Nutrients最新文献

Background: Colorectal cancer (CRC) stands as one of the most prevalent cancer types and among the most frequent causes of cancer-related death globally. Acacia concinna (AC) is a medicinal and edible plant that exhibits a multitude of biological properties, including anticancer properties. This study aimed to investigate the impact of the AC extract on apoptosis induction and the underlying mechanisms associated with this effect in KRAS-mutated human colon HCT116 cells.

Methods: The effect of AC extract on cell cytotoxicity was evaluated using MTT assay. Nuclear morphological changes were visualized with Hoechst 33342 staining, while mitochondrial membrane potential (MMP) was assessed via JC-1 staining. Flow cytometry was employed for cell cycle analysis, and intracellular ROS levels were determined using DCFH-DA staining.

Results: The results showed that HCT116 cells exposed to AC extract showed reduced cell growth and prompted apoptosis, as indicated by an increase in chromatin condensation, apoptotic bodies, the sub-G1 apoptotic cell population, and disrupted MMP. Expression levels of apoptosis mediator proteins determined by Western blot analysis showed an increase in pro-apoptotic proteins (Bak and Bax) while decreasing anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1), leading to caspase-7 activation and PARP inactivation. AC extract was also found to enhance intracellular reactive oxygen species (ROS) levels and stimulate endoplasmic reticulum (ER) stress. Furthermore, AC extract increases the phosphorylation of ERK1/2, p38, and c-Jun while downregulating PI3K, Akt, β-catenin, and their downstream target proteins.

Conclusions: These results demonstrate that AC extract could inhibit cancer cell growth via ROS-induced ER stress associated with apoptosis and regulate the MAPK, PI3K/Akt, and Wnt/β-catenin signaling pathways in HCT116 cells. Therefore, AC extract may be a novel candidate for natural anticancer resources for colon cancer treatment.

Background/Objectives: Prospective cohort studies are useful for studying how biomolecular status affects risk of adverse health outcomes. Less well known is that the longer the follow-up time, the lower the association (or "apparent effect") due to "regression dilution". Here, we evaluate how follow-up interval from baseline to "event" affects the relationship between baseline serum 25-hydroxyvitamin D [25(OH)D] concentration and the later incidence of stroke and major cardiovascular events (MACEs). Methods: Findings for the relative risk (RR) of stroke and MACEs with respect to serum 25(OH)D concentrations at baseline from prospective cohort studies were plotted against mean follow-up time. Fifteen studies from mainly European countries and the United States were used for stroke and nine studies for MACEs. Linear regression analyses were used to study data for follow-up periods of up to 10 years and for more than 10 years. Results: For stroke, the linear regression fit for 1-10 years is RR = 0.34 + (0.065 × follow-up [years]), r = 0.84, adjusted r² = 0.67, p < 0.001. No significant variations in association were found for studies with follow-up periods of 10-20 years. For MACEs, the linear fit for 1-8.1 years is RR = 0.61 + (0.055 × follow-up [years]), r = 0.81, adjusted r² = 0.59, p = 0.03. Discussion: The shorter the follow-up period, the greater the apparent effect of better vitamin D status in reducing risk of stroke and MACEs. In addition, the apparent effect of higher 25(OH)D concentration found for the shortest follow-up time is more than twice as great as the estimate based on average follow-up intervals for all studies. Mechanisms have been found to explain how higher serum 25(OH)D concentrations could reduce risk of stroke and MACEs. Randomized controlled trials have not shown that vitamin D supplementation significantly reduces risk of either stroke or MACEs, probably because risk of both outcomes increases rapidly below 15 ng/mL (38 nmol/L) and it is difficult in Western developed countries to enroll enough participants with concentrations that low. Nonetheless, vitamin D's role in reducing risk of stroke and MACEs could be considered causal on the basis of an evaluation of the evidence using Hill's criteria for causality in a biological system. Conclusions: Serum 25(OH)D concentrations above 20 ng/mL are associated with significantly reduced risk of stroke and MACEs prospectively and in an apparent causal manner. Raising serum 25(OH)D concentrations to >20 ng/mL should, therefore, be recommended for everyone likely to be at risk for stroke or MACEs and indeed in the general population.

Background: Determinants and motives related to food selection have evolved in a globalized and changing world. The traditional and useful Food Choice Questionnaire (FCQ), created in 1995, needs to be updated, adapted to new scenarios, and validated.

Objectives: This study aimed to: (1) assess face validity (FV) of the original 36-item FCQ, (2) generate an Updated-FCQ (U-FCQ) and assess its content validity (CV) (instrument suitability), and (3) evaluate its construct validity and reliability in a Spanish-speaking population from Mexico.

Methods: FV involved a panel of nutrition professionals (NPs) rating the original items' clarity, relevance, specificity, and representativeness. A literature review process updated the FCQ by adding new items. CV with a second NP panel allowed calculating content validity ratio (CVR). Construct validation was performed via exploratory and confirmatory factor analysis (EFA-CFA). Internal consistency through Cronbach's alpha (CA) and test-retest reliability via intra-class correlation (ICC) were assessed.

Results: The FV (n = 8) resulted in the modification of 11 original items. The literature review added 36 new items (15 from previous adaptations and 21 original items). The CV (n = 13) identified nine items (non-acceptable CVR), prompting reformulation of seven and removal of two. The NPs' feedback added six new items. The EFA-CFA (n = 788) developed a 75-item U-FCQ with eight dimensions: sensory appeal, mood, health and nutritional content, price, food identity, environmental and wildlife awareness, convenience, and image management. CA ranged from 0.74-0.97 (good-excellent) and ICC from 0.51-0.78 (moderate-good).

Conclusions: This study provides a useful instrument for the assessment of food choices and lays the groundwork for future cross-cultural comparisons, expanding its applicability in wider settings.

Background: Increased inflammation and heightened physiological stress reactivity have been associated with pathophysiology of depressive symptoms. The underlying biological mechanisms by which inflammation and stress may influence neurogenesis are changes in the kynurenine (KYN) pathway, which is activated under stress. Supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) has anti-inflammatory properties and can increase stress resilience. Whether n-3 PUFAs alter KYN stress response is unknown. Objectives: This placebo-controlled study investigated the effect of n-3 PUFAs on KYN metabolism, inflammation, depressive symptoms, and mood. Moreover, stress-induced changes following a laboratory stressor have been assessed. Methods: In this placebo-controlled study, 47 healthy male adults received either 4 g n-3 PUFAs per day (Omega-3 group) or a placebo (Placebo group) for 12 weeks. Results: A significant group-by-time interaction was found for the inflammatory markers gp130 (F = 7.07, p = 0.011), IL-6R alpha (F = 10.33, p = 0.003), and TNF_RI (F= 10.92, p = 0.002). No significant group-by-time interactions were found for KYN metabolites, depressive symptoms, and mood (except for Hedonic tone (F = 6.50, p = 0.014)), nor for stress-induced changes in KYN metabolites and mood following a laboratory stressor. Conclusions: Overall, increased n-3 PUFA levels in healthy men ameliorate inflammatory markers but do not ameliorate KYN metabolism, depressive symptoms, mood, or KYN metabolism and mood following a stress induction. This study was registered at ClinicalTrials.gov with the identifier NCT05520437 (30/08/2022 first trial registration).

Background/objectives: The pathophysiology of cancer anorexia is multifactorial and unclear. Transcriptomic analysis from PBMCs RNA showed diverse patterns of gene expression pathways in anorexic cancer patients. We assessed whether the different transcriptomic signatures are modulated by DNA methylation in lung cancer patients presenting with poor appetite.

Methods: Lung cancer patients and controls were enrolled, and anorexia was assessed by the FAACT-score questionnaire. Genome-wide DNA methylation was determined by Human Infinium MethylationEPIC BeadChip Kit. Data from genome-wide methylation analysis were merged with those from gene expression analysis, previously obtained by RNA sequencing (NGS). Four groups of genes were identified for each comparison: hypermethylated repressed, hypermethylated induced, hypomethylated repressed, and hypomethylated induced.

Results: Cancer patients (n = 16) showed 382 differentially methylated genes when compared with controls (n = 8). Anorexic patients (n = 8) presented 586 hypomethylated and 174 hypermethylated genes compared with controls. In anorexic patients vs. non-anorexic (n = 8), 211 genes were identified as hypomethylated and 90 hypermethylated. When microarray methylation data were merged with transcriptomic data by RNA sequencing, we observed significant differences in anorexic patients vs. controls; a total of 42 genes resulted as hypomethylated and induced, 5 hypermethylated repressed, 10 hypermethylated induced, and 15 hypomethylated repressed. The CG sites analyzed by targeted bisulfite NGS in four genes of interest (FLNA, PGRMC1, GNL3L, and FHL1) resulting as hypomethylated in anorexic vs. controls allowed the validation of the data obtained from DNA methylation. Interestingly, the four genes resulted as hypomethylated in anorexic patients vs. non-anorexic patients and vs. controls (p < 0.0001).

Conclusions: Our data support that methylation is implicated in cancer-associated anorexia and nutritional derangements among lung cancer patients.

Background/Objectives: Historically racialized status (HRS) and low socioeconomic position (SEP) are independent risk factors for food insecurity and poor academic achievement among college students. Despite increased enrollment of students from historically racialized groups and low SEP, little is known regarding the intersectional experience of these contemporary student characteristics with food security status or academic achievement. The purpose of this study was to examine the intersections of racialized status and SEP with food insecurity and academic achievement among undergraduate students attending a public university system in California. Methods: This cross-sectional study included 1170 undergraduates who utilized their campus food pantry between June and August 2019 at nine University of California campuses. Racialized status and SEP were used to construct four distinct intersectional positions: (1) White, not low SEP (i.e., traditional students; reference), and three contemporary student groups: (2) White, low SEP; (3) HRS, not low SEP; and (4) HRS, low SEP. Using regression analyses, these intersectional positions were examined with food insecurity and grade point average (GPA), while controlling for other student characteristics. Results: HRS, low SEP students had significantly higher odds of experiencing food insecurity (OR = 2.72; 95% CI: 1.52-4.97) and lower GPA (B = -0.14, p = 0.05) than traditional students, after adjustment. Conclusions: Contemporary students are at increased risk of food insecurity and lower academic achievement compared to traditional students.

Background: Plant derived isolated compounds or extracts enjoy great popularity among cancer patients, although knowledge about their mode of action is unclear. The present study investigated whether the combination of two herbal drugs, the cyanogenic diglucoside amygdalin and the isothiocyanate sulforaphane (SFN), influences growth and proliferation of renal cell carcinoma (RCC) cell lines. Methods: A498, Caki-1, and KTCTL-26 cells were exposed to low-dosed amygdalin (1 or 5 mg/mL), or SFN (5 µM) or to combined SFN-amygdalin. Tumor growth and proliferation were analyzed by MTT, BrdU incorporation, and clone formation assays. Cell cycle phases and cell cycle-regulating proteins were analyzed by flow cytometry and Western blotting, respectively. The effectiveness of the amygdalin-SFN combination was determined using the Bliss independence model. Results: 1 mg/mL amygdalin or 5 µM SFN, given separately, did not suppress RCC cell growth, and 5 mg/mL amygdalin only slightly diminished A498 (but not Caki-1 and KTCTL-26) cell growth. However, already 1 mg/mL amygdalin potently inhibited growth of all tumor cell lines when combined with SFN. Accordingly, 1 mg/mL amygdalin suppressed BrdU incorporation only when given together with SFN. Clonogenic growth was also drastically reduced by the drug combination, whereas only minor effects were seen under single drug treatment. Superior efficacy of co-treatment, compared to monodrug exposure, was also seen for cell cycling, with an enhanced G0/G1 and diminished G2/M phase in A498 cells. Cell cycle regulating proteins were altered differently, depending on the applied drug schedule (single versus dual application) and the RCC cell line, excepting phosphorylated Akt which was considerably diminished in all three cell lines with maximum effects induced by the drug combination. The Bliss independence analysis verified synergistic interactions between amygdalin and SFN. Conclusions: These results point to synergistic effects of amygdalin and SFN on RCC cell growth and clone formation and Akt might be a relevant target protein. The combined use of low-dosed amygdalin and SFN could, therefore, be beneficial as a complementary option to treat RCC. To evaluate clinical feasibility, the in vitro protocol must be applied to an in vivo model.

Background: More than 70% of pregnant adolescents in developing countries experience inappropriate gestational weight gain (GWG).

Objective: To determine the association of the number of antenatal care visits (ANC) with GWG, birth weight, and their differences between two countries.

Methods: A prospective study was conducted in two cohorts of adolescents, one from Mexico and one from Colombia. The study calculated pregestational body mass index (BMI), obtained GWG and birth weight, and collected socioeconomic characteristics. Birth weight was categorized according to gestational age. A total of 690 mother-child pairs were included, of which 42.6% were Colombian and 57.4% Mexican.

Results: The study found no association between socioeconomic characteristics and GWG or birth weight. Colombian adolescents were more likely to experience insufficient GWG (68%), compared with 36% of Mexican adolescents. Colombian adolescents who attended fewer than eight ANC visits were at increased risk of insufficient GWG, whereas Mexican adolescents were at increased risk of excessive GWG. Mexican adolescents who began their pregnancies overweight or obese were at increased risk of excessive GWG. Fewer than eight ANC visits were associated with small for gestational age (SGA) in the Mexican cohort.

Conclusions: Inadequate numbers of ANC visits were associated with excessive and insufficient GWG, and SGA. Promoting ANC in adolescent pregnancy is essential to prevent suboptimal GWG and SGA. This study highlights the need for interventions targeting pregnant adolescents from low socioeconomic backgrounds, prioritizing early initiation of prenatal care (first trimester) and a drastic reduction in the high rates of cesarean sections in this group.

Background/Objectives:Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves' extracts contain high amounts of flavonoids and terpenoids, endowed with several beneficial effects. However, its anticancer activity towards colorectal cancer (CRC) has not been investigated in depth. Methods: The effect of a methanolic extract of D. kaki leaves, rich in kaempferol and quercetin derivatives, have been evaluated on an E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS-activating mutation. Results: This extract is effective in reducing tumor cells' viability without affecting the healthy mucosa cell line CCD 841. In fact, Western blot experiments showed its ability to induce apoptosis in cancer cells by increasing oxidative stress and disrupting mitochondrial functionality, as shown by reactive oxygen species measurement and Seahorse analysis. Conclusions: With the aim of increasing healthspan, as well as the substantial societal and macroeconomic costs associated with cancer, our results could pave the way to a role for D. kaki extract in both CRC treatment and prevention.

Background/objectives: Alnustone (Aln) is an effective compound of Alpinia katsumadae Hayata. Aln possesses various pharmacological activities such as antibacterial, anti-inflammatory, and anti-cancer effects. However, the inhibitory effect of Aln on colorectal cancer (CRC) has not yet been identified. Thus, research was conducted to clarify whether Aln can suppress the proliferative and metastatic ability of CRC cells.

Methods: A cell viability assay was performed to confirm the decrease in CRC cell viability following Aln treatment. Flow cytometry was carried out to evaluate the effects of Aln on cell cycle arrest, autophagy, and apoptosis in CRC cells. In addition, a lung metastasis animal model was used to check the inhibitory effect of Aln on the metastasis of CRC cells.

Results: Aln remarkably diminished the viability and colony-forming ability of several CRC cell lines. In addition, Aln led to a halt at the G0/G1 phase through downregulating cyclin D1-CDK4 in CRC cells. The upregulation of LC3B and p62 expression by Aln triggered autophagy of CRC cells. Moreover, Aln promoted mitochondrial depolarization, resulting in apoptosis of CRC cells. Oral administration of Aln significantly restrained the metastasized lung tumor nodules.

Conclusions: This study demonstrated that Aln can suppress the survival and lung metastasis of CRC cells by promoting cell cycle arrest, autophagy, and apoptosis.