Enviromental Risk Factors Associated with Primary Liver Cancer in Western Kenya: A Mini-review

Primary Liver Cancer (PLC) is a global health burden, which is poorly addressed in developing countries. It is ranked the third leading cause of cancer-related mortality worldwide, with high incidence rates reported in Asia and Africa. Currently, in Kenya, there is an upward trend of PLC cases reported with no confirmed causes. Furthermore, there is lack of sufficient knowledge on the prognosis mechanisms of PLC, despite some of its known risk factors being established. These additional factors, ranging from lifestyle choices to pre-existing environmental concomitants, could actually play role on the etiology of the disease yet remain unexplored. Due to this, there was a need on evaluating the impacts of exposure to environmental risk factors such as pesticides, food contaminated with aflatoxin, or harmful cyanobacteria algae blooms in regions where PLC is endemic. As a result, this mini-review, aimed at analyzing relevant epidemiological data on primary liver cancer underpinning the mechanism of action of environmental toxin as an emergent risk factor in Western Kenya. This was achieved through meta-synthesis analysis of the previous research findings, with the purpose of integrating their results to inform the present intrinsic case study. Among the many epidemiological studies associating PLC and environmental toxin as an emergent risk factor reviewed in the current study, environmental exposure to microcystin toxin was inferred to constitute a public health hazard due to the continued presence in drinking water sources. Majority of the epidemiological data are in support of the potential association between environmental microcystin toxins and Primary Liver cancer in developing countries. These findings can be used to edify the health and medical professionals at all levels of prevention, including the diagnosis and treatment of liver disease patients, also these findings can act as baseline data that is required for better and informed Lake management water quality.

A review of chemical defense in harlequin toads (Bufonidae; Atelopus)

Toads of the genus Atelopus are chemically defended by a unique combination of endogenously synthesized cardiotoxins (bufadienolides) and what are likely exogenously sequestered neurotoxins (guanidinium alkaloids). Investigation into Atelopus small-molecule chemical defenses has been primarily concerned with identifying and characterizing various forms of these toxins while largely overlooking their ecological roles and evolutionary implications. In addition to describing the extent of knowledge about Atelopus toxin structures, pharmacology, and biological sources, we review the detection, identification, and quantification methods used in studies of Atelopus toxins to date and conclude that many known toxin profiles are unlikely to be comprehensive because of methodological and sampling limitations. Patterns in existing data suggest that both environmental (toxin availability) and genetic (capacity to synthesize or sequester toxins) factors influence toxin profiles. From an ecological and evolutionary perspective, we summarize the possible selective pressures acting on Atelopus toxicity and toxin profiles, including predation, intraspecies communication, disease, and reproductive status. Ultimately, we intend to provide a basis for future ecological, evolutionary, and biochemical research on Atelopus.

An arsenic stress signaling code in yeast

Arsenic is an environmental toxin that exists mainly as pentavalent arsenate and trivalent arsenite. Both forms activate the yeast SAPK Hog1, but with different consequences. We describe a mechanism by which cells distinguish between these arsenicals through one-step metabolism to differentially regulate the bidirectional glycerol channel Fps1, an adventitious port for arsenite. Cells exposed to arsenate reduce it to thiol-reactive arsenite, which modifies a set of cysteine residues in target proteins; whereas cells exposed to arsenite metabolize it to methylarsenite, which modifies an additional set of cysteine residues. Hog1 becomes arsenylated, which prevents it from closing Fps1. However, this block is overcome in cells exposed to arsenite through methylarsenylation of Acr3, an arsenite efflux pump that we found also regulates Fps1 directly. This adaptation allows cells to restrict arsenite entry through Fps1, but also allows its exit when produced from arsenate exposure. These results have broad implications for understanding how SAPKs activated by diverse stressors can drive stress-specific outputs.

Ultra-lightweight living structural material for enhanced stiffness and environmental sensing

Natural materials such as bone, wood, and bamboo can inspire the fabrication of stiff, lightweight structural materials. Biofilms are one of the most dominant forms of life in nature. However, little is known about their physical properties as a structural material. Here we report an Escherichia coli biofilm having a Young′s modulus close to 10 GPa with ultra-low density, indicating a high-performance structural material. The mechanical and structural characterization of the biofilm and its components illuminates its adaptable bottom-up design, consisting of lightweight microscale cells covered by a dense network of amyloid nanofibrils on the surface. We engineered E. coli such that 1) carbon nanotubes assembled on the biofilm, enhancing its stiffness to over 30 GPa, or that 2) the biofilm sensitively detected heavy metal as an example of an environmental toxin. These demonstrations offer new opportunities for developing responsive living structural materials to serve many real-world applications.

Altered Testicular Histomorphometric and Antioxidant Levels Following In vivo Bisphenol-A Administration

Background: Bisphenol-A (BPA) is a pervasive environmental toxin that is used in the production processes of many consumables and equipment that are in daily application. The aim of this study was to determine the effects of BPA on the structural and functional integrity of the reproductive system in male Wistar rats and its interaction with melatonin. Methods: Adult female rats in pro-estrus phases were mated with adult male rats and the conception determined. The male pups were divided into two groups of A and B. These groups were further subdivided into six subgroups each. They were administered varying low doses of BPA (25 or 50mg/kg) and melatonin (10mg/kg) at neonatal and adolescent ages. The testes, epididymis and blood samples were collected for histological, semen and biochemical investigations, respectively. Results: The results show that BPA caused histological alterations, reduced quality and quantity of sperm cells, and induced oxidative stress at birth and adolescence. Conclusion: Bisphenol A exposure, even at low dose, is toxic to the male reproductive system, and melatonin administration did not significantly improve the alterations caused by the BPA.

Lipopolysaccharide-Enhanced Responses against Aryl Hydrocarbon Receptor in FcgRIIb-Deficient Macrophages, a Profound Impact of an Environmental Toxin on a Lupus-Like Mouse Model

Fc gamma receptor IIb (FcgRIIb) is the only inhibitory-FcgR in the FcgR family, and FcgRIIb-deficient (FcgRIIb−/−) mice develop a lupus-like condition with hyper-responsiveness against several stimulations. The activation of aryl hydrocarbon receptor (Ahr), a cellular environmental sensor, might aggravate activity of the lupus-like condition. As such, 1,4-chrysenequinone (1,4-CQ), an Ahr-activator, alone did not induce supernatant cytokines from macrophages, while the 24 h pre-treatment by lipopolysaccharide (LPS), a representative inflammatory activator, prior to 1,4-CQ activation (LPS/1,4-CQ) predominantly induced macrophage pro-inflammatory responses. Additionally, the responses from FcgRIIb−/− macrophages were more prominent than wild-type (WT) cells as determined by (i) supernatant cytokines (TNF-α, IL-6, and IL-10), (ii) expression of the inflammation associated genes (NF-κB, aryl hydrocarbon receptor, iNOS, IL-1β and activating-FcgRIV) and cell-surface CD-86 (a biomarker of M1 macrophage polarization), and (iii) cell apoptosis (Annexin V), with the lower inhibitory-FcgRIIb expression. Moreover, 8-week-administration of 1,4-CQ in 8 week old FcgRIIb−/− mice, a genetic-prone lupus-like model, enhanced lupus characteristics as indicated by anti-dsDNA, serum creatinine, proteinuria, endotoxemia, gut-leakage (FITC-dextran), and glomerular immunoglobulin deposition. In conclusion, an Ahr activation worsened the disease severity in FcgRIIb−/− mice possibly through the enhanced inflammatory responses. The deficiency of inhibitory-FcgRIIb in these mice, at least in part, prominently enhanced the pro-inflammatory responses. Our data suggest that patients with lupus might be more vulnerable to environmental pollutants.

GardeninA confers neuroprotection against environmental toxin in a Drosophila model of Parkinson’s disease

Parkinson’s disease is an age-associated neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons from the midbrain. Epidemiological studies have implicated exposures to environmental toxins like the herbicide paraquat as major contributors to Parkinson’s disease etiology in both mammalian and invertebrate models. We have employed a paraquat-induced Parkinson’s disease model in Drosophila as an inexpensive in vivo platform to screen therapeutics from natural products. We have identified the polymethoxyflavonoid, GardeninA, with neuroprotective potential against paraquat-induced parkinsonian symptoms involving reduced survival, mobility defects, and loss of dopaminergic neurons. GardeninA-mediated neuroprotection is not solely dependent on its antioxidant activities but also involves modulation of the neuroinflammatory and cellular death responses. Furthermore, we have successfully shown GardeninA bioavailability in the fly heads after oral administration using ultra-performance liquid chromatography and mass spectrometry. Our findings reveal a molecular mechanistic insight into GardeninA-mediated neuroprotection against environmental toxin-induced Parkinson’s disease pathogenesis for novel therapeutic intervention.

Cognitive Impairment Induced by Lead Exposure during Lifespan: Mechanisms of Lead Neurotoxicity

Lead (Pb) is considered a strong environmental toxin with human health repercussions. Due to its widespread use and the number of people potentially exposed to different sources of this heavy metal, Pb intoxication is recognized as a public health problem in many countries. Exposure to Pb can occur through ingestion, inhalation, dermal, and transplacental routes. The magnitude of its effects depends on several toxicity conditions: lead speciation, doses, time, and age of exposure, among others. It has been demonstrated that Pb exposure induces stronger effects during early life. The central nervous system is especially vulnerable to Pb toxicity; Pb exposure is linked to cognitive impairment, executive function alterations, abnormal social behavior, and fine motor control perturbations. This review aims to provide a general view of the cognitive consequences associated with Pb exposure during early life as well as during adulthood. Additionally, it describes the neurotoxic mechanisms associated with cognitive impairment induced by Pb, which include neurochemical, molecular, and morphological changes that jointly could have a synergic effect on the cognitive performance.