The existence of neural stem cells(NSC)in specific areas of the adult mammalian brain leads to the generation of new neurons involved in homeostatic mechanisms.This is the case of the NSC of the subventricular zone(SV...The existence of neural stem cells(NSC)in specific areas of the adult mammalian brain leads to the generation of new neurons involved in homeostatic mechanisms.This is the case of the NSC of the subventricular zone(SVZ)that produces olfactory bulb(OB)neurons.These neurons integrate into circuits to modulate sensory information and participate in olfactory processing(Bragado Alonso et al.,2019).A series of hierarchical events need to take place to produce OB neurons from NSC of the SVZ.First,the activation of quiescent NSC is necessary to produce intermediate transit amplifying progenitors(TAP),which will generate neuroblasts.The latter are cells that maintain a proliferative phenotype while in an immature phase.However,once they initiate migration toward the OB,they progressively undergo their differentiation into neurons(Kjell et al.,2020).展开更多
M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The acti...M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration.Even though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor secretion.Astrocytes can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate neurodegeneration.This A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and neurons.Howeve r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the disease.The colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia.Importantly,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain.In this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of microglial effects on the progression of demyelinating diseases and the strengths and weaknesses of microglial modulation in therapy design.展开更多
The purpose of this review is to briefly summarize the central role of iron(Fe)in terms of cellular alterations of the oxidative/protective balance with special emphasis on its possible involvement in ferroptosis-depe...The purpose of this review is to briefly summarize the central role of iron(Fe)in terms of cellular alterations of the oxidative/protective balance with special emphasis on its possible involvement in ferroptosis-dependent disruption in aquatic organisms.In ferroptotic cells or tissues,the intracellular Fe level increases;meanwhile the treatment with Fe chelators limits ferroptosis.Eukaryotic algae can assimilate Fe from the environment through several mechanisms,and aquatic animals incorporate dissolved Fe and Fe bound to both inorganic particles and organic matter.The central role of lipid peroxidation mediating ferroptosis was demonstrated in some algae where both low and high Fe concentrations could induce oxidative stress and programmed cell death.Aquatic animals have high levels of polyunsaturated fatty acids and numerous studies have analyzed Fe effects on the lipidic fraction which could be related to ferroptosis.The ferroptosis reaction can be regulated through the antioxidant defense system,in combination with the protein degradation structure,metabolism,and gene transcription.Early depletion of nonenzymatic antioxidants like reduced glutathione(GSH)in animals,and the reduction of both GSH and ascorbate in photosynthetic organisms,are characteristic features of ferroptosis.Therefore,ferroptosis can be prevented if Fe chelators,certain antioxidants,and specifically regulating genes are activated.Thus,the global scenario for the Fe role as a toxic component in biological systems seems to be even more complicated than it was previously understood.Much more research on this subject is needed to improve the life span and survival of aquatic organisms after exposure to natural and anthropogenic adverse conditions.展开更多
At the moment, there is a growing concern about the negative effects on human health and the environment due to the widespread and indiscriminate use of conventional insecticides. Since plants have been used throughou...At the moment, there is a growing concern about the negative effects on human health and the environment due to the widespread and indiscriminate use of conventional insecticides. Since plants have been used throughout history to control microorganisms and insects, the safety is an aspect that must also be evaluated to guarantee that its use does not affect human health and the environment. The aim of the present study was to evaluate the safety of the dichloromethane extract of Hysterionica pinifolia, species with insecticidal activity, to be employed as a raw material for the development of biopesticides. The acute and subacute toxicity and the dermal and ocular irritation were evaluated. In these studies, the dichloromethane extract of H. pinifolia showed no ocular and a slight dermal irritation. Oral acute toxicity was greater than 2000 mg/Kg and less than 5000 mg/Kg (slightly hazardous) and no signs of toxicity were observed at repeated doses of 100 mg/kg body weight. These promising results showed that Hysterionica pinifolia could be considered as a potential raw material for the development of an insecticide from natural sources, safe for human health and the environment.展开更多
Parkinson’s disease:Parkinson’s disease(PD) is the second most prevalent neurodegenerative disease,after Alzheimer’s disease,affecting 1%of the general population over the age of 65years.According to data from the ...Parkinson’s disease:Parkinson’s disease(PD) is the second most prevalent neurodegenerative disease,after Alzheimer’s disease,affecting 1%of the general population over the age of 65years.According to data from the World Health Organization(WHO),its prevalence has doubled in the past 25 years.In 2019,global estimates indicated over 8.5 million individuals with PD and it is suggested that PD caused 329000 deaths,an increase of over 100% since 2000(WHO,2022).展开更多
AIM： TO investigate the severity of acute pancreatitis （AP） is associated to the intensity of leukocyte activation, inflammatory up-regulation and microcirculatory disruption associated to ischernia-reperfusion inj...AIM： TO investigate the severity of acute pancreatitis （AP） is associated to the intensity of leukocyte activation, inflammatory up-regulation and microcirculatory disruption associated to ischernia-reperfusion injury. Hicrovascular integrity and inhibition of pro-inflammatory mediators are key-factors in the evolution of AP. Relaxin is an insulin-like hormone that has been attributed vasorelaxant properties via the nitric oxide pathway while behaving as a glucocorticoid receptor agonist. METHODS： AP was induced by the bilio-pancreatic duct-outlet-exclusion closed-duodenal-loops model. Treatment with relaxin was done at different timepoints. Nitric oxide synthase inhibition by L-NAME and glucocorticoid receptor （GR） blockage by mifepristone was considered. AP severity was assessed by biochemical and histopathological analyses. RESULTS： Treatment with relaxin reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, LDH and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate were also decreased. ATP depletion and ADP/ATP ratio were reduced while caspases 2-3-8 and 9 activities were increased. L-NAME and mifepristone decreased the efficiency of relaxin. CONCLUSION： Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist while preserving the microcirculation and favoring apoptosis over necrosis.展开更多
AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats w...AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.展开更多
AIM: To study the mechanism of cytotoxicity of a new active 5-alkyl resorcinol [1, 3-dihydroxy-5- (tridec-4’, 7’ -dienyl) benzene] isolated from Lithraea molleoides leaves on liver tumor cells. METHODS: Human hepato...AIM: To study the mechanism of cytotoxicity of a new active 5-alkyl resorcinol [1, 3-dihydroxy-5- (tridec-4’, 7’ -dienyl) benzene] isolated from Lithraea molleoides leaves on liver tumor cells. METHODS: Human hepatocarcinoma cell lines (HepG2 and Hep3B) in culture were treated with inhibitory concentrations, 50% of the compound, for 24 h. The induction of apoptosis was detected in treated cells by analysis of DNA fragmentation, DNA content, and acridine orange and propidium iodide staining. RESULTS: After 24 h of 5-alkyl resorcinol treatment, both cell lines showed: (1) the typical morphological alterations of apoptosis; (2) DNA fragmentation, detected by laddering and appearance of a subG0 population by flow cytometry; and (3) condensed and fragmented nuclei by acridine orange-propidium iodide staining. CONCLUSION: Based on the results, this compound exerts its cytotoxic effect in both hepatocellular cell lines through apoptotic cell death. For Hep3B, cells with mutated p53 and Fas, apoptosis would proceed by p53- or Fas-independent pathways.展开更多
The quantitative estimation of amikacin （AMK） in AMK sulfate injection samples is reported using FTIR-derivative spectrometric method in a continuous flow system. Fourier transform of mid-IR spectra were recorded wi...The quantitative estimation of amikacin （AMK） in AMK sulfate injection samples is reported using FTIR-derivative spectrometric method in a continuous flow system. Fourier transform of mid-IR spectra were recorded without any sample pretreatment. A good linear calibration （r40.999, %RSDo 2.0） in the range of 7.7-77.0 mg/mL was found. The results showed a good correlation with the manufacturer＇s and overall they all fell within acceptable limits of most pharmacopoeial monographs on AMK sulfate.展开更多
AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (...AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA). METHODS: Rats, intravenously (iv ) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip ) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mecha-nisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract. RESULTS: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P < 0.05) different compared with that of the TA group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. CONCLUSION: These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in post-necrotic proliferative liver states.展开更多
Objective:To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache mexicana(A.mexicana).Also,to establish the pharmacophoric requirem...Objective:To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache mexicana(A.mexicana).Also,to establish the pharmacophoric requirements of tilianin,as a possible ligand of GABA_A/BZD receptor,by the alignment of diazepam.CGS-9896 and diindole,using a previously described pharmacophoric model.Methods:Tilianin(30 to 300 mg/kg.ip.and 300 mg/kg,pa.) and methanol crude extract(10 to 300 mg/kg,ip.and 300 mg/kg po.) from A.mexicana were evaluated for potential sedative and anxiolytic-like response drugs by using open-field,hole-board,cylinder of exploration,plus-maze and sodium pentobarbital-induced hypnosis mice methods.Results:Methanol extract and tilianin showed anxiolytic-like activity from a dosage of 30 mg/kg,ip.or 300 mg/kg,po.and were less potent than diazepam 0.1 mg/kg.a reference anxiolytic drug used.Moreover,depressant activity of both potentiates sodium pentobarbital(SP)-induced sleeping time.The anxiolytic-like effect of 30 mg/kg ip.observed for the extract and tilianin,by using the plus-maze model,was partially prevented in the presence of flumazenil(a GABA_A/BZD antagonist,5 mg/kg ip.) but not in the presence of WAY100635(a selective 5-HT_(1A) receptor antagonist,0.32 mg/kg.ip.).Pharmacophoric modeling alignments of three agonist of GABA_A/BZD allow identify seven chemical features.Tilianin contains six of the seven features previously determined.Conclusions:Results indicate that tilianin is one of the bioactive metabolites in the anxiolytic-like activity of 4.mexicana.reinforcing its central nervous system uses,where GABA_A/BZD,but not 5-HT_(1A),receptors are partially involved.展开更多
<i><span style="font-family:Verdana;">Lithraea</span></i><span style="font-family:;" "=""> <i><span style="font-family:Verdana;">m...<i><span style="font-family:Verdana;">Lithraea</span></i><span style="font-family:;" "=""> <i><span style="font-family:Verdana;">molleoides</span></i><span style="font-family:Verdana;"> (Anacardiaceae) is a tree that grows in South America including Southern Brazil, Southern, and Eastern Bolivia, Southern Paraguay, Northern, and Central Argentina. Infusions, decoctions, or tinctures from its aerial parts (leaves, buds, and young stems) are employed in ethnomedicine mainly against respiratory, and digestive inflammations and illnesses. Antibacterial, antiviral, antioxidant, anti-inflammatory, and antinociceptive activities, among others, have been reported for </span><i><span style="font-family:Verdana;">L.</span></i> <i><span style="font-family:Verdana;">molleoides</span></i><span style="font-family:Verdana;">. Many of its biological activities have been associated with the reported presence of 5-alkenyl resorcinols. Alkyl/alkenyl catechols and alkyl/alkenyl resorcinols are very common in members of the Anacardiaceae family and several activities have been attributed to them. This work describes the isolation and the structural elucidation of three new 5-alkenyl resorcinols isolated from </span><i><span style="font-family:Verdana;">Lithraea</span></i> <i><span style="font-family:Verdana;">molleoides</span></i><span style="font-family:Verdana;"> reported in nature for the first time.</span></span>展开更多
The purpose of this study was to evaluate the redox status changes of primary visual targets in the rat brain of a high pressure-induced glaucoma model.The animal model consisted of inducing ocular hypertension by cau...The purpose of this study was to evaluate the redox status changes of primary visual targets in the rat brain of a high pressure-induced glaucoma model.The animal model consisted of inducing ocular hypertension by cauterizing two episcleral veins on the left eye.The markers of oxidative damage and the oxidative balance evaluated in the brain seven days postoperative were:nitrites concentration,levels of non-enzymatic antioxidants and antiox-idant enzymes activity.The increase in the nitrite content,which could be the result of the enhancement in the production of nitrogen species,and in the activity of NADPH oxidase in the glaucoma group could lead to an increase on lipid and protein damage.The decrease on the non-enzymatic antioxidants and the compensatory increase of the superoxide dismutase and glutathione peroxidase activities could be a consequence of the increase of oxidative processes.The decrease in the activity of glutathione reductase leads to a decrease in the recycling of thiol groups.We suggest that oxidative stress can possibly acts as a risk factor for neurodegeneration in the brain.Therapeu-tic strategies to stop the progression of the disease in glaucoma should also be considered the central neuronal degeneration beyond the retina and the optic nerve.展开更多
Fe is essential for human life because it constitutes the required cofactor for proteins of diverse biological functions.However,the development of oxidative stress by exposure to excessive Fe,share signaling pathways...Fe is essential for human life because it constitutes the required cofactor for proteins of diverse biological functions.However,the development of oxidative stress by exposure to excessive Fe,share signaling pathways with other treatments including activation of redox-sensitive factors.This study was focused on the comparison on the effects of Fe in the brain and other organs in vivo.The oxidative effects triggered by Fe overload strongly depend not only on the administration protocol,but also on the Fe-compound used,and the studied organ.In both the liver and the brain,Fe content drastically increased after Fe-dextran administration.However,the comparatively low lipid peroxidation in the brain as compared to the liver,suggested that Fe-dependent oxidative stress might involve mechanisms of different nature.In the brain,acute and subchronic administration of Fe-dextran triggered signaling processes that lead to the prevention of injury by the participation of catalase activity as an antioxidant protection.This brief summary opens a huge range of possible points of risk,as well as opportunities,to encounter situations in which the appropriate election of the Fe management protocol could be able of allow oxidative stress to exert beneficial effects.展开更多
Protein powders from Eisenia foetida were prepared using different drying processes and fractionation. Differential scanning calorimetry was used to show that heat denaturation occurred during the drying process above...Protein powders from Eisenia foetida were prepared using different drying processes and fractionation. Differential scanning calorimetry was used to show that heat denaturation occurred during the drying process above 42°C. Protein solubility was also studied. The addition of dissociating reagents allowed concluding that solubility was decreased during oven drying due to thermo denaturation including hydrogen bonds. The volatile compounds of the different powders were extracted by solid phase micro-extraction and identified by mass spectrometry. Volatile compounds were related to lipid oxidation and Maillard reactions occurring during the preparation of the powders. High drying temperatures led to more volatile compounds resulting from Maillard reactions. In the protein powder preparation process, a fractionation step led to a “pulp fraction” and a “juice fraction” of earthworms. The “pulp fraction” contained less odorant volatile compounds resulting from Maillard reactions than the “juice fraction” did.展开更多
Neuroinflammation in neurodegenerative diseases:Inflammatory processes play a critical role in neurodegenerative diseases,such as Parkinson’s disease(PD).Thus,neuroinflammation is involved in the progression and deve...Neuroinflammation in neurodegenerative diseases:Inflammatory processes play a critical role in neurodegenerative diseases,such as Parkinson’s disease(PD).Thus,neuroinflammation is involved in the progression and development of these diseases,becoming an important pathological hallmark.Microglial cells,the“macrophages”from central nervous system,are the initiating cells of the innate immune response against different stimuli in the brain.展开更多
An infusion was developed based on green romaine lettuce leaves and banana. Further, its sensorial acceptability was evaluated as a possible alternative treatment for insomnia. The romaine lettuces and bananas used we...An infusion was developed based on green romaine lettuce leaves and banana. Further, its sensorial acceptability was evaluated as a possible alternative treatment for insomnia. The romaine lettuces and bananas used were washed, chopped, dehydrated and ground. Optimal lettuce dehydration time was determined through charting the weight lost and examining the curve. This was found after 180 minutes at 60<sup>°<span></span></sup><span>C</span><span>. Two formulas were developed, the first with 1.1 g of dehydrated romaine lettuce and 0.2 g of dehydrated banana, and the second with 1.1 g of dehydrated romaine lettuce and 0.4 g of dehydrated banana. Sensory analysis was conducted using sorting tests for taste, aroma, paired preferences and intention to purchase. Tasters preferred the formula with a lower quantity of dehydrated banana. 85%</span><span> of tasters indicated that they would buy this infusion due to its potential functional properties for overcoming insomnia.</span>展开更多
Chemically based rodent models are used to assess the positive effects promoted by foods and gut microbiota on gut health. Lectins with enzymatic activity, such as type 2 ribosome-inactivating proteins, might also pro...Chemically based rodent models are used to assess the positive effects promoted by foods and gut microbiota on gut health. Lectins with enzymatic activity, such as type 2 ribosome-inactivating proteins, might also prove useful for exploring these issues. Sub-lethal doses of the lectin nigrin from Sambucus nigra L. to mice promoted reversible derangement of gut epithelium by induction of apoptosis of transit amplifying cells of the small intestine crypts in a time-dependent course. The present work seeks to study vitamin B6 accumulation in plasma from an oral bolus in a mouse nigrin model. 24 h after sub-lethal nigrin b treatment, there was clear body weight reduction associated to a notable increase in Evan’s blue stain accumulation in excised small intestine, an increase in myeloperoxidase activity, and a near 50% reduction in plasma accumulation of vitamin B6. Histological analysis of small intestine sections of nigrin b-treated animals also revealed significant derangement of intestinal crypts. Seventy two hours after nigrin b treatment, stain uptake decreased and vitamin B6 accumulation was almost restored despite villi derangement. Large intestine crypts were scarcely or not at all affected. Eight days after nigrin b treatment, vitamin B6 uptake and intestinal crypt structure had fully recovered. The nigrin b mice model supports the view that, under these conditions, the carrier-mediated vitamin B6 uptake component of the small intestine crypts is probably the most active when the vitamin is administered orally as a bolus. The findings provide insights into the suitability of the present mice model for nutritional or drug absorption studies in conditions of partially altered or injured intestinal mucosa.展开更多
The effect of the administration of large amounts of green tea polyphenols is a matter of controversy. We explored whether a polyphenol mixture from a concentrated green tea extract (Polyphenon 60) could alter the eff...The effect of the administration of large amounts of green tea polyphenols is a matter of controversy. We explored whether a polyphenol mixture from a concentrated green tea extract (Polyphenon 60) could alter the effects on mice of the type 2 (two chains) ribosome-inactivating protein nigrin b isolated from Sambucus nigra L. Nigrin b triggers specific reversible toxic effects on the mouse intestines featured by apoptosis of mice Lieberkühn crypt cells upon parenteral administration of sub-lethal amounts. Independent administration to mice of 30 mg/kg body weight of Polyphenon 60 by oral gavage or 10 mg/kg body weight of nigrin b administered via the intraperitoneal route (i.p.) did not affect survival. In contrast, the simultaneous treatment greatly enhanced nigrin b toxicity leading to the death of some animals. The histological analysis revealed that the most serious injury was inflicted on the small intestine crypts, which disappeared, and on the liver, which evidenced hepatotoxicity showing haemorrhagic areas. These findings raise concerns about the abuse of high concentrations of green tea polyphenols especially when the intestinal mucosa is damaged, for instance by toxins or therapeutic drugs.展开更多
Objective： To develop a highly sensitive LC-MS/MS （liquid chromatography-mass spectxometry/mass spectrometry） method applied to the detection and quantitation of UDCA （ursodeoxycholic acid） related substances suc...Objective： To develop a highly sensitive LC-MS/MS （liquid chromatography-mass spectxometry/mass spectrometry） method applied to the detection and quantitation of UDCA （ursodeoxycholic acid） related substances such as CA （cholic acid）, DCA （deoxycholic acid）, CDCA （chenodeoxycholic acid） and LCA （lithocholic acid） in raw material and pharmaceutical formulation. Methods： The method was validated for specificity, linearity, accuracy, precision, robustness. A triple quadrupole mass detector was employed, equipped with an ESI （electrospray ionization） source operated in the negative ion mode. The chromatographic system consisted of a Symmetry C 18 column （150 mm × 4.6 mm, id; particle size 5 μm） and methanol-acetonitrile-ammonium acetate （pH 7.6; 10 mM） （40：40：20, v/v/v） as the mobile phase. The chromatographic conditions were 25 uL injection volume, flow rate of 0.4 mL/min and column temperature set at 35℃. Key tindings： The method requires a minimum sample amount and presents very low LOD （limits of detection） for CA （0.29 ng/mL）, DCA （0.59 ng/mL）, CDCA （0.13 ng/mL） and LCA （0.44 ng/mL） in comparison to LC methods coupled to different detectors like UV （ultraviolet）, fluorescence and refractive index. Conclusions： The developed and validated LC-MS/MS method for the determination of UDCA and related substances in raw material and in a suspension was advantageous since it required a minimum sample amount. In turn, it could be used as a stability indicating method.展开更多
基金supported by the Spanish Ministerio de Ciencia, Innovación y Universidades, No. RTI2018-099908-B-C21 (to CC)the Consejería de Economía, Conocimiento, Empresas y Universidades, No. FEDER-UCA18-106647 (to CC)the Consejería de Salud y Familias 80% co-financed by EDRF ITI regional funds, No. ITICadiz-0042-2019 (to CC).
文摘The existence of neural stem cells(NSC)in specific areas of the adult mammalian brain leads to the generation of new neurons involved in homeostatic mechanisms.This is the case of the NSC of the subventricular zone(SVZ)that produces olfactory bulb(OB)neurons.These neurons integrate into circuits to modulate sensory information and participate in olfactory processing(Bragado Alonso et al.,2019).A series of hierarchical events need to take place to produce OB neurons from NSC of the SVZ.First,the activation of quiescent NSC is necessary to produce intermediate transit amplifying progenitors(TAP),which will generate neuroblasts.The latter are cells that maintain a proliferative phenotype while in an immature phase.However,once they initiate migration toward the OB,they progressively undergo their differentiation into neurons(Kjell et al.,2020).
文摘M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration.Even though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor secretion.Astrocytes can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate neurodegeneration.This A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and neurons.Howeve r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the disease.The colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia.Importantly,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain.In this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of microglial effects on the progression of demyelinating diseases and the strengths and weaknesses of microglial modulation in therapy design.
基金supported by grants from the University of Buenos Aires(UBACyT 20020170100199BA)the National Agency of Research,Technological Development and Innovation(ANPCyT)(PICT-2020-SERIEA-03542)the National Council for Science and Technology(CONICET)(PIP 11220210100183CO).
文摘The purpose of this review is to briefly summarize the central role of iron(Fe)in terms of cellular alterations of the oxidative/protective balance with special emphasis on its possible involvement in ferroptosis-dependent disruption in aquatic organisms.In ferroptotic cells or tissues,the intracellular Fe level increases;meanwhile the treatment with Fe chelators limits ferroptosis.Eukaryotic algae can assimilate Fe from the environment through several mechanisms,and aquatic animals incorporate dissolved Fe and Fe bound to both inorganic particles and organic matter.The central role of lipid peroxidation mediating ferroptosis was demonstrated in some algae where both low and high Fe concentrations could induce oxidative stress and programmed cell death.Aquatic animals have high levels of polyunsaturated fatty acids and numerous studies have analyzed Fe effects on the lipidic fraction which could be related to ferroptosis.The ferroptosis reaction can be regulated through the antioxidant defense system,in combination with the protein degradation structure,metabolism,and gene transcription.Early depletion of nonenzymatic antioxidants like reduced glutathione(GSH)in animals,and the reduction of both GSH and ascorbate in photosynthetic organisms,are characteristic features of ferroptosis.Therefore,ferroptosis can be prevented if Fe chelators,certain antioxidants,and specifically regulating genes are activated.Thus,the global scenario for the Fe role as a toxic component in biological systems seems to be even more complicated than it was previously understood.Much more research on this subject is needed to improve the life span and survival of aquatic organisms after exposure to natural and anthropogenic adverse conditions.
文摘At the moment, there is a growing concern about the negative effects on human health and the environment due to the widespread and indiscriminate use of conventional insecticides. Since plants have been used throughout history to control microorganisms and insects, the safety is an aspect that must also be evaluated to guarantee that its use does not affect human health and the environment. The aim of the present study was to evaluate the safety of the dichloromethane extract of Hysterionica pinifolia, species with insecticidal activity, to be employed as a raw material for the development of biopesticides. The acute and subacute toxicity and the dermal and ocular irritation were evaluated. In these studies, the dichloromethane extract of H. pinifolia showed no ocular and a slight dermal irritation. Oral acute toxicity was greater than 2000 mg/Kg and less than 5000 mg/Kg (slightly hazardous) and no signs of toxicity were observed at repeated doses of 100 mg/kg body weight. These promising results showed that Hysterionica pinifolia could be considered as a potential raw material for the development of an insecticide from natural sources, safe for human health and the environment.
基金Authors are also grateful to RHO’s postdoctoral contract (Ayuda IJC2020-045695-I financed by MCIN/AEI/10.13039/501100011033,European Union NextGeneration EU/PRTR)。
文摘Parkinson’s disease:Parkinson’s disease(PD) is the second most prevalent neurodegenerative disease,after Alzheimer’s disease,affecting 1%of the general population over the age of 65years.According to data from the World Health Organization(WHO),its prevalence has doubled in the past 25 years.In 2019,global estimates indicated over 8.5 million individuals with PD and it is suggested that PD caused 329000 deaths,an increase of over 100% since 2000(WHO,2022).
基金Supported by a research grant given to Dr Laura Iris CosenBinker by GlaxoSmithKline S.A.
文摘AIM： TO investigate the severity of acute pancreatitis （AP） is associated to the intensity of leukocyte activation, inflammatory up-regulation and microcirculatory disruption associated to ischernia-reperfusion injury. Hicrovascular integrity and inhibition of pro-inflammatory mediators are key-factors in the evolution of AP. Relaxin is an insulin-like hormone that has been attributed vasorelaxant properties via the nitric oxide pathway while behaving as a glucocorticoid receptor agonist. METHODS： AP was induced by the bilio-pancreatic duct-outlet-exclusion closed-duodenal-loops model. Treatment with relaxin was done at different timepoints. Nitric oxide synthase inhibition by L-NAME and glucocorticoid receptor （GR） blockage by mifepristone was considered. AP severity was assessed by biochemical and histopathological analyses. RESULTS： Treatment with relaxin reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, LDH and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate were also decreased. ATP depletion and ADP/ATP ratio were reduced while caspases 2-3-8 and 9 activities were increased. L-NAME and mifepristone decreased the efficiency of relaxin. CONCLUSION： Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist while preserving the microcirculation and favoring apoptosis over necrosis.
基金Supported by Grant #TB 56 from the University of Buenos Aires,Argentina
文摘AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.
基金Supported by research grants from Agencia Nacional de Promocion Cientifi ca y Tecnologica of Argentina, No.PICT 8355, and from Universidad de Buenos Aires, No.B033 and B036
文摘AIM: To study the mechanism of cytotoxicity of a new active 5-alkyl resorcinol [1, 3-dihydroxy-5- (tridec-4’, 7’ -dienyl) benzene] isolated from Lithraea molleoides leaves on liver tumor cells. METHODS: Human hepatocarcinoma cell lines (HepG2 and Hep3B) in culture were treated with inhibitory concentrations, 50% of the compound, for 24 h. The induction of apoptosis was detected in treated cells by analysis of DNA fragmentation, DNA content, and acridine orange and propidium iodide staining. RESULTS: After 24 h of 5-alkyl resorcinol treatment, both cell lines showed: (1) the typical morphological alterations of apoptosis; (2) DNA fragmentation, detected by laddering and appearance of a subG0 population by flow cytometry; and (3) condensed and fragmented nuclei by acridine orange-propidium iodide staining. CONCLUSION: Based on the results, this compound exerts its cytotoxic effect in both hepatocellular cell lines through apoptotic cell death. For Hep3B, cells with mutated p53 and Fas, apoptosis would proceed by p53- or Fas-independent pathways.
基金the CDCHTA of the University of Los Andes for providing financial support through several approved projectsthe National Fund for Science, Technology and Innovation (FONACIT) of Venezuelan Ministry of Science and Technology for providing financial support, SPE 112–370 and Project G-2005000641
文摘The quantitative estimation of amikacin （AMK） in AMK sulfate injection samples is reported using FTIR-derivative spectrometric method in a continuous flow system. Fourier transform of mid-IR spectra were recorded without any sample pretreatment. A good linear calibration （r40.999, %RSDo 2.0） in the range of 7.7-77.0 mg/mL was found. The results showed a good correlation with the manufacturer＇s and overall they all fell within acceptable limits of most pharmacopoeial monographs on AMK sulfate.
文摘AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA). METHODS: Rats, intravenously (iv ) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip ) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mecha-nisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract. RESULTS: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P < 0.05) different compared with that of the TA group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. CONCLUSION: These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in post-necrotic proliferative liver states.
基金partially supported by CONACYT 80811.NC123280 grantFaculty of Pharmacy Budgets(FECES 2011 and 2012)
文摘Objective:To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache mexicana(A.mexicana).Also,to establish the pharmacophoric requirements of tilianin,as a possible ligand of GABA_A/BZD receptor,by the alignment of diazepam.CGS-9896 and diindole,using a previously described pharmacophoric model.Methods:Tilianin(30 to 300 mg/kg.ip.and 300 mg/kg,pa.) and methanol crude extract(10 to 300 mg/kg,ip.and 300 mg/kg po.) from A.mexicana were evaluated for potential sedative and anxiolytic-like response drugs by using open-field,hole-board,cylinder of exploration,plus-maze and sodium pentobarbital-induced hypnosis mice methods.Results:Methanol extract and tilianin showed anxiolytic-like activity from a dosage of 30 mg/kg,ip.or 300 mg/kg,po.and were less potent than diazepam 0.1 mg/kg.a reference anxiolytic drug used.Moreover,depressant activity of both potentiates sodium pentobarbital(SP)-induced sleeping time.The anxiolytic-like effect of 30 mg/kg ip.observed for the extract and tilianin,by using the plus-maze model,was partially prevented in the presence of flumazenil(a GABA_A/BZD antagonist,5 mg/kg ip.) but not in the presence of WAY100635(a selective 5-HT_(1A) receptor antagonist,0.32 mg/kg.ip.).Pharmacophoric modeling alignments of three agonist of GABA_A/BZD allow identify seven chemical features.Tilianin contains six of the seven features previously determined.Conclusions:Results indicate that tilianin is one of the bioactive metabolites in the anxiolytic-like activity of 4.mexicana.reinforcing its central nervous system uses,where GABA_A/BZD,but not 5-HT_(1A),receptors are partially involved.
文摘<i><span style="font-family:Verdana;">Lithraea</span></i><span style="font-family:;" "=""> <i><span style="font-family:Verdana;">molleoides</span></i><span style="font-family:Verdana;"> (Anacardiaceae) is a tree that grows in South America including Southern Brazil, Southern, and Eastern Bolivia, Southern Paraguay, Northern, and Central Argentina. Infusions, decoctions, or tinctures from its aerial parts (leaves, buds, and young stems) are employed in ethnomedicine mainly against respiratory, and digestive inflammations and illnesses. Antibacterial, antiviral, antioxidant, anti-inflammatory, and antinociceptive activities, among others, have been reported for </span><i><span style="font-family:Verdana;">L.</span></i> <i><span style="font-family:Verdana;">molleoides</span></i><span style="font-family:Verdana;">. Many of its biological activities have been associated with the reported presence of 5-alkenyl resorcinols. Alkyl/alkenyl catechols and alkyl/alkenyl resorcinols are very common in members of the Anacardiaceae family and several activities have been attributed to them. This work describes the isolation and the structural elucidation of three new 5-alkenyl resorcinols isolated from </span><i><span style="font-family:Verdana;">Lithraea</span></i> <i><span style="font-family:Verdana;">molleoides</span></i><span style="font-family:Verdana;"> reported in nature for the first time.</span></span>
基金Grants support 01/W948 UBACYT 2011-2014,UBACYT 20020130100796 BA 2014-2017 Universidad de Buenos Aires.Buenos Aires.Argentina.
文摘The purpose of this study was to evaluate the redox status changes of primary visual targets in the rat brain of a high pressure-induced glaucoma model.The animal model consisted of inducing ocular hypertension by cauterizing two episcleral veins on the left eye.The markers of oxidative damage and the oxidative balance evaluated in the brain seven days postoperative were:nitrites concentration,levels of non-enzymatic antioxidants and antiox-idant enzymes activity.The increase in the nitrite content,which could be the result of the enhancement in the production of nitrogen species,and in the activity of NADPH oxidase in the glaucoma group could lead to an increase on lipid and protein damage.The decrease on the non-enzymatic antioxidants and the compensatory increase of the superoxide dismutase and glutathione peroxidase activities could be a consequence of the increase of oxidative processes.The decrease in the activity of glutathione reductase leads to a decrease in the recycling of thiol groups.We suggest that oxidative stress can possibly acts as a risk factor for neurodegeneration in the brain.Therapeu-tic strategies to stop the progression of the disease in glaucoma should also be considered the central neuronal degeneration beyond the retina and the optic nerve.
文摘Fe is essential for human life because it constitutes the required cofactor for proteins of diverse biological functions.However,the development of oxidative stress by exposure to excessive Fe,share signaling pathways with other treatments including activation of redox-sensitive factors.This study was focused on the comparison on the effects of Fe in the brain and other organs in vivo.The oxidative effects triggered by Fe overload strongly depend not only on the administration protocol,but also on the Fe-compound used,and the studied organ.In both the liver and the brain,Fe content drastically increased after Fe-dextran administration.However,the comparatively low lipid peroxidation in the brain as compared to the liver,suggested that Fe-dependent oxidative stress might involve mechanisms of different nature.In the brain,acute and subchronic administration of Fe-dextran triggered signaling processes that lead to the prevention of injury by the participation of catalase activity as an antioxidant protection.This brief summary opens a huge range of possible points of risk,as well as opportunities,to encounter situations in which the appropriate election of the Fe management protocol could be able of allow oxidative stress to exert beneficial effects.
文摘Protein powders from Eisenia foetida were prepared using different drying processes and fractionation. Differential scanning calorimetry was used to show that heat denaturation occurred during the drying process above 42°C. Protein solubility was also studied. The addition of dissociating reagents allowed concluding that solubility was decreased during oven drying due to thermo denaturation including hydrogen bonds. The volatile compounds of the different powders were extracted by solid phase micro-extraction and identified by mass spectrometry. Volatile compounds were related to lipid oxidation and Maillard reactions occurring during the preparation of the powders. High drying temperatures led to more volatile compounds resulting from Maillard reactions. In the protein powder preparation process, a fractionation step led to a “pulp fraction” and a “juice fraction” of earthworms. The “pulp fraction” contained less odorant volatile compounds resulting from Maillard reactions than the “juice fraction” did.
文摘Neuroinflammation in neurodegenerative diseases:Inflammatory processes play a critical role in neurodegenerative diseases,such as Parkinson’s disease(PD).Thus,neuroinflammation is involved in the progression and development of these diseases,becoming an important pathological hallmark.Microglial cells,the“macrophages”from central nervous system,are the initiating cells of the innate immune response against different stimuli in the brain.
文摘An infusion was developed based on green romaine lettuce leaves and banana. Further, its sensorial acceptability was evaluated as a possible alternative treatment for insomnia. The romaine lettuces and bananas used were washed, chopped, dehydrated and ground. Optimal lettuce dehydration time was determined through charting the weight lost and examining the curve. This was found after 180 minutes at 60<sup>°<span></span></sup><span>C</span><span>. Two formulas were developed, the first with 1.1 g of dehydrated romaine lettuce and 0.2 g of dehydrated banana, and the second with 1.1 g of dehydrated romaine lettuce and 0.4 g of dehydrated banana. Sensory analysis was conducted using sorting tests for taste, aroma, paired preferences and intention to purchase. Tasters preferred the formula with a lower quantity of dehydrated banana. 85%</span><span> of tasters indicated that they would buy this infusion due to its potential functional properties for overcoming insomnia.</span>
文摘Chemically based rodent models are used to assess the positive effects promoted by foods and gut microbiota on gut health. Lectins with enzymatic activity, such as type 2 ribosome-inactivating proteins, might also prove useful for exploring these issues. Sub-lethal doses of the lectin nigrin from Sambucus nigra L. to mice promoted reversible derangement of gut epithelium by induction of apoptosis of transit amplifying cells of the small intestine crypts in a time-dependent course. The present work seeks to study vitamin B6 accumulation in plasma from an oral bolus in a mouse nigrin model. 24 h after sub-lethal nigrin b treatment, there was clear body weight reduction associated to a notable increase in Evan’s blue stain accumulation in excised small intestine, an increase in myeloperoxidase activity, and a near 50% reduction in plasma accumulation of vitamin B6. Histological analysis of small intestine sections of nigrin b-treated animals also revealed significant derangement of intestinal crypts. Seventy two hours after nigrin b treatment, stain uptake decreased and vitamin B6 accumulation was almost restored despite villi derangement. Large intestine crypts were scarcely or not at all affected. Eight days after nigrin b treatment, vitamin B6 uptake and intestinal crypt structure had fully recovered. The nigrin b mice model supports the view that, under these conditions, the carrier-mediated vitamin B6 uptake component of the small intestine crypts is probably the most active when the vitamin is administered orally as a bolus. The findings provide insights into the suitability of the present mice model for nutritional or drug absorption studies in conditions of partially altered or injured intestinal mucosa.
文摘The effect of the administration of large amounts of green tea polyphenols is a matter of controversy. We explored whether a polyphenol mixture from a concentrated green tea extract (Polyphenon 60) could alter the effects on mice of the type 2 (two chains) ribosome-inactivating protein nigrin b isolated from Sambucus nigra L. Nigrin b triggers specific reversible toxic effects on the mouse intestines featured by apoptosis of mice Lieberkühn crypt cells upon parenteral administration of sub-lethal amounts. Independent administration to mice of 30 mg/kg body weight of Polyphenon 60 by oral gavage or 10 mg/kg body weight of nigrin b administered via the intraperitoneal route (i.p.) did not affect survival. In contrast, the simultaneous treatment greatly enhanced nigrin b toxicity leading to the death of some animals. The histological analysis revealed that the most serious injury was inflicted on the small intestine crypts, which disappeared, and on the liver, which evidenced hepatotoxicity showing haemorrhagic areas. These findings raise concerns about the abuse of high concentrations of green tea polyphenols especially when the intestinal mucosa is damaged, for instance by toxins or therapeutic drugs.
文摘Objective： To develop a highly sensitive LC-MS/MS （liquid chromatography-mass spectxometry/mass spectrometry） method applied to the detection and quantitation of UDCA （ursodeoxycholic acid） related substances such as CA （cholic acid）, DCA （deoxycholic acid）, CDCA （chenodeoxycholic acid） and LCA （lithocholic acid） in raw material and pharmaceutical formulation. Methods： The method was validated for specificity, linearity, accuracy, precision, robustness. A triple quadrupole mass detector was employed, equipped with an ESI （electrospray ionization） source operated in the negative ion mode. The chromatographic system consisted of a Symmetry C 18 column （150 mm × 4.6 mm, id; particle size 5 μm） and methanol-acetonitrile-ammonium acetate （pH 7.6; 10 mM） （40：40：20, v/v/v） as the mobile phase. The chromatographic conditions were 25 uL injection volume, flow rate of 0.4 mL/min and column temperature set at 35℃. Key tindings： The method requires a minimum sample amount and presents very low LOD （limits of detection） for CA （0.29 ng/mL）, DCA （0.59 ng/mL）, CDCA （0.13 ng/mL） and LCA （0.44 ng/mL） in comparison to LC methods coupled to different detectors like UV （ultraviolet）, fluorescence and refractive index. Conclusions： The developed and validated LC-MS/MS method for the determination of UDCA and related substances in raw material and in a suspension was advantageous since it required a minimum sample amount. In turn, it could be used as a stability indicating method.
