• Breast cancer
• clinical trials
• different population
• genistein
• molecular mechanism
• therapeutic benefits

• Humans
• Genistein/pharmacology
• Breast Neoplasms/drug therapy
• Breast Neoplasms/pathology
• Female
• Age Factors
• Biological Availability
• Animals
• Estrogen Receptor beta/metabolism
• Apoptosis/drug effects
• Oxidative Stress/drug effects
• Antioxidants/pharmacology

Consumer demand for food nutritional content and quality is driving the design of plant-based foods that are enhanced with proteins. In this study, we aimed to reveal the nutrient compositional differences of various states of soy flours. We compared soy protein concentrate (SPC) with full fat (FF), raw soy flour (RSF), and defatted (DF) soy flour for investigating nutritional content, phytochemicals, and in vitro antioxidant activity. The results showed that the SPC contained significantly (p < 0.001) higher protein content (65.14%) and low-fat content (0.54%) than RSF, FF, and DF. Furthermore, the findings revealed that all products contain a significant (ANOVA, p < 0.001) amount of essential minerals. The RSF contains significantly higher (p < 0.001) potassium (1178.6 mg), calcium (216.77 mg), and magnesium (247 mg) per 100 g than FF, DF, and SPC. SPC contains essential amino acids, but we were unable to detect phenylalanine and tryptophan due to a limitation in the method. Furthermore, using methanolic and aqueous extracts of RSF, FF, DF, and SPC, the flavonoid, phenolics, and antioxidant capacity were also evaluated. According to the findings, soy products in methanolic extract had higher phenolic (about 12-34 mg/g) and flavonoid (about 63-150 mg/g) levels than aqueous extract. Results also demonstrated that FF had higher phenolic content, and SPC had higher flavonoid content than the other products. In vitro models such as phosphomolybdenum blue, FRAP, DPPH, and ABTS assays were used to study the total antioxidant and free radical scavenging potential of soy products, and results found that soy products contained a significant (p < 0.001) amount of antioxidant equivalent to gallic acid and vitamin C standard. In the DPPH and ABTS assays, the results also showed that soy products can reduce free radicals in different in vitro models. Altogether, these findings suggest that soy flours, particularly DF and SPC, could be a beneficial food ingredient in the formulation of functional foods.

• chronic kidney disease
• ketoanalogues of essential amino acids
• low-protein diet
• soy protein

• Female
• Amino Acids, Essential
• Body Weight
• Diet, Protein-Restricted/adverse effects
• Phosphorus
• Renal Insufficiency, Chronic/diet therapy
• Soybean Proteins/administration & dosage
• Urea
• Humans
• Male

• Botanical
• Diabetes
• Inflammation
• Islet
• Obesity

Podocytes play a vital role in the pathogenesis of nephrotic syndrome (NS), which is clinically characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia, and peripheral edema. The pathogenesis of NS has evolved through several hypotheses ranging from immune dysregulation theory and increased glomerular permeability theory to the current concept of podocytopathy. Podocytopathy is characterized by dysfunction or depletion of podocytes, which may be caused by unknown permeability factor, genetic disorders, drugs, infections, systemic disorders, and hyperfiltration. Over the last two decades, numerous studies have been done to explore the molecular mechanisms of podocyte injuries or NS and to develop the novel therapeutic strategies targeting podocytopathy for treatment of NS. Recent studies have shown that normal sphingolipid metabolism is essential for structural and functional integrity of podocytes. As a basic component of the plasma membrane, sphingolipids not only support the assembly of signaling molecules and interaction of receptors and effectors, but also mediate various cellular activities, such as apoptosis, proliferation, stress responses, necrosis, inflammation, autophagy, senescence, and differentiation. This review briefly summarizes current evidence demonstrating the regulation of sphingolipid metabolism in podocytes and the canonical or noncanonical roles of podocyte sphingolipid signaling in the pathogenesis of NS and associated therapeutic strategies.

• Sphingolipid; Acid ceramidase; Sphingomyelin-like phosphodiesterase 3b; Podocyte; Nephrotic syndrome

• Anticarcinogenic Agents/pharmacology
• Anticarcinogenic Agents/therapeutic use
• Genistein/pharmacology
• Genistein/therapeutic use
• Humans

Given the growing number of type 2 diabetic individuals and the substantial social and financial costs associated with diabetes management, every effort should be made to improve its prevention and treatment methods. There is an ongoing search for natural dietary compounds that could be used for this purpose. This narrative review focuses on the therapeutic potential of isoflavones in diabetes prevention and treatment. This review summarizes (i) the molecular mechanisms of isoflavones action that are critical to their anti-diabetic properties; (ii) preclinical (in vitro and in vivo) studies evaluating the influence of isoflavones on the function of key organs involved in the pathogenesis of diabetes; and (iii) epidemiological studies and clinical trials that assessed the effectiveness of isoflavones in the prevention and treatment of type 2 diabetes in humans. Apart from discussing the effects of isoflavones on the function of organs “classically” associated with the pathogenesis of diabetes (pancreas, liver, muscles, and adipose tissue), the impact of these compounds on other organs that contribute to the glucose homeostasis (gastrointestinal tract, kidneys, and brain) is also reviewed.

• biochanin A
• daidzein
• formononetin
• genistein
• glyctin
• isoflavones
• type 2 diabetes

Background: Genistein is one among the several other known isoflavones that is found in different soybeans and soy products. The chemical name of genistein is 4′,5,7-trihydroxyisoflavone. Genistein has drawn attention of scientific community because of its potential beneficial effects on human grave diseases, such as cancer. Mechanistic insight of genistein reveals its potential for apoptotic induction, cell cycle arrest, as well as antiangiogenic, antimetastatic, and anti-inflammatory effects.

Objective: The purpose of this review is to unravel and analyze various molecular mechanisms of genistein in diverse cancer models.

Data sources: English language literature was searched using various databases, such as PubMed, ScienceDirect, EBOSCOhost, Scopus, Web of Science, and Cochrane Library. Key words used in various combinations included genistein, cancer, anticancer, molecular mechanisms prevention, treatment, in vivo, in vitro, and clinical studies.

Study selection: Study selection was carried out strictly in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Data extraction: Four authors independently carried out the extraction of articles.

Data synthesis: One hundred one papers were found suitable for use in this review.

Conclusion: This review covers various molecular interactions of genistein with various cellular targets in cancer models. It will help the scientific community understand genistein and cancer biology and will provoke them to design novel therapeutic strategies.

• apoptosis
• cancer
• genistein
• in vitro
• in vivo
• metastasis
• proliferation

Primary nephrotic syndrome (PNS) is a common glomerular disease in children. T cell dysfunction plays a crucial role in the pathogenesis of PNS. Moreover, dysbiosis of gut microbiota contributes to immunological disorders. Whether the initial therapy of PNS affects gut microbiota remains an important question. Our study investigated compositional changes of gut microbiota after initial therapy.

Fecal samples of 20 children with PNS were collected before and after 4-week initial therapy. Total bacteria DNA were extracted and the V3-V4 regions of bacteria 16S ribosomal RNA gene were sequenced. The composition of gut microbiota before and after initial therapy was analyzed by bioinformatics methods. The function of altered gut microbiota was predicted with PICRUSt method.

The richness and diversity of gut microbiota were similar before and after 4-week initial therapy. Gut microbiota at the phylum level was dominated by four phyla including Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria, but the increased relative abundance after initial therapy was found in Deinococcus-Thermus and Acidobacteria. At the genus level, the increased abundance of gut microbiota after initial therapy was observed in short chain fat acids (SCFA)-producing bacteria including Romboutsia, Stomatobaculum and Cloacibacillus (p < 0.05). Moreover, the predicted functional profile of gut microbiota showed that selenocompound metabolism, isoflavonoid biosynthesis and phosphatidylinositol signaling system weakened after initial therapy of PNS.

Initial therapy of PNS increased SCFA-producing gut microbiota, but might diminish selenocompound metabolism, isoflavonoid biosynthesis and phosphatidylinositol signaling system in children.

• Children
• Glucocorticoids
• Gut microbiota
• Primary nephrotic syndrome

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. The aim of the present research was to examine the therapeutic efficacy of Peg interferon alpha 2a (Peg-IFN α-2a) as a serine protease inhibitor on EAE model.

EAE induction was performed in female C57BL/6 mice by myelin oligodendrocyte glycoprotein (35-55) (MOG_35-55) in Complete Freund’s Adjuvant (CFA) emulsion, and Peg-IFN α-2a was used for the treatment of EAE. During the course of the study, clinical evaluation was assessed, and on day 21 post-immunisation blood samples were taken from the heart of mice for evaluation of IL-6, and enzymatic and non-enzymatic antioxidants. The mice were sacrificed and the brains and cerebellums were removed for histological analysis.

Our findings indicated that Peg-IFN α-2a had beneficial effects on EAE by attenuation of the severity and a delay in the onset of disease. Histological analysis showed that treatment with Peg-IFN α-2a can reduce inflammation criteria. Moreover, in Peg-IFN α-2a-treated mice the serum level of IL-6 was significantly less than in controls, and total antioxidant capacity was significantly more than in the control animals.

These data indicate that Peg-IFN α-2a as an anti-serine protease with immunomodulatory properties may be useful for the treatment of MS.

• Peg interferon alpha 2a
• antioxidant
• experimental autoimmune encephalomyelitis
• multiple sclerosis

Di-(2-ethylhexyl) phthalate (DEHP) and genistein (GEN) are of the most common endocrine disrupting chemicals (EDCs) present in the environment or the diet. However, investigation of the effects of acute exposure to these two EDCs during prepuberty has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from PND22 to PND35 with vehicle control, GEN 50 mg/kg body weight (bw)/day, DEHP50, 150 and 450 mg/kg bw/day, and combined treatment. Reproductive parameters including testis weight, anogenital distance and organ coefficient were evaluated on PND36. Enzyme activity involved in the regulation of testicular redox state as well as expression of genes and proteins related to anti-oxidative ability and apoptosis were also investigated. The results revealed that by PND36, DEHP treatment had significantly decreased the testis weight, organ coefficient, testicular anti-oxidative enzyme activities and caused tubular vacuolation; however, co-administration of GEN partially alleviated DEHP-induced testicular injuries and enhanced testicular anti-oxidative enzyme activities and upregulated the expression of NF-E2 related factor 2 and heme oxygenase-1, which indicated that GEN partially attenuated DEHP-induced male reproductive system damage through anti-oxidative action following acute prepubertal exposure to DEHP. Thus, GEN may have use in attenuating the damaging effects of other EDCs that lead to reproductive disorders.

Chronic kidney disease (CKD) is a serious universal problem that is the main risk for several diseases including cardiovascular disease. Dietary factors are important to prevent and control the kidney disease. Some evidence has shown that modifying the amount and the types of dietary protein exert a major effect on renal failure so limiting dietary protein and substituting animal protein with soy protein has suggested. However, there is a lot of controversy about it, especially in human. Thus, this paper will review the clinical trial studies conducted on the effects of soy protein intake on CKD in both animal and human and its effect mechanism.

• Chronic kidney disease
• soy protein
• soybeans

Mono-(2-ethylhexyl) phthalate (MEHP) and genistein are two of the most prevalent endocrine-disrupting chemicals (EDCs) that present in the environment and food. However, how these two EDCs would affect prepubertal Sertoli cells development was rarely studied. In this study, primary prepubertal Sertoli cells were isolated from 22-day-old Sprague Dawley rats and exposed to MEHP at 1 μmol/L, 10 μmol/L, and 100 μmol/L (M1, M10, and M100), genistein at 10 μmol/L (G), and their combination (G + M1, G + M10, and G + M100). Cell proliferation inhibition rate, apoptosis and necrosis rate, and cellular redox state were evaluated. Our results revealed that MEHP could significantly increase cell proliferation inhibition rate, apoptosis rate, necrosis rate, and intracellular reactive oxidative species level. However, coadministration of genistein could partially alleviate MEHP-induced prepubertal Sertoli cells oxidative injuries via enhancement of testicular antioxidative enzymes activities and upregulation of Nrf2 and HO-1, indicating that genistein could partially attenuate MEHP-induced prepubertal Sertoli cells damage through antioxidative action and may have promising future on its curative role for attenuating other EDCs-induced reproductive disorders.

Chronic kidney disease (CKD) is a significant public health problem as risk factors such as advanced age, obesity, hypertension and diabetes rise in the global population. Currently there are no effective pharmacologic treatments for this disease. The role of diet is important for slowing the progression of CKD and managing symptoms in later stages of renal insufficiency. While low protein diets are generally recommended, maintaining adequate levels of intake is critical for health. There is an increasing appreciation that the source of protein may also be important. Soybean protein has been the most extensively studied plant-based protein in subjects with kidney disease and has demonstrated renal protective properties in a number of clinical studies. Soy protein consumption has been shown to slow the decline in estimated glomerular filtration rate and significantly improve proteinuria in diabetic and non-diabetic patients with nephropathy. Soy’s beneficial effects on renal function may also result from its impact on certain physiological risk factors for CKD such as dyslipidemia, hypertension and hyperglycemia. Soy intake is also associated with improvements in antioxidant status and systemic inflammation in early and late stage CKD patients. Studies conducted in animal models have helped to identify the underlying molecular mechanisms that may play a role in the positive effects of soy protein on renal parameters in polycystic kidney disease, metabolically-induced kidney dysfunction and age-associated progressive nephropathy. Despite the established relationship between soy and renoprotection, further studies are needed for a clear understanding of the role of the cellular and molecular target(s) of soy protein in maintaining renal function.

• Chronic kidney disease
• Diet
• Proteinuria
• Protein
• Soy

• Madin-Darby canine kidney cells
• antioxidant
• genistein
• reactive oxygen species
• resveratrol

• Diabetes
• Genistein
• Oxidative stress
• Pancreatic β-cells

• Caenorhabditis elegans
• Genistein
• Lifespan extension
• Stress tolerance
• Vigna angularis

Di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plastizer in the world and can suppress testosterone production via activation of oxidative stress. Genistein (GEN) is one of the isoflavones ingredients exhibiting weak estrogenic and potentially antioxidative effects. However, study on reproductive effects following prepubertal multiple endocrine disrupters exposure has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from postnatal day 22 (PND22) to PND35 with vehicle control, GEN at 50 mg/kg body weight (bw)/day (G), DEHP at 50, 150, 450 mg/kg bw/day (D50, D150, D450) and their mixture (G + D50, G + D150, G + D450). On PND90, general morphometry (body weight, AGD, organ weight, and organ coefficient), testicular redox state, and testicular histology were studied. Our results indicated that DEHP could significantly decrease sex organs weight, organ coefficient, and testicular antioxidative ability, which largely depended on the dose of DEHP. However, coadministration of GEN could partially alleviate DEHP-induced reproductive injuries via enhancement of testicular antioxidative enzymes activities, which indicates that GEN has protective effects on DEHP-induced male reproductive system damage after prepubertal exposure and GEN may have promising future in its curative antioxidative role for reproductive disorders caused by other environmental endocrine disruptors.