Hyperglycemia-linked oxidative stress and/or consequent endoplasmic reticulum (ER) stress are the causative factors of pathogenesis of diabetic retinopathy. Dietary bioactive components which mitigate oxidative stress may serve as potential chemopreventive agents to prevent or slow down the disease progression. Wolfberry is a traditional Asian fruit consumed for years to prevent aging eye diseases in Asian countries. Here we report that dietary wolfberry ameliorated mouse retinal abnormality at the early stage of type 2 diabetes in db/db mice. Male mice at six weeks of age were fed the control diet with or without 1% (kcal) wolfberry for eight weeks. Dietary wolfberry restored the thickness of the whole retina, in particular the inner nuclear layer and photoreceptor layer, and the integrity of the retinal pigment epithelia (RPE), and the ganglion cell number in db/db mice. Western blotting of whole retinal cell lysates revealed that addition of wolfberry lowered expression of ER stress biomarkers binding immunoglobulin protein (BiP), protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and caspase-12, and restored AMP-activated protein kinase (AMPK), thioredoxin, Mn superoxide dismutase (Mn SOD) and forkhead O transcription factor 3 α (FOXO3 α) activities. To determine if our observations were due to the high contents of zeaxanthin and lutein in wolfberry, additional studies using these carotenoids were conducted. Using the human adult diploid RPE cell line ARPE-19, we demonstrated that both zeaxanthin and lutein could mimic the wolfberry preventive effect on activation of AMPK, thioredoxin, Mn SOD, FOXO3 α activities, normalize cellular reactive oxygen species and attenuate ER stress in ARPE-19 cells exposed to a high glucose challenge. The zeaxanthin preventive effect was abolished by small interfering RNA knockdown of AMPK α. These results suggested that AMPK activation appeared to play a key role in upregulated expression of thioredoxin and Mn SOD, and mitigation of cellular oxidative stress and/or ER stress by wolfberry and zeaxanthin and/or lutein. Taken together, dietary wolfberry on retinal protection in diabetic mice is, at least partially, due to zeaxanthin and/or lutein.

The accumulation of reactive oxygen species (ROS, for example H₂O₂) is linked to several chronic pathologies, including cancer and cardiovascular and neurodegenerative diseases (Gate, L., Paul, J., Ba, G. N., Tew, K. D., and Tapiero, H. (1999) Biomed. Pharmacother. 53, 169–180). Protein kinase C (PKC) γ is a unique isoform of PKC that is found in neuronal cells and eye tissues. This isoform is activated by ROS such as H₂O₂. Mutations (H101Y, G118D, S119P, and G128D) in the PKCγ Cys-rich C1B domain caused a form of dominant non-episodic cerebellar ataxia in humans (Chen, D.-H., Brkanac, Z., Verlinde, C. L. M. J., Tan, X.-J., Bylenok, L., Nochli, D., Matsushita, M., Lipe, H., Wolff, J., Fernandez, M., Cimino, P. J., Bird, T. D., and Raskind, W. H. (2003) Am. J. Hum. Genet. 72, 839–849; van de Warrenburg, B. P. C., Verbeek, D. S., Piersma, S. J., Hennekam, F. A. M., Pearson, P. L., Knoers, N. V. A. M., Kremer, H. P. H., and Sinke, R. J. (2003) Neurology 61, 1760–1765). This could be due to a failure of the mutant PKCγ proteins to be activated by ROS and to subsequently inhibit gap junctions. The purpose of this study was to demonstrate the cellular mechanism of activation of PKCγ by H₂O₂ and the resultant effects on gap junction activity. H₂O₂ stimulated PKCγ enzyme activity independently of elevations in cellular diacylglycerol, the natural PKC activator. Okadaic acid, a phosphatase inhibitor, did not affect H₂O₂-stimulated PKCγ activity, indicating that dephosphorylation was not involved. The reductant, dithiothreitol, abolished the effects of H₂O₂, suggesting a direct oxidation of PKCγ at the Cys-rich C1 domain. H₂O₂ induced the C1 domain of PKCγ to translocate to plasma membranes, whereas the C2 domain did not. Direct effects of H₂O₂ on PKCγ were demonstrated using two-dimensional SDS-PAGE. Results demonstrated that PKCγ formed disulfide bonds in response to H₂O₂. H₂O₂-activated PKCγ was targeted into caveolin-1- and connexin 43-containing lipid rafts, and the PKCγ phosphorylated the connexin 43 gap junction proteins on Ser-368. This resulted in disassembly of connexin 43 gap junction plaques and decreased gap junction activity. Results suggested that H₂O₂ caused oxidation of the C1 domain, activation of the PKCγ, and inhibition of gap junctions. This inhibition of gap junctions could provide a protection to cells against oxidative stress.

Dysbiosis, a broad spectrum of imbalance of the gut microbiota, may progress to microbiota dysfunction. Dysbiosis is linked to some human diseases, such as inflammation-related disorders and metabolic syndromes. However, the underlying mechanisms of the pathogenesis of dysbiosis remain elusive. Recent findings suggest that the microbiome and gut immune responses, like immunoglobulin A production, play critical roles in the gut homeostasis and function, and the progression of dysbiosis. In the past two decades, much progress has been made in better understanding of production of immunoglobulin A and its association with commensal microbiota. The present minireview summarizes the recent findings in the gut microbiota dysbiosis and dysfunction of immunoglobulin A induced by the imbalance of pathogenic bacteria and commensal microbiota. We also propose the potentials of dietary carotenoids, such as β-carotene and astaxanthin, in the improvement of the gut immune system maturation and immunoglobulin A production, and the consequent promotion of the gut health.Impact statement: The concept of carotenoid metabolism in the gut health has not been well established in the literature. Here, we review and discuss the roles of retinoic acid and carotenoids, including pro-vitamin A carotenoids and xanthophylls in the maturation of the gut immune system and IgA production. This is the first review article about the carotenoid supplements and the metabolites in the regulation of the gut microbiome. We hope this review would provide a new direction for the management of the gut microbiota dysbiosis by application of bioactive carotenoids and the metabolites.

Six lactic acid bacterial (LAB) strains were isolated from traditionally fermented Xinjiang cheese and evaluated for functional and probiotic properties and potentials as starter cultures. The isolated six LAB strains comprised Lactobacillus rhamnosus (one strain), Lactobacillus helveticus (one strain), and Enterococcus hirae (four strains). All of the six strains were tolerant to acidic and bile salt conditions. Among which, the L. rhamnosus R4 strain showed more desirable antimicrobial, auto-aggregation, and hydrophobic activity. In addition, the strain L. rhamnosus R4 exhibited the highest level of free radical scavenging activity (53.78% of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and 45.79% of hydroxyl radicals). L. rhamnosus R4 also demonstrated cholesterol and triglyceride degradation by 50.97% and 28.92%, respectively. To further examine the health-promoting effects of these LAB strains on host lifespan, Caenorhabditis elegans was used as an in vivo model. Worms fed LAB as a food source had significant differences in lifespan compared to those fed Escherichia coli OP50 (as a negative control). Feeding of L. rhamnosus R4 extended the mean lifespan of C. elegans by up to 36.1% compared to that of the control. The results suggest that the strains isolated from Xinjiang fermented dairy products have high potential as starter cultures in the cheese industry.

Extreme environments test the limits of life; yet, some organisms thrive in harsh conditions. Extremophile lineages inspire questions about how organisms can tolerate physiochemical stressors and whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H ₂ S)—a toxicant that impairs mitochondrial function—across evolutionarily independent lineages of a fish ( Poecilia mexicana , Poeciliidae) from H ₂ S-rich springs. Using comparative biochemical and physiological analyses, we found that mitochondrial function is maintained in the presence of H ₂ S in sulfide spring P. mexicana but not ancestral lineages from nonsulfidic habitats due to convergent adaptations in the primary toxicity target and a major detoxification enzyme. Genome-wide local ancestry analyses indicated that convergent evolution of increased H ₂ S tolerance in different populations is likely caused by a combination of selection on standing genetic variation and de novo mutations. On a macroevolutionary scale, H ₂ S tolerance in 10 independent lineages of sulfide spring fishes across multiple genera of Poeciliidae is correlated with the convergent modification and expression changes in genes associated with H ₂ S toxicity and detoxification. Our results demonstrate that the modification of highly conserved physiological pathways associated with essential mitochondrial processes mediates tolerance to physiochemical stress. In addition, the same pathways, genes, and—in some instances—codons are implicated in H ₂ S adaptation in lineages that span 40 million years of evolution.