Global longitudinal strain is superior to ejection fraction for detecting myocardial dysfunction in end-stage renal disease with hyperparathyroidism

BACKGROUND The estimation of left ventricular ejection fraction(LVEF)by 2D echocardiography(2D-ECHO)is the most used tool to assess LV systolic function(LVSF).Global longitudinal strain(GLS)has recently been suggested as a superior method for several evaluations.This study explored the association and prevalence of LV systolic dysfunction(LVSD)by using these methods in patients with end-stage renal disease(ESRD)and severe hyperparathyroidism(SHPTH);both associated with cardiovascular events(CEs).AIM To evaluate the myocardial function in patients with ESRD and SHPTH by using the GLS and LVEF measured through conventional 2D-ECHO.METHODS In 62 patients with ESRD and SHPTH,asymptomatic,and without a history of CEs,LVSF was evaluated by 2D-ECHO,obtaining the EF,by the Simpson biplane method,and GLS by speckle tracking.RESULTS The total patients with ESRD had a preserved LVEF(>50%)but abnormal GLS(<13.55%).Additionally,multivariate analysis showed an independent association of GLS and serum parathyroid hormone(PTH),LV mass index,and hemoglobin.Also,PTH was independently associated with lateral e'wave and tricuspid regurgitation velocity.CONCLUSION In patients with SHPTH linked to ESRD,the use of GLS by 2D-ECHO is a more sensitive tool than LVEF for detecting LVSD.

Boron-containing compounds as labels,drugs,and theranostic agents for diabetes and its complications

Diabetes is a disease with a high global burden.Current strategies have failed to limit the advancement and impact of the disease.Successful early diagnosis and treatment will require the development of new agents.In this sense,boroncontaining compounds have been reported as agents with the ability to reduce glycemia and lipidemia.They have also been used for labeling and measuring carbohydrates and other molecules linked to the initial stages of diabetes and its progression.In addition,certain boron compounds bind to molecules related to diabetes development and their biological activity in the regulation of elevated glycemia.Finally,it should be noted that some boron compounds appear to exert beneficial effects on diabetes complications such as accelerating wound healing while ameliorating pain in diabetic patients.

Polyphenols as potential enhancers of stem cell therapy against neurodegeneration

The potential of polyphenols for treating chronic-degenerative diseases(particularly neurodegenerative diseases)is attractive.However,the selection of the best polyphenol for each treatment,the mechanisms by which they act,and their efficacy are frequently discussed.In this review,the basics and the advances in the field,as well as suggestions for using natural and synthetic polyphenols alone or in a combinatorial strategy with stem cell assays,are compiled and discussed.Thus,stem cells exhibit several responses when polyphenols are added to their environment,which could provide us with knowledge for advancing the elucidation of the origin of neurodegeneration.But also,polyphenols are being included in the innovative strategies of novel therapies for treating neurodegenerative diseases as well as metabolic diseases related to neurodegeneration.In this regard,flavonoid compounds are suggested as the best natural polyphenols due to their several mechanisms for acting in ameliorative effects;but increasing reports are involving other polyphenols.Even if some facts limiting bioactivity prevent them from conventional use,some natural polyphenols and derivatives hold the promise for being improved compounds,judged by their induced effects.The current results suggest polyphenols as enhancers of stem cell therapy against the targeted diseases.

Hepatoprotective effect of Geranium schiedeanum against ethanol toxicity during liver regeneration

AIM: To evaluate the effect of an extract of Geranium schiedeanum(Gs) as a hepatoprotective agent against ethanol(Et OH)-induced toxicity in rats. METHODS: Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy(PH); they were then divided into three groups(groups 1-3). During the experiment, animals in group 1 drank only water. The other two groups(2-3) drank an aqueous solution of Et OH(40%, v/v). Additionally, rats in group 3 received a Gs extract daily at a dose of 300 mg/kg body weight intragastically. Subsequently, to identify markers of liver damage in serum, alanine aminotransferase, aspartate aminotransferase, albumin and bilirubin were measured by colorimetric methods. Glucose, triglyceride and cholesterol concentrations were also determined. In addition, oxidative damage was estimated by measuring lipid peroxidation [using thiobarbituric-acid reactive substances(TBARS)] in both plasma and the liver and by measuring the total concentration of antioxidants in serum and the total antioxidant capacity in the liver. In addition, a liver mass gain assessment, total DNA analysis and a morpho-histological analysis of the liver from animals in all three groups were performed and compared. Finally, the number of deaths observed in the three groups was analyzed.RESULTS: Administration of the Geranium shiedeanum extract significantly reduced the unfavorable effect of ethanol on liver regeneration(restitution liver mass: PHEt OH group 60.68% vs PH-Gs-Et OH group 69.22%). This finding was congruent with the reduced levels of hepatic enzymes and the sustained or increased levels of albumin and decreased bilirubin in serum. The extract also modified the metabolic processes that regulate glucose and lipid levels, as observed from the serum measurements. Lower antioxidant levels and the liver damage induced by Et OH administration appeared to be mitigated by the extract, as observed from the TBARs(PH-Et OH group 200.14 mmol/mg vs PH-Gs-Et OH group 54.20 mmol/mg; P < 0.05), total status of antioxidants(PH-Et OH group 1.43 mmol/L vs PH-Gs-Et OH group 1.99 mmol/L; P < 0.05), total antioxidant capacity values, liver mass gain and total DNA determination(PH-Et OH group 4.80 mg/g vs PH-Gs-Et OH 9.10 mg/g; P < 0.05). Overall, these processes could be related to decreased mortality in these treated animals.CONCLUSION: The administered extract showed a hepatoprotective effect, limiting the Et OH-induced hepatotoxic effects. This effect can be related tomodulating oxido-reduction processes.

Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.

Effect of dichloromethylene diphosphonate on liver regeneration following thioacetamide-induced necrosis in rats

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.

Transparent conductive stannic oxide coatings employing an ultrasonic spray pyrolysis technique:The relevance of the molarity content in the aerosol solution for improvement the electrical properties

Highly transparent conductive stoichiometric nanocrystalline stannic oxide coatings were deposited onto Corning®EAGLE XG®slim glass substrates.Including each coating,it was deposited for various concentrations in the aerosol solution with the substrate temperature maintained at 623.15 K by an ultrasonic spray pyrolysis(USP)technique.Nitrogen was em-ployed both as the solution carrier in addition to aerosol directing gas,maintaining its flow rates at 3500.0 and 500.0 mL/min,respectively.The coatings were polycrystalline,with preferential growth along the stannic oxide(112)plane,irrespective of the molarity content in the spray solution.The coating prepared at 0.2 M,a concentration in the aerosol solution,showed an average transmission of 60%in the visible light region spectrum with a maximum conductivity of 24.86 S/cm.The coatings deposited exhibited in the general photoluminescence spectrum emission colors of green,greenish white,and bluish white calculated on the intensities of the excitonic and oxygen vacancy defect level emissions.

Scope of translational medicine in developing boroncontaining compounds for therapeutics

The ubiquitousness of naturally occurring boron-containing compounds(BCCs) has led to their constant contact with humankind.Recently,many synthetic BCCs have been elaborated for a broad spectrum of purposes,especially boric,boronic and borinic acids.Although BCCs were once employed primarily as antiseptics and later as antibiotics,they have become an increasingly relevant therapeutic tool.Nevertheless,this potential of BCCs has been drastically limited due to some unfortunate intra-hospital accidents in the 1940 s and 1950 s.The increasing use of BCCs as insecticides,antimicrobials,and other agents is providing new insights into their role in the physiology of several living species and in the pathophysiology of humans.It is becoming clear that BCCs act through a wide range of mechanisms,as do their corresponding boron-free counterparts.When comparing BCCs and similar boron-free compounds,in many cases the former show advantages in the medical field.The current minireview focuses on how BCCs have been developed by means of translational medicine,a process connecting biomedical research with clinical applications.This process of discovery is currently in an exponential stage.

Liver disorders in COVID-19,nutritional approaches and the use of phytochemicals

Coronavirus disease 2019(COVID-19),which is caused by severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2),has affected millions of people globally.It was declared a pandemic by the World Health Organization in March 2020.The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a“cytokine storm”and the high oxidative stress responsible for the associated symptomatology.Not only respiratory symptoms are reported,but gastrointestinal symptoms(diarrhea,vomiting,and nausea)and liver abnormalities(high levels of aspartate aminotransferase,alanine aminotransferase transaminases,and bilirubin)are observed in at least 30%of patients.Reduced food intake and a delay in medical services may lead to malnutrition,which increases mortality and poor outcomes.This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury,taking energy and nutrient requirements and their impact on the immune response into account.The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.

Morphological and biochemical effects of weekend alcohol consumption in rats: Role of concentration and gender

AIM To examine the association between weekend alcohol consumption and the biochemical and histological alterations at two different concentrations of alcohol in both genders in rats.METHODS Wistar rats weighing 170-200 g were divided into groups as follows:(1) Control groups; and(2) weekend alcohol-consumption group: 2 d/weekly per 12 wk, at two different concentrations:(1) Group of males or females with a consumption of a solution of alcohol at 40%; and(2) group of males or females with a consumption of a solution of alcohol at 5%. At the end of the experiment, serum and liver samples were obtained. The following enzymes and metabolites were determined in serum: Alanine Aminotransferase(ALT), Aspartate Aminotransferase(AST), Lactate Dehydrogenase, and Gamma-Glutamyltransferase, and glucose, triglycerides, cholesterol, bilirubin, and albumin. Liver samples from each group were employed to analyze morphological abnormalities by light microscopy.RESULTS In all of the weekend alcohol-consumption groups, AST activity presented a significant, 10-fold rise. Regarding ALT activity, the groups with weekend alcohol consumption presented a significant increase that was six times greater. Bilirubin levels increased significantly in both groups of females. We observed a significant increase in the parameters of fatty change and inflammation due to weekend alcohol consumption. Only the group of females that consumed alcohol at 40% presented slight hepatocel ular disorganization CONCLUSION The results obtained herein provide solid evidence that weekend alcohol consumption gives rise to liver damage, demonstrated by biochemical and histological alterations, first manifested acutely, and prolonged weekend alcohol consumption can cause greater, irreversible damage.

Effect of Cyclooxygenase-2 Blockade on Renal Hypertrophy Development during Early Diabetes Mellitus

Diabetes mellitus is the leading cause of diabetic nephropathy;the early phase of diabetes is associated with kidney growth and hyperfiltration;several factors modulate these changes, among them, prostaglandins and angiotensin II. Previous studies have shown that cyclooxygenase-2 is implicated in experimental models of diabetes. The aim of this work was to study the effect of celecoxib treatment on renal hypertrophy development in early diabetes mellitus. In our rats with early streptozotocin-induced diabetes there was renal hypertrophy, and increased renal expression of cyclooxygenase-2, AT1 receptor, and transforming growth factor-β1. Treatment with the selective cyclooxygenase-2 inhibitor celecoxib reduced the urinary excretion of prostaglandins such as prostaglandin E2, 6-keto prostaglandin F1α, and thromboxane B2. Kidney hypertrophy was reversed by the treatment, and the renal expression of cyclooxygenase-2, AT1 receptor, and transforming growth factor-β1 decreased. The renoprotective effects of celecoxib were independent of the changes in plasma glucose levels. These results confirm that cyclooxygenase-2 inhibition in rats with streptozotocin-induced diabetes decrease renal hypertrophy;this effect in turn, may be mediated by reduction of the expression of AT1 receptors and transforming growth factor-b1 in the kidney.

Safety and Efficacy of Oral Mirodenafil in Mexican with Erectile Dysfunction

Erectile dysfunction is treated with 5-phospodiesterase inhibitors as Mirodenafil, which has shown its efficacy and safety in Koreans, however;no information in other populations is available. An open clinical trial study was designed to evaluate the efficacy and safety in real life of a fixed-dose of Mirodenafil in Mexican patients with erectile dysfunction. Forty-seven male patients received a 100 mg tablet of Mirodenafil, during 12 weeks. Primary outcome efficacy measure was the percentage of male patients with successful intercourse. Secondary outcomes measures included patient satisfaction, mood and self-esteem level. Safety assessments included laboratory tests, vital signs, physical examination, 12-lead electrocardiogram recordings, and incidence of adverse events by patients. Oral administration of Mirodenafil improved in an 80% - 90% the number of successful intercourses from 7 to 84 days of treatment. Moreover, patients reported a significant increment in their sexual satisfaction, mood and self-esteem. Mirodenafil treatment did not modify vital signs nor anthropometric parameters during 84 days. Mild headache was the most frequent adverse event (17.0%) and there were no severe adverse events during pharmacological treatment. Data suggest that oral Mirodenafil is safety, well tolerated and effective in the Mexican population with erectile dysfunction.

Oral Pharmacokinetics of Mirodenafil in Mexican Healthy Volunteers

Mirodenafil is a 5-phosphodiesterase inhibitor that is currently marketed in Korea for the treatment of erectile dysfunction;however, no information in other populations is available. It has been described that Mirodenafil is metabolized by CYP3A4, a metabolic pathway in which interethnic differences have been reported. The purpose of this study was to characterize the oral pharmacokinetics of Mirodenafil in Mexicans. Seventeen male healthy volunteers were enrolled in this study. After an overnight fast, volunteers received an oral 100 mg dose and blood samples were collected at selected times during 24 h. Plasma was stored frozen and analyzed by an HPLC method. Pharmacokinetic parameters obtained were: Cmax 331.129 ± 32.689 ng/mL, tmax 1.574 ± 0.293 h, AUC24h 883.293 ± 104.088 ng·h/mL, AUC￥ 976.477 ± 108.812 ng·h/mL and t1/2 1.807 ± 0.171 h. Parameter values observed in this study are similar to those reported in Koreans. Since efficacy and safety studies of Mirodenafil have been conducted in Koreans, it is expected that dosage regime to employ in Mexicans should be similar to the approved for Korean population.

Evaluation of the Influence of Hyoscine Butylbromide on the Oral Bioavailability of Lansoprazole in Healthy Adult Volunteers

The gastroesophageal reflux and/or peptic ulcer diseases are clinical conditions that occur usually accompanied of symptomatic pain. Lansoprazole, a proton pump inhibitor class drug is widely used in clinical practice for treatment of these diseases. However, its efficacy can be improved by combining with spasmolytic and/or visceral analgesic such as hyoscine butylbromide. Since hyoscine butylbromide is barely absorbed and exerts some local effects at gastrointestinal tract which may modify the absorption of lansoprazole, it is important to establish if there is a pharmacokinetic interaction after the oral concomitant administration of both drugs. For this objective, twenty-five subjects received under a crossover design an oral administration of lansoprazole (15 mg) plus placebo or a fixed-dose combination with hyoscine butiylbromide (15 mg + 10 mg, respectively). Plasma samples were obtained at different times during 10 hours. Lansoprazole plasma concentrations were determined by a high performance liquid chromatography method coupled to tandem mass spectrometry. Fixed-dose combination was well tolerated. Lansoprazole pharmacokinetic parameters were: Cmax 621.81 ± 212.79 and 450.38 ± 192.14 ng/mL;AUC0-t 1941.36 ± 845.57 and 1454.66 ± 757.28 ng·h/mL;tmax 2.83 ± 0.99 and 3.40 ± 1.82h;t1/2 1.35 ± 0.39 and 1.45 ± 0.51 h, for alone and combined fixed-dose formulation, respectively. Pharmacokinetic parameters were compared by analysis of variance and ratios of AUC0-t, Cmax and 90% confidence intervals obtained. Since confidence intervals exceed the 80% - 125% limits for these parameters, we conclude that there is a significantly pharmacokinetic interaction of lansoprazole when it is administered concomitantly with hyoscine butylbromide.

Biophysical Mechanism of the SAHA Inhibition of Zn^（2+）-Histone Deacetylase-Like Protein(FB188 HDAH)Assessed via Crystal Structure Analysis

The zinc-containing enzyme HDAC-like amidohydrolase (FB188 HDAH), identified in the Bordetella alcaligenes bacteria, is similar to enzymes that participate in epigenetic mechanisms such as histone modifications. The X-ray crystal structure of FB188 HDAH complexed with the antagonist SAHA (suberoylanilide hydroxamic acid) has been solved (PDB ID: 1ZZ1). Notably, the complex crystallizes as a tetramer in the asymmetric unit cell of the crystal. The crystal yielded a suitable structure to analyze the dynamics of the inhibitory mechanism of SAHA on this histone deacetylase. Applying computational chemistry techniques and quantum mechanics theory, several physicochemical properties were calculated to compare the active site of the enzyme of the four monomers. Significant differences were observed in the areas and volumes of the binding pocket, as well as hydrophobic interactions, dipole moments, atomic charges and electrostatic potential, among other properties. Remarkably, a free-energy curve resulting from the evaluation of the energies of SAHA and the interacting amino acids of the four crystal monomers unveiled the biophysical mechanism of the FB188 HDAH inhibition exerted by SAHA to a greater extent. The biophysical mechanism of SAHA inhibition on FB188 deacetylase was clearly observed as a dynamic process. It is possible to define the physicochemical dynamics of the molecular complex by the application of computational chemistry techniques and quantum mechanics theory by studying the crystal structures of the interacting molecules.

Hypersensitivity to Aspirin as a Factor for Poor Control in Hereditary Angioedema

Background: Hereditary angioedema (HAE) is a primary immunodeficiency disorder characterized by C1 complement inhibitor deficiency and unregulated activation of complement. Aspirin hypersensitivity is related to an increase in the amount of leukotrienes with eosinophil and mast cell activation and increased levels of glandular kallikrein with upregulated local conversion of bradykinin. Both conditions can be present in the same patient. Objectives: We present five patients with HAE;they were all being treated in similar ways according to the therapeuthic options available in our institute (danazol). However, three of them had recurrent episodes of angioedema;in these cases, it was identified aspirin hypersensitivity as a cause of poor disease control. A review of the literature is included. Case Presentation: We present the cases of four females and one male (age range 21 - 58 years) with type I HAE. Subjects were all ISSSTE beneficiaries (state workers) treated at the National Medical Center “20 de Noviembre”. Aspirin hypersensitivity was identified in three patients. Elimination of NSAIDs along with dietary elimination of high salicylate-containing foods improved control of angioedema crisis (severe and/ or recurrent episodes). Discussion: Aspirin hypersensitivity was identified as a factor for poor control in our patients with HAE. Such cases improved with dietary elimination of high salicylate-containing foods and avoidance of NSAIDs. Conclusions: This is the first report of patients with HAE and aspirin hypersensitivity as a cause of poor control. We recommend a deliberate search of these comorbidities, especially in cases of poor disease control. Further studies are needed to continue the investigation on this topic.

Hepatoprotective effect of silymarin

The use of medicinal plants in treating illnesses has been reported since ancestral times.In the case of hepatic diseases,several species such as Silybum marianum,Phyllanthus niruri,and Panus giganteus(Berk.)have been shown to ameliorate hepatic lesions.Silymarin is a natural compound derived from the species Silybum marianum,which is commonly known as Milk thistle.This plant contains at least seven flavoligands and the flavonoid taxifolin.The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol,acetaminophen,and carbon tetrachloride.The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation.Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver.It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity.A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.

Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles （NFTs）; these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone （TIB） have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB （0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks） on the content of total and hyperphosphorylated Tau （PHF-1） proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB： it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.

Review of natural products with hepatoprotective effects

The liver is one of the most important organs in the body,performing a fundamental role in the regulationof diverse processes,among which the metabolism,secretion,storage,and detoxification of endogenous and exogenous substances are prominent.Due to these functions,hepatic diseases continue to be among the main threats to public health,and they remain problems throughout the world.Despite enormous advances in modern medicine,there are no completely effective drugs that stimulate hepatic function,that offer complete protection of the organ,or that help to regenerate hepatic cells.Thus,it is necessary to identify pharmaceutical alternatives for the treatment of liver diseases,with the aim of these alternatives being more effective and less toxic.The use of some plants and the consumption of different fruits have played basic roles in human health care,and diverse scientific investigations have indicated that,in those plants and fruits so identified,their beneficial effects can be attributed to the presence of chemical compounds that are called phytochemicals.The present review had as its objective the collecting of data based on research conducted into some fruits(grapefruit,cranberries,and grapes)and plants[cactus pear(nopal)and cactus pear fruit,chamomile,silymarin,and spirulina],which are consumed frequently by humans and which have demonstrated hepatoprotective capacity,as well as an analysis of a resin(propolis)and some phytochemicals extracted from fruits,plants,yeasts,and algae,which have been evaluated in different models of hepatotoxicity.

Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system

Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.