Adherence to Plant-Based Diets and Risk of CKD Progression and All-Cause Mortality: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Studies have shown that generally healthy individuals who consume diets rich in plant foods have a lower risk of incident chronic kidney disease (CKD) and cardiovascular disease. This study investigated the prospective associations of plant-based diets with the risk of CKD progression and all-cause mortality in individuals with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,539 participants with CKD recruited between 2003-2008 into the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Responses on the Diet History Questionnaire were used to calculate scores for the overall plant-based diet index, healthy plant-based diet index, and unhealthy plant-based diet index. OUTCOME: (1) CKD progression defined as≥50% estimated glomerular filtration rate decline from baseline or kidney replacement therapy (dialysis, transplant) and (2) all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards models to compute hazard ratios and 95% confidence intervals adjusting for lifestyle, socioeconomic, and clinical covariates. RESULTS: There were 977 CKD progression events and 836 deaths during a median follow-up period of 7 and 12 years, respectively. Participants with the highest versus lowest adherence to overall plant-based diets and healthy plant-based diets had 26% (HR, 0.74 [95% CI, 0.62-0.88], P trend<0.001) and 21% (HR, 0.79 [95% CI, 0.66-0.95], P trend=0.03) lower risks of all-cause mortality, respectively. Each 10-point higher score of unhealthy plant-based diets was modestly associated with a higher risk of CKD progression (HR, 1.14 [95% CI, 1.03-1.25) and all-cause mortality (HR, 1.11 [95% CI, 1.00-1.23). LIMITATIONS: Self-reported diet may be subject to measurement error. CONCLUSIONS: Adherence to an overall plant-based diet and a healthy plant-based diet is associated with a reduced risk of all-cause mortality among individuals with CKD. An unhealthy plant-based was associated with an elevated risk of CKD progression and all-cause mortality. PLAIN-LANGUAGE SUMMARY: Plant-based diets are healthful dietary patterns that have been linked to a lower risk of chronic diseases. However, the impact of plant-based diets on clinical outcomes in patients with chronic kidney disease (CKD) is not well established. In 2,539 individuals with CKD, we examined the associations of adherence to 3 different types of plant-based diets with the risks of CKD progression and all-cause mortality. We found that following an overall plant-based diet and a healthy plant-based diet was associated with a lower risk of all-cause mortality. By contrast, following an unhealthy plant-based diet was associated with a higher risk of CKD progression and all-cause mortality. These results suggest that the quality of plant-based diets may be important for CKD management.

Effects of Dichlorodiphenyltrichloroethane on the Female Reproductive Tract Leading to Infertility and Cancer: Systematic Search and Review.

Persistent Organic Pollutants (POPs) such as dichlorodimethyltrichloroethane (DDT) are present and ubiquitous in the environment due to their resilient nature. DDT is a prevalent endocrine disruptor still found in detectable amounts in organisms and the environment even after its use was banned in the 1970s. Medline and Google Scholar were systematically searched to detect all relevant animal and human studies published in the last 20 years (January 2003 to February 2023) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. In total, 38 studies were included for qualitative synthesis. This systematic search and review indicated that exposure to DDT is associated with female reproductive health issues, such as reduced fecundability; increased risk of preterm/premature deliveries; increased periods of gestation; alterations in the synthesis of crucial reproductive hormones (Progesterone and Oxytocin) through ion imbalances and changes in prostaglandin synthesis, myometrial and stromal hypertrophy, and edema; and variations in uterine contractions through increased uterine wet weight. There was also limited evidence indicating DDT as a carcinogen sufficient to instigate reproductive cancers. However, this review only takes into account the in vitro studies that have established a possible pathway to understand how DDT impacts female infertility and leads to reproductive cancers. Links between the pathways described in various studies have been developed in this review to produce a summarized picture of how one event might lead to another. Additionally, epidemiological studies that specifically targeted the exposure to DDT of females belonging to various ethnicities have been reviewed to develop an overall picture of prevailing female reproductive health concerns in different nations.

Sustainable Isolation of Bioactive Compounds and Proteins from Plant-Based Food (and Byproducts).

Plant-based food produces significantly less greenhouse gases, and due to its wealth of bioactive components and/or plant-based protein, it becomes an alternative in a sustainable food system. However, the processing and production of products from plant sources creates byproducts, which can be waste or a source of useful substances that can be reused. The waste produced during the production and processing of food is essentially nutrient- and energy-rich, and it is recognized as an excellent source of secondary raw materials that could be repurposed in the process of manufacturing and preparing food, or as feed for livestock. This review offers an overview of the sources and techniques of the sustainable isolation of bioactive substances and proteins from various sources that might represent waste in the preparation or production of food of plant origin. The aim is to uncover novel approaches to use waste and byproducts from the process of making food to provide this waste food an additional benefit, not forgetting the expectations of the end user, the consumer. For the successful isolation of bioactive ingredients and proteins from food of plant origin, it is crucial to develop more eco-friendly and efficient extraction techniques with a low CO2 footprint while considering the economic aspects.

Holistic expression of miR-17-92 cluster in obesity, kidney diseases, cardiovascular diseases, and diabetes.

miR-17-92 cluster encodes six micro RNAs (miRNAs) and plays a crucial role in the regulation of various cellular processes. Aberrant expression of this cluster may result in the onset of several diseases. Initially, the role of miR-17-92 cluster in tumorigenesis was discovered but recent research has also uncovered its role in other diseases. Members of the cluster may serve as potential biomarkers in the prognosis, diagnosis, and treatment of several diseases and their complications. In this article, we have reviewed the recent research carried out on the expression pattern of miR-17-92 cluster in non-communicable diseases i.e., obesity, cardiovascular diseases (CVD), kidney diseases (KD) and diabetes mellitus (DM). We examined miR-17-92 role in pathological processes and their potential importance as biomarkers. Each member of the cluster miR-17-92 was upregulated in obesity. miR-18a, miR-19b-3p, miR20a, and miR92a were significantly upregulated in CVD. An equal fraction of the cluster was dysregulated (upregulated and downregulated) in diabetes; however, miR-17-92 was downregulated in most studies on CKD.

Dysregulation of mitochondrial sirtuin genes is associated with human male infertility.

Mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) are post-translational modifiers that regulate energy production, body homeostasis and mitochondrial activities via different substrates in response to environmental stressors. The present study aimed at assessing the expression of SIRT3, SIRT4, and SIRT5 in the semen of infertile men. Expression analysis was performed using q-RT PCR. All mitochondrial sirtuin genes were significantly down-regulated in the semen of infertile men compared to fertile men. Mitochondrial sirtuin genes expression levels were correlated with mitochondrial HSP90 expression. HSP90 expression was positively correlated with SIRT3, SIRT4 and SIRT5 expression in the semen of fertile men, while a negative correlation was observed between HSP90 in the semen of infertile men and mitochondrial sirtuin genes in the semen of fertile men. These data suggest that dysregulation of mitochondrial sirtuin genes causes mitochondrial dysfunction due to stress, which appears to be associated with human male infertility by compromising functional and structural sperm integrity.

Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review.

Increasing contamination of the environment by toxic compounds such as endocrine disrupting chemicals (EDCs) is one of the major causes of reproductive defects in both sexes. Estrogen/androgen pathways are of utmost importance in gonadal development, determination of secondary sex characteristics and gametogenesis. Most of the EDCs mediate their action through respective receptors and/or downstream signaling. The purpose of this review is to highlight the mechanism by which EDCs can trigger antagonistic or agonistic response, acting through estrogen/androgen receptors causing reproductive defects that lead to infertility. In vitro, in vivo and in silico studies focusing on the impact of EDCs on estrogen/androgen pathways and related proteins published in the last decade were considered for the review. PUBMED and PUBCHEM were used for literature search. EDCs can bind to estrogen receptors (ERα and ERß) and androgen receptors or activate alternative receptors such as G protein-coupled receptors (GPCR), GPR30, estrogen-related receptor (ERRγ) to activate estrogen signaling via downstream kinases. Bisphenol A, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, polychlorinated biphenyls and phthalates are major toxicants that interfere with the normal estrogen/androgen pathways leading to infertility in both sexes through many ways, including DNA damage in spermatozoids, altered methylation pattern, histone modifications and miRNA expression.

Impact of organochlorine pollutants on semen parameters of infertile men in Pakistan.

Male infertility is a major problem with important socioeconomic consequences. It is associated with several pathological factors, including but not limited to endocrine disruption as a result of environmental pollution and the alarming decline in sperm count over the decades is indicative of involvement of many environmental and lifestyle changes around the globe. Organochlorine pollutants such as dichlorodiphenyltrichlorethanes (DDTs), polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) disrupt male reproductive system but the exact effect of environmental exposure on semen parameters in human is still not clear. This study was designed to monitor PCBs, DDTs and HCB in hair, urine and serum samples of infertile and healthy fertile men. Solid-phase microextraction gas chromatography-mass spectrometry (SPME/GC-MS) was used to monitor analytes. All tested compounds were detected, indicating recent use/persistent accumulation. Hair samples revealed no significant association with serum/urine concentrations of the analytes, while serum/urine concentrations were significantly correlated positively. Concentrations were higher in serum compared to other samples. The levels of organochlorine pollutants were higher in infertile men compared to controls with few exceptions. Among PCBs, and DDTs, PCB-153 and pp'-DDT were detected in highest concentrations, respectively. op'-DDT and pp'-DDT levels were significantly higher in infertile men compared to controls. HCB was significantly correlated negatively with sperm motility in all samples. Serum concentrations of all compounds were higher in men with defective semen parameters compared to normospermics. Serum was the best biological sample for assessing health outcomes in relation to exposure levels.

Characterization of the Gastrointestinal and Reproductive Tract Microbiota in Fertile and Infertile Pakistani Couples.

The human microbiota is recognized as a vital "virtual" organ of the human body that influences human health, metabolism, and physiology. While the microbiomes of the gut, oral cavity, and skin have been extensively studied in the literature, relatively little work has been done on characterizing the microbiota of the human reproductive tract organs, and specifically on investigating its association to fertility. Here, we implemented a 16S ribosomal RNA (rRNA) amplicon sequencing approach to sequence and characterize the gut and genital tract microbiomes from several married Pakistani couples. The recruited individuals included 31 fertile and 35 infertile individuals, with ages ranging from 19-45 years. We identified several fluctuations in the diversity and composition of the gut and genital microbiota among fertile and infertile samples. For example, measures of α-diversity varied significantly between the genital samples donated by fertile and infertile men and there was overall greater between-sample variability in genital samples regardless of gender. In terms of taxonomic composition, Actinobacteria, Bacteroidetes, and Firmicutes fluctuated significantly between the gut microbiomes of fertile and infertile samples. Finally, biomarker analyses identified features (genera and molecular functions and pathways) that differed significantly between the fertile and infertile samples and in the past have been associated with bacterial vaginosis. However, we emphasize that 16S amplicon data alone has no bearing on individual health and is merely representative of microbial taxonomic differences that could also arise due to multiple other factors. Our findings, however, represent the first effort to characterize the microbiome associated with fertile and infertile couples in Pakistan and will hopefully pave the way for more comprehensive and broad-scale investigations in the future.

Unbiased approach for the identification of molecular mechanisms sensitive to chemical exposures.

Targeted methods that dominated toxicological research until recently did not allow for screening of all molecular changes involved in toxic response. Therefore, it is difficult to infer if all major mechanisms of toxicity have already been discovered, or if some of them are still overlooked. We used data on 591,084 unique chemical-gene interactions to identify genes and molecular pathways most sensitive to chemical exposures. The list of identified pathways did not change significantly when analyses were done on different subsets of data with non-overlapping lists of chemical compounds indicative that our dataset is saturated enough to provide unbiased results. One of the most important findings of this study is that almost every known molecular mechanism may be affected by chemical exposures. Predictably, xenobiotic metabolism pathways, and mechanisms of cellular response to stress and damage were among the most sensitive. Additionally, we identified highly sensitive molecular pathways, which are not widely recognized as major targets of toxicants, including lipid metabolism pathways, longevity regulation cascade, and cytokine-mediated signaling. These mechanisms are relevant to significant public health problems, such as aging, cancer, metabolic and autoimmune disease. Thus, public health field will benefit from future focus of toxicological research on identified sensitive mechanisms.

Data on chemical-gene interactions and biological categories enriched with genes sensitive to chemical exposures.

A dataset of chemical-gene interactions was created by extracting data from the Comparative Toxicogenomics Database (CTD) with the following filtering criteria: data was extracted only from experiments that used human, rat, or mouse cells/tissues and used high-throughput approaches for gene expression analysis. Genes not present in genomes of all three species were filtered out. The resulting dataset included 591,084 chemical-gene interaction. All chemical compounds in the database were annotated for their major uses. For every gene in the database number of chemical-gene interactions was calculated and used as a metric of gene sensitivity to a variety of chemical exposures. The lists of genes with corresponding numbers of chemical-gene interactions were used in gene-set enrichment analysis (GSEA) to identify potential sensitivity to chemical exposures of molecular pathways in Hallmark, KEGG and Reactome collections. Thus, data presented here represent unbiased and searchable datasets of sensitivity of genes and molecular pathways to a broad range of chemical exposures. As such the data can be used for a diverse range of toxicological and regulatory applications. Approach for the identification of molecular mechanisms sensitive to chemical exposures may inform regulatory toxicology about best toxicity testing strategies. Analysis of sensitivity of genes and molecular pathways to chemical exposures based on these datasets was published in Chemosphere (Suvorov et al., 2021) [1].