformation ratio to <20%, showing a significant role of high pH in denitratation. Metagenomics combined with metatranscriptomics indicated that six microorganisms, including a Thauera member, dominated the community and encoded the various genes responsible for hydrogen oxidation and the complete denitrification process. During denitratation at high pH, transcription of periplasmic genes napA, nirS, and nirK, whose products perform nitrate and nitrite reduction, decreased sharply compared to that under neutral conditions, while narG, encoding a membrane-associated nitrate reductase, remained transcriptionally active, as were genes involved in intracellular proton homeostasis. Together with no reduction in only nitrite-amended samples, these results disproved the electron competition between reductions of nitrate and nitrite but highlighted a lack of protons outside cells constraining biological nitrite reduction. Overall, our study presents a stably efficient strategy for nitrite production and provides a major advance in the understanding of denitratation.
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Nitratos , Nitritos , Nitritos/química , Desnitrificación , Oxidación-Reducción , Concentración de Iones de Hidrógeno , Reactores Biológicos , NitrógenoRESUMEN
Coastal enhanced weathering (CEW) is a carbon dioxide removal (CDR) approach whereby crushed silicate minerals are spread in coastal zones to be naturally weathered by waves and tidal currents, releasing alkalinity and removing atmospheric carbon dioxide (CO2). Olivine has been proposed as a candidate mineral due to its abundance and high CO2 uptake potential. A life cycle assessment (LCA) of silt-sized (10 µm) olivine revealed that CEW's life-cycle carbon emissions and total environmental footprint, i.e., carbon and environmental penalty, amount to around 51 kg CO2eq and 3.2 Ecopoint (Pt) units per tonne of captured atmospheric CO2, respectively, and these will be recaptured within a few months. Smaller particle sizes dissolve and uptake atmospheric CO2 even faster; however, their high carbon and environmental footprints (e.g., 223 kg CO2eq and 10.6 Pt tCO2-1, respectively, for 1 µm olivine), engineering challenges in comminution and transportation, and possible environmental stresses (e.g., airborne and/or silt pollution) might restrict their applicability. Alternatively, larger particle sizes exhibit lower footprints (e.g., 14.2 kg CO2eq tCO2-1 and 1.6 Pt tCO2-1, respectively, for 1000 µm olivine) and could be incorporated in coastal zone management schemes, thus possibly crediting CEW with avoided emissions. However, they dissolve much slower, requiring 5 and 37 years before the 1000 µm olivine becomes carbon and environmental net negative, respectively. The differences between the carbon and environmental penalties highlight the need for using multi-issue life cycle impact assessment methods rather than focusing on carbon balances alone. When CEW's full environmental profile was considered, it was identified that fossil fuel-dependent electricity for olivine comminution is the main environmental hotspot, followed by nickel releases, which may have a large impact on marine ecotoxicity. Results were also sensitive to transportation means and distance. Renewable energy and low-nickel olivine can minimize CEW's carbon and environmental profile.
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Dióxido de Carbono , Níquel , Animales , Silicatos , Minerales , Estadios del Ciclo de VidaRESUMEN
Animal slurry storage is a significant source of greenhouse gas (GHG) and ammonia (NH3) emissions. pH is a basic but key factor that could pose great influence on gas emissions, but the simultaneous evaluation of its influence on GHG and NH3 emissions and the understanding of its underlying mechanism are not enough. In this work, pH was adjusted between 5.5 and 10.0 by a step of 0.5 unit by adding lactic acid and sodium hydroxide (NaOH) properly and frequently to the stored slurry during a 43-day storage period. The cumulative NH3 emissions were linearly correlated with the slurry pH, with R2 being 0.982. Maintaining the slurry pH at 5.5-6.0 could reduce NH3 emissions by 69.4%-85.1% compared with the non-treated group (CK). The pH ranges for maximum methane (CH4) and nitrous oxide (N2O) emissions were 7.5-8.5 and 6.5-8.5, respectively, and the slurry under pH 7.5-8.5 showed the highest GHG emissions. Acidification to pH 5.5 helped reduce the CH4, N2O, and total GHG emissions by 98.0%, 29.3%, and 81.7%, respectively; while alkalinization to pH 10.0 helped achieve the mitigation effects of 74.1%, 24.9%, and 30.6%, respectively. The Pearson's correlation factor between CH4 and the gene copy of mcrA under different pH values was 0.744 (p < 0.05). Meanwhile, the correlation factors between N2O and the gene copies of amoA, narG, and nirS were 0.644 (p < 0.05), 0.719 (p < 0.05), and 0.576 (p = 0.081), respectively. The gene copies of mcrA, amoA, narG, and nirS were maintained at the lowest level under pH 5.5. These results recommended keeping slurry pH lower than 5.5 with lactic acid can help control GHG and NH3 emissions simultaneously and effectively.
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Gases de Efecto Invernadero , Estiércol , Animales , Amoníaco , Metano/análisis , Óxido Nitroso , Concentración de Iones de Hidrógeno , SueloRESUMEN
Prunus japonica var. nakaii is used in traditional Korean medicine to treat various conditions; however, it has not been investigated for treating male infertility. In this study, we investigated the in vitro effects of the ethanolic extract of P. japonica seeds on human sperm motility and identified its mechanism of action. Eleven male volunteers were selected, and the effects of the extract on human spermatozoa were assessed through a computer-assisted semen analysis. The P. japonica seed extract increased the percentage of total and progressive motility of spermatozoa. To understand the mechanism of action, we monitored intracellular alkalization using flow cytometry and obtained electrophysiological recordings of human voltage-gated proton channels hHv1 that were overexpressed in HEK-293 cells. The extract shifted the activation curves in a concentration-dependent manner. Two major constituents of the extract, linoleic acid and oleic acid, exhibited proton channel activity. Our in vitro experiments suggested that P. japonica seed extract could be potentially used to rescue sperm motility in idiopathic infertility patients via pharmacological modulation of the proton channels during capacitation. Therefore, our results indicate the therapeutic potential of P. japonica seed extract for treating male infertility.
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Infertilidad Masculina , Prunus , Células HEK293 , Humanos , Masculino , Extractos Vegetales/farmacología , Protones , Capacitación Espermática , Motilidad Espermática , EspermatozoidesRESUMEN
This study was designed to show the changes in glycolmacropeptides (GMPs) of whey protein solution (WPS) due to different pretreatments before and after ultrafiltration (UF). The combined form of two variants (A&B) of GMPs is a helpful compound for nutritional management of phenylketonuria and ulcerative-colitis diseases and has low content of phenylalanine (Phe). WPS with 10% concentration was prepared, acidified (adjusted to pH = 3.0), and passed through a PES (polyethersulfone) membrane in the 1st-stage of ultrafiltration (UF-1). Then the resulting permeate was neutralized and went through the 2nd-stage of ultrafiltration (UF-2) under similar conditions. Four experiments of TRT-CON, CON-TRT, TRT-TRT, and CON-CON were used with different pretreatments, where TRT was a mixing-treatment of 30 min at 150 RPM applied either after acidification of WPS or after neutralization of first permeate and before UF-2 process. While the concentration and purity of the combined GMPs in UF-2 retentate in TRT-TRT respectively were >95.6 and 99.5%, its Phe became <10 ppm among the experiments. Highly glycolyzed polymers of GMPs (MW = 45-50 kDa) were formed in the TRT-TRT experiment and went through the pore sizes of PES membrane of UF-1 easily because of their flexible structure. However, they remained in the UF-2 retentate, due to to the formation of bulky polymers. The TRT-TRT experiment had the highest reversible and irreversible resistances for passing through the UF-1 and remaining on the UF-2 membranes, and its fouling index was significantly less than other experiments.
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OBJECTIVES: To compare the efficacy and safety of citrate mixture and sodium bicarbonate on urine alkalization in gout patients under benzbromarone treatment. METHODS: A prospective, randomized, parallel controlled trial was conducted among 200 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University. The participants were randomly divided into two groups (1:1), sodium bicarbonate group (3 g/day) and citrate mixture group (7 g/day). All patients were prescribed with 25 mg/day benzbromarone at initiation and maintained at a dose of 50 mg/day. Clinical and biochemical data were collected at each follow-up time point (baseline, weeks 2, 4, 8 and 12). RESULTS: A total of 182 patients completed the 12-week urine alkalization study. The urine pH value of both groups increased significantly from the baseline to the final follow-up time point (sodium bicarbonate group, 5.50-6.00, P < 0.05; citrate mixture group, 5.53-5.93, P < 0.05). While the comparisons regarding urine pH between treatment groups showed no significant differences for each time point. The estimated glomerular filtration rate (eGFR) dropped significantly after 12 weeks' trial in the sodium bicarbonate group (P < 0.01), while it was comparable between baseline and the last follow-up (P > 0.05) in the citrate mixture group. Results of urine analysis showed that the incident rate of occult blood in the sodium bicarbonate group was higher than that in the citrate mixture group (38 vs 24%, P < 0.05), accompanied by a similar occurrence of kidney stones. After 12-week follow-up, the frequency of twice gout flare in the citrate mixture group was significantly lower than that in sodium bicarbonate group (4 vs 12%, P = 0.037). No treatment-emergent adverse events occurred. CONCLUSION: The efficacy of citrate mixture on urine alkalization is comparable to sodium bicarbonate under benzbromarone treatment without significant adverse events. Citrate mixture is superior to sodium bicarbonate in lowering the incidence of urine occult blood and the frequency of gout attacks. TRIAL REGISTRATION: Registered with ChiCTR (http://www.chictr.org.cn), No. ChiCTR1800018518.
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Benzbromarona/uso terapéutico , Citratos/uso terapéutico , Gota/tratamiento farmacológico , Bicarbonato de Sodio/uso terapéutico , Uricosúricos/uso terapéutico , Adulto , Benzbromarona/administración & dosificación , China , Citratos/efectos adversos , Esquema de Medicación , Tasa de Filtración Glomerular/efectos de los fármacos , Gota/orina , Humanos , Concentración de Iones de Hidrógeno , Incidencia , Cálculos Renales/inducido químicamente , Cálculos Renales/epidemiología , Sangre Oculta , Estudios Prospectivos , Bicarbonato de Sodio/efectos adversos , Uricosúricos/administración & dosificaciónRESUMEN
Human neutrophils have a vital role in host defense and inflammatory responses in innate immune systems. Growing evidence shows that the overproduction of reactive oxygen species and granular proteolytic enzymes from activated neutrophils is linked to the pathogenesis of acute inflammatory diseases. However, adequate therapeutic targets are still lacking to regulate neutrophil functions. Herein, we report that MVBR-28, synthesized from the Mannich bases of heterocyclic chalcone, has anti-neutrophilic inflammatory effects through regulation of intracellular pH. MVBR-28 modulates neutrophil functions by attenuating respiratory burst, degranulation, and migration. Conversely, MVBR-28 has no antioxidant effects and fails to alter elastase activity in cell-free systems. The anti-inflammatory effects of MVBR-28 are not seen through cAMP pathways. Significantly, MVBR-28 potently inhibits extracellular Ca2+ influx in N-formyl-methionyl-leucyl-phenylalanine (fMLF)- and thapsigargin-activated human neutrophils. Notably, MVBR-28 attenuates fMLF-induced intracellular alkalization in a K+ -dependent manner, which is upstream of Ca2+ pathways. Collectively, these findings provide new insight into Mannich bases of heterocyclic chalcone regarding the regulation of neutrophil functions and the potential for the development of MVBR-28 as a lead compound for treating neutrophilic inflammatory diseases.
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Chalconas/farmacología , Morfolinas/farmacología , Neutrófilos/efectos de los fármacos , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Señalización del Calcio/efectos de los fármacos , Degranulación de la Célula/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Chalconas/síntesis química , Chalconas/química , Humanos , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Morfolinas/síntesis química , Morfolinas/química , N-Formilmetionina Leucil-Fenilalanina/farmacología , Activación Neutrófila/efectos de los fármacos , Neutrófilos/patología , Neutrófilos/fisiología , Potasio/metabolismo , Estallido Respiratorio/efectos de los fármacosRESUMEN
Photochemical conversion of CO2into solar fuels is one of the promising strategies to reducing the CO2emission and developing a sustainable carbon economy. For the more efficient utilization of solar spectrum, several approaches were adopted to pursue the visible-light-driven SrTiO3. Herein, oxygen vacancy was introduced over the commercial SrTiO3(SrTiO3-x) via the NaBH4thermal treatment, to extend the light absorption and promote the CO2adsorption over SrTiO3. Due to the mid-gap states resulted from the oxygen deficiency, combined with the intrinsic energy level of SrTiO3, the SrTiO3-xcatalyst exhibited excellent CO productivity (4.1 µmolËg-1Ëh-1) and stability from the CO2photodissociation under the visible-light irradiation (λ > 400 nm). Then, surface alkalization over SrTiO3-x(OH-SrTiO3-x) was carried out to further enhance the CO2adsorption/activation over the surface base sites and provide the OH ions as hole acceptor, the surface alkali OH connected with Sr site of SrTiO3could also weaken the Sr-O bonding thus facilitate the regeneration of surface oxygen vacancy under the light illumination, thus resulting in 1.5 times higher CO productivity additionally. This study demonstrates that the synergetic modulation of alkali OH and oxygen vacancy over SrTiO3could largely promote the CO2photodissociation activity.
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Sperm-specific K+ ion channel (KSper) and Ca2+ ion channel (CatSper), whose elimination causes male infertility in mice, determine the membrane potential and Ca2+ influx, respectively. KSper and CatSper can be activated by cytosolic alkalization, which occurs during sperm going through the alkaline environment of the female reproductive tract. However, which intracellular pH (pHi) regulator functionally couples to the activation of KSper/CatSper remains obscure. Although Na+/H+ exchangers (NHEs) have been implicated to mediate pHi in sperm, there is a lack of direct evidence confirming the functional coupling between NHEs and KSper/CatSper. Here, 5-(N, N-dimethyl)-amiloride (DMA), an NHEs inhibitor that firstly proved not to affect KSper/CatSper directly, was chosen to examine NHEs function on KSper/CatSper in mouse sperm. The results of patch clamping recordings showed that, when extracellular pH was at the physiological level of 7.4, DMA application caused KSper inhibition and the depolarization of membrane potential when pipette solutions were not pH-buffered. In contrast, these effects were minimized when pipette solutions were pH-buffered, indicating that they solely resulted from pHi acidification caused by NHEs inhibition. Similarly, DMA treatment reduced CatSper current and intracellular Ca2+, effects also dependent on the buffer capacity of pH in pipette solutions. The impairment of sperm motility was also observed after DMA incubation. These results manifested that NHEs activity is coupled to the activation of KSper/CatSper under physiological conditions.
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Amilorida/análogos & derivados , Canales de Calcio/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Espermatozoides/fisiología , Amilorida/farmacología , Animales , Calcio/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Infertilidad Masculina/metabolismo , Masculino , Potenciales de la Membrana , Ratones , Técnicas de Placa-Clamp , Motilidad Espermática/efectos de los fármacos , Espermatozoides/efectos de los fármacosRESUMEN
In age-related macular degeneration (AMD), hydroquinone (HQ)-induced oxidative damage in retinal pigment epithelium (RPE) is believed to be an early event contributing to dysregulation of inflammatory cytokines and vascular endothelial growth factor (VEGF) homeostasis. However, the roles of antioxidant mechanisms, such as autophagy and the ubiquitin-proteasome system, in modulating HQ-induced oxidative damage in RPE is not well-understood. This study utilized an in-vitro AMD model involving the incubation of human RPE cells (ARPE-19) with HQ. In comparison to hydrogen peroxide (H2O2), HQ induced fewer reactive oxygen species (ROS) but more oxidative damage as characterized by protein carbonyl levels, mitochondrial dysfunction, and the loss of cell viability. HQ blocked the autophagy flux and increased proteasome activity, whereas H2O2 did the opposite. Moreover, the lysosomal membrane-stabilizing protein LAMP2 and cathepsin D levels declined with HQ exposure, suggesting loss of lysosomal membrane integrity and function. Accordingly, HQ induced lysosomal alkalization, thereby compromising the acidic pH needed for optimal lysosomal degradation. Pretreatment with MG132, a proteasome inhibitor and lysosomal stabilizer, upregulated LAMP2 and autophagy and prevented HQ-induced oxidative damage in wildtype RPE cells but not cells transfected with shRNA against ATG5. This study demonstrated that lysosomal dysfunction underlies autophagy defects and oxidative damage induced by HQ in human RPE cells and supports lysosomal stabilization with the proteasome inhibitor MG132 as a potential remedy for oxidative damage in RPE and AMD.
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Autofagia , Lisosomas/metabolismo , Degeneración Macular/etiología , Complejo de la Endopetidasa Proteasomal/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Catepsina D/metabolismo , Células Cultivadas , Humanos , Hidroquinonas , Leupeptinas , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Degeneración Macular/metabolismo , Mitocondrias/metabolismo , Epitelio Pigmentado de la Retina/citologíaRESUMEN
Allyl isothiocyanate (AITC) induces stomatal closure accompanied by reactive oxygen species (ROS) production and glutathione (GSH) depletion in Arabidopsis thaliana. In this study, stomatal responses to three other isothiocyanates (ITCs), benzyl isothiocyanate (BITC), sulforaphane (SFN), and phenethyl isothiocyanate (PEITC), were investigated in A. thaliana. All these ITCs significantly induced stomatal closure, where PEITC and BITC were most effective. The selected ITCs also induced ROS accumulation, cytosolic alkalization, and GSH depletion in guard cells. Moreover, all ITCs increased the frequency of cytosolic free calcium ([Ca2+]cyt) spikes (transient elevation), while PEITC and BITC showed the highest frequency. There was a strong positive correlation between the number of [Ca2+]cyt spikes per guard cell and the decrease in stomatal aperture. Both cytosolic alkalization and GSH content have a positive correlation with the decrease in stomatal aperture, but ROS production did not have a significant correlation with the decrease in stomatal apertures. These results indicate that the molecules with a functional ITC group induce stomatal closure that is accompanied by GSH depletion, cytosolic alkalization, [Ca2+]cyt spikes, and ROS production, and that the former three cellular events, rather than ROS production, are highly correlated with the decrease in stomatal aperture.
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Arabidopsis , Citosol , Isotiocianatos/farmacología , Estomas de Plantas , Especies Reactivas de OxígenoRESUMEN
Two lysosome-targeting fluorescent anion transporters derived from coumarins, trifluoromethylated arylsquaramides and morpholines were synthesized, and their specificity and efficiency to target and alkalize lysosomes were investigated. They are able to target lysosomes specifically. Compared with the previous analogue without trifluoromethyl substituents, these two conjugates, in particular the one having a 3,5-bis(trifluoromethyl) substituent, exhibit significantly higher ability to facilitate the transport of chloride anions, alkalize lysosomes and reduce the activity of lysosomal Cathepsin B enzyme. The present finding suggests that improving the anionophoric activity of lysosome-targeting fluorescent anion transporters is favorable to the efficiency to alkalize lysosomes and deactivate lysosomal Cathepsin B enzyme.
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Catepsina B/antagonistas & inhibidores , Cumarinas/farmacología , Ciclobutanos/farmacología , Transporte Iónico/efectos de los fármacos , Lisosomas/efectos de los fármacos , Cloruros/metabolismo , Cumarinas/síntesis química , Ciclobutanos/síntesis química , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Morfolinas/síntesis química , Morfolinas/farmacologíaRESUMEN
This study focused on the effect of saline and alkaline stress on six typical wetland plant species during seed germination and early seedling growth stages. Based on the indicators of germination, seedling growth and ionic absorption in seedlings, relatively saline and alkaline tolerant plant species were selected and tolerance mechanism was discussed. Results showed that the existence of saline and alkaline stress inhibited the capacity of germination and early seedling growth of most tested plant species to varying degrees, therein effects of saline-alkaline stress were greater than saline stress. Based on the results of principal component analysis (PCA), germination percentage, K+ content, plant height, Na+ content and Na+/K+ ratios can be selected as representative indicators for saline and alkaline tolerance evaluation during seed germination and early seedling growth stages. Among tested species, Juncus effusus and Vetiveria zizanioides exhibited relatively higher saline and alkaline tolerant capacity during their seed germination and early seedling growth. Additionally, both species increase K+ accumulation and retain lower Na+/K+ ratios, which might be their tolerance mechanisms at ion level. In conclusion, V. zizaniodes and J. effusus were recommended as potential plant species for restoring degraded saline-alkaline wetlands and/or establishing constructed wetlands for treating saline wastewater.
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Germinación , Plantones , Biodegradación Ambiental , Semillas , HumedalesRESUMEN
Alkalization, also known as "Dutching," is an optional, but very useful, step taken in the production chain of cocoa to darken its color, modify its taste, and increase natural cocoa solubility. Over the years, various attempts have been made to design new and more effective alkalization methods. Moreover, different authors have attempted to elucidate the impact of alkalization on the physicochemical, nutritional, functional, microbiological, and sensory characteristics of alkalized cocoa. The aim of this review is to provide a clear guide about not only the conditions that can be applied to alkalize cocoa, but also the reported effects of alkalization on the nutritional, functional, microbiological, and sensory characteristics of cocoa. The first part of this review describes different cocoa alkalization systems and how they can be tuned to induce specific changes in cocoa properties. The second part is a holistic analysis of the effects of the alkalization process on different cocoa features, performed by emphasizing the biochemistry behind all these transformations.
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Cacao/química , Manipulación de Alimentos/métodos , Álcalis/química , Cacao/microbiología , Color , Valor Nutritivo , GustoRESUMEN
Alkalization modifies the color and flavor of the cocoa products. The aim of the present survey was to determine how different types and dosage of alkaline relate to the color quality, total polyphenol amount and alkylpyrazine content of cocoa powder. Cameroon cacao beans were used to produce cocoa nibs. The nibs were alkalized with the solutions of NaOH, K2CO3, and NH4HCO3 at their different concentrations and combinations. The browning index (OD460/OD525) and alkylpyrazine content were changed significantly (p ≤ 0.01) with changing the type and the concentration of the alkali solution. The browning index, moisture, ash, and acid-insoluble ash content increased as the concentration of the alkali increased. In general, the not-alkaline products had more polyphenol and ratio of tetramethylpyrazine to trimethylpyrazine than the alkalized ones. Besides, the polyphenol and alkylpyrazine amounts decreased as the concentration of the alkali increased (p ≤ 0.01). At the same concentration, alkalization with a NaOH solution produced a higher polyphenol and alkylpyrazine content, but lower OD460/OD525 value than that with a K2CO3 solution. The samples with a high concentration of alkaline solution had the lowest ratio of monomer anthocyanins to yellow and brown polymers content (F1/F3) value.
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INTRODUCTION: Uric acid (UA) nephrolithiasis represents 10% of kidney stones in the US with low urine pH and high saturation of UA as the main risk factors for stone development. Dissolution therapy for UA kidney stones via urinary alkalization has been described as a treatment option. We present our experience in treating UA nephrolithiasis with medical dissolution therapy. METHODS: A retrospective review was performed of UA stone patients referred for surgery but treated with dissolution therapy between July 2007 and July 2016. Patients were identified using ICD-9 codes. Patients were treated with potassium citrate alone or in combination with allopurinol. Serial imaging and urine pH were obtained at follow-up. Demographics, aggregate stone size, time to stone clearance, urine pH (office dip), and complications were recorded. RESULTS OBTAINED: Twenty-four patients (14 men and 10 women) were identified that started medical dissolution therapy for UA nephrolithiasis after initial referral for surgical management. Three patients (13%) did not tolerate the initiation of dissolution therapy and discontinued this treatment. Of the 21 patients that were maintained on dissolution therapy, 14 patients (67%) showed complete resolution of nephrolithiasis and 7 patients (33%) showed partial reduction. Patients with partial response had a mean reduction in stone burden of 68%. There were 3 recorded complications (UTI, GI upset with therapy, and throat irritation) and 4 recorded stone recurrences among these 21 patients. CONCLUSION: Based on our study population, medical dissolution therapy is a well-tolerated, non-invasive option for UA nephrolithiasis.