John M. Pezzuto

Based on promising preclinical results, translational work has shown that grape consumption could increase the resilience of skin to UV irradiation in a subset of human subjects. With four human subjects who did not appear resilient to UV-exposure following grape consumption, we currently demonstrate grape consumption: (1) diminished UV-induced malondialdehyde generation, (2) modulated the plasma lipidome, and (3) induced expression of a suite of genes in skin capable of safeguarding against environmental factors like UV radiation, chemicals, and pathogens, e.g., keratinization and cornification. This is the first report demonstrating gene modulation resulting from grape consumption in a human somatic tissue other than peripheral blood monocytes. Expression patterns show remarkable inter- and intraindividual differences but were omnipresent and interpretable by applying bioanalytics. Consistently, our overall supposition is that grape phytochemicals interact with the microbiome, followed by transmission through the gut–organ axes, resulting in modulation of gene expression and subsequent downstream responses.

Superfood, an au courant word in the American vernacular, refers to mainstream foods that are basically individual components of the Mediterranean diet, i.e., berries, fish, olive oil, cruciferous vegetables, legumes, etc., and perceived as "healthy." There is no regulation; the main source of information is the Internet. Blueberries and strawberries are generally featured as superior. However, when tested as a whole food in human beings, grapes modulate the gut microbiome, the metabolome and gene expression, and there are associated health benefits. Thus, based on actual scientific data, grapes have earned what should be a prominent position in the superfood family.

(1) Background: Nutrigenomics investigates how diet influences gene expression and how genetic variation impacts dietary responses. Grapes, rich in phytochemicals, exhibit potential disease-preventive properties through nutrigenomic mechanisms rather than direct chemical interactions. This study aimed to explore the modulation of gene expression in muscle tissue resulting from long-term grape consumption. (2) Methods: A mouse model was employed to assess gene expression in the skeletal muscles of males and females fed a grape-enriched diet versus a bland diet over 2.5 years. Heatmaps and principal component analyses were performed to identify patterns, and pathway analyses using KEGG, GO, and Reactome were conducted. (3) Results: Significant sex-specific gene expression changes were observed, with female phenotypes showing greater alterations and converging toward male-like characteristics. Twenty-five differentially expressed genes associated with muscle health were identified. Up-regulated genes such as Ahsg, Alb, Apoa1, and Arg1, and down-regulated genes including Camp, Lcn2, and Irf4, suggest improved muscle function. (4) Conclusions: Long-term grape consumption appears to enhance female muscle traits toward a male-like phenotype, potentially indicating broader health benefits. Further studies and clinical trials are needed to confirm human applicability and the physiological implications of these findings. Nonetheless, this research underscores the role of nutrigenomics in understanding dietary influences on gene expression and sex-specific responses.

Starting at 4 weeks of age, male and female C57BL/6J mice were provided with a semi-synthetic diet for a period of one year and then continued on the semi-synthetic diet with or without grape supplementation for the duration of their lives. During the course of the study, no variation of body weights was noted between the groups. At 2.5 years of age, the body-weight-to-tissue-weight ratios did not vary for the liver, colon, muscle, prostate, or ovary. However, relative to the standard diet, the body/kidney weight ratio was significantly lower in the male and female groups with grape-supplemented diets. With the mice provided with the standard diet, the BUN/creatinine ratios were 125 and 152 for males and females, respectively, and reduced to 63.7 and 40.4, respectively, when provided with the grape diet. A histological evaluation suggested that this may be due to enhanced/improved perfusion in the kidney as a preventive/protective effect. In response to the dietary grapes, an RNA seq analysis revealed up-regulation of 21 and 109 genes with male and female mice, respectively, with a corresponding down-regulation of 108 and 65 genes. The downward movement of the FPKM values in the males (alox5, btk, fga, fpr1, hmox1, lox, ltf, lyve1, marco, mmp8, prg4, s100a8/9, serpina3n, and vsig4) and upward movement of the FPKM values in the females (camp, cd300lf, cd72, fcgr4, fgr, fpr2, htra4, il10, lilrb4b, lipg, pilra, and tlr8) suggest beneficial kidney effects. The expression of some genes related to the immunological activity was also modulated by the grape diet, mainly downward in the males and upward in the females. The reactome pathway analysis, KEGG analysis, and GSEA normalized enrichment scores illustrate that several pathways related to immune function, collagenase degradation, extracellular matrix regulation, metabolism of vitamins and cofactors, pancreatic secretion, aging, and mitochondrial function were enriched in both the males and females provided with the grape diet. Overall, these results indicate that the long-term dietary consumption of grapes contributes to renal health and resilience against fibrosis and related pathologies.

Over the past three years, 7,978 graduates of pharmacy programs have failed the North American Pharmacist Licensure Examination (NAPLEX) on the first attempt. At present, the ACPE monitors programs with a passage rate of ≥2 standard deviations (SD) below the national mean pass rate. In 2023, this would lead to monitoring seven programs that produced 140 failures out of the total of 2,472 failures (i.e., 5.7%). In our view, this is neither equitable nor demonstrative of sufficient accountability. Analysis of failure counts among the 144 programs reported by NABP demonstrates a distribution curve highly skewed to the right. After evaluating average failure counts across all the programs, we suggest that schools with absolute failures ≥2 SD higher than the average number of failures of all programs should be flagged for monitoring. Based on the 2023 data, this corresponds to ≥35 failures/program. This threshold would flag 18 programs and 36.5% of the total failures. Of the seven programs that will be monitored based on the current Accreditation Council for Pharmacy Education criteria, only one would be captured by the ≥35 failure method of selection with the remaining six contributing only 85 total failures to the pool. Thus, if both criteria were to be applied, i.e., ≥35 failures and of ≥2 standard deviations below the national mean pass rate, a total of 24 programs would be monitored (16.6% of the 144 programs), that contribute 987 (39.9%) of the total failures.

As a whole food, the potential health benefits of table grapes have been widely studied. Some individual constituents have garnered great attention, particularly resveratrol, but normal quantities in the diet are meniscal. On the other hand, the grape contains hundreds of compounds, many of which have antioxidant potential. Nonetheless, the achievement of serum or tissue concentrations of grape antioxidants sufficient to mediate a direct quenching effect is not likely, which supports the idea of biological responses being mediated by an indirect catalytic-type response. We demonstrate herein with Hsd:ICR (CD-1^® Outbred, 18–24 g, 3–4 weeks old, female) mice that supplementation of a semi-synthetic diet with a grape surrogate, equivalent to the human consumption of 2.5 servings per day for 12 months, modulates gene expression in the liver, kidney, colon, and ovary. As might be expected when sampling changes in a pool of over 35,000 genes, there are numerous functional implications. Analysis of some specific differentially expressed genes suggests the potential of grape consumption to bolster metabolic detoxification and regulation of reactive oxygen species in the liver, cellular metabolism, and anti-inflammatory activity in the ovary and kidney. In the colon, the data suggest anti-inflammatory activity, suppression of mitochondrial dysfunction, and maintaining homeostasis. Pathway analysis reveals a combination of up- and down-regulation in the target tissues, primarily up-regulated in the kidney and down-regulated in the ovary. More broadly, based on these data, it seems logical to conclude that grape consumption leads to modulation of gene expression throughout the body, the consequence of which may help to explain the broad array of activities demonstrated in diverse tissues such as the brain, heart, eye, bladder, and colon. In addition, this work further supports the profound impact of nutrigenomics on mammalian phenotypic expression.