In this issue of the Biomedical Journal, we take a close look at the microbial metropolis of the gut and examine its impact on human health. We also highlight an interesting animal study showing that short-term treatment with antioxidants can protect tissues against the genotoxic effects of ionizing radiation. Such reports continue to fuel the hotly debated topic of the benefits of antioxidants. This issue also features several clinical studies examining the efficacy of current treatment regimens for primary breast lymphoma, Helicobacter pylori, and multidrug-resistant Acinetobacter baumannii.

The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a "love-hate relationship." Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases.

Recent studies have revealed that the gut microbiota regulates many physiological functions, ranging from energy regulation and cognitive processes to toxin neutralization and immunity against pathogens. Accordingly, alterations in the composition of the gut microbiota have been shown to contribute to the development of various chronic diseases. The main objectives of this review are to present recent breakthroughs in the study of the gut microbiota and show that intestinal bacteria play a critical role in the development of different disease conditions, including obesity, fatty liver disease, and lung infection. We also highlight the potential application of prebiotics and probiotics in maintaining optimal health and treating chronic inflammatory and immunity-related diseases.

Activation-induced Cytidine Deaminase (AID) is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

Adenosine 5′ triphosphate (ATP), discovered in 1929 by Karl Lohmannest, is described as an essential energy source for cells. In the biochemistry of all living organisms, ATP hydrolysis provides the energy required for the chemical reactions of metabolism. It is the precursor of a number of essential enzyme cofactors, such as nicotinamide adenine dinucleotide (NAD ⁺ ) and coenzyme A [NAD ⁺ , flavin adenine dinucleotide (FAD), and is ATP coenzyme A are all formed from ATP] and is the source of the phosphoryl group in most kinase-mediated phosphorylation reactions. Another essential, but less known function is that ATP plays a very important role as an extracellular signaling molecule, allowing cells and tissues to communicate. ATP is converted into cAMP, a major second messenger involved in many cellular processes, by adenylyl cyclase, a membrane-associated enzyme. In this review, we describe the role of ATP as a beneficial extracellular molecule released by healthy red blood cells (RBCs) in response to hypoxia to mediate a vasodilator signal, by oxidatively stressed RBCs, and by Plasmodium falciparum-infected RBCs (iRBCs), and its similarity with released ATP that by the combined action of the ectonucleotidases CD39 and CD73 is converted to adenosine that mediates sickling in sickle cell disease (SCD).

Background: Lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) of type 2 diabetes patients produce more interleukin (IL)-12 under glucose treatment. The aim of this study was to determine whether increased IL-12 response in hyperglycemic LPS-stimulated PBMCs is due to increased gene expression or osmolarity. Methods: LPS-stimulated PBMCs of 13 type 2 diabetes patients and 8 healthy controls were used for culture in the presence or absence of glucose or mannitol for 24 h. The IL-12 gene expressions of PBMCs and IL-12 protein levels in supernatants were evaluated. Results: After 24 h, the stimulated PBMCs of diabetes patients expressed more IL-12 mRNA and produced more IL-12 protein following glucose treatment than those without glucose treatment and with mannitol treatment. Stimulated PBMCs of controls did not express more IL-12 mRNA and produce more IL-12 protein following glucose treatment than those without glucose treatment and with mannitol treatment. Conclusions: Glucose increases the IL-12 production in stimulated PBMCs of diabetes patients through increased IL-12 gene expression.

Background: Prostate cancer is the second leading malignancy worldwide and the second prominent cause of cancer-related deaths among men. Therefore, there is a serious necessity for finding advanced alternative therapeutic measures against this lethal malignancy. In this article, we report the cytotoxicity and the mechanism of cell death of the methanolic extract prepared from Echinophora platyloba DC plant against human prostate adenocarcinoma PC 3 cell line and Human Umbilical Vein Endothelial Cells HUVEC cell line. Methods: Cytotoxicity and viability of the methanolic extract were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dye exclusion assay. Cell death enzyme-linked immunosorbent assay (ELISA) was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and DNA fragmentation gel electrophoresis. Results: E. platyloba could decrease cell viability in malignant cells in a dose- and time-dependent manner. The IC50 values against PC 3 were determined as 236.136 ± 12.4, 143.400 ± 7.2, and 69.383 ± 1.29 μg/ml after 24, 36, and 48 h, respectively, but there was no significant activity in HUVEC normal cell (IC50 > 800 μg/ml). Morphological characterizations and DNA laddering assay showed that the methanolic extract treated cells displayed marked apoptotic characteristics such as nuclear fragmentation, appearance of apoptotic bodies, and DNA laddering fragment. Increase in an early apoptotic population was observed in a dose-dependent manner. PC 3 cell death elicited by the extract was found to be apoptotic in nature based a clear indication of TUNEL assay and gel electrophoresis DNA fragmentation, which is a hallmark of apoptosis. Conclusions: In summary, the E. platyloba extract attenuated the human prostate adenocarcinoma cell proliferation in vitro possibly by inducing apoptosis. E. platyloba is likely to be valuable for the treatment of human prostate adenocarcinoma.

Background: Ionizing radiation induces a variety of genetic damages through the formation free radicals such as reactive oxygen species (ROS). Appropriate antioxidant intervention may inhibit or reduce free radical toxicity and thus offer protection against radiation. Rutin (RUT) and quercetin (QRT) are flavonoids known to be potent dietary antioxidants. Methods: The present study tested the antigenotoxic effect of RUT and QRT in vivo against radiation- induced chromosomal damage. Swiss albino mice were administered orally with RUT and QRT (10 and 20 mg/kg b.wt.) once daily for five consecutive days. One hour after the last administration of RUT and QRT on the fifth day, the animals were whole body exposed to 3 Gy gamma radiation. The anti-genotoxic potential was assessed in terms of chromosomal aberrations, micronucleus test, and alkaline comet assay. Results: Significant decline in dicentric formation was observed in RUT and QRT treated group. Further, the antigenotoxic potential of RUT and QRT caused a significant (p < 0.001) reduction in micronucleated polychromatic, normochromatic erythrocytes; increased PCE/NCE ratio was observed in the RUT and QRT treated group. Administration of RUT and QRT before irradiation resulted in a significant (p < 0.01) decrease in the DNA damage at the post-irradiation time when compared with irradiation alone group. Conclusions: Present findings demonstrate the potential of RUT and QRT in mitigating radiation-induced mortality and cytogenetic damage, which may be attributed to scavenging of radiation-induced free radicals.

Background: The increased prevalence of multidrug-resistant Acinetobacter baumannii (MDRAB) poses a worldwide treatment challenge. Although aerosolized colistin therapy for MDRAB pneumonia has attracted increasing interest, factors influencing successful eradication remain unclear. Methods: This retrospective study evaluated 135 consecutively admitted adult patients showing positive respiratory secretion cultures for MDRAB who underwent aerosolized colistin therapy between January 2007 and November 2011. Possible factors related to pneumonia and MDRAB eradication were collected for analysis. Results: Patients with successful MDRAB eradication on Day 14 had a shorter interval between the day the positive MDRAB sputum cultures were yielded and the day colistin inhalation treatment began (4.0 ± 2.5 vs. 7.3 ± 6.5; p = 0.002). Patients with a worsening chest X-ray on Day 7 of the colistin inhalation had a lower chance of 14-day MDRAB eradication [1/44 (2.3%) vs. 8/37 (21.6%); p = 0.006]. Patients with diabetes mellitus also had a lower chance of early MDRAB eradication [13/44 (29.5%) vs. 20/37 (54.1%); p = 0.025]. Conclusions: Early intervention using aerosolized colistin in patients with MDRAB pneumonia or colonization can achieve better eradication.

Background: Breast is an uncommon location of lymphoma involvement. The most common type of primary breast lymphoma (PBL) is diffuse large B-cell lymphoma (DLBCL). Rituximab is the widely used monoclonal antibody against CD20+ B-cell lymphoma, especially DLBCL. We aimed to analyze the clinical features, prognostic factors, and treatment outcome with or without rituximab in primary breast DLBCL. Methods: We retrospectively analyzed patients diagnosed with PBL from October 1987 to March 2012 in our hospital, excluding metastasis by whole-body computed tomography and bone marrow study. Results: Twenty-three patients were diagnosed with PBL. All were females. Eighteen patients were stage IE and five were stage IIE according to the Ann Arbor staging system. Two patients had lymphoma other than DLBCL. The median age of primary breast DLBCL patients was 48 years (range 27-79). Two were excluded from the analysis due to refusal or ineligibility for chemotherapy. No significant prognostic factor was found. Patients receiving chemotherapy with (RC) or without (C) rituximab were not significantly different in the 5-year overall survival (RC: 57.1%; C: 58.3%; p = 0.457) or progression-free survival (RC: 57.1%; C: 50.0%; p = 0.456). A high incidence of relapse in the central nervous system (CNS) (17.6%) was observed. Conclusions: In accordance with prior literature reports, our Taiwanese cohort of primary breast DLBCL seemed younger than those reported in Japan, Korea, and Western societies. Relapse in the CNS was not uncommon. The benefit of rituximab in addition to chemotherapy was not statistically significant. Treatment modality remained to be defined by further large-scale studies.

Background: Quinolone-containing triple therapy is recommended as an option for non-bismuth containing second-line Helicobacter pylori eradication. Current available Taiwanese reports in the literature used 7-day quinolone-containing triple therapy. As a result, some physicians still prescribe 7-day regimens in real-world practice in Taiwan. This study aimed to further assess the appropriateness of 7-day levofloxacin-containing triple therapy as second-line therapy. Methods: We enrolled 61 patients who failed H. pylori eradication using the standard triple therapy for 7 days and were prescribed levofloxacin-containing second-line triple therapy (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily). Routine follow-up with either endoscopy or urea breath test was done 8 weeks later to assess treatment response. Results: The eradication rates were 78.7% in the intention-to-treat analysis and 81% in the per-protocol analysis. The incidence of adverse events was 6.6%. Drug compliance was 95.1%. Antibiotic resistance showed the following results: Amoxicillin (0%), levofloxacin (23.5%), clarythromycin (35.3%), metronidazole (17.6%), and tetracycline (0%). Conclusion: The 7-day levofloxacin-containing triple therapy provides an unacceptable per-protocol report card as the second-line treatment for anti-H. pylori eradication in Taiwan and should be modified by either extending the duration to 10-14 days or seeking other regimens.

Background: Apart from the crucial role of micronutrients like copper, iron, and zinc in the functions of body enzymes, it seems that changes in the serum levels of these biomarkers may play a role in the pathogenesis of oral cancer. The aim of this study was to measure the serum levels of ferritin, copper, and zinc in patients with oral malignancies. Methods: Sixty consecutive patients with oral cancer, together with 66 age- and sex-matched controls were enrolled in this cross-sectional study. The serum levels of ferritin, copper, and zinc were measured in both patients and healthy individuals. Data were statistically analyzed by Student's t-test and Mann-Whitney U test. Results: In patients with oral cancer, the serum levels of ferritin, copper, and zinc were 267.41 ± 249.45, 209.85 ± 160.28, and 113.51 ± 52.30 mg/dl, respectively. In the control group, the serum levels of ferritin, copper, and zinc were reported to be 106.13 ± 72.96, 114.20 ± 38.69, and 64.57 ± 31.54 mg/dl, respectively. The mean serum values of ferritin, copper, and zinc in cancerous patients were significantly higher than in controls (p < 0.001). Conclusions: The serum levels of ferritin, copper, and zinc in oral cancer patients were significantly higher than in control group subjects.

The process of modernization has brought about changes in lifestyle of people leading to improvement in standard of living but it is associated with certain unwanted life styles like decreased physical activity and increased sedentary work. Thus, improvement in motorized transport availability of house hold gadgets like washing machine, vaccum cleaners, dish washers all tend to reduce activity level. Obese and overweight individuals are less active than their lean counterparts. Cross sectional data often reveals that there is an inverse relationship between BMI and physical activity both among adults and children.