Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic Candida species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in Candida species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: tac1 and mrr1; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent Candida species. Notably, N. glabrata, P. kudriavzevii and C. auris demonstrate fluconazole resistance.

The linear no-threshold (LNT) model is currently used to estimate low dose radiation (LDR) induced health risks. This model lacks safety thresholds and postulates that health risks caused by ionizing radiation is directly proportional to dose. Therefore even the smallest radiation dose has the potential to cause an increase in cancer risk. Advances in LDR biology and cell molecular techniques demonstrate that the LNT model does not appropriately reflect the biology or the health effects at the low dose range. The main pitfall of the LNT model is due to the extrapolation of mutation and DNA damage studies that were conducted at high radiation doses delivered at a high dose-rate. These studies formed the basis of several outdated paradigms that are either incorrect or do not hold for LDR doses. Thus, the goal of this review is to summarize the modern cellular and molecular literature in LDR biology and provide new paradigms that better represent the biological effects in the low dose range. We demonstrate that LDR activates a variety of cellular defense mechanisms including DNA repair systems, programmed cell death (apoptosis), cell cycle arrest, senescence, adaptive memory, bystander effects, epigenetics, immune stimulation, and tumor suppression. The evidence presented in this review reveals that there are minimal health risks (cancer) with LDR exposure, and that a dose higher than some threshold value is necessary to achieve the harmful effects classically observed with high doses of radiation. Knowledge gained from this review can help the radiation protection community in making informed decisions regarding radiation policy and limits.

The field of cardiovascular fetal programming has emphasized the importance of the uterine environment on postnatal cardiovascular health. Studies have linked increased fetal glucocorticoid exposure, either from exogenous sources (such as dexamethasone (Dex) injections), or from maternal stress, to the development of adult cardiovascular pathologies. Although the mechanisms are not fully understood, alterations in gene expression driven by altered oxidative stress and epigenetic pathways are implicated in glucocorticoid-mediated cardiovascular programming. Antioxidants, such as the naturally occurring polyphenol epigallocatechin gallate (EGCG), or the superoxide dismutase (SOD) 4-hydroxy-TEMPO (TEMPOL), have shown promise in the prevention of cardiovascular dysfunction and programming. This study investigated maternal antioxidant administration with EGCG or TEMPOL and their ability to attenuate the fetal programming of hypertension via Dex injections in WKY rats. Results from this study indicate that, while Dex-programming increased blood pressure in male and female adult offspring, administration of EGCG or TEMPOL via maternal drinking water attenuated Dex-programmed increases in blood pressure, as well as changes in adrenal mRNA and protein levels of catecholamine biosynthetic enzymes phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), dopamine beta hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), in a sex-specific manner. Furthermore, programmed male offspring displayed reduced antioxidant glutathione peroxidase 1 (Gpx1) expression, increased superoxide dismutase 1 (SOD1) and catalase (CAT) expression, and increased pro-oxidant NADPH oxidase activator 1 (Noxa1) expression in the adrenal glands. In addition, prenatal Dex exposure alters expression of epigenetic regulators histone deacetylase (HDAC) 1, 5, 6, 7, 11, in male and HDAC7 in female offspring. These results suggest that glucocorticoids may mediate the fetal programming of hypertension via alteration of epigenetic machinery and oxidative stress pathways.

The hallmarks of cancer have been the focus of much research and have influenced the development of risk models for radiation-induced cancer. However, natural defenses against cancer, which constitute the hallmarks of cancer prevention, have largely been neglected in developing cancer risk models. These natural defenses are enhanced by low doses and dose rates of ionizing radiation, which has aided in the continuation of human life over many generations. Our natural defenses operate at the molecular, cellular, tissue, and whole-body levels and include epigenetically regulated (epiregulated) DNA damage repair and antioxidant production, selective p53-independent apoptosis of aberrant cells (e.g. neoplastically transformed and tumor cells), suppression of cancer-promoting inflammation, and anticancer immunity (both innate and adaptive components). This publication reviews the scientific bases for the indicated cancer-preventing natural defenses and evaluates their implication for assessing cancer risk after exposure to low radiation doses and dose rates. Based on the extensive radiobiological evidence reviewed, it is concluded that the linear-no-threshold (LNT) model (which ignores natural defenses against cancer), as it relates to cancer risk from ionizing radiation, is highly implausible. Plausible models include dose-threshold and hormetic models. More research is needed to establish when a given model (threshold, hormetic, or other) applies to a given low-dose-radiation exposure scenario.

Type 2 diabetes mellitus (T2DM) remains a global health concern. Emerging clinical trial (CT) evidence suggests that probiotic intervention may promote a healthy gut microbiome in individuals with T2DM, thereby improving management of the disease. This systematic literature review summarizes thirty-three CTs investigating the use of oral probiotics for the management of T2DM. Here, twenty-one studies (64%) demonstrated an improvement in at least one glycemic parameter, while fifteen studies (45%) showed an improvement in at least one lipid parameter. However, no article in this review was able to establish a uniform decrease in glycemic, lipid, or blood pressure profiles. The lack of consistency across the studies may be attributed to differences in probiotic composition, duration of probiotic consumption, and probiotic dose. An interesting finding of this literature review was the beneficial trend of metformin and probiotic co-administration. Here, patients with T2DM taking metformin demonstrated enhanced glycemic control via the co-administration of probiotics. Taken together, the overall positive findings reported across the studies in combination with minimal adverse effects constitute ground for further quality CTs. This review provides recommendations for future CTs that may address the shortcomings of the current studies and help to extract useful data from future investigations of the use of probiotics in T2DM management.

Radiation therapy for abdominopelvic malignancies often results in damage to the gastrointestinal tract (GIT) and permanent changes in bowel function. An overlooked component of the pathophysiology of radiation-induced bowel injury is the role of the gut microbiome. The goal of this research was to identify the impacts of acute radiation exposure on the GIT and gut microbiome. C57BL/6 mice exposed to whole-body X-rays (0.1–3 Gy) were assessed for histological and microbiome changes 48 h post-radiation exposure. Within the ileum, a dose of 3 Gy significantly decreased crypt depth as well as the number of goblet cells, but increased overall goblet cell size. Overall, radiation altered the microbial distribution within each of the main phyla in a dose- and tissue-dependent manner. Within the Firmicutes phylum, high dose irradiation resulted in significant alterations in bacteria from the class Bacilli within the small bowels, and from the class Clostridia in the large bowels. The 3 Gy radiation also significantly increased the abundance of bacterial families from the Bacteroidetes phylum in the colon and feces. Overall, we identified various alterations in microbiome composition following acute radiation exposure, which could potentially lead to novel biomarkers for tracking patient toxicities or could be used as targets for mitigation strategies against radiation damage.