Tioconazole(TCZ), a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial mycoses.The mai...Tioconazole(TCZ), a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial mycoses.The main goal of this work is to report an exhaustive identification and characterization procedure to improve and facilitate the online quality control and continuous process monitoring of TCZ in bulk material and loaded in two different dosage forms: ovules and nail lacquer. The methodologies were based on thermal(differential scanning calorimetry(DSC), melting point, and thermogravimetry(TG)),spectroscopic(ultraviolet(UV), Raman, near infrared(NIR), infrared spectroscopy coupled to attenuated total reflectance(FTIR-ATR), and nuclear magnetic resonance(NMR)), microscopic and X-ray diffraction(XRD). The TCZ bulk powder showed a high crystallinity, as observed by XRD, with a particles size distribution(3–95 mm) resolved by microscopic measurements. TCZ melting point(82.8 °C) and a degradation peak centered at 297.8 °C were obtained by DSC and DTG, respectively. An unambiguous structure elucidation of TCZ was obtained by mono-and two-dimensional1 H and13 C NMR spectral data analysis. The FTIR-ATR, Raman and NIR spectra of both the raw material and the commercial products were analyzed and their characteristic bands were tabulated. The best methods for TCZ identification in ovules were DSC, TG, XRD, NIR and Raman, while NIR and FTIR-ATR were the most appropriate techniques to analyze it in the nail lacquer. DSC, TG, DRX, Raman, FTIR-ATR and NIR spectroscopy are effective techniques to be used in online process analysis, because they do not require sample preparation, and they are considerably sensitive to analyze complex samples.展开更多
Background: An adequate hydration status is critical to ensure efficiency during mental and physical activities.Our goal was to assess the hydration status of a Spanish group of aeronautical military men and to determ...Background: An adequate hydration status is critical to ensure efficiency during mental and physical activities.Our goal was to assess the hydration status of a Spanish group of aeronautical military men and to determine the association of hydration status with body composition and anxiety.Methods: A total of 188 men were evaluated through a validated hydration questionnaire, anthropometric and biochemical parameters, and an anxiety questionnaire. Based on these methods, the criteria of hydration were established.Results: Of the total sample, 81% met the hydration criteria(urine color = well hydrated, water balance ≥0 ml, and total water intake/weight ≥35 ml/kg), and 19% did not meet the hydration criteria(urine color = not sufficiently hydrated or dehydrated, water balance <0 ml, and total water intake/weight <35 ml/kg). Subjects not meeting the hydration criteria had lower urine pH, negative water balance, and lower water intake. The latter also had higher anxiety status(score=4 vs. 3, P=0.026), weight [(84.7±10.5) kg vs.(80.5±10.2) kg], body mass index [(26.3±3.1) kg/m;vs.(25.2±2.8) kg/m;], body fat [(22.3±5.6)% vs.(18.3±6.5)%], urine specific gravity, and urine color. Using a logistic binary regression model, hydration status was related significantly with the percentage of body fat(P=0.004), but no relation was found with age, comorbidities, or medications. Furthermore, total water intake/weight was positively correlated with percentage of body water(r=0.357, P=0.000) and negatively with body fat(kg)(r=–0.427, P=0.000), percentage of body fat(r=–0.405, P=0.000), and waist/hip ratio(r=–0.223, P=0.002). Based on a linear regression model, total water intake/weight was related significantly with percentage of body fat(P=0.001) and percentage of body water content(P=0.035). No relation was found, however, with waist/hip ratio, age, comorbidities, or medications.Conclusions: These findings all suggest a relationship between hydration status and body composition but also set the bases for future studies that relate hydration status and anxiety status. These results can be used to improve the hydration status and body composition of military personnel.展开更多
Dear Editor,In a recent study,we isolated a protein from human oviductal secretion that could bind to spermatozoa[1].This protein was identified through chromatography and tandem mass spectrometry as human S100A9 and ...Dear Editor,In a recent study,we isolated a protein from human oviductal secretion that could bind to spermatozoa[1].This protein was identified through chromatography and tandem mass spectrometry as human S100A9 and was detected in human tubal epithelium and oviductal secretions.S100A9 belongs to the S100 protein family[2],which has been found in various body fluids and tissues,and plays a role in extracellular functions,such as the enhancement of neutrophil extravasation,induction of proinflammatory cytokine release,antimicrobial properties through divalent ion sequestration,and modulation of cellular proliferation,differentiation,and apoptosis,as well as acting as a chemotactic factor[3–4].Because S100A9 is involved in various pathologies and the physiology of inflammation,research on S100A9 effects continues to grow rapidly.Recently,we have shown the presence of binding sites for S100A9 on human spermatozoa,and also found that S100A9 modulated certain sperm capacitation parameters in vitro,such as the induced acrosome reaction(AR)[1].To continue our studies on sperm function parameters,the current study aimed to express and purify human recombinant S100A9 and to assess its effect on sperm capacitation parameters,specifically the AR.展开更多
Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and...Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs.Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent,and their α-glucosidase inhibition properties were compared.For the most bioactive mixture,a chemically modified propolis extract,enzyme inhibition increased 22 times due to the reaction sequence.Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin.The inhibitor results from the action of the two reagents used on four common functional groups present in natural products(carbonyl,phenol,aromatic carbon,and a double bond).The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one,as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material,all within a complex mixture of natural products.Overall,these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.展开更多
The Trombe Wall(TW)is a low-cost,passive heating system known for its high thermal efficiency,particularly in cold and temperate climates.Recent research has explored its adaptability to warm-dry climates with high th...The Trombe Wall(TW)is a low-cost,passive heating system known for its high thermal efficiency,particularly in cold and temperate climates.Recent research has explored its adaptability to warm-dry climates with high thermal variability,such as those found in central Mexico.This study presents a dynamic simulation-based analysis of the TW’s thermal performance in a representative social housing unit located in Pachuca de Soto,Hidalgo.Two models were compared—one with a south-facing TW system and one without—to evaluate indoor thermal comfort throughout a full annual cycle.The simulations were conducted using OpenStudio and EnergyPlus,integrating detailed climate data and construction parameters.Results indicate significant improvements in interior temperature stability and comfort during winter,with temperature increases of up to 5.1℃ in living areas.The system’s implementation made it possible to attain a new level of average winter indoor temperature of 18.3℃ by using solar energy,up from 14.4℃ without mechanical heating.The introduction of the TW significantly reduces the interior thermal oscillation and enhances the habitability conditions during the winter,with an increase of 167%in the annual number of hours within the thermal comfort range of 18℃–24℃ vs.the base model.Currently,temperature fluctuations inside buildings due to climate change affect the health of users.The system presented in this study reduces these temperature fluctuations to improve quality of life.展开更多
Mosquitoes(Diptera:Culicidae)are vectors of various pathogens of public health concern,but replacing conventional insecticides remains a challenge.In this regard,natural products represent valuable sources of potentia...Mosquitoes(Diptera:Culicidae)are vectors of various pathogens of public health concern,but replacing conventional insecticides remains a challenge.In this regard,natural products represent valuable sources of potential insecticidal compounds,thus increasingly attracting research interest.Commiphora myrrha(T.Nees)Engl.(Burseraceae)is a medicinal plant whose oleo-gum resin is used in food,cosmetics,fragrances,and pharmaceuticals.Herein,the larvicidal potential of its essential oil(EO)was assessed on four mosquito species(Aedes albopictus Skuse,Ae.aegypti L.,Anopheles gambiae Giles and An.stephensi Liston),with LC_(50) values ranging from 4.42 to 16.80 μg/mL.The bio-guided EO fractionation identified furanosesquiterpenes as the main larvicidal compounds.A GC-MS-driven untargeted metabolomic analysis revealed 32 affected metabolic pathways in treated larvae.The EO non-target toxicity on Daphnia magna Straus(LC_(50)=4.51 μL/L)and its cytotoxicity on a human kidney cell line(HEK293)(IC50 of 14.38 μg/mL)were also assessed.This study shows the potential of plant products as innovative insecticidal agents and lays the ground-work for the possible exploitation of C.myrrha EO in the sustainable approaches for mosquito management.展开更多
Multiparent advanced generation inter-cross(MAGIC)populations improve the accuracy of quantitative trait loci mapping compared to biparental populations by increasing diversity and reducing linkage disequilibrium betw...Multiparent advanced generation inter-cross(MAGIC)populations improve the accuracy of quantitative trait loci mapping compared to biparental populations by increasing diversity and reducing linkage disequilibrium between variants.Here we describe the development of two MAGIC populations derived from a cross of 11 founder lines from the INTA(National Institute for Agricultural Technology in Argentina)sunflower breeding program.The founder lines are fertility maintainer inbred lines that exhibit genetic diversity in several traits,including flowering cycle,plant architecture,disease resistance,oil content and oil quality.The crossing scheme applied follows the design of two-way,four-way and eight-way crosses with a modification to increase the number of recombinations and shorten the linkage disequilibrium.Phenotyping a subset of F_(2)families and F_5 lines for different traits shows an increase in the diversity of the analyzed traits compared to the parental lines.In addition,we identified lines with transgressive segregation for Sunflower Verticillium Wilt resistance.These results confirm that the MAGIC populations will serve as unique genetic and genomic resources to better characterize the genetics of complex traits and identify potentially superior alleles for sunflower breeding.It will also enrich the gene pool of fertility maintainers(A/B line)of the sunflower germplasm and facilitate the introduction of new breeding methods to select female parents for use in AxR combinations to obtain superior sunflower hybrids.展开更多
The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular t...The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular transporters:multidrug resistance protein 1(MDR1, ABCB1),also known as P-glycoprotein,multidrug resistance-associated protein 2(MRP2,ABCC2),and the breast cancer resistance protein(BCRP,ABCG2).Their activities depend on regulation of expression and proper localization at the canalicular membrane,as regulated by transcriptional and post-transcriptional events,respectively.At transcriptional level,specific nuclear receptors(NR)s modulated by ligands,co-activators and co-repressors,mediate the physiological requirements of these transporters.This complex system is also responsible for alterations occurring in specific liver pathologies.We briefly describe the major ClassⅡNRs, pregnane X receptor(PXR)and constitutive androstane receptor(CAR),and their role in regulating expression of multidrug resistance proteins.Several therapeutic agents regulate the expression of relevant drug transporters through activation/inactivation of these NRs.We provide some representative examples of the action of therapeutic agents modulating liver drug transporters, which in addition,involve CAR or PXR as mediators.展开更多
This review focuses on current knowledge on hepato-cyte aquaporins(AQPs)and their significance in bile formation and cholestasis.Canalicular bile secretion results from a combined interaction of several solute transpo...This review focuses on current knowledge on hepato-cyte aquaporins(AQPs)and their significance in bile formation and cholestasis.Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate water flow in response to the osmotic gradients created. During choleresis,hepatocytes rapidly increase their canalicular membrane water permeability by modulating the abundance of AQP8.The question was raised as to whether the opposite process,i.e.a decreased canalicular AQP8 expression would contribute to the development of cholestasis.Studies in several experimental models of cholestasis,such as extrahepatic obstructive cholestasis,estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition,biophysical studies in canalicular plasma membranes revealed decreased water permeability associated with AQP8 protein downregulation.The combined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow.Thus cholestasis may result from a mutual occurrence of impaired solute transport and decreased water permeability.展开更多
The paper posits that kin sociality and eusociality are derived from the handicap-care principles based on the need-based care to the handicappers from the caregivers for the self-interest of the caregivers. In this p...The paper posits that kin sociality and eusociality are derived from the handicap-care principles based on the need-based care to the handicappers from the caregivers for the self-interest of the caregivers. In this paper, handicap is defined as the difficulty to survive and reproduce independently. Kin sociality is derived from the childhood handicap-care principle where the children are the handicapped children who receive the care from the kin caregivers in the inclusive kin group to survive. The caregiver gives care for its self-interest to reproduce its gene. The individual’s gene of kin sociality contains the handicapped childhood and the caregiving adulthood. Eusociality is derived from the adulthood handicap-care principle where responsible adults are the handicapped adults who give care and receive care at the same time in the interdependent eusocial group to survive and reproduce its gene. Queen bees reproduce, but must receive care from worker bees that work but must rely on queen bees to reproduce. A caregiver gives care for its self-interest to survive and reproduce its gene. The individual’s gene of eusociality contains the handicapped childhood-adulthood and the caregiving adulthood. The chronological sequence of the sociality evolution is individual sociality without handicap, kin sociality with handicapped childhood, and eusociality with handicapped adulthood. Eusociality in humans is derived from bipedalism and the mixed habitat. The chronological sequence of the eusocial human evolution is 1) the eusocial early hominins with bipedalism and the mixed habitat, 2) the eusocial early Homo species with bipedalism, the larger brain, and the open habitat, 3) the eusocial late Homo species with bipedalism, the largest brain, and the unstable habitat, and 4) extended eusocial Homo sapiens with bipedalism, the shrinking brain, omnipresent imagination, and the harsh habitat. The omnipresence of imagination in human culture converts eusociality into extended eusociality with both perception and omnipresent imagination.展开更多
Vesicle-based traffi cking of hepatocellular transporters involves delivery of the newly-synthesized carriers from the rough endoplasmic reticulum to either the plasma membrane domain or to an endosomal,submembrane co...Vesicle-based traffi cking of hepatocellular transporters involves delivery of the newly-synthesized carriers from the rough endoplasmic reticulum to either the plasma membrane domain or to an endosomal,submembrane compartment,followed by exocytic targeting to the plasma membrane. Once delivered to the plasma membrane,the transporters usually undergo recycling between the plasma membrane and the endosomal compartment,which usually serves as a reservoir of pre-existing transporters available on demand. The balance between exocytic targeting and endocytic internalization from/to this recycling compartment is therefore a chief determinant of the overall capability of the liver epithelium to secrete bile and to detoxify endo and xenobiotics. Hence,it is a highly regulated process. Impaired regulation of this balance may lead to abnormal localization of these transporters,which results in bile secretory failure due to endocytic internalization of key transporters involved in bile formation. This occurs in several experimental models of hepatocellular cholestasis,and in most human cholestatic liver diseases. This review describes the molecular bases involved in the biology of the dynamic localization of hepatocellular transporters and its regulation,with a focus on the involvement of signaling pathways in this process. Their alterations in different experimental models of cholestasis and in human cholestatic liver disease are reviewed. In addition,the causes explaining the pathological condition (e.g. disorganization of actin or actin-transporter linkers) and the mediators involved (e.g. activation of cholestatic signaling transduction pathways) are also discussed. Finally,several experimental therapeutic approaches based upon the administration of compounds known to stimulate exocytic insertion of canalicular transporters (e.g. cAMP,tauroursodeoxycholate) are described.展开更多
Objective: Although Angelica archangelica is a medicinal and aromatic plant with a long history of use for both medicinal and food purposes, there are no studies regarding the antineoplastic activity of its root.This ...Objective: Although Angelica archangelica is a medicinal and aromatic plant with a long history of use for both medicinal and food purposes, there are no studies regarding the antineoplastic activity of its root.This study aimed to evaluate the cytotoxicity and antitumor effects of the crude extract of A. archangelica root(CEAA) on breast cancer.Methods: The cytotoxicity of CEAA against breast adenocarcinoma cells(4T1 and MCF-7) was evaluated by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) assay. Morphological and biochemical changes were detected by Hoechst 33342/propidium iodide(PI) and annexin V/PI staining. Cytosolic calcium mobilization was evaluated in cells staining with FURA-4 NW. Immunoblotting was used to determine the effect of CEAA on anti-and pro-apoptotic proteins(Bcl-2 and Bax, respectively).The 4 T1 cell-challenged mice were used for in vivo assay.Results: Using ultra-high-performance liquid chromatography–mass spectrometry analysis, angelicin, a constituent of the roots and leaves of A. archangelica, was found to be the major constituent of the CEAA evaluated in this study(73 mg/mL). The CEAA was cytotoxic for both breast cancer cell lines studied but not for human fibroblasts. Treatment of 4 T1 cells with the CEAA increased Bax protein levels accompanied by decreased Bcl-2 expression, in the presence of cleaved caspase-3 and cytosolic calcium mobilization, suggesting mitochondrial involvement in breast cancer cell death induced by the CEAA in this cell line. No changes on the Bcl-2/Bax ratio were observed in CEAA-treated MCF7 cells. Gavage administration of the CEAA(500 mg/kg) to 4T1 cell-challenged mice significantly decreased tumor growth when compared with untreated animals.Conclusion: Altogether, our data show the antitumor potential of the CEAA against breast cancer cells in vitro and in vivo. Further research is necessary to better elucidate the pharmacological application of the CEAA in breast cancer therapy.展开更多
The disposition of most drugs is highly dependent on specialized transporters. OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells, identified as contr...The disposition of most drugs is highly dependent on specialized transporters. OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells, identified as contributors to xenobiotic and endogenous organic anion secretion. It is well known that cholestasis may cause renal damage. Impairment of kidney function produces modifications in the renal elimination of drugs. Recent studies have demonstrated that the renal abundance of OAT1 and OAT3 plays an important role in the renal elimination of organic anions in the presence of extrahepatic cholestasis. Time elapsed after obstructive cholestasis has an important impact on the regulation of both types of organic anion transporters. The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease.展开更多
基金Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Agencia Nacional de Promoción de Ciencia y Tecnología (ANPCyT )Universidad Nacional de Rosario (UNR) for financial support
文摘Tioconazole(TCZ), a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial mycoses.The main goal of this work is to report an exhaustive identification and characterization procedure to improve and facilitate the online quality control and continuous process monitoring of TCZ in bulk material and loaded in two different dosage forms: ovules and nail lacquer. The methodologies were based on thermal(differential scanning calorimetry(DSC), melting point, and thermogravimetry(TG)),spectroscopic(ultraviolet(UV), Raman, near infrared(NIR), infrared spectroscopy coupled to attenuated total reflectance(FTIR-ATR), and nuclear magnetic resonance(NMR)), microscopic and X-ray diffraction(XRD). The TCZ bulk powder showed a high crystallinity, as observed by XRD, with a particles size distribution(3–95 mm) resolved by microscopic measurements. TCZ melting point(82.8 °C) and a degradation peak centered at 297.8 °C were obtained by DSC and DTG, respectively. An unambiguous structure elucidation of TCZ was obtained by mono-and two-dimensional1 H and13 C NMR spectral data analysis. The FTIR-ATR, Raman and NIR spectra of both the raw material and the commercial products were analyzed and their characteristic bands were tabulated. The best methods for TCZ identification in ovules were DSC, TG, XRD, NIR and Raman, while NIR and FTIR-ATR were the most appropriate techniques to analyze it in the nail lacquer. DSC, TG, DRX, Raman, FTIR-ATR and NIR spectroscopy are effective techniques to be used in online process analysis, because they do not require sample preparation, and they are considerably sensitive to analyze complex samples.
基金partially supported by the “Centro de Instrucción Militar Aeroespacial”(CIMA)。
文摘Background: An adequate hydration status is critical to ensure efficiency during mental and physical activities.Our goal was to assess the hydration status of a Spanish group of aeronautical military men and to determine the association of hydration status with body composition and anxiety.Methods: A total of 188 men were evaluated through a validated hydration questionnaire, anthropometric and biochemical parameters, and an anxiety questionnaire. Based on these methods, the criteria of hydration were established.Results: Of the total sample, 81% met the hydration criteria(urine color = well hydrated, water balance ≥0 ml, and total water intake/weight ≥35 ml/kg), and 19% did not meet the hydration criteria(urine color = not sufficiently hydrated or dehydrated, water balance <0 ml, and total water intake/weight <35 ml/kg). Subjects not meeting the hydration criteria had lower urine pH, negative water balance, and lower water intake. The latter also had higher anxiety status(score=4 vs. 3, P=0.026), weight [(84.7±10.5) kg vs.(80.5±10.2) kg], body mass index [(26.3±3.1) kg/m;vs.(25.2±2.8) kg/m;], body fat [(22.3±5.6)% vs.(18.3±6.5)%], urine specific gravity, and urine color. Using a logistic binary regression model, hydration status was related significantly with the percentage of body fat(P=0.004), but no relation was found with age, comorbidities, or medications. Furthermore, total water intake/weight was positively correlated with percentage of body water(r=0.357, P=0.000) and negatively with body fat(kg)(r=–0.427, P=0.000), percentage of body fat(r=–0.405, P=0.000), and waist/hip ratio(r=–0.223, P=0.002). Based on a linear regression model, total water intake/weight was related significantly with percentage of body fat(P=0.001) and percentage of body water content(P=0.035). No relation was found, however, with waist/hip ratio, age, comorbidities, or medications.Conclusions: These findings all suggest a relationship between hydration status and body composition but also set the bases for future studies that relate hydration status and anxiety status. These results can be used to improve the hydration status and body composition of military personnel.
文摘Dear Editor,In a recent study,we isolated a protein from human oviductal secretion that could bind to spermatozoa[1].This protein was identified through chromatography and tandem mass spectrometry as human S100A9 and was detected in human tubal epithelium and oviductal secretions.S100A9 belongs to the S100 protein family[2],which has been found in various body fluids and tissues,and plays a role in extracellular functions,such as the enhancement of neutrophil extravasation,induction of proinflammatory cytokine release,antimicrobial properties through divalent ion sequestration,and modulation of cellular proliferation,differentiation,and apoptosis,as well as acting as a chemotactic factor[3–4].Because S100A9 is involved in various pathologies and the physiology of inflammation,research on S100A9 effects continues to grow rapidly.Recently,we have shown the presence of binding sites for S100A9 on human spermatozoa,and also found that S100A9 modulated certain sperm capacitation parameters in vitro,such as the induced acrosome reaction(AR)[1].To continue our studies on sperm function parameters,the current study aimed to express and purify human recombinant S100A9 and to assess its effect on sperm capacitation parameters,specifically the AR.
基金support by Universidad Nacional de Rosario(80020180300114UR and 80020180100128UR)CONICET(PIP No 11220200102423)FONCYT(PICT2019-02232 and PICT2021-1034)for the development of this work.
文摘Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules.Prepared through direct derivatization of natural extracts,they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs.Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent,and their α-glucosidase inhibition properties were compared.For the most bioactive mixture,a chemically modified propolis extract,enzyme inhibition increased 22 times due to the reaction sequence.Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin.The inhibitor results from the action of the two reagents used on four common functional groups present in natural products(carbonyl,phenol,aromatic carbon,and a double bond).The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one,as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material,all within a complex mixture of natural products.Overall,these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.
文摘The Trombe Wall(TW)is a low-cost,passive heating system known for its high thermal efficiency,particularly in cold and temperate climates.Recent research has explored its adaptability to warm-dry climates with high thermal variability,such as those found in central Mexico.This study presents a dynamic simulation-based analysis of the TW’s thermal performance in a representative social housing unit located in Pachuca de Soto,Hidalgo.Two models were compared—one with a south-facing TW system and one without—to evaluate indoor thermal comfort throughout a full annual cycle.The simulations were conducted using OpenStudio and EnergyPlus,integrating detailed climate data and construction parameters.Results indicate significant improvements in interior temperature stability and comfort during winter,with temperature increases of up to 5.1℃ in living areas.The system’s implementation made it possible to attain a new level of average winter indoor temperature of 18.3℃ by using solar energy,up from 14.4℃ without mechanical heating.The introduction of the TW significantly reduces the interior thermal oscillation and enhances the habitability conditions during the winter,with an increase of 167%in the annual number of hours within the thermal comfort range of 18℃–24℃ vs.the base model.Currently,temperature fluctuations inside buildings due to climate change affect the health of users.The system presented in this study reduces these temperature fluctuations to improve quality of life.
基金granted by the project PRIN 2022“Bioformulations for controlled release of botanical pesticides for sustainable agriculture”(prot.202274BK9L)supported by the Italian Ministry of University and Research(MUR)the Technology agency of the Czech Republic for its financial support concerning botanical pesticide(Project No.FW06010376).
文摘Mosquitoes(Diptera:Culicidae)are vectors of various pathogens of public health concern,but replacing conventional insecticides remains a challenge.In this regard,natural products represent valuable sources of potential insecticidal compounds,thus increasingly attracting research interest.Commiphora myrrha(T.Nees)Engl.(Burseraceae)is a medicinal plant whose oleo-gum resin is used in food,cosmetics,fragrances,and pharmaceuticals.Herein,the larvicidal potential of its essential oil(EO)was assessed on four mosquito species(Aedes albopictus Skuse,Ae.aegypti L.,Anopheles gambiae Giles and An.stephensi Liston),with LC_(50) values ranging from 4.42 to 16.80 μg/mL.The bio-guided EO fractionation identified furanosesquiterpenes as the main larvicidal compounds.A GC-MS-driven untargeted metabolomic analysis revealed 32 affected metabolic pathways in treated larvae.The EO non-target toxicity on Daphnia magna Straus(LC_(50)=4.51 μL/L)and its cytotoxicity on a human kidney cell line(HEK293)(IC50 of 14.38 μg/mL)were also assessed.This study shows the potential of plant products as innovative insecticidal agents and lays the ground-work for the possible exploitation of C.myrrha EO in the sustainable approaches for mosquito management.
基金supported by a doctoral grant from the National Scientific and Technical Research Council(Consejo Nacional de Investigaciones Científicas y T ecnicas,CONICET)the National Institute of Agricultural Technology(INTA)+1 种基金by projects funded by INTA(CP_2019–2023 I-114,I-127,I-090/2023–2025 I-111,I-87)Agencia Nacional de Promocio n Científica y T ecnica(PICT 2017N?2523)。
文摘Multiparent advanced generation inter-cross(MAGIC)populations improve the accuracy of quantitative trait loci mapping compared to biparental populations by increasing diversity and reducing linkage disequilibrium between variants.Here we describe the development of two MAGIC populations derived from a cross of 11 founder lines from the INTA(National Institute for Agricultural Technology in Argentina)sunflower breeding program.The founder lines are fertility maintainer inbred lines that exhibit genetic diversity in several traits,including flowering cycle,plant architecture,disease resistance,oil content and oil quality.The crossing scheme applied follows the design of two-way,four-way and eight-way crosses with a modification to increase the number of recombinations and shorten the linkage disequilibrium.Phenotyping a subset of F_(2)families and F_5 lines for different traits shows an increase in the diversity of the analyzed traits compared to the parental lines.In addition,we identified lines with transgressive segregation for Sunflower Verticillium Wilt resistance.These results confirm that the MAGIC populations will serve as unique genetic and genomic resources to better characterize the genetics of complex traits and identify potentially superior alleles for sunflower breeding.It will also enrich the gene pool of fertility maintainers(A/B line)of the sunflower germplasm and facilitate the introduction of new breeding methods to select female parents for use in AxR combinations to obtain superior sunflower hybrids.
文摘先天性长QT综合征(LQTS)是发病率在1/2 500左右的恶性遗传性心脏疾病。LQTS的典型心脏表现包括可导致心脏骤停和心脏猝死的晕厥发作,以及包括QT间期延长和T波异常在内的心电图异常。90年代中期,LQTS的治病基因被首次发现,至今已有13型被确认。致病基因主要是离子通道和转运相关蛋白。对于具有典型特征的患者,医生并无诊断困难。对于模棱两可的病例,需要参照特殊诊断标准,比如心电图,病史和家族史等等。此外,基因扫描正日益成为诊断过程的一部分。除非有明确的禁忌证,治疗上还是要首选β受体阻滞剂。若在接受足量β受体阻滞剂期间,还有1次以上的晕厥,需立即采取左侧交感神经切除术,并根据病人特征(年龄、性别、临床病史、24 h Holter在内的心电图特征、基因表型等)考虑安装埋藏式心脏转复除颤器。病人接受适当治疗后,一般预后较好。但是LQTS8(Timothy综合征)病人,携带KCNQ1突变的Jervel Lange-Nielsen综合征患者,以及伴有2∶1房室传导阻滞,病窦综合征或Brugada综合征的LQT3病患的预后极其不容乐观。
基金Grants from Agencia Nacional de Promoción Científicay Tecnológica (PICT N° 05-26306)Consejo Nacional de Investigaciones Científicasy Técnicas (PIP N° 6442)Universidad Nacional de Rosario,Argentina
文摘The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular transporters:multidrug resistance protein 1(MDR1, ABCB1),also known as P-glycoprotein,multidrug resistance-associated protein 2(MRP2,ABCC2),and the breast cancer resistance protein(BCRP,ABCG2).Their activities depend on regulation of expression and proper localization at the canalicular membrane,as regulated by transcriptional and post-transcriptional events,respectively.At transcriptional level,specific nuclear receptors(NR)s modulated by ligands,co-activators and co-repressors,mediate the physiological requirements of these transporters.This complex system is also responsible for alterations occurring in specific liver pathologies.We briefly describe the major ClassⅡNRs, pregnane X receptor(PXR)and constitutive androstane receptor(CAR),and their role in regulating expression of multidrug resistance proteins.Several therapeutic agents regulate the expression of relevant drug transporters through activation/inactivation of these NRs.We provide some representative examples of the action of therapeutic agents modulating liver drug transporters, which in addition,involve CAR or PXR as mediators.
基金Grant PICT 05-31670(R.A.Marinelli) from Agencia Nacional de Promoción Científica y Tecnológicaby Grant PIP 6440 from Consejo Nacional de Investigaciones Científicas y Técnicas
文摘This review focuses on current knowledge on hepato-cyte aquaporins(AQPs)and their significance in bile formation and cholestasis.Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate water flow in response to the osmotic gradients created. During choleresis,hepatocytes rapidly increase their canalicular membrane water permeability by modulating the abundance of AQP8.The question was raised as to whether the opposite process,i.e.a decreased canalicular AQP8 expression would contribute to the development of cholestasis.Studies in several experimental models of cholestasis,such as extrahepatic obstructive cholestasis,estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition,biophysical studies in canalicular plasma membranes revealed decreased water permeability associated with AQP8 protein downregulation.The combined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow.Thus cholestasis may result from a mutual occurrence of impaired solute transport and decreased water permeability.
文摘The paper posits that kin sociality and eusociality are derived from the handicap-care principles based on the need-based care to the handicappers from the caregivers for the self-interest of the caregivers. In this paper, handicap is defined as the difficulty to survive and reproduce independently. Kin sociality is derived from the childhood handicap-care principle where the children are the handicapped children who receive the care from the kin caregivers in the inclusive kin group to survive. The caregiver gives care for its self-interest to reproduce its gene. The individual’s gene of kin sociality contains the handicapped childhood and the caregiving adulthood. Eusociality is derived from the adulthood handicap-care principle where responsible adults are the handicapped adults who give care and receive care at the same time in the interdependent eusocial group to survive and reproduce its gene. Queen bees reproduce, but must receive care from worker bees that work but must rely on queen bees to reproduce. A caregiver gives care for its self-interest to survive and reproduce its gene. The individual’s gene of eusociality contains the handicapped childhood-adulthood and the caregiving adulthood. The chronological sequence of the sociality evolution is individual sociality without handicap, kin sociality with handicapped childhood, and eusociality with handicapped adulthood. Eusociality in humans is derived from bipedalism and the mixed habitat. The chronological sequence of the eusocial human evolution is 1) the eusocial early hominins with bipedalism and the mixed habitat, 2) the eusocial early Homo species with bipedalism, the larger brain, and the open habitat, 3) the eusocial late Homo species with bipedalism, the largest brain, and the unstable habitat, and 4) extended eusocial Homo sapiens with bipedalism, the shrinking brain, omnipresent imagination, and the harsh habitat. The omnipresence of imagination in human culture converts eusociality into extended eusociality with both perception and omnipresent imagination.
基金Supported by Grants from CONICET (PIP 6442)Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT PICT 05-26115 and 05-26306),Argentina
文摘Vesicle-based traffi cking of hepatocellular transporters involves delivery of the newly-synthesized carriers from the rough endoplasmic reticulum to either the plasma membrane domain or to an endosomal,submembrane compartment,followed by exocytic targeting to the plasma membrane. Once delivered to the plasma membrane,the transporters usually undergo recycling between the plasma membrane and the endosomal compartment,which usually serves as a reservoir of pre-existing transporters available on demand. The balance between exocytic targeting and endocytic internalization from/to this recycling compartment is therefore a chief determinant of the overall capability of the liver epithelium to secrete bile and to detoxify endo and xenobiotics. Hence,it is a highly regulated process. Impaired regulation of this balance may lead to abnormal localization of these transporters,which results in bile secretory failure due to endocytic internalization of key transporters involved in bile formation. This occurs in several experimental models of hepatocellular cholestasis,and in most human cholestatic liver diseases. This review describes the molecular bases involved in the biology of the dynamic localization of hepatocellular transporters and its regulation,with a focus on the involvement of signaling pathways in this process. Their alterations in different experimental models of cholestasis and in human cholestatic liver disease are reviewed. In addition,the causes explaining the pathological condition (e.g. disorganization of actin or actin-transporter linkers) and the mediators involved (e.g. activation of cholestatic signaling transduction pathways) are also discussed. Finally,several experimental therapeutic approaches based upon the administration of compounds known to stimulate exocytic insertion of canalicular transporters (e.g. cAMP,tauroursodeoxycholate) are described.
基金the Coordenacao de Aperfeicoamento de Pessoal de Nível Superior-Brasil (CAPES)FAPESPCNPq for the financial support
文摘Objective: Although Angelica archangelica is a medicinal and aromatic plant with a long history of use for both medicinal and food purposes, there are no studies regarding the antineoplastic activity of its root.This study aimed to evaluate the cytotoxicity and antitumor effects of the crude extract of A. archangelica root(CEAA) on breast cancer.Methods: The cytotoxicity of CEAA against breast adenocarcinoma cells(4T1 and MCF-7) was evaluated by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) assay. Morphological and biochemical changes were detected by Hoechst 33342/propidium iodide(PI) and annexin V/PI staining. Cytosolic calcium mobilization was evaluated in cells staining with FURA-4 NW. Immunoblotting was used to determine the effect of CEAA on anti-and pro-apoptotic proteins(Bcl-2 and Bax, respectively).The 4 T1 cell-challenged mice were used for in vivo assay.Results: Using ultra-high-performance liquid chromatography–mass spectrometry analysis, angelicin, a constituent of the roots and leaves of A. archangelica, was found to be the major constituent of the CEAA evaluated in this study(73 mg/mL). The CEAA was cytotoxic for both breast cancer cell lines studied but not for human fibroblasts. Treatment of 4 T1 cells with the CEAA increased Bax protein levels accompanied by decreased Bcl-2 expression, in the presence of cleaved caspase-3 and cytosolic calcium mobilization, suggesting mitochondrial involvement in breast cancer cell death induced by the CEAA in this cell line. No changes on the Bcl-2/Bax ratio were observed in CEAA-treated MCF7 cells. Gavage administration of the CEAA(500 mg/kg) to 4T1 cell-challenged mice significantly decreased tumor growth when compared with untreated animals.Conclusion: Altogether, our data show the antitumor potential of the CEAA against breast cancer cells in vitro and in vivo. Further research is necessary to better elucidate the pharmacological application of the CEAA in breast cancer therapy.
基金Supported by Grants from FONCyT (PICT 05-20201) and CONICET (PIP 5592)
文摘The disposition of most drugs is highly dependent on specialized transporters. OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells, identified as contributors to xenobiotic and endogenous organic anion secretion. It is well known that cholestasis may cause renal damage. Impairment of kidney function produces modifications in the renal elimination of drugs. Recent studies have demonstrated that the renal abundance of OAT1 and OAT3 plays an important role in the renal elimination of organic anions in the presence of extrahepatic cholestasis. Time elapsed after obstructive cholestasis has an important impact on the regulation of both types of organic anion transporters. The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease.
