Polyphenolic Compounds: Orchestrating Intestinal Microbiota Harmony during Aging.

In the aging process, physiological decline occurs, posing a substantial threat to the physical and mental well-being of the elderly and contributing to the onset of age-related diseases. While traditional perspectives considered the maintenance of life as influenced by a myriad of factors, including environmental, genetic, epigenetic, and lifestyle elements such as exercise and diet, the pivotal role of symbiotic microorganisms had been understated. Presently, it is acknowledged that the intestinal microbiota plays a profound role in overall health by signaling to both the central and peripheral nervous systems, as well as other distant organs. Disruption in this bidirectional communication between bacteria and the host results in dysbiosis, fostering the development of various diseases, including neurological disorders, cardiovascular diseases, and cancer. This review aims to delve into the intricate biological mechanisms underpinning dysbiosis associated with aging and the clinical ramifications of such dysregulation. Furthermore, we aspire to explore bioactive compounds endowed with functional properties capable of modulating and restoring balance in this aging-related dysbiotic process through epigenetics alterations.

Metabolic Insights into Caffeine's Anti-Adipogenic Effects: An Exploration through Intestinal Microbiota Modulation in Obesity.

Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via adipocyte hyperplasia being a key adipogenesis mechanism. As efforts intensify to address this global health crisis, understanding the complex interplay of contributing factors becomes critical for effective public health interventions and improved patient outcomes. In this context, gut microbiota-derived metabolites play an important role in orchestrating obesity modulation. Microbial lipopolysaccharides (LPS), secondary bile acids (BA), short-chain fatty acids (SCFAs), and trimethylamine (TMA) are the main intestinal metabolites in dyslipidemic states. Emerging evidence highlights the microbiota's substantial role in influencing host metabolism and subsequent health outcomes, presenting new avenues for therapeutic strategies, including polyphenol-based manipulations of these microbial populations. Among various agents, caffeine emerges as a potent modulator of metabolic pathways, exhibiting anti-inflammatory, antioxidant, and obesity-mitigating properties. Notably, caffeine's anti-adipogenic potential, attributed to the downregulation of key adipogenesis regulators, has been established. Recent findings further indicate that caffeine's influence on obesity may be mediated through alterations in the gut microbiota and its metabolic byproducts. Therefore, the present review summarizes the anti-adipogenic effect of caffeine in modulating obesity through the intestinal microbiota and its metabolites.

Profile of per- and polyfluoroalkyl substances, source appointment, and determinants in Argentinean postpartum women.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals with potential adverse health effects. Information concerning PFAS concentrations in relation to pregnancy is scarce in South America and non-existent in Argentina. AIM: We aimed to investigate an extended maternal PFAS profile herein serum concentrations in a regional and global view, source appointment, and determinants in Argentinean women. METHODS: A cross-sectional study with a sampling period from 2011 to 2012 included 689 women from Ushuaia and Salta in Argentina. Serum samples collected two days postpartum were analyzed by ultra-high pressure liquid chromatography coupled to electrospray negative ionisation tandem-quadrupole mass-spectrometry. Principal Component Analysis (PCA) following absolute principal component score-multiple linear regression (APCS-MLR) was used for PFAS source appointments. Determinants of PFAS were explored through a MLR approach. A review of previous studies within the same period was conducted to compare with present levels. RESULTS: Argentinean PFAS concentrations were the lowest worldwide, with PFOS (0.74 ng/mL) and PFOA (0.11 ng/mL) as the dominant substances. Detection frequencies largely aligned with the compared studies, indicating the worldwide PFAS distribution considering the restrictions. The PCA revealed region-specific loading patterns of two component groups of PFAS, a mixture of replaced and legacy substances in Ushuaia and long-chain in Salta. This might relate to a mix of non-diet and diet exposure in Ushuaia and diet in Salta. Region, age, lactation, parity, household members, migration, bottled water, and freshwater fish were among the determinants of various PFAS. CONCLUSION: This is the first study to monitor human PFAS exposure in Argentina. Maternal PFAS concentrations were the lowest observed worldwide in the same period. Exposure contributions are suggested to be affected by restrictions and substitutions. Given the limited population-based studies and the emergence of PFAS, it is essential to conduct further monitoring of PFAS in Argentina and South America.

The Effects of Green Tea Catechins in Hematological Malignancies.

Green tea catechins are bioactive polyphenol compounds which have attracted significant attention for their diverse biological activities and potential health benefits. Notably, epigallocatechin-3-gallate (EGCG) has emerged as a potent apoptosis inducer through mechanisms involving caspase activation, modulation of Bcl-2 family proteins, disruption of survival signaling pathways and by regulating the redox balance, inducing oxidative stress. Furthermore, emerging evidence suggests that green tea catechins can modulate epigenetic alterations, including DNA methylation and histone modifications. In addition to their apoptotic actions, ROS signaling effects and reversal of epigenetic alterations, green tea catechins have shown promising results in promoting the differentiation of leukemia cells. This review highlights the comprehensive actions of green tea catechins and provides valuable insights from clinical trials investigating the therapeutic potential of green tea catechins in leukemia treatment. Understanding these multifaceted mechanisms and the outcomes of clinical trials may pave the way for the development of innovative strategies and the integration of green tea catechins into clinical practice for improving leukemia patient outcomes.

Maternal Blood Levels of Toxic and Essential Elements and Birth Outcomes in Argentina: The EMASAR Study.

Pregnant women's levels of toxic and essential minerals have been linked to birth outcomes yet have not been adequately investigated in South America. In Argentina, n = 696 maternal whole blood samples from Ushuaia (n = 198) and Salta (n = 498) were collected in 2011-2012 among singleton women at 36 ± 12 h postpartum and analyzed for blood concentrations of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), copper (Cu), manganese (Mn), selenium (Se) and zinc (Zn). This study examined the associations between maternal elements levels and birth outcomes, and sociodemographic factors contributing to elements levels. Maternal age, parity, body mass index, smoking, and education were linked to concentrations of some but not all elements. In adjusted models, one ln-unit increase in Pb levels was associated with increased gestational age (0.2 weeks, 95% CI = 0.01-0.48) and decreased birth weight (-88.90 g, 95% CI = -173.69 to -4.11) and birth length (-0.46 cm, 95% CI = -0.85 to -0.08) in the Salta sample. Toxic elements concentrations were not associated with birth outcomes in Ushuaia participants. Birth outcomes are multifactorial problems, and these findings provide a foundation for understanding how the body burden of toxic and essential elements, within the socioeconomic context, may influence birth outcomes.

Polyphenolic Flavonoid Compound Quercetin Effects in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Flavonoids are ubiquitous groups of polyphenolic compounds present in most natural products and plants. These substances have been shown to have promising chemopreventive and chemotherapeutic properties with multiple target interactions and multiple pathway regulations against various human cancers. Polyphenolic flavonoid compounds can block the initiation or reverse the promotion stage of multistep carcinogenesis. Quercetin is one of the most abundant flavonoids found in fruits and vegetables and has been shown to have multiple properties capable of reducing cell growth in cancer cells. Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) therapy remains a challenge for hematologists worldwide, and the outcomes for patients with both disorders continue to be poor. This scenario indicates the increasing demand for innovative drugs and rational combinative therapies. Herein, we discuss the multitarget effects of the flavonoid quercetin, a naturally occurring flavonol, on AML and MDS.

Exosomes in the serum of Acute Myeloid Leukemia patients induce dendritic cell tolerance: Implications for immunotherapy.

Exosomes may represent an interesting antigenic pulse for new forms of anti-tumor immunotherapy. We evaluated exosomes from serum of patients with acute myeloid leukemia (AML) as an antigenic source for dendritic cells (DC) and the effects upon antitumor cytotoxicity, assessed by the percentage of specific lysis of K562 leukemic cells in co-cultures. Surprisingly, incubation of exosomes with DCs decreased lysis of K562, which may correspond to a mechanism of tumor evasion in vivo. However, when immature DCs were pulsed with exosomes purified from K562 culture supernatants, the lysis of target cells was notably enhanced, associated with a substantial increase in the expression of the maturation marker CD83. Thus, the development of vaccines using patients' exosomes would probably add no benefits to the treatment of AML; alternately, exosomes from cultured cells may represent an effective way for maturing DCs into a cytotoxic phenotype, without the immunosuppression observed with patients' exosomes.

Small Particles, Big Effects: The Interplay Between Exosomes and Dendritic Cells in Antitumor Immunity and Immunotherapy.

Dendritic cells play a fundamental role in the antitumor immunity cycle, and the loss of their antigen-presenting function is a recognized mechanism of tumor evasion. We have recently demonstrated the effect of exosomes extracted from serum of patients with acute myeloid leukemia as important inducers of dendritic cell immunotolerance, and several other works have recently demonstrated the effects of these nanoparticles on immunity to other tumor types as well. The aim of this review was to highlight the recent findings on the effects of tumor exosomes on dendritic cell functions, the mechanisms by which they can lead to tumor evasion, and their manipulation as a possible strategy in cancer treatment.

Up-regulation of SPINT2/HAI-2 by Azacytidine in bone marrow mesenchymal stromal cells affects leukemic stem cell survival and adhesion.

The role of tumour microenvironment in neoplasm initiation and malignant evolution has been increasingly recognized. However, the bone marrow mesenchymal stromal cell (BMMSC) contribution to disease progression remains poorly explored. We previously reported that the expression of serine protease inhibitor kunitz-type2 (SPINT2/HAI-2), an inhibitor of hepatocyte growth factor (HGF) activation, is significantly lower in BMMSC from myelodysplastic syndromes (MDS) patients compared to healthy donors (HD). Thus, to investigate whether this loss of expression was due to SPINT2/HAI-2 methylation, BMMSC from MDS and de novo acute myeloid leukaemia (de novo AML) patients were treated with 5-Azacitidine (Aza), a DNA methyltransferase inhibitor. In MDS- and de novo AML-BMMSC, Aza treatment resulted in a pronounced SPINT2/HAI-2 levels up-regulation. Moreover, Aza treatment of HD-BMMSC did not improve SPINT2/HAI-2 levels. To understand the role of SPINT2/HAI-2 down-regulation in BMMSC physiology, SPINT2/HAI-2 expression was inhibited by lentivirus. SPINT2 underexpression resulted in an increased production of HGF by HS-5 stromal cells and improved survival of CD34+ de novo AML cells. We also observed an increased adhesion of de novo AML hematopoietic cells to SPINT2/HAI-2 silenced cells. Interestingly, BMMSC isolated from MDS and de novo AML patients had increased expression of the integrins CD49b, CD49d, and CD49e. Thus, SPINT2/HAI-2 may contribute to functional and morphological abnormalities of the microenvironment niche and to stem/progenitor cancer cell progression. Hence, down-regulation in SPINT2/HAI-2 gene expression, due to methylation in MDS-BMMSC and de novo AML-BMMSC, provides novel insights into the pathogenic role of the leukemic bone marrow microenvironment.

The polyphenol quercetin induces cell death in leukemia by targeting epigenetic regulators of pro-apoptotic genes.

BACKGROUND: In the present study, we investigated the molecular mechanisms underlying the pro-apoptotic effects of quercetin (Qu) by evaluating the effect of Qu treatment on DNA methylation and posttranslational histone modifications of genes related to the apoptosis pathway. This study was performed in vivo in two human xenograft acute myeloid leukemia (AML) models and in vitro using HL60 and U937 cell lines. RESULTS: Qu treatment almost eliminates DNMT1 and DNMT3a expression, and this regulation was in part STAT-3 dependent. The treatment also downregulated class I HDACs. Furthermore, treatment of the cell lines with the proteasome inhibitor, MG132, together with Qu prevented degradation of class I HDACs compared to cells treated with Qu alone, indicating increased proteasome degradation of class I HDACS by Qu. Qu induced demethylation of the pro-apoptotic BCL2L11, DAPK1 genes, in a dose- and time-dependent manner. Moreover, Qu (50 µmol/L) treatment of cell lines for 48 h caused accumulation of acetylated histone 3 and histone 4, resulting in three- to ten fold increases in the promoter region of DAPK1, BCL2L11, BAX, APAF1, BNIP3, and BNIP3L. In addition, Qu treatment significantly increased the mRNA levels of all these genes, when compared to cells treated with vehicle only (control cells) (*p < 0.05). CONCLUSIONS: In summary, our results showed that enhanced apoptosis, induced by Qu, might be caused in part by its DNA demethylating activity, by HDAC inhibition, and by the enrichment of H3ac and H4ac in the promoter regions of genes involved in the apoptosis pathway, leading to their transcription activation.

Effect of Helicobacter pylori Infection on GATA-5 and TFF1 Regulation, Comparison Between Pediatric and Adult Patients.

BACKGROUND: GATA factors, which constitute a family of transcription regulatory proteins, participate in gastrointestinal development. Trefoil factor 1 (TFF1) plays a crucial role in mucosal defense and healing, and evidence suggests that GATA-5 mediated its regulation. Gastric cancer is a multiple-step process triggered by Helicobacter pylori and is characterized by accumulation of molecular and epigenetic alteration. The aim of this study was to evaluate the effect of H. pylori infection on the regulation of GATA-5 and TFF1 in vitro and in vivo. RESULTS: Infected cells exhibited upregulation of GATA-5 and TFF1 after 48 h. An increase in GATA-5 and TFF1 mRNA levels was also found in mice samples after 6 and 12 months of infection, respectively. In human samples, we found an association between H. pylori infection and GATA-5 upregulation. In fact, among H. pylori-infected patients, hypermethylation was observed in 45.5% of pediatric samples, in 62.6% of chronic gastritis samples, and in 63% of gastric cancer samples. Regarding TFF1, the expression levels were similar in pediatrics and adults patients, and were independent of H. pylori infection, and the expression of these factors was downregulated in gastric cancer samples. GATA-5 promoter methylation was associated with a decrease in TFF1 mRNA levels. CONCLUSIONS: Our results suggest that the upregulation of GATA-5 and TFF1 observed in vitro and in vivo may be correlated with a protective effect of the mucosa in response to infection. The epigenetic inactivation of GATA-5 observed in human biopsies from infected patients may suggest that this alteration is an early event occurring in association with H. pylori infection.

Variations in serum concentrations of selected organochlorines among delivering women in Argentina. The EMASAR study.

The EMASAR study is the first study to describe the body burden of OCs in Argentinian women after delivery. In total, 698 maternal serum samples from Salta (n = 498) and Ushuaia (n = 200) were collected in 2011-2012 and analyzed for a total of 7 polychlorinated biphenyls (PCBs) and 12 pesticide-related compounds. Only 11 of the compounds had detection rates above 60% in one or both places. Compared with Ushuaian women, those from Salta exhibited higher lipid-adjusted concentrations of p,p'-DDE, p,p'-DDT, ß-HCH, and PCB 118 (p ≤ 0.003), with no differences in concentrations of PCB 153 and 138. After controlling for age, parity and heritage (born in the province or migrated there from other regions of Argentina), concentrations of p,p'-DDE, p,p'-DDT, ß-HCH and all PCBs were significantly higher in Salta natives compared with Ushuaia natives or migrants (p ≤ 0.010). No variations between native and migrated Ushuaian women were observed other than for PCB 153 (6.1 versus 8.6 µg kg-1 lipid, p = 0.022). Age was generally associated positively with the body burden of nearly all OCs and parity negatively so, with p,p'-DDD, o,p'-DDT, and o,p'-DDD residues and α-HCH in Ushuaia being the exceptions. The regional differences in OC concentrations are explained by contrasting domestic sources, historical and current uses, industrial emissions, dietary patterns and lifestyle factors, as well as long-range-transport. The relatively high PCB 118/PCB 180 ratio observed for both Argentinian communities likely reflects the use of technical mixtures with congener-specific composition. In a comprehensive comparison with other countries, the Argentinian OC concentrations were mostly in the lower range. It is concluded that a latitude effect equivalent to that operative in the Arctic region seems unlikely.

Deferasirox associated with liver failure and death in a sickle cell anemia patient homozygous for the -1774delG polymorphism in the Abcc2 gene.

This manuscript describes the case of a patient with sickle cell anemia who died of fulminant hepatitis after therapy with the iron chelator Deferasirox. The patient was homozygous for the -1774delG polymorphism in the Abcc2 gene, which raises the concern about the use of hepatotoxic drugs in this specific context.

The Argentinian mother-and-child contaminant study: a cross-sectional study among delivering women in the cities of Ushuaia and Salta.

Several ongoing international multidisciplinary projects have examined linkages between environmental chemicals and health. In contrast to Arctic regions, information for the Southern Hemisphere is scarce. Because of the inherent practice of pesticide utilisation and mismanagement, food security is potentially threatened. The most vulnerable period in human life occurs during pregnancy and early childhood, thus a focus on the body burdens of PTS in pregnant or delivering women is warranted. The current study was designed to investigate health risks related to exposure to PTS and food security in two regions of Argentina (Ushuaia and Salta). Our aims were to quantify concentrations of organic and inorganic toxins in serum or whole blood of delivering women and to collect pertinent dietary and medical information. The overall study design, the basic demographic features and essential clinical chemistry findings are described in the current paper. The socioeconomic differences between the two study areas were evident. On average, the women in Ushuaia were 4 years older than those in Salta (28.8 vs. 24.7 years). Respectively, the proportion of current smokers was 4.5 vs. 9.6%; and Salta had a higher birth rate, with 15.6% being para four or more. Saltanean women reported longer breastfeeding periods. Caesarean sections were more frequent in Ushuaia, with 43% of Caesarean deliveries compared with only 6% in Salta. Employment was high in both communities. Recognised environmental pollution sources in the vicinity of participant dwellings were widespread in Salta (56.1%) compared to Ushuaia (9%). The use of pesticides for insect control in homes was most common in Salta (80%). There is an urgent need for a comprehensive assessment of exposures in areas of the Southern Hemisphere. Our data set and the planned publications of observed concentrations of inorganic and organic environmental contaminants in both mothers and their newborns will contribute to this objective.

Influence of maternal and sociodemographic characteristics on the accumulation of organohalogen compounds in Argentinian women. The EMASAR study.

The occurrence of organohalogen compounds in venous serum from post-partum mothers from two Argentinian cities, Salta and Ushuaia, has been investigated (n = 698). 4,4'-DDE was the most abundant compound in these cities, with geometric means of 33 and 67ng/g lipid weight, respectively. City of residence, age and parity were the main determinants of the accumulation of these compounds. Hexachlorobenzene (HCB) was the second most abundant pollutant in Ushuaia, 8.7ng/g lipid, and ß-hexachlorocyclohexane (ß-HCH) in Salta, 7.8ng/g lipid. Decabromodiphenyl ether was higher in Ushuaia than Salta, 8.2 and 4.1ng/g lipid, respectively. The predominance of ß-HCH, 4,4'-DDE and 4,4'-DDT in Salta was related with higher use of pesticides for agricultural applications. The observed higher concentrations of 4,4'-DDE and 4,4'-DDT in the mothers from rural+semi-urban sites than in urban areas were consistent with this agricultural origin. In addition, the most volatile organochlorine compounds included in this study, HCB and α-HCH, were mainly found in Ushuaia. The concentrations of the studied organohalogen pollutants in Argentina were lower than those found in other similar studies which is consistent with the location of these cities in the southern hemisphere. Age, mainly for 4,4'-DDE and polychlorobiphenyl (PCB) congeners 138, 153 and 180, and parity, mainly for HCB, ß-HCH, 4,4'-DDT and PCB congener 118, were the second main determinants of the concentrations of these compounds. Gestational weight gain also influenced on the maternal levels of HCB, ß-HCH, 4,4'-DDT and PCB congeners 118, 138 and 153. Higher weight accumulation during pregnancy involved dilution of these persistent pollutants. Body mass index (BMI) was a statistically significant determinant for 4,4'-DDT, α-HCH and PCB congeners 153 and 180. The observed direct correspondence between higher BMI and 4,4'-DDT concentrations was in agreement with the above reported inputs related with agricultural applications. The reverse correspondence of BMI with α-HCH and the PCB congeners indicated higher dilution at higher weight increase.

Methylation pattern of THBS1, GATA-4, and HIC1 in pediatric and adult patients infected with Helicobacter pylori.

BACKGROUND: Helicobacter pylori infection is usually acquired in childhood and persists into adulthood if untreated. The bacterium induces a chronic inflammatory response, which is associated with epigenetic alterations in oncogenes, tumor-suppressor genes, cell-cycle regulators, and cell-adhesion molecules. AIM: The aim of this study was to analyze the effect of H. pylori infection on the methylation status of Thrombospondin-1 (THBS1), Hypermethylated in cancer 1 (HIC1) and Gata binding protein-4 (GATA-4) in gastric biopsy samples from children and adults infected or uninfected with the bacterium and in samples obtained from gastric cancer patients. METHODS: The methylation pattern was analyzed with methylation-specific PCR. RESULTS: Our results showed that H. pylori infection was associated with methylation of the promoter regions of the THBS1 and GATA-4 genes in pediatric and adult samples (p < 0.01). HIC1 showed the lowest level of methylation, which was not an early event during gastric carcinogenesis. CONCLUSIONS: The results from this study indicate that methylation of THBS1 and GATA-4 occurs in the early stages of chronic gastritis and gastric cancer in association with H. pylori infection; however, in gastric cancer samples, other mechanisms cooperate with the down-regulation of these genes. Methylation of HIC1 may not be the principal mechanism implicated in its down-regulation in gastric cancer samples.

MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults.

AIM: To evaluate the association between Helicobacter pylori (H. pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability (MSI). METHODS: The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction (MSP-PCR) in gastric biopsy samples from uninfected or H. pylori-infected children (n = 50), from adults with chronic gastritis (n = 97) and from adults with gastric cancer (n = 92). MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene (ß actin). MSI analysis was performed by screening MSI markers at 4 loci (Bat-25, Bat-26, D17S250 and D2S123) with PCR; PCR products were analysed by single strand conformation polymorphism followed by silver staining. Statistical analyses were performed with either the χ(2) test with Yates continuity correction or Fisher's exact test, and statistical significance for expression analysis was assessed using an unpaired Student's t-test. RESULTS: Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children, regardless of H. pylori infection status. The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H. pylori infection (P < 0.05); this region was methylated in 66% of gastric cancer patients, and the difference in the percentage of methylated samples between these patients and those from H. pylori-infected chronic gastritis patients was statistically significant (P < 0.05). MLH1 methylation frequencies among H. pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%, respectively. We observed methylation of the MLH1 promoter (39%) and increased MSI levels (68%) in samples from gastric cancer patients in comparison to samples from H. pylori-infected adult chronic gastritis patients (P < 0.001 and P < 0.01, respectively). The frequency of promoter methylation for both genes was higher in gastric cancer samples than in H. pylori-positive chronic gastritis samples (P < 0.05). The levels of MLH1 and MGMT mRNA were significantly reduced in chronic gastritis samples that were also hypermethylated (P < 0.01). CONCLUSION: In summary, MGMT and MLH1 methylation did not occur in earlier-stage H. pylori infections and thus might depend on the duration of infection.

Effects of Helicobacter pylori infection on the expressions of Bax and Bcl-2 in patients with chronic gastritis and gastric cancer.

The aim of the present study is to evaluate the influence of Helicobacter pylori on Bax and Bcl-2 mRNA and protein levels in patients with chronic gastritis and gastric cancer. The study included 217 patients, of which 26 were uninfected; 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by PCR, and the expression values were determined by quantitative real-time PCR and immunohistochemistry. Our data showed that the up-regulationary effects of H. pylori infection on the pro-apoptotic gene, Bax, were stronger than its induction of Bcl-2; this effect may increase apoptosis in patients with chronic gastritis. In patients with gastric cancer, the up-regulation of the anti-apoptotic gene, Bcl-2, counteracted the pro-apoptotic effects of Bax, leading to a deregulation of apoptosis-associated gene expression, favoring cell proliferation. Thus, the disturbance in Bax and Bcl-2 balance, induced by H. pylori, might be important in gastric cancer development.