Identification of ABCC3 and its isoforms as potential biomarker in hepatocellular carcinoma.

Liver diseases preceding the occurrence of hepatocellular carcinoma (HCC) play a crucial role in the progression and establishment of HCC, a malignancy ranked as the third deadliest cancer worldwide. Late diagnosis, alongside ineffective treatment, leads patients to a poor survival rate. This scenario argues for seeking novel alternatives for detecting liver alterations preceding the early occurrence of HCC. Experimental studies have reported that ABCC3 protein increases within HCC tumors but not in adjacent tissue. Therefore, we analyzed ABCC3 expression in public databases and investigated the presence of ABCC3 and its isoforms in plasma, urine and its release in extracellular vesicles (EVs) cargo from patients bearing cirrhosis and HCC. The UALCAN and GEPIA databases were used to analyze the expression of ABCC3 in HCC. The results were validated in a case-control study including 41 individuals bearing cirrhosis and HCC, and the levels of ABCC3 in plasma and urine samples, as well as EVs, were analyzed by ELISA and western blot. Our data showed that ABCC3 expression was higher in HCC tissues than in normal tissues and correlated with HCC grade and stage. ABCC3 protein levels were highly increased in both plasma and urine and correlated with liver disease progression and severity. The isoforms MRP3A and MRP3B of ABCC3 were significantly increased in both EVs and plasma/urine of patients bearing HCC. ABCC3 expression gradually increases in HCC tissues, and its protein levels are increased in both plasma and urine of patients with cirrhosis and HCC. MRP3A and MRP3B isoforms have the potential to be prognostic biomarkers of HCC.

LL-37 Triggers Antimicrobial Activity in Human Platelets.

Platelets play a crucial role in hemostasis and the immune response, mainly by recognizing signals associated with vascular damage. However, it has recently been discovered that the antimicrobial peptide LL-37 activates platelets in functions related to thrombus formation and inflammation. Therefore, this work aims to evaluate the effect of LL-37 on the activation of antimicrobial functions of human platelets. Our results show that platelets treated with LL-37 increase the surface expression of receptors (Toll-like receptors (TLRs) 2 and -4, CD32, CD206, Dectin-1, CD35, LOX-1, CD41, CD62P, and αIIbß3 integrins) for the recognition of microorganisms, and molecules related to antigen presentation to T lymphocytes (CD80, CD86, and HLA-ABC) secrete the antimicrobial molecules: bactericidal/permeability-increasing protein (BPI), azurocidin, human neutrophil peptide (HNP) -1, and myeloperoxidase. They also translate azurocidin, and have enhanced binding to Escherichia coli, Staphylococcus aureus, and Candida albicans. Furthermore, the supernatant of LL-37-treated platelets can inhibit E. coli growth, or platelets can employ their LL-37 to inhibit microbial growth. In conclusion, these findings demonstrate that LL-37 participates in the antimicrobial function of human platelets.

3'5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by parenchymal scarring, leading progressively to alveolar architecture distortion, respiratory failure, and eventually death. Currently, there is no effective treatment for IPF. Previously, 3'5-dimaleamylbenzoic acid (3'5-DMBA), a maleimide, demonstrated pro-apoptotic, anti-inflammatory, and anti-cancer properties; however, its potential therapeutic effects on IPF have not been addressed. Bleomycin (BLM) 100 U/kg was administered to CD1 mice through an osmotic minipump. After fourteen days of BLM administration, 3'5-DMBA (6 mg/kg or 10 mg/kg) and its vehicle carboxymethylcellulose (CMC) were administered intragastrically every two days until day 26. On day 28, all mice were euthanized. The 3'5-DMBA effect was assessed by histological and immunohistochemical staining, as well as by RT-qPCR. The redox status on lung tissue was evaluated by determining the glutathione content and the GSH/GSSG ratio. 3'5-DMBA treatment re-established typical lung histological features and decreased the expression of BLM-induced fibrotic markers: collagen, α-SMA, and TGF-ß1. Furthermore, 3'5-DMBA significantly reduced the expression of genes involved in fibrogenesis. In addition, it decreased reduced glutathione and increased oxidized glutathione content without promoting oxidative damage to lipids, as evidenced by the decrease in the lipid peroxidation marker 4-HNE. Therefore, 3'5-DMBA may be a promising candidate for IPF treatment.

Human Platelets Contain, Translate, and Secrete Azurocidin; A Novel Effect on Hemostasis.

Platelets play a significant role in hemostasis and perform essential immune functions, evidenced by the extensive repertoire of antimicrobial molecules. Currently, there is no clear description of the presence of azurocidin in human platelets. Azurocidin is a 37 kDa cationic protein abundant in neutrophils, with microbicidal, opsonizing, and vascular permeability-inducing activity. Therefore, this work aimed to characterize the content, secretion, translation, and functions of azurocidin in platelets. Our results show the presence of azurocidin mRNA and protein in α-granules of platelet and megakaryoblasts, and stimulation with thrombin, ADP, and LPS leads to the secretion of free azurocidin as well as within extracellular vesicles. In addition, platelets can translate azurocidin in a basal or thrombin-induced manner. Finally, we found that the addition of low concentrations of azurocidin prevents platelet aggregation and activation. In conclusion, we demonstrate that platelets contain, secrete, and translate azurocidin, and this protein may have important implications for hemostasis.

Proteomic Analysis Reveals Differential Expression Profiles in Idiopathic Pulmonary Fibrosis Cell Lines.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible lung disorder of unknown cause. This disease is characterized by profibrotic activation of resident pulmonary fibroblasts resulting in aberrant deposition of extracellular matrix (ECM) proteins. However, although much is known about the pathophysiology of IPF, the cellular and molecular processes that occur and allow aberrant fibroblast activation remain an unmet need. To explore the differentially expressed proteins (DEPs) associated with aberrant activation of these fibroblasts, we used the IPF lung fibroblast cell lines LL97A (IPF-1) and LL29 (IPF-2), compared to the normal lung fibroblast cell line CCD19Lu (NL-1). Protein samples were quantified and identified using a label-free quantitative proteomic analysis approach by liquid chromatography-tandem mass spectrometry (LC-MS/MS). DEPs were identified after pairwise comparison, including all experimental groups. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) network construction were used to interpret the proteomic data. Eighty proteins expressed exclusively in the IPF-1 and IPF-2 clusters were identified. In addition, 19 proteins were identified up-regulated in IPF-1 and 10 in IPF-2; 10 proteins were down-regulated in IPF-1 and 2 in IPF-2 when compared to the NL-1 proteome. Using the search tool for retrieval of interacting genes/proteins (STRING) software, a PPI network was constructed between the DEPs and the 80 proteins expressed exclusively in the IPF-2 and IPF-1 clusters, containing 115 nodes and 136 edges. The 10 hub proteins present in the IPP network were identified using the CytoHubba plugin of the Cytoscape software. GO and KEGG pathway analyses showed that the hub proteins were mainly related to cell adhesion, integrin binding, and hematopoietic cell lineage. Our results provide relevant information on DEPs present in IPF lung fibroblast cell lines when compared to the normal lung fibroblast cell line that could play a key role during IPF pathogenesis.

Involvement of 4-hydroxy-2-nonenal in the pathogenesis of pulmonary fibrosis.

Pulmonary fibrosis is a chronic progressive disease with high incidence, prevalence, and mortality rates worldwide. It is characterized by excessive accumulation of extracellular matrix in the lung parenchyma. The cellular and molecular mechanisms involved in its pathogenesis are complex, and some are still unknown. Several studies indicate that oxidative stress, characterized by overproduction of 4-hydroxy-2-nonenal (4-HNE), is an important player in pulmonary fibrosis. 4-HNE is a highly reactive compound derived from polyunsaturated fatty acids that can react with proteins, phospholipids, and nucleic acids. Thus, many of the altered cellular mechanisms that contribute to this disease can be explained by the participation of 4-HNE. Here, we summarize the current knowledge on the molecular states and signal transduction pathways that contribute to the pathogenesis of pulmonary fibrosis. Furthermore, we describe the participation of 4-HNE in various mechanisms involved in pulmonary fibrosis development, with a focus on the cell populations involved in the initiation, development, and maintenance of the fibrotic process, mainly alveolar cells, endothelial cells, macrophages, and inflammatory cells. Due to its characteristic activity as a second messenger, 4-HNE, in addition to being a consequence of oxidative stress, can support maintenance of the inflammatory and fibrotic process by spreading the effects of reactive oxygen species (ROS). Thus, regulation of 4-HNE levels could be a viable strategy to reduce its effects on the mechanisms involved in pulmonary fibrosis development.

CDC42 drives RHOA activity and actin polymerization during capacitation.

Mammalian sperm cells acquire fertilizing capacity as a result of a process termed capacitation. Actin polymerization is important for capacitation; inhibiting actin polymerization prevents the adhesion and fusion of the sperm with the ovule. The main function of RHO proteins CDC42 and RHOA is to direct actin polymerization. Although these two RHO proteins are present in mammalian sperm, little is known about their role in capacitation, the acrosome reaction, and the way in which they direct actin polymerization. The purpose of this study was to determine the participation of CDC42 and RHOA in capacitation and the acrosome reaction and their relationship with actin polymerization using guinea pig sperm. Our results show that the inhibition of CDC42 and RHOA alters the kinetics of actin polymerization, capacitation, and the acrosome reaction in different ways. Our results also show that the initiation of actin polymerization and RHOA activation depend on the activation of CDC42 and that RHOA starts its activity and effect on actin polymerization when CDC42 reaches its maximum activity. Given that the inhibition of ROCK1 failed to prevent the acrosomal reaction, the participation of RHOA in capacitation and the acrosomal reaction is independent of its kinase 1 (ROCK1). In general, our results indicate that CDC42 and RHOA have different roles in capacitation and acrosomal reaction processes and that CDC42 plays a preeminent role.

Chronic administration of diethylnitrosamine to induce hepatocarcinogenesis and to evaluate its synergistic effect with other hepatotoxins in mice.

Hepatocellular carcinoma (HCC) arises after a long period of exposition to etiological factors that might be either independent or collectively contributing. Several rodent models resemble human HCC; however, the major limitation of these models is the lack of chronic injury that reproducibly mimics the molecular alterations as it occurs in humans. Thus, we hypothesized that chronic administration of different DEN treatments identifies the best-fit dose to induce the HCC and/or to determine whether small DEN doses act synergistically with other known hepatotoxins to induce HCC in mice. C57BL/6 J male mice were intraperitoneally injected twice a week for 6 weeks with different DEN doses ranging from 2.5 to 40 mg/kg body weight; then, selected doses (2.5, 5 and 20 mg/kg) for 6, 10, 14, and 18 weeks. We demonstrated that DEN at 20 mg/kg promoted reactive oxygen species and 4-hydroxynonenal production, cell proliferation inflammatory infiltrate, and fibrosis, which in turn induced liver cancer by week 18. These parameters were established by evaluating histopathological changes, HCC markers such as glutathione S-transferase placental-1 (Gstp1), Cytokeratin-19 (Ck19) and prostaglandin reductase-1 (Ptgr1); that of Cyp2e1, a DEN metabolizing enzyme; and the expression of the proliferation marker Ki67. While DEN at 2.5 and 5 mg/kg increased Gstp1 and Ck19, DEN at 20 mg/kg decreased them and Cyp2e1 expression and activity. In summary, our results demonstrate that DEN chronically administrated at 20 mg/kg induces the HCC, while DEN at 2.5 and 5 mg/kg could be useful in elucidating its synergistic effect with other hepatotoxic agents in mice.

Protective Effect of Chickpea Protein Hydrolysates on Colon Carcinogenesis Associated With a Hypercaloric Diet.

OBJECTIVE: Colon cancer occupies the third place in incidence worldwide; eating habits, in particular, consumption of hypercaloric diets, are relevant in its etiopathogenesis. On the other hand, foods can also modulate carcinogenesis: for example, proteins, which when hydrolyzed release peptides with biological activities, and legumes, especially, chickpea, represent a good source of hydrolysates. The objective of this work was to verify the inhibitory effect of chickpea hydrolyzed protein on azoxymethane (AOM)-induced carcinogenesis in mice fed a hypercaloric diet. METHODS: We hydrolyzed chickpea protein by pepsin, pancreatin, and a combined pepsin-pancreatin system, to test its anticarcinogenic and hypercaloric activity in mice that had consumed a hypercaloric diet or a normal diet but were injected with azoxymethane (AOM). RESULTS: A concentrate (70% proteins) was obtained from chickpea seeds (18.5% proteins), and extensive hydrolysates were obtained at 15 minutes, in all tested enzyme systems. The greatest activity was evidenced in the hydrolysates obtained with pepsin-pancreatin at 90 minutes. Animals that consumed the hypercaloric diet had a higher concentration of cholesterol and a higher atherogenic index, which were significantly reduced with the administration of chickpea protein hydrolysates with a dose-response effect (10, 20, or 30 mg/kg), whereas no effect was observed in animals that consumed the normal diet. In animals given AOM, aberrant crypts were observed, at a higher rate in animals that consumed the hypercaloric diet; with the consumption of hydrolysates by the animals that consumed either diet, the number of aberrant crypts was reduced with the 3 doses tested, and the effect was better in those animals fed the hypercaloric diet. The best effect in all tests was with 30 mg/kg body weight. CONCLUSION: The consumption of chickpea protein hydrolysates might confer a protective effect against colon carcinogenesis.

Absence of aryl hydrocarbon receptor alters CDC42 expression and prevents actin polymerization during capacitation.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates the toxicity of a variety of environmental chemicals. The absence of this receptor causes serious reproductive complications. Ahr-knockout (Ahr-KO) male mice, for example, are considerably less fertile: Half of the few spermatozoa they produce exhibit morphological alterations, and those with typical morphology may have pathologic modifications. We therefore investigated the consequences of AHR loss on capacitation and the acrosome reaction, and asked if these effects are a consequence of changes to actin polymerization and the expression of Cdc42, which encodes Cell division control protein 42 (CDC42), a RHO protein that controls assembly of the actin cytoskeleton in somatic cells as well as during spermatogenesis. Nearly 50% of spermatozoa produced by Ahr-KO mice had alterations in the flagellum. Ahr-KO spermatozoa were frequently capacitated, but showed reduced spontaneous and progesterone-induced acrosome reaction-which is related to low CDC42 abundance and very limited actin polymerization during capacitation. Thus, the expression of CDC42 might be regulated by AHR, and both proteins are fundamental to the development of normal spermatozoa and the acrosome reaction. Mol. Reprod. Dev. 83: 1015-1026, 2016 © 2016 Wiley Periodicals, Inc.

lncRNA-mRNA Co-Expression and Regulation Analysis in Lung Fibroblasts from Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by abnormal accumulation of extracellular matrix (ECM) due to dysregulated expression of various RNAs in pulmonary fibroblasts. This study utilized RNA-seq data meta-analysis to explore the regulatory network of hub long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in IPF fibroblasts. The meta-analysis unveiled 584 differentially expressed mRNAs (DEmRNA) and 75 differentially expressed lncRNAs (DElncRNA) in lung fibroblasts from IPF. Among these, BCL6, EFNB1, EPHB2, FOXO1, FOXO3, GNAI1, IRF4, PIK3R1, and RXRA were identified as hub mRNAs, while AC008708.1, AC091806.1, AL442071.1, FAM111A-DT, and LINC01989 were designated as hub lncRNAs. Functional characterization revealed involvement in TGF-ß, PI3K, FOXO, and MAPK signaling pathways. Additionally, this study identified regulatory interactions between sequences of hub mRNAs and lncRNAs. In summary, the findings suggest that AC008708.1, AC091806.1, FAM111A-DT, LINC01989, and AL442071.1 lncRNAs can regulate BCL6, EFNB1, EPHB2, FOXO1, FOXO3, GNAI1, IRF4, PIK3R1, and RXRA mRNAs in fibroblasts bearing IPF and contribute to fibrosis by modulating crucial signaling pathways such as FoxO signaling, chemical carcinogenesis, longevity regulatory pathways, non-small cell lung cancer, and AMPK signaling pathways.

Detection of Asymptomatic Sickle Cell Hemoglobin Carriers and Fetal Hemoglobin Regulating Genetic Variants in African Descendants from Oaxaca, Mexico.

Sickle cell anemia has been classified as a noninfectious neglected tropical disease and, although not exclusively, affects African descendants more frequently. This study aimed to detect asymptomatic sickle cell hemoglobin carriers (HbAS) in marginalized and vulnerable populations during a public health screening in African descendants from Oaxaca, Mexico, and to validate an amplification refractory mutation system (ARMS)-PCR methodology to detect fetal-hemoglobin (HbF)-regulating genetic variants in BCL11A toward affordable routine association of single nucleotide variants (SNVs) with HbF concentrations. To this aim, hemoglobin variants were detected by acidic citrate agar and alkaline cellulose acetate electrophoreses. SNVs in the hemoglobin subunit beta gene (HBB) were identified by the ß-globin mutation detection assay (ß-GMDA) and ARMS-PCR, respectively, and validated by Sanger sequencing. The association between genotypes and HbF concentrations was evaluated using Spearman's correlation coefficient. The results obtained during a directed screening in 140 self-identified African descendants revealed 42 HbS-carriers (30%), of which 39 showed normal total hemoglobin concentrations (92.8%), only 3 presented anemia (7.2%), and 9 showed quantifiable HbF concentration (21.4%). As validated by Sanger sequencing, the designed ARMS-PCR efficiently detected homozygous and heterozygous variants in BCL11A. In a cohort of 42 heterozygous (HbAS) and 27 healthy (HbAA) individuals from the same population, only one SNV (rs766432) showed statistically significant association with increasing HbF concentration, and two new unrelated homozygous silent variants were identified. This study reveals the need to raise coverage of HbS screening in vulnerable populations and shows a feasible low-cost ARMS-PCR methodology to determine the presence of SNVs in quantitative trait loci affecting HbF.

Protocol to detect senescence-associated ß-galactosidase and immunoperoxidase activity in fresh-frozen murine tissues.

Double labeling to identify different markers in the same tissue section represents a useful tool either for in situ diagnosis or characterization of molecular associations. Here, we present a protocol to detect senescence-associated ß-galactosidase (SA-ßGal) and immunoperoxidase (IPO) activity in fresh-frozen murine tissues. We describe steps for tissue collection, solution preparation, SA-ßGal staining, IPO staining, hematoxylin counterstaining, microscopic observation, and signal quantification. This protocol can be used to detect in situ proteins alongside SA-ßGal activity. For complete details on the use and execution of this protocol, please refer to Pacheco-Rivera et al.1.

Identification of key markers for the stages of nonalcoholic fatty liver disease: An integrated bioinformatics analysis and experimental validation.

BACKGROUND: The identification of biomarkers for the early diagnosis of nonalcoholic fatty liver disease (NAFLD) is urgently needed. Here, we aimed to identify NAFLD biomarkers in the early stages of steatosis (SS) and nonalcoholic steatohepatitis (NASH) based on differential gene expression from bioinformatics data. METHODS: A meta-analysis was performed from transcriptomic databases retrieved from public repositories containing data from biopsies of patients at various stages of NAFLD development. The status of the selected molecules was validated in the serum of patients with NAFLD by ELISA. RESULTS: We identified 121 differentially expressed genes (DEGs) associated with SS and 402 associated with NASH. Gene Ontology (GO) enrichment revealed that the altered genes were primarily associated with dysfunction of primary cellular processes, and pathway analyses were mainly related to cholesterol metabolism. We identified ACSS2, PCSK9, and CYP7A1 as candidate biomarkers for SS and ANGPTL3, CD36, CYP51A1, FASN, FAS, FDFT1, and LSS as candidate biomarkers for NASH. CONCLUSIONS: By experimental validation of bioinformatics data from patients with NAFLD, we identified promising biomarkers for detecting SS and NASH that might be useful for screening and diagnosing early NAFLD stages in humans.

Discovery of candidate biomarkers from plasma-derived extracellular vesicles of patients with cirrhosis and hepatocellular carcinoma: an exploratory proteomic study.

Extracellular vesicles (EVs) represent an attractive source of biomarkers due to their biomolecular cargo. The aim of this study was to identify candidate protein biomarkers from plasma-derived EVs of patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Plasma-derived EVs from healthy participants (HP), LC, and HCC patients (eight samples each) were subjected to label-free quantitative proteomic analysis using LC-MS/MS. A total of 248 proteins were identified, and differentially expressed proteins (DEPs) were obtained after pairwise comparison. We found that DEPs mainly involve complement cascade activation, coagulation pathways, cholesterol metabolism, and extracellular matrix components. By choosing a panel of up- and down-regulated proteins involved in cirrhotic and carcinogenesis processes, TGFBI, LGALS3BP, C7, SERPIND1, and APOC3 were found to be relevant for LC patients, while LRG1, TUBA1C, TUBB2B, ACTG1, C9, HP, FGA, FGG, FN1, PLG, APOB and ITIH2 were associated with HCC patients, which could discriminate both diseases. In addition, we identified the top shared proteins in both diseases, which included LCAT, SERPINF2, A2M, CRP, and VWF. Thus, our exploratory proteomic study revealed that these proteins might play an important role in the disease progression and represent a panel of candidate biomarkers for the prognosis and diagnosis of LC and HCC.

A model of alcoholic liver disease based on different hepatotoxics leading to liver cancer.

The worst-case scenario related to alcoholic liver disease (ALD) arises after a long period of exposure to the harmful effect of alcohol consumption along with other hepatotoxics. ALD encompasses a broad spectrum of liver-associated disorders, such as steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Based on the chronic administration of different hepatotoxics, including ethanol, sucrose, lipopolysaccharide, and low doses of diethylnitrosamine over a short period, here we aimed to develop a multiple hepatotoxic (MHT)-ALD model in the mouse that recapitulates the human ALD-associated disorders. We demonstrated that the MHT-ALD model induces ADH1A and NXN, an ethanol metabolizer and a redox-sensor enzyme, respectively; promotes steatosis associated with the induction of the lipid droplet forming FSP27, inflammation identified by the infiltration of hepatic neutrophils-positive to LY-6G marker, and the increase of MYD88 level, a protein involved in inflammatory response; and stimulates the early appearance of cellular senescence identified by the senescence markers SA-ß-gal activity and p-H2A.XSer139. It also induces fibrosis associated with increased desmin, a marker of hepatic stellate cells whose activation leads to the deposition of collagen fibers, accompanied by cell death and compensatory proliferation revealed by increased CASP3-mediated apoptosis, and KI67- and PCNA-proliferation markers, respectively. It also induces histopathological traits of malignancy and the level of the HCC marker, GSTP1. In conclusion, we provide a useful model for exploring the chronological ALD-associated alterations and stages, and addressing therapeutic approaches.

Nucleoredoxin Redox Interactions Are Sensitized by Aging and Potentiated by Chronic Alcohol Consumption in the Mouse Liver.

Aging is characterized by increased reactive species, leading to redox imbalance, oxidative damage, and senescence. The adverse effects of alcohol consumption potentiate aging-associated alterations, promoting several diseases, including liver diseases. Nucleoredoxin (NXN) is a redox-sensitive enzyme that targets reactive oxygen species and regulates key cellular processes through redox protein-protein interactions. Here, we determine the effect of chronic alcohol consumption on NXN-dependent redox interactions in the liver of aged mice. We found that chronic alcohol consumption preferentially promotes the localization of NXN either into or alongside senescent cells, declines its interacting capability, and worsens the altered interaction ratio of NXN with FLII, MYD88, CAMK2A, and PFK1 proteins induced by aging. In addition, carbonylated protein and cell proliferation increased, and the ratios of collagen I and collagen III were inverted. Thus, we demonstrate an emerging phenomenon associated with altered redox homeostasis during aging, as shown by the declining capability of NXN to interact with partner proteins, which is enhanced by chronic alcohol consumption in the mouse liver. This evidence opens an attractive window to elucidate the consequences of both aging and chronic alcohol consumption on the downstream signaling pathways regulated by NXN-dependent redox-sensitive interactions.

Chemopreventive Effect of Cooked Chickpea on Colon Carcinogenesis Evolution in AOM/DSS-Induced Balb/c Mice.

Chickpeas are one of the most widely consumed legumes worldwide and they might prevent diseases such as cancer. Therefore, this study evaluates the chemopreventive effect of chickpea (Cicer arietinum L.) on the evolution of colon carcinogenesis induced with azoxymethane (AOM) and dextran sodium sulfate (DSS) in a mice model at 1, 7, and 14 weeks after induction. Accordingly, the expression of biomarkers-such as argyrophilic nucleolar organizing regions (AgNOR), cell proliferation nuclear antigen (PCNA), ß-catenin, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)-was assessed in the colon of BALB/c mice fed diets supplemented with 10 and 20% cooked chickpea (CC). The results showed that a 20% CC diet significantly reduced tumors and biomarkers of proliferation and inflammation in AOM/DSS-induced colon cancer mice. Moreover, body weight loss decreased and the disease activity index (DAI) was lower than the positive control. Lastly, tumor reduction was more evident at week 7 in the groups fed a 20% CC diet. In conclusion, both diets (10% and 20% CC) exert a chemopreventive effect.

Identification of Hub Genes in Idiopathic Pulmonary Fibrosis and Their Association with Lung Cancer by Bioinformatics Analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible disease with a high mortality rate worldwide. However, the etiology and pathogenesis of IPF have not yet been fully described. Moreover, lung cancer is a significant complication of IPF and is associated with increased mortality. Nevertheless, identifying common genes involved in developing IPF and its progression to lung cancer remains an unmet need. The present study aimed to identify hub genes related to the development of IPF by meta-analysis. In addition, we analyzed their expression and their relationship with patients' progression in lung cancer. METHOD: Microarray datasets GSE24206, GSE21369, GSE110147, GSE72073, and GSE32539 were downloaded from Gene Expression Omnibus (GEO). Next, we conducted a series of bioinformatics analysis to explore possible hub genes in IPF and evaluated the expression of hub genes in lung cancer and their relationship with the progression of different stages of cancer. RESULTS: A total of 1888 differentially expressed genes (DEGs) were identified, including 1105 upregulated and 783 downregulated genes. The 10 hub genes that exhibited a high degree of connectivity from the PPI network were identified. Analysis of the KEGG pathways showed that hub genes correlate with pathways such as the ECM-receptor interaction. Finally, we found that these hub genes are expressed in lung cancer and are associated with the progression of different stages of lung cancer. CONCLUSIONS: Based on the integration of GEO microarray datasets, the present study identified DEGs and hub genes that could play an essential role in the pathogenesis of IPF and its association with the development of lung cancer in these patients, which could be considered potential diagnostic biomarkers or therapeutic targets for the disease.

[Epidemiological profile of rheumatoid arthritis]. / Perfil epidemiológico de la artritis reumatoide.

Background: Rheumatoid arthritis affects approximately between 0.3 and 1.2% of the world population. In Latin America, different studies have estimated a prevalence between 0.2 and 0.5% in the population over 16 years of age. Objective: To identify the epidemiological profile of rheumatoid arthritis. Material and methods: Descriptive cross-sectional design carried out in an urban population of a social security institution in Mexico. The information of the clinical file of 373 patients was studied. The epidemiological profile included the sociodemographic dimension, family history, health, clinical, therapeutic, biochemical, extra-articular manifestations and complications. Statistical analysis percentages, means, confidence intervals for percentages and confidence intervals for averages were calculated. Results: The wrists were the most affected joints with 44.6% (95% CI: 39.5-49.6%). The extra-articular manifestation with the highest prevalence was asthenia with 9.9% (95% CI: 6.9-12.9%); predominant diagnosis according to ICD-10 was seropositive rheumatoid arthritis with 59.8% (95% CI: 54.8-64.8%), and the rheumatoid factor was highly positive in 78.3% (95% CI: 74.1-82.5%); predominant treatment was with combined therapy at diagnosis in 97.6% (95% CI: 96.0-99.1%). The duration of treatment was > 10 years in 34.1% (95% CI: 29.2-38.8%). Conclusion: This work has described the epidemiological profile of the patient with rheumatoid arthritis in different dimensions.

Introducción: la artritis reumatoide afecta aproximadamente entre 0.3 y 1.2% de la población mundial. En Latinoamérica diferentes estudios han estimado una prevalencia entre 0.2 y 0.5% en población mayor de 16 años de edad. Objetivo: identificar el perfil epidemiológico de la artritis reumatoide. Material y métodos: diseño transversal descriptivo llevado a cabo en población urbana de una institución de seguridad social en México. Se estudió la información del expediente clínico de 373 pacientes. El perfil epidemiológico incluyó la dimensión sociodemográfica, antecedentes heredofamiliares, de salud, clínicos, terapéuticos, bioquímicos, de manifestaciones extraarticulares y de complicaciones. Se calcularon porcentajes, promedios, e intervalos de confianza para porcentajes y promedios. Resultados: las muñecas fueron las articulaciones más afectadas con 44.6% (IC 95%: 39.5-49.6%). La manifestación extraarticular con más alta prevalencia fue la astenia con 9.9% (IC 95%: 6.9-12.9%); el diagnóstico predominante de acuerdo con el CIE-10 fue la artritis reumatoide seropositiva con 59.8% (IC 95%: 54.8-64.8%) y se encontró el factor reumatoide positivo alto en un 78.3% (IC 95%: 74.1%-82.5%); el tratamiento predominante fue con terapia combinada al diagnóstico en un 97.6%, (IC 95%: 96.0-99.1%). La duración del tratamiento fue > 10 años en el 34.1% (IC 95%: 29.2-38.8%). Conclusión: este trabajo ha descrito el perfil epidemiológico del paciente con artritis reumatoide en diferentes dimensiones.