Multidrug Resistance Reversed by Maleimide Interactions. A Biological and Synthetic Overview for an Emerging Field.

Multidrug Resistance (MDR) can be considered one of the most frightening adaptation types in bacteria, fungi, protozoa, and eukaryotic cells. It allows the organisms to survive the attack of many drugs used in the daily basis. This force the development of new and more complex, highly specific drugs to fight diseases. Given the high usage of medicaments, poor variation in active chemical cores, and self-medication, the appearance of MDR is more frequent each time, and has been established as a serious medical and social problem. Over the years it has been possible the identification of several genes and proteins responsible for MDR and with that the development of blockers of them to reach MDR reversion and try to avoid a global problem. These mechanisms also have been observed in cancer cells, and several calcium channel blockers have been successful in MDR reversion, and the maleimide can be found included in them. In this review we explore the history, mechanisms, reversion efforts, and we specifically focused on the maleimide synthesis as MDR-reversers in co-administration, as well as their biological applications in a urge to expand the available information and explore a very plausible MDR reversion source.

Effects of trade and poaching pressure on extinction risk for cacti in the Atacama Desert.

In this era of a global biodiversity crisis, vascular plants are facing unprecedented extinction rates. We conducted an assessment of the extinction risk of 32 species and 7 subspecies of Copiapoa, a genus endemic to Chile's fog-dependent coastal Atacama Desert. We applied the International Union for Conservation of Nature Red List Categories and Criteria enhanced by expert insights and knowledge. Our primary aim was to analyze the impact of trade and poaching on their extinction risk. We employed machine learning models, including multinomial logistic regression (MLR), decision tree (DT), and random forest (RF), to analyze the relationships between conservation status and various factors. These factors encompassed trade and poaching activities, landscape condition, human footprint, monthly cloud frequency, and biological traits such as evolutionary distinctiveness and maximum diameter. Seven taxa had an area of occupancy (AOO) of <10 km2, 10 additional taxa had an AOO of <20 km2, and 16 taxa had an AOO of ≤100 km2. This reassessment exposed a critical level of extinction risk for the genus; 92% of the taxa were classified as threatened, 41% as critically endangered, 41% as endangered, and 10% as vulnerable. MLR, DT, and RF exhibited accuracies of 0.784, 0.730, and 0.598, respectively, and identified trade and poaching pressure and landscape condition as the primary drivers of extinction risk. Our assessment of Copiapoa showed trade, poaching, habitat degradation, and their synergic impacts as the main drivers of the genus' extinction risk. Our results highlight the urgent need for nations to develop and enforce strategies to monitor and control trade and poaching pressure because these factors are crucial for the long-term persistence of desert plants.

Retos para la regulación del uso comercial de serpientes elápidas marinas en el Indo­Pacífico Resumen En estos tiempos de la crisis mundial de la biodiversidad, las plantas vasculares enfrentan una tasa de extinción sin precedentes. Evaluamos el riesgo de extinción de 32 especies y siete subespecies de Copiapoa, un género endémico al Desierto de Atacama. Aplicamos los Criterios y Categorías de la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza mejoradas con información y conocimiento de expertos. Nuestro principal objetivo era analizar el impacto del mercado y la colecta ilegal sobre el riesgo de extinción de estas plantas. Usamos modelos de aprendizaje automático, incluyendo la regresión logística multinominal, los árboles de decisión y los bosques aleatorios, para analizar las relaciones entre el estado de conservación y diversos factores. Estos factores englobaron las actividades de mercado y colecta ilegal, condiciones del terreno, huella humana, frecuencia mensual de nubes y características biológicas como la singularidad evolutiva y el diámetro máximo. Siete taxones tuvieron un área de ocupación (ADO) <10 km2, diez taxones más tuvieron ADO <20 km2 y 16 taxones tuvieron ADO ≤100 km2. Este análisis expuso el nivel crítico del riesgo de extinción del género Copiapoa: el 92% de los taxones están clasificados como amenazados, 41% como en peligro crítico, 41% como en peligro y 10% como vulnerable. La regresión logística multinominal, los árboles de decisión y los bosques aleatorios exhibieron una certeza del 0.784, 0.730 y 0.598, respectivamente. También identificaron a la presión del mercado y la colecta ilegal y las condiciones del terreno como los principales factores detrás de riesgo de extinción. Nuestro análisis del género Copiapoa mostró que el mercado, la colecta ilegal, la degradación del hábitat y sus impactos sinérgicos como los principales factores detrás del riesgo de extinción del género. Nuestros resultados resaltan la necesidad urgente de que las naciones desarrollen y apliquen estrategias para monitorear y controlar la presión del mercado y la colecta ilegal pues estos son factores cruciales para la persistencia a largo plazo de las plantas de los desiertos.

Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment.

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation-satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds.

Upregulated Nuclear Expression of Soluble Epoxide Hydrolase Predicts Poor Outcome in Breast Cancer Patients: Importance of the Digital Pathology Approach.

Breast cancer (BC) is the most common cancer in women, with incidence rates increasing globally in recent years. Therefore, it is important to find new molecules with prognostic and therapeutic value to improve therapeutic response and quality of life. The polyunsaturated fatty acids (PUFAs) metabolic pathway participates in various physiological processes, as well as in the development of malignancies. Although aberrancies in the PUFAs metabolic pathway have been implicated in carcinogenesis, the functional and clinical relevance of this pathway has not been well explored in BC. To evaluate the clinical significance of soluble epoxide hydrolase (EPHX2) expression in Mexican patients with BC using tissue microarrays (TMAs) and digital pathology (DP). Immunohistochemical analyses were performed on 11 TMAs with 267 BC samples to quantify this enzyme. Using DP, EPHX2 protein expression was evaluated solely in tumor areas. The association of EPHX2 with overall survival (OS) was detected through bioinformatic analysis in public databases and confirmed in our cohort via Cox regression analysis. Clear nuclear expression of EPHX2 was identified. Receiver operating characteristics (ROC) curves revealed the optimal cutoff point at 2.847062 × 10-3 pixels, with sensitivity of 69.2% and specificity of 67%. Stratification based on this cutoff value showed elevated EPHX2 expression in multiple clinicopathological features, including older age and nuclear grade, human epidermal growth factor receptor 2 (HER2) and triple negative breast cancer (TNBC) subtypes, and recurrence. Kaplan-Meier curves demonstrated how higher nuclear expression of EPHX2 predicts shorter OS. Consistently, multivariate analysis confirmed EPHX2 as an independent predictor of OS, with a hazard ratio (HR) of 3.483 and a 95% confidence interval of 1.804-6.724 (p < 0.001). Our study demonstrates for the first time that nuclear overexpression of EPHX2 is a predictor of poor prognosis in BC patients. The DP approach was instrumental in identifying this significant association. Our study provides valuable insights into the potential clinical utility of EPHX2 as a prognostic biomarker and therapeutic target in BC.

Levels of Plasma Endothelin-1, Circulating Endothelial Cells, Endothelial Progenitor Cells, and Cytokines after Cardiopulmonary Bypass in Children with Congenital Heart Disease: Role of Endothelin-1 Regulation.

Congenital heart disease (CHD) can be complicated by pulmonary arterial hypertension (PAH). Cardiopulmonary bypass (CPB) for corrective surgery may cause endothelial dysfunction, involving endothelin-1 (ET-1), circulating endothelial cells (CECs), and endothelial progenitor cells (EPCs). These markers can gauge disease severity, but their levels in children's peripheral blood still lack consensus for prognostic value. The aim of our study was to investigate changes in ET-1, cytokines, and the absolute numbers (Ɲ) of CECs and EPCs in children 24 h before and 48 h after CPB surgery to identify high-risk patients of complications. A cohort of 56 children was included: 41 cases with CHD-PAH (22 with high pulmonary flow and 19 with low pulmonary flow) and 15 control cases. We observed that Ɲ-CECs increased in both CHD groups and that Ɲ-EPCs decreased in the immediate post-surgical period, and there was a strong negative correlation between ET-1 and CEC before surgery, along with significant changes in ET-1, IL8, IL6, and CEC levels. Our findings support the understanding of endothelial cell precursors' role in endogenous repair and contribute to knowledge about endothelial dysfunction in CHD.

Confirmation of the presence of Rickettsia felis infecting Ornithodoros puertoricensis in Mexico.

Soft ticks are neglected competent vectors of a wide range of pathogenic microorganisms, among which bacteria of the genera Rickettsia and Borrelia stand out. In Mexico, previous studies have shown the presence of a member of the Ornithodoros talaje complex in the Virginia opossum (Didelphis virginiana Didelphimorphia: Didelphidae Kerr) from southeastern Mexico. However, its specific identification has not been achieved. Two D. virginiana were treated in a private clinic during the period of April-May 2022. Tick larvae were manually removed, DNA extraction was performed, and some genes from various bacterial and parasitic pathogens were amplified and sequenced. A total of 96 larvae were recovered, which were morphologically identified as Ornithodoros puertoricensis (Ixodida: Argasidae Fox); the 16 S sequences showed a similarity of 96.79%-99.51% with sequences of O. puertoricensis from Panama and Colombia. The presence of Rickettsia felis (Rickettsiales: Rickettsiaceae Bouyer et al.) was detected in 15 specimens from one host. The soft tick O. puertoricensis is recorded for the first time as an ectoparasite of the Virginia opossum in America and represents the second report for this soft tick in Mexico since 1963. This represents the most northern record of this tick species in its geographic distribution and brings a new soft tick-Rickettsia association.

Chemometric Evaluation of RI-Induced Phytochemicals in Phaseolus vulgaris Seeds Indicate an Improvement on Liver Enzymes in Obese Rats.

Liver enzymes alterations (activity or quantity increase) have been recognized as biomarkers of obesity-related abnormal liver function. The intake of healthy foods can improve the activity of enzymes like aspartate and alanine aminotransferases (AST, ALT), γ-glutaminyl transferase (GGT), and alkaline phosphatase (ALP). Beans have a high concentration of several phytochemicals; however, Restriction Irrigation (RI) during plant development amends their synthesis. Using chemometric tools, we evaluated the capacity of RI-induced phytochemicals to ameliorate the high activity of liver enzymes in obese rats. The rats were induced with a high-fat diet for 4 months, subsequently fed with 20% cooked beans from well-watered plants (100/100), or from plants subjected to RI at the vegetative or reproduction stage (50/100, 100/50), or during the whole cycle (50/50) for 3 months. A partial least square discriminant analysis indicated that mostly flavonols have a significant association with serum AST and ALT activity, while isoflavones lowered GGT and ALP. For AST and ALT activity in the liver, saponins remained significant for hepatocellular protection and flavonoids remained significant as hepatobiliary protectants by lowering GGT and ALP. A principal component analysis demonstrated that several flavonoids differentiated 100/50 treatment from the rest, while some saponins were correlated to 50/100 and 50/50 treatments. The intake of beans cultivated under RI improves obesity-impaired liver alterations.

Proliferation, Migration and Invasion of Breast Cancer Cell Lines Are Inhibited by 1,5-Disubstituted Tetrazol-1,2,3-triazole Hybrids through Interaction with p53.

The anticarcinogenic potential of a series of 1,5-disubstituted tetrazole-1,2,3-triazole hybrids (T-THs) was evaluated in the breast cancer (BC)-derived cell lines MCF-7 (ER+, PR+, and HER2-), CAMA-1 (ER+, PR+/-, and HER2-), SKBR-3 (ER+, PR+, and HER2+), and HCC1954 (ER+, PR+, and HER2+). The T-THs 7f, 7l, and 7g inhibited the proliferation of MCF-7 and CAMA-1, HCC1954, and SKBR-3 cells, respectively. The compounds with stronger effect in terms of migration and invasion inhibition were 7o, 7b, 7n, and 7k for the CAMA-1, MCF-7, HCC1954, and SKBR-3 cells respectively. Interestingly, these T-THs were the compounds with a fluorine present in their structures. To discover a possible target protein, a molecular docking analysis was performed for p53, p38, p58, and JNK1. The T-THs presented a higher affinity for p53, followed by JNK1, p58, and lastly p38. The best-predicted affinity for p53 showed interactions between the T-THs and both the DNA fragment and the protein. These results provide an opportunity for these compounds to be studied as potential drug candidates for breast cancer treatment.

Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1.

Post-translational modifications directly control protein activity and, thus, they represent an important means to regulate the responses of cells to different stimuli. Protein SUMOylation has recently been recognised as one such modification, and it has been associated with various diseases, including different types of cancer. However, the precise way that changes in SUMOylation influence the tumorigenic properties of cells remains to be fully clarified. Here, we show that blocking the SUMO pathway by depleting SUMO1 and UBC9, or by exposure to ginkgolic acid C15:1 or 2-D08 (two different SUMOylation inhibitors), induces cell death, also inhibiting the invasiveness of tumour cells. Indeed, diminishing the formation of SUMO1 complexes induces autophagy-mediated cancer cell death through increasing the expression of Tribbles pseudokinase 3 (TRIB3). Moreover, we found that blocking the SUMO pathway inhibits tumour cell invasion by decreasing RAC1 SUMOylation. These findings shed new light on the mechanisms by which SUMO1 modifications regulate the survival, and the migratory and invasive capacity of tumour cells, potentially establishing the bases to develop novel anti-cancer treatments based on the inhibition of SUMOylation.

UVB Inhibits Proliferation, Cell Cycle and Induces Apoptosis via p53, E2F1 and Microtubules System in Cervical Cancer Cell Lines.

Ultraviolet (UV) exposure has been linked to skin damage and carcinogenesis, but recently UVB has been proposed as a therapeutic approach for cancer. Herein, we investigated the cellular and molecular effects of UVB in immortal and tumorigenic HPV positive and negative cells. Cells were irradiated with 220.5 to 1102.5 J/m2 of UVB and cell proliferation was evaluated by crystal violet, while cell cycle arrest and apoptosis analysis were performed through flow cytometry. UVB effect on cells was recorded at 661.5 J/m2 and it was exacerbated at 1102.5 J/m2. All cell lines were affected by proliferation inhibition, cell cycle ablation and apoptosis induction, with different degrees depending on tumorigenesis level or HPV type. Analysis of the well-known UV-responsive p53, E2F1 and microtubules system proteins was performed in SiHa cells in response to UVB through Western-blotting assays. E2F1 and the Microtubule-associated protein 2 (MAP2) expression decrease correlated with cellular processes alteration while p53 and Microtubule-associated Protein 1S (MAP1S) expression switch was observed since 882 J/m2, suggesting they were required under more severe cellular damage. However, expression transition of α-Tubulin3C and ß-Tubulin was abruptly noticed until 1102.5 J/m2 and particularly, γ-Tubulin protein expression remained without alteration. This study provides insights into the effect of UVB in cervical cancer cell lines.

Bell Peppers (Capsicum annum L.) Losses and Wastes: Source for Food and Pharmaceutical Applications.

Currently, the high added-value compounds contained in plant by-products and wastes offer a wide spectrum of opportunities for their reuse and valorization, contributing to the circular economy. The bell pepper (Capsicum annum L.) is an exotic vegetable with high nutritional value that, after processing, leaves wastes (peel, seeds, and leaves) that represent desirable raw material for obtaining phytochemical compounds. This review summarizes and discusses the relevant information on the phytochemical profile of bell peppers and their related biological properties as an alternative to revalorize losses and wastes from bell peppers for their application in the food and pharmaceutical industries. Bell pepper fruits, seeds, and leaves contain bioactive compounds (phenols, flavonoids, carotenoids, tocopherol, and pectic polysaccharides) that exhibit antioxidant, antibacterial, antifungal, immunosuppressive and immunostimulant properties, and antidiabetic, antitumoral and neuroprotective activities, and have a potential use as functional food additives. In this context, the revalorization of food waste is positioned as a technological and innovative research area with beneficial effects for the population, the economy, and the environment. Further studies are required to guarantee the safety use of these compounds and to understand their mechanisms of action.

A One-Pot Six-Component Reaction for the Synthesis of 1,5-Disubstituted Tetrazol-1,2,3-Triazole Hybrids and Their Cytotoxic Activity against the MCF-7 Cell Line.

A high-order multicomponent reaction involving a six-component reaction to obtain the novel linked 1,5-disubstituted tetrazole-1,2,3-triazole hybrids in low to moderate yield is described. This one-pot reaction is carried out under a cascade process consisting of three sequential reactions: Ugi-azide, bimolecular nucleophilic substitution (SN2), and copper-catalyzed alkyne-azide reaction (CuAAC), with high atom and step-economy due the formation of six new bonds (one C-C, four C-N, and one N-N). Thus, the protocol developed offers operational simplicity, mild reaction conditions, and structural diversity. Finally, to evaluate the antitumoral potential of the synthetized molecules, a proliferation study was performed in the breast cancer (BC) derived cell line MCF-7. The hybrid compounds showed several degrees of cell proliferation inhibition with a remarkable effect in those compounds with cyclohexane and halogens in their structures. These compounds represent potential drug candidates for breast cancer treatment. However, additionally assays are needed to elucidate their complete effect over the cellular hallmarks of cancer.

Racial/Ethnic Residential Segregation and the First Wave of SARS-CoV-2 Infection Rates: A Spatial Analysis of Four U.S. Cities.

Previous research has linked racial/ethnic residential segregation to a number of poor health conditions, including infectious disease. Here, we examine how racial/ethnic residential segregation is related to the novel coronavirus, SARS-CoV-2. We examine infection rates by zip code level segregation in four major cities across the U.S.: New York City, Chicago, Houston, and San Diego. We also include a number of area-level Census variables in order to analyze how other factors may help account for the infection rate. We find that both Black and Latino residential clustering are significantly and positively related to a higher SARS-CoV-2 infection rate across all four cities, and that this effect is strong even when accounting for a number of other social conditions and factors that are salient to the transmission of infectious disease. As a result, we argue that neighborhood-level racial/ethnic patterning may serve as an important structural mechanism for disparities in SARS-CoV-2 infection.

Mast Cells in the Tumor Microenvironment.

Mast cells are tissue-resident, innate immune cells that play a key role in the inflammatory response and tissue homeostasis. Mast cells accumulate in the tumor stroma of different human cancer types, and increased mast cell density has been associated to either good or poor prognosis, depending on the tumor type and stage. Mast cells play a multifaceted role in the tumor microenvironment by modulating various events of tumor biology, such as cell proliferation and survival, angiogenesis, invasiveness, and metastasis. Moreover, tumor-associated mast cells have the potential to shape the tumor microenvironment by establishing crosstalk with other tumor-infiltrating cells. This chapter reviews the current understanding of the role of mast cells in the tumor microenvironment. These cells have received much less attention than other tumor-associated immune cells but are now recognized as critical components of the tumor microenvironment and could hold promise as a potential target to improve cancer immunotherapy.

An In Vitro Model of Mast Cell Recruitment and Activation by Breast Cancer Cells Supports Anti-Tumoral Responses.

Breast cancer (BrC) affects millions of women yearly. Mast cells (MCs) are common components of breast tumors with documented agonistic and antagonistic roles in tumor progression. Understanding the participation of MCs in BrC may lead to new therapies to control tumor growth. In this study, we looked into mechanistic models of MC responses triggered by BrC cells (BrCC), assessing both early degranulation and late transcriptional activities. We used aggressive and non-aggressive BrCC to model the progressive staging of the disease over HMC1 and LAD-2 human MC lines. We found that both MC lines were chemoattracted by all BrCC, but their activation was preferentially induced by aggressive lines, finding differences in their active transcriptional programs, both at basal level and after stimulation. Among those genes with altered expression were down-regulated SPP1, PDCD1, IL17A and TGFB1 and up-regulated KITLG and IFNG. A low expression of SPP1 and a high expression of KITLG and IFNG were associated with increased overall survival of BrC patients from public databases. The set of altered genes is more often associated with tumor stromas enriched with anti-tumoral signals, suggesting that MCs may participate in tumor control.

Small-Molecule Morphogenesis Modulators Enhance the Ability of 14-Helical ß-Peptides To Prevent Candida albicans Biofilm Formation.

Candida albicans is an opportunistic fungal pathogen responsible for mucosal candidiasis and systemic candidemia in humans. Often, these infections are associated with the formation of drug-resistant biofilms on the surfaces of tissues or medical devices. Increased incidence of C. albicans resistance to current antifungals has heightened the need for new strategies to prevent or eliminate biofilm-related fungal infections. In prior studies, we designed 14-helical ß-peptides to mimic the structural properties of natural antimicrobial α-peptides (AMPs) in an effort to develop active and selective antifungal compounds. These amphiphilic, cationic, helical ß-peptides exhibited antifungal activity against planktonic C. albicans cells and inhibited biofilm formation in vitro and in vivo Recent studies have suggested the use of antivirulence agents in combination with antifungals. In this study, we investigated the use of compounds that target C. albicans polymorphism, such as 1-dodecanol, isoamyl alcohol, and farnesol, to attempt to improve ß-peptide efficacy for preventing C. albicans biofilms. Isoamyl alcohol, which prevents hyphal formation, reduced the minimum biofilm prevention concentrations (MBPCs) of ß-peptides by up to 128-fold. Combinations of isoamyl alcohol and antifungal ß-peptides resulted in less than 10% hemolysis at the antifungal MBPCs. Overall, our results suggest potential benefits of combination therapies comprised of morphogenesis modulators and antifungal AMP peptidomimetics for preventing C. albicans biofilm formation.

Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study.

BACKGROUND: Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL. METHODS: A multicenter cohort study was conducted. ALL children younger than 15 years old were included and followed-up during the first 24 months after diagnosis. Overweight and obesity were classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Early mortality and early relapses were the main outcomes. RESULTS: A total of 1070 children were analyzed. Overweight/obesity at diagnosis were predictors of early mortality (WHO: HR = 1.4, 95%CI:1.0-2.0; CDC: HR = 1.6, 95%CI:1.1-2.3). However, no associations between overweight (WHO: HR = 1.5, 95%CI:0.9-2.5; CDC: HR = 1.0; 95% CI:0.6-1.6) and obesity (WHO: HR = 1.5, 95%CI:0.7-3.2; CDC: HR = 1.4; 95%CI:0.9-2.3) with early relapse were observed. CONCLUSIONS: Overweight and obese patients embody a subgroup with high risk of dying during leukemia treatment.

Hepatoprotective, Antihyperlipidemic and Radical Scavenging Activity of Hawthorn (Crataegus oxyacantha) and Rosemary (Rosmarinus officinalis) on Alcoholic Liver Disease.

Alcohol catabolism produces oxidative stress, causing cell death and inflammation in liver tissue principally. Hawthorn (Crataegus oxyacantha) and Rosemary (Rosmarinus officinalis) are medicinal plants that have shown a potent antioxidant activity related with anti-inflammatory properties. The objective of this study was the evaluation of Hawthorn and Rosemary methanol extracts as preventive treatment in alcoholic liver disease (ALD). ALD rat model was used to measure serum hepatic enzyme levels (AST, ALT, γ-GT and ACP), total bilirubin, liver glycogen, lipid peroxidation, total antioxidant capacity (TAC) and serum lipid profile (total cholesterol, triglycerides, LDL and HDL) as well as histopathological analysis in hepatic tissues was recorder. Phytotreatments showed preventive effect, decreasing AST, γ-GT, lipid peroxidation and bilirubin indictors while TAC and liver glycogen stores increase. Interestingly, Rosemary diminished the levels of ALT and ACP. Remarkable both treatments show liver tissue damage reduction. Hawthorn proved antihyperlipidemic effect, eviting increase in all lipid indicators, while Rosemary showed antihyperlipidemic effect only in LDL levels without affecting HDL levels. The results indicate that Hawthorn and Rosemary treatments have different mechanisms of action; however they show hepatoprotective effect against ALD in rat model. Hawthorn and Rosemary could be used to prevent or help in the treatment of ALD.

5p and 3p Strands of miR-34 Family Members Have Differential Effects in Cell Proliferation, Migration, and Invasion in Cervical Cancer Cells.

The micro RNA (miR)-34 family is composed of 5p and 3p strands of miR-34a, miR-34b, and miR-34c. The 5p strand's expression and function is studied in cervical cancer. The 3p strand's function and regulation remain to be elucidated. To study the function of the passenger strands of miR-34 family members, we overexpressed 5p and 3p strands using a synthetic miRNA in cervical cell lines. Cell proliferation was evaluated using crystal violet. Migration and invasion were tested using transwell assays, Western blot, and zymography. Possible specific targets and cell signaling were investigated for each strand. We found that miR-34a-5p inhibited proliferation, migration, and cell invasion accompanied by matrix metalloproteinase 9 (MMP9) activity and microtubule-associated protein 2 (MAP2) protein reduction. We also found that miR-34b-5p and miR-34c-5p inhibit proliferation and migration, but not invasion. In contrast, miR-34c-5p inhibits MMP9 activity and MAP2 protein, while miR-34b-5p has no effect on these genes. Furthermore, miR-34a-3p and miR-34b-3p inhibit proliferation and migration, but not invasion, despite the later reducing MMP2 activity, while miR-34c-3p inhibit proliferation, migration, and cell invasion accompanied by MMP9 activity and MAP2 protein inhibition. The difference in cellular processes, MMP2 and MMP9 activity, and MAP2 protein inhibition by miR-34 family members suggests the participation of other regulated genes. This study provides insights into the roles of passenger strands (strand*) of the miR-34 family in cervical cancer.

Identification and Characterization of Novel Fusion Genes with Potential Clinical Applications in Mexican Children with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia is the most common type of childhood cancer worldwide. Mexico City has one of the highest incidences and mortality rates of this cancer. It has previously been recognized that chromosomal translocations are important in cancer etiology. Specific fusion genes have been considered as important treatment targets in childhood acute lymphoblastic leukemia (ALL). The present research aimed at the identification and characterization of novel fusion genes with potential clinical implications in Mexican children with acute lymphoblastic leukemia. The RNA-sequencing approach was used. Four fusion genes not previously reported were identified: CREBBP-SRGAP2B, DNAH14-IKZF1, ETV6-SNUPN, ETV6-NUFIP1. Although a fusion gene is not sufficient to cause leukemia, it could be involved in the pathogenesis of the disease. Notably, these new translocations were found in genes encoding for hematopoietic transcription factors which are known to play an important role in leukemogenesis and disease prognosis such as IKZF1, CREBBP, and ETV6. In addition, they may have an impact on the prognosis of Mexican pediatric patients with ALL, with the potential to be included in the current risk stratification schemes or used as therapeutic targets.