ADIPOQ-rs2241766 polymorphism is associated with changes in cholesterol levels of Mexican adolescents.

BACKGROUND: The ADIPOQ gene encodes a fat-derived protein hormone with a preponderant role in the homeostasis of glucose and fatty acids. However, previous association studies between ADIPOQ genetic variants and metabolic disorders have shown controversial results. In this study, we evaluated the effect of the ADIPOQ-rs2241766 polymorphism on diverse biochemical parameters (i.e., insulin resistance, atherogenic index, overweight and obesity) in an adolescent population from Mexico. METHODS: A cross-sectional study with convenience sampling was carried out in 356 adolescents from Northern Mexico. They were classified by sex and BMI-z score. The biochemical parameters were measured from blood samples using conventional methods. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In low and normal weight groups, GG carriers had a significantly higher cholesterol level (P ≤ 0.05) than TG and TT carriers. However, there was no association between ADIPOQ-rs2241766 polymorphism and atherogenic index, overweight, or obesity. CONCLUSIONS: Our findings suggest that the cholesterol levels are under the influence of the ADIPOQ-rs2241766 polymorphism in Mexican adolescents and may explain how ADIPOQ variants increase the risk of developing metabolic disorders. Nevertheless, further studies are required to rule out the influence of other genetic and non-genetic factors.

Punicalin and ellagic acid from pomegranate peel extract facilitate apoptotic behaviour in the Hela cell line.

Polyphenols may be an effective therapy for both the prevention and treatment of cancer. Previous studies have found that these compounds may inactive Hela cells, which may even be converted into a normal cells post-treatment. The present study extracted phenolic compounds from pomegranate peel, with the polyphenols then purified using different solvents and identified by means of high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS). Once the phenolic compounds had been purified, we evaluated their cytotoxic effects on both the Hela and NIH-3T3 cell lines, on which an apoptosis assay was also carried out. Additionally, apoptosis assay was carried out on Hela and NIH-3T3. Lastly, the proteome profile was analysed via two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). We isolated and then purified punicalagin and ellagic acid (EA) from pomegranate peel, with both compounds likely to have a cytotoxic effect on Hela and NIH-3T3. However, this effect depends on both concentration and exposure time. Results obtained using a Cayman commercial assay kit suggests that punicalin and EA regulate the apoptosis on the Hela and NIH-3T3 cell lines. Finally, we observed that polyphenols compounds regulate the expression of proteins related to apoptosis. In conclusion, punicalin and EA have a cytotoxic effect on Hela and, furthermore, reactive the apoptotic pathway in this cell.

Thymidylate synthase polymorphism in Mexican patients with colon cancer treated with 5-fluorouracil.

PURPOSE: We analyzed the genotype and allele frequency of variable number tandem repeats (VNTR)-thymidylate synthase (TS) and its relationship with the disease evolution in colon cancer patients. METHODS: We selected 24 paraffin-embedded colon cancer tissue samples from Mexican patients who received a 5-fluorouracil (5-FU)-based chemotherapy regimen. Tumor tissue was digested with proteinase K and genomic DNA was isolated by the standard method with phenol-chloroform extraction. Polymerase chain reaction (PCR) was performed for TS genotyping of VNTR and the results were evaluated directly in a stained agarose gel. RESULTS: The allele frequency of 2 repeats (2R) was greater (0.66) than 3R (0.34) in metastatic colon cancer (x2=10.24; p=0.001)) however, no difference in allelic distribution between 2R (0.54) and 3R (0.46) in non metastatic patients was observed (x2=0.640; p=0.424). CONCLUSION: Our results suggest that Mexican patients with colon cancer present differences in the allelic distribution, the 2R allele being the most frequent.

Nanoparticle­based antiviral strategies to combat the influenza virus (Review).

The rapid availability of effective antiviral treatments would be beneficial during the early phases of a pandemic, as they could reduce viral loads and control serious infections until antigenic vaccines become widely available. One promising alternative therapy to combat pandemics is nanotechnology, which has the potential to inhibit a wide variety of viruses, including the influenza virus. This review summarizes the recent progress using gold, copper, silver, silicone, zinc and selenium nanoparticles, since these materials have shown remarkable antiviral capacity against influenza A virus.

Association of rs4711998 of IL-17A, rs2275913 of IL-17A and rs763780 IL-17F gene polymorphisms with non-segmental vitiligo in a Mexican population.

Vitiligo is the most common depigmenting disease characterized by achromic macules due to selective loss of melanocytes. The pathogenesis remains poorly elucidated, and multiple hypotheses exist regarding its pathogenesis. Evidence suggests that stress on melanocytes can result in activation of the immune system, and involvement of both activated cluster of differentiation (CD8+) cytotoxic and CD4+ T cells in the dysfunction, depigmentation, and apoptosis of melanocytes. Recent studies show that the interleukin 17 (IL-17) axis plays a central role in the pathogenesis of the disease. IL-17 is an important regulatory effector cytokine in this pathway. The aim of this study was to evaluate the association of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) with vitiligo in a Northeastern Mexican population. This was a case-control study and included 116 patients with vitiligo and 116 control subjects. Genotype characterization of IL-17A rs4711998 (-832A/G), IL-17A rs2275913 (-197G/A), and IL-17F rs763780 (7488A/G) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A p ≤ 0.05 was considered significant. It was observed that the combination of the genotypes GG/GA for IL-17F rs763780 (7488A/G) was associated with an increased risk for the development of vitiligo (OR 2.0943, 95% Cl 1.2375-3.5445, p = 0.0056). Regarding IL-17A rs4711998 (-832A/G) and IL-17A rs2275913 (-197G/A) genotyping, no association with vitiligo development was found. In conclusion, the SNP rs763780 in the IL-17F gene appears to be a risk factor for vitiligo development in this Mexican population and it may be useful in future studies, especially for the development of new therapies.

Molecular mechanisms of multidrug resistance in clinically relevant enteropathogenic bacteria (Review).

Multidrug resistant (MDR) enteropathogenic bacteria are a growing problem within the clinical environment due to their acquired tolerance to a wide range of antibiotics, thus causing severe illnesses and a tremendous economic impact in the healthcare sector. Due to its difficult treatment, knowledge and understanding of the molecular mechanisms that confer this resistance are needed. The aim of the present review is to describe the mechanisms of antibiotic resistance from a genomic perspective observed in bacteria, including naturally acquired resistance. The present review also discusses common pharmacological and alternative treatments used in cases of infection caused by MDR bacteria, thus covering necessary information for the development of novel antimicrobials and adjuvant molecules inhibiting bacterial proliferation.

Association between the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants with vitiligo: study on a Mexican population.

BACKGROUND: Vitiligo is characterized by an autoimmune response targeting melanocytes, thus resulting in skin depigmentation. There are several genetic components involved in the development of vitiligo, of which various gene polymorphisms are currently considered as risk factors. For example, the CTLA4 (T-lymphocyte antigen 4) +49A/G (rs231775) and CT60 (rs3087243) gene variants have been associated with a predisposition for autoimmune diseases in different populations; however, their involvement in the development of vitiligo remains controversial. OBJECTIVE: We evaluated the association between vitiligo and the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants in a Mexican population. METHODS: A total of 116 vitiligo patients and 117 control subjects from northeast Mexico were included in the study and analyzed through PCR-RFLP to determine whether there is an association between vitiligo and CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants. RESULTS: No statistical difference was observed for both gene polymorphisms between vitiligo patients and controls (p > 0.05). Otherwise, vitiligo activity, family history of vitiligo, personal history of autoimmune diseases, or sex did not show any difference (p > 0.05). CONCLUSION: As suggested by the analysis of a northeastern Mexican population, the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants do not constitute a risk factor in the development of vitiligo.

Transcriptional Profile of HCV Replicon Cells after Treatment with Acetylsalicylic Acid.

OBJECTIVE: It has been demonstrated in vitro that acetylsalicylic acid (ASA) treatment halves hepatitis C virus (HCV) expression in hepatocarcinoma cells. However, the signaling pathway that promotes this ASA-induced antiviral effect has not yet been identified. AIM: The aim of this work was to identify alterations in the transcriptional profile of Huh-7-HCV-subgenomic replicon cells with vs. without ASA treatment. This comparison sheds light onto the signaling pathways and molecular mechanisms involved in the antiviral effects of ASA. METHODS: Human hepatocellular carcinoma (Huh-7) cells that express non-structural HCV proteins (Huh-7-HCV-replicon cells) were exposed to 4 mM ASA for 0, 24, 48, and 72 hours. Total RNA was isolated, and cDNA was synthesized. Transcripts were then tagged with biotin and purified. Thereafter, they were fragmented and hybridized on HG-U133 Plus 2 Gene Expression chips. Hybridization signals were captured using a GeneChip 3000 7G Scanner and analyzed via Expression Console and dChip Software. RESULTS: When exposed to ASA, hepatocarcinoma cells with non-structural HCV proteins were found to differentially regulate genes with oxidative roles in the cell. The most upregulated genes were interleukin 8 (IL-8), cytochrome P450 (CYP450), and metallothioneins (MTs), while the most downregulated genes were ribonucleotide reductases (RRs). CONCLUSION: These results show that ASA modulates the expression of genes with antioxidant functions. This suggests that ASA induces a remodeling of the antioxidant microenvironment, which may in turn interfere with the replication of HCV.

Purshia plicata Triggers and Regulates Proteins Related to Apoptosis in HeLa Cancer Cells.

Cervical cancer represents a public health problem, develops resistance to traditional therapies and cost-of-treatment is high. These disadvantages have led to the search for alternative bioactive-compound-based therapies. Said bioactive compounds include phenolic compounds, flavonoids, and tannins. The present study aimed to evaluate the therapeutic effect of a P. plicata extract on the HeLa cell line. Viability and apoptosis assays were run on the two cell lines treated with the extract. The peptides, up- and down-expressed in both cell lines, were identified by PDQuest analysis software and high-performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). Our results show that a 500 mg/L treatment deregulated cell viability, with different apoptotic morphologies observed which are associated with the presence of bio-compounds, which up- and down-regulated the peptides. In conclusion, P. plicata regulates proteins associated with apoptosis in HeLa cancer cells.

Depressive Symptoms are Associated with low Serotonin Levels in Plasma but are not 5-HTTLPR Genotype Dependent in Older Adults.

Depressive symptoms are diagnosed by physicians using scales but their pathophysiology is unclear. Low serotonin (5-HT) levels play an important role in depression, and the 5-HT transporter (5-HTT) is an important regulator of plasma serotonin levels and reuptake. Additionally, the 5-HTT gene-linked polymorphic region (5-HTTLPR) is associated with depression. The aim was to clarify the roles of plasma serotonin levels in plasma and the 5HTTPLR polymorphism in depressive symptoms in older adults. A total of 84 older adult participants were evaluated. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale of 20 items (CESD-20). The plasma serotonin levels were determined by ELISA, and the 5-HTTLPR genotype was analyzed by PCR. Depressive symptoms were present in 39.3% (N = 33) of the participants. The median plasma serotonin level was 204.34 ng/mL (SD = 93.88). A significant correlation was found between the CESD-20 scale and plasma serotonin levels (r = -.256; p = .019). Low serotonin levels were associated with the presence of depressive symptoms (p = .001). The 5-HTTLPR analysis showed that of the 84 older adults, 35.7% had the SS genotype, 10.7% had the LL genotype, and 53.6% were heterozygous. The 5-HTTLPR polymorphism was not associated with depressive symptoms (p = .587) and plasma serotonin levels (p = 0.391). Depressive symptoms correlate with low serotonin levels in plasma, but not with the 5-HTTLPR polymorphism in older Mexican adults.

Updates and new medical treatments for vitiligo (Review).

Vitiligo is a multifactorial disease characterized by the loss of skin pigment, which results in achromic macules and patches. There are currently several medical treatments available, which aim to arrest progression and induce skin repigmentation. These treatments alone or combined have exhibited varying degrees of pigmentation, and the majority are safe and effective. All therapies for vitiligo are limited, and no known treatment can consistently produce repigmentation in all patients. Individualized treatment is appropriate according to the location, clinical presentation and the presence of disease activity. The present review summarizes the medical treatments available for vitiligo: Systemic and topic pharmacological therapies, physical and depigmentation treatments. Several treatments are still underway and have not yet been approved. However, due to the promising preliminary results, these are also mentioned in the present review.

Novel immunological and genetic factors associated with vitiligo: A review.

Vitiligo is a skin disorder characterized by depigmentation of the skin due to a lack of melanin. This condition affects men and woman of all ages and its incidence is not restricted by ethnicity or region. Vitiligo is a multifactorial disease, in which melanocytes, which serve important functions in skin pigmentation and immune processes, are impaired. There is sufficient evidence that immunological and genetic factors are primarily responsible for the destruction and dysfunction of melanocytes. Therefore, genetic DNA sequence variants that participate in skin homeostasis, pigmentation and immune response regulation, as well as altered expression patterns, may contribute to the risk of developing vitiligo. The current review presented an overview of the mechanism of pigmentation and of currently known factors involved in depigmentation, as well as the classification, epidemiology, associated comorbidities, risk factors, immunopathogenesis and several genetic and molecular changes associated with vitiligo.

Down regulation of tumour biomarkers in colon cancer cells with IRNA PFK-1 plus metformin.

PURPOSE: Metformin has been widely used for the treatment of Type 2 Diabetes Mellitus (T2DM), hyperglycemia and polycystic ovarian syndrome. Recent studies have suggested the potential of this substance as a cancer chemopreventive agent. We evaluated the antitumoral effect of iRNA-PFK-1 and the combined therapy iRNA-PFK-1 + metformin in RKO p53-positive cells. METHODS: mRNA levels of tumor suppressor genes AMPK, APC, and c-MYC, KRAS oncogenes were measured by qRT-PCR in RKO cells treated with 25 µM metformin alone or combined with iRNA-PFK-1, to evaluate the effect of both treatments. RESULTS: At 72 h after treatment with either 25 µM metformin, 150 nM iRNA-PFK-1, or the combined treatment, the transcriptional levels of these biomarkers were decreased by ~73% (p˂0.05), ~99.9%, (p˂0.01), and ~76% (p˂0.05), respectively. CONCLUSION: These in vitro results support the potential therapeutic role of metformin and PFK-1 in the treatment of colon cancer via down-modulation of the expression of several important cancer biomarkers.

Expression of melanocortin 1 receptor before and after narrowband UVB phototherapy treatment in patients with stable vitiligo: A prospective study.

Vitiligo is a disease characterized by skin depigmentation caused by the selective destruction of melanocytes. The melanocortin system participates as a regulator of melanogenesis and skin pigmentation. Narrowband UVB phototherapy (nb-UVB) is currently considered to be the gold standard and first choice treatment method for vitiligo vulgaris. The aim of the present study was to analyze the clinical and biochemical parameters of vitiligo, as well as to determine the expression of proopiomelanocortin (POMC), melanocortin 1 receptor (MC1R) and melanocortin 4 receptor (MC4R) genes in the skin of patients with stable vitiligo receiving nb-UVB phototherapy. Patient clinical and biochemical parameters, and the skin biopsies of 22 patients with stable vitiligo were analyzed. These biopsies were obtained before and after nb-UVB phototherapy. The genetic expression analysis of POMC, MC1R and MC4R genes was performed via RNA-Sequence analysis. A statistical evaluation of the clinical and biochemical parameters, the degree of response to treatment and the expression profiles of the melanocortin system genes were performed to identify their association with treatment response. A two-sided P≤0.05 value was considered to indicate a statistically significant difference. Alterations were observed in the expression profiles of MC1R following nb-UVB phototherapy (P≤0.05). In addition, elevated levels of triiodothyronine were associated with a poor response to nb-UVB phototherapy. In conclusion the current study revealed that nb-UVB phototherapy altered the expression profile of the MC1R gene.

CTLA4 +49AG (rs231775) and CT60 (rs3087243) gene variants are not associated with alopecia areata in a Mexican population from Monterrey Mexico.

BACKGROUND: Alopecia areata is an autoimmune disease that produces non-scarring hair loss around the body. Gene variants of the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, a negative regulator of T-cell response, have been associated with a predisposition to autoimmune diseases in different populations; however, the involvement of these genetic variants in the development of AA is controversial. OBJECTIVE: The present study evaluated the potential association of two CTLA4 gene variants with alopecia areata in a Mexican population. METHODS: We genotyped +49AG (rs231775) and CT60 (rs3087243) variants in 50 AA patients and 100 healthy control participants through PCR-RFLP. RESULTS: No statistical difference was observed for either of the gene variants regarding allele or genotype frequencies between AA patients and the controls when the parameters of family/personal history of autoimmune diseases or gender were considered (p>0.05). STUDY LIMITATIONS: Small sample size of patients and the data were obtained from Northeast Mexico population. CONCLUSION: The genetic variants rs231775 and rs3087243 of the CTLA4 gene are not a risk factor for the development of alopecia areata in the analyzed Mexican population.

Inhibition of miR31 and miR92a as Oncological Biomarkers in RKO Colon Cancer Cells Treated with Kaempferol-3-O-Glycoside Isolated from Black Bean.

MicroRNAs (miRNAs) are small molecules of 19-23 nucleotides of RNA that act as regulators of the expression of proteins in eukaryotic cells. Currently, the participation of miRNAs in the development of different types of cancer has been observed. To evaluate the inhibitory effect of kaempferol-3-O-glycoside on the expression of oncological biomarkers, miR31 and miR92a in a colon cancer cell line (RKO) were analyzed. Cells were cultured and treated with 1 mM kaempferol-3-O-glycoside isolated from black bean. Expression levels of miR31 and miR92a were evaluated by real-time PCR using TaqMan probes; in addition, two oncogenes (KRAS and c-MYC) and two tumor suppressors (AMP-activated protein kinase [AMPK] and adenomatous tumors of polyposis coli [APC]) were quantified to validate the biological effects; normalization of expression levels were carried out by 2-ΔΔCt. Results were analyzed by one-way ANOVA. The expression levels of miR31, miR92a, KRAS oncogene, and the c-MYC transcription factor were subexpressed upon 72 h post-treatment with kaempferol-3-O-glycoside compared with the control without treatment (P < .05); in contrast, the tumor suppressor genes AMPK (∼4.85, P = .005) and APC (∼2.71, P = .066) tumor suppressors genes were overexpressed. Our results showed the inhibitory effect of isolated black bean flavonoid kaempferol-3-O-glycoside on cancer biomarkers: miR31 and miR92a; based on our results, this flavonoid may have interesting nutritional, therapeutic, and/or prophylactic applications to combat colon cancer.

Association of the Vascular Endothelial Growth Factor Gene Polymorphism +936 C/T with Diabetic Neuropathy in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Peripheral neuropathy is one of the most common late complications of diabetes. Vascular endothelial growth factor (VEGF) gene polymorphisms have been associated with the development of peripheral neuropathy in different populations of patients with type 2 diabetes mellitus (DM2). OBJECTIVE: To analyze the prevalence of the +936 C/T VEGF gene polymorphism among patients with DM2 with and without peripheral neuropathy. STUDY DESIGN AND METHODOLOGY: 218 unrelated DM2 patients, 90 with and 128 without peripheral neuropathy were genotyped for the +936 C/T VEGF gene polymorphism using PCR amplification followed by restriction length polymorphism analysis. RESULTS: The CC homozygous VEGF+936 C/T (rs3025039) was the predominant genotype in DM2 patients with peripheral neuropathy, whereas the predominant genotype in patients without neuropathy was the heterozygous C/T. No statistical association was found between genotype distribution and the presence of neuropathy (p = 0.063). The distribution of the genotypes according to the dominant (CC vs. CT + TT) and recessive (TT vs. CT + CC) models showed that the homozygous CC and TT genotypes, respectively, are not risk factors for neuropathy. The CT genotype conferred a protective effect as seen in the over-dominant model (CT vs. CC + TT) (OR = 0.52; 95% CI = 0.300-0.90; p = 0.019). CONCLUSION: We conclude that the VEGF+936 C/T (rs3025039) gene polymorphisms are related to peripheral neuropathy in Mexican DM2 patients, with the heterozygous genotype potentially conferring a protective effect.

Uridine 5'-diphospho-glucronosyltrasferase: Its role in pharmacogenomics and human disease.

Biotransformation is an enzyme-catalyzed process in which the body converts endogenous compounds, xenobiotics and toxic substances into harmless or easily excreted metabolites. The biotransformation reactions are classified as phase I and II reactions. Uridine 5'-diphospho (UDP)-glucuronosyltransferases (UGTs) are a superfamily of phase II enzymes which have roles in the conjugation of xenobiotics or endogenous compounds, including drugs and bilirubin, with glucuronic acid to make them easier to excrete. The method the human body uses to achieve glucuronidation may be affected by a large interindividual variation due to changes in the sequences of the genes encoding these enzymes. In the last five years, the study of the genetic variants of the UGTs at a molecular level has become important due to its association with several diseases and the ability to predict adverse events due to drug metabolism. In the present review, the structure and the prominent genetic variants of the UGT1A subfamily and their metabolic and clinical implications are described.

Evaluation of skin expression profiles of patients with vitiligo treated with narrow-band UVB therapy by targeted RNA-seq.

BACKGROUND: Vitiligo is characterized by a lack of pigmentation in the skin. To date, there are no studies that analyze the changes in gene expression in the skin of vitiligo patients in response to narrow-band ultraviolet B (nb-UVB) phototherapy treatment. OBJECTIVE: Explore the usefulness of new generation RNA sequencing in the identification of gene expression changes in the skin of vitiligo patients treated with nb-UVB phototherapy. METHODS: Four skin biopsies (4mm in diameter) were collected from 45 Mexican vitiligo vulgaris patients, 2 specimens before and 2 after treatment with nb-UVB phototherapy, obtained from pigmented and non-pigmented tissue. RNA extracted from the biopsies was analyzed using the Illumina TruSeq Targeted RNA Expression protocol to study the expression of genes that participate in pathways of skin homeostasis. The 2 groups were compared using Student's t-test and the Mann-Whitney U-test. RESULTS: The expression analysis identified differences in 12 genes included in this study after comparing the samples obtained before and after treatment: 5 genes involved in skin pigmentation, 2 genes involved in apoptosis, 2 genes involved in cell survival, 2 genes involved in oxidative stress responses and 1 gene involved in signal transduction mechanisms (p<0.05). STUDY LIMITATIONS: The small size of skin biopsies limits the amount of RNA obtained, the number of genes to be analyzed and the use of conventional techniques such as RT-qPCR. CONCLUSION: We demonstrated usefulness of new generation RNA sequencing in the identification of gene expression changes, in addition to identifying new targets in the study of vitiligo.