Effect of natural products on hematopoiesis

Prirodne sastavnice (sekundarni biljni metaboliti) su tvari sintetizirane u sekundarnim reakcijama iz primarnih metabolita. Danas se sve više istražuju njihova svojstva i sve smo više upoznati s njihovim učinkom na ljudsko zdravlje. U ovom radu izložen je kratak pregled procesa hematopoeze, krvnih stanica i prirodnih sastavnica te njihovog utjecaja na zdravlje i hematopoezu. Mnogi biljni pripravci kao i pojedine biljne sastavnice imaju antimikrobno, protuupalno te antitumorsko djelovanje te se njihova svojstva sve više istražuju u svrhu zaštite ljudskog zdravlja. Učinak prirodnih sastavnica na hematopoezu je uglavnom stimulativan, iako postoje i neke prirodne sastavnice koje inhibiraju razvoj određene hematopoetske linije. Također je pokazano da štite stanice koštane srži od zračenja te djeluju stimulativno na oporavak nakon kemoterapije.Natural products (plant secondary metabolites) are supstances derived from primary metabolites in secondary reactions. Now their chemical properties are being increasingly investigated and we become more and more aware of their impact on human health. This paper represent a brief review of hematopoiesis, blood cells and natural products and their effect on health and hematopoiesis. Many plant extracts and natural products have antimicrobal, anti-inflammatory and antitumor effect thus their properties are increasingly invesigated for the purpose of protecting human health. Effects of natural products on hematopoiesis is mainly stimulatory, although some natural products have inhibitory effect on development of specific hematopoietic lineage. It has been also proved that they have an protective and stimulative effect on bone marrow cells in case of radiation

Effect of natural products on hematopoiesis

Prirodne sastavnice (sekundarni biljni metaboliti) su tvari sintetizirane u sekundarnim reakcijama iz primarnih metabolita. Danas se sve više istražuju njihova svojstva i sve smo više upoznati s njihovim učinkom na ljudsko zdravlje. U ovom radu izložen je kratak pregled procesa hematopoeze, krvnih stanica i prirodnih sastavnica te njihovog utjecaja na zdravlje i hematopoezu. Mnogi biljni pripravci kao i pojedine biljne sastavnice imaju antimikrobno, protuupalno te antitumorsko djelovanje te se njihova svojstva sve više istražuju u svrhu zaštite ljudskog zdravlja. Učinak prirodnih sastavnica na hematopoezu je uglavnom stimulativan, iako postoje i neke prirodne sastavnice koje inhibiraju razvoj određene hematopoetske linije. Također je pokazano da štite stanice koštane srži od zračenja te djeluju stimulativno na oporavak nakon kemoterapije.Natural products (plant secondary metabolites) are supstances derived from primary metabolites in secondary reactions. Now their chemical properties are being increasingly investigated and we become more and more aware of their impact on human health. This paper represent a brief review of hematopoiesis, blood cells and natural products and their effect on health and hematopoiesis. Many plant extracts and natural products have antimicrobal, anti-inflammatory and antitumor effect thus their properties are increasingly invesigated for the purpose of protecting human health. Effects of natural products on hematopoiesis is mainly stimulatory, although some natural products have inhibitory effect on development of specific hematopoietic lineage. It has been also proved that they have an protective and stimulative effect on bone marrow cells in case of radiation

Effect of natural products on hematopoiesis

Prirodne sastavnice (sekundarni biljni metaboliti) su tvari sintetizirane u sekundarnim reakcijama iz primarnih metabolita. Danas se sve više istražuju njihova svojstva i sve smo više upoznati s njihovim učinkom na ljudsko zdravlje. U ovom radu izložen je kratak pregled procesa hematopoeze, krvnih stanica i prirodnih sastavnica te njihovog utjecaja na zdravlje i hematopoezu. Mnogi biljni pripravci kao i pojedine biljne sastavnice imaju antimikrobno, protuupalno te antitumorsko djelovanje te se njihova svojstva sve više istražuju u svrhu zaštite ljudskog zdravlja. Učinak prirodnih sastavnica na hematopoezu je uglavnom stimulativan, iako postoje i neke prirodne sastavnice koje inhibiraju razvoj određene hematopoetske linije. Također je pokazano da štite stanice koštane srži od zračenja te djeluju stimulativno na oporavak nakon kemoterapije.Natural products (plant secondary metabolites) are supstances derived from primary metabolites in secondary reactions. Now their chemical properties are being increasingly investigated and we become more and more aware of their impact on human health. This paper represent a brief review of hematopoiesis, blood cells and natural products and their effect on health and hematopoiesis. Many plant extracts and natural products have antimicrobal, anti-inflammatory and antitumor effect thus their properties are increasingly invesigated for the purpose of protecting human health. Effects of natural products on hematopoiesis is mainly stimulatory, although some natural products have inhibitory effect on development of specific hematopoietic lineage. It has been also proved that they have an protective and stimulative effect on bone marrow cells in case of radiation

Sex-Related Differences in Oxidant and Antioxidant Profiles of Murine Kidney and Brain: A Focus on Sirt3-Mediated Regulation

Background: Sirt3 is a mitochondrial deacetylase with an important role in maintainance of cellular redox and metabolic homeostasis and mitochondrial function. As growing evidence support the existence of sex-specific responses to metabolic and oxidative stress, we aimed to investigate sex- and organ-specific effects of Sirt3 loss. Materials and methods: Expression of Sirt3, PGC-1a, CuZnSOD, MnSOD and Cat proteins in kidneys and brains of Sirt3-wild type (Sirt3 WT) and Sirt3-knockout (Sirt3 KO) mice was assessed by Western blotting. Protein carbonylation and lipid peroxidation levels were measured using ELISA and fluorometric assays, respectively. SOD and Cat activities were determined using standard enzymatic assays. Results: Significant sex- and organ- specific differences in response to Sirt3 loss were detected. Sirt3 knockout affected kidneys more than brain tissue, with females showing lower levels PC and LPO. In kidneys, female KO showed higher MnSOD, but lower CuZnSOD and Cat activity compared to males. In brains, WT females show higher activities of these enzymes than males, suggesting a sex-specific protection mechanism, but female KO brains show a larger decrease in these parameters. Conclusion: Our study provides comprehensive insights into the complex interplay of Sirt3, oxidative stress, and antioxidant defenses in murine kidney and brain. The observed differences between the two organs and the impact of sex highlight the need for studying Sirt3 function in diverse physiological contexts. The tissue-specific responses and sex-related variations underscore the importance of considering these factors in the development of therapeutic strategies targeting mitochondrial function and redox homeostasis

Role of Sirt3 in Differential Sex-Related Responses to a High-Fat Diet in Mice

Metabolic homeostasis is differently regulated in males and females. Little is known about the mitochondrial Sirtuin 3 (Sirt3) protein in the context of sex-related differences in the development of metabolic dysregulation. To test our hypothesis that the role of Sirt3 in response to a high-fat diet (HFD) is sex-related, we measured metabolic, antioxidative, and mitochondrial parameters in the liver of Sirt3 wild-type (WT) and knockout (KO) mice of both sexes fed with a standard or HFD for ten weeks. We found that the combined effect of Sirt3 and an HFD was evident in more parameters in males (lipid content, glucose uptake, pparγ, cyp2e1, cyp4a14, Nrf2, MnSOD activity) than in females (protein damage and mitochondrial respiration), pointing towards a higher reliance of males on the effect of Sirt3 against HFD-induced metabolic dysregulation. The male-specific effects of an HFD also include reduced Sirt3 expression in WT and alleviated lipid accumulation and reduced glucose uptake in KO mice. In females, with a generally higher expression of genes involved in lipid homeostasis, either the HFD or Sirt3 depletion compromised mitochondrial respiration and increased protein oxidative damage. This work presents new insights into sex-related differences in the various physiological parameters with respect to nutritive excess and Sirt3

Interdisciplinary study of the effects of dipeptidyl-peptidase III cancer mutations on the KEAP1-NRF2 signaling pathway

Dipeptidyl peptidase III (DPP III) is associated with cancer progression via interaction with KEAP1, leading to upregulation of the KEAP1-NRF2 oxidative stress pathway. Numerous DPP III mutations have been found in human tumor genomes, and it is suggested that some of them may alter affinity for KEAP1. One such example is the DPP III-R623W variant, which in our previous study showed much higher affinity for the Kelch domain of KEAP1 than the wild-type protein. In this work, we have investigated the effects of this mutation in cultured cells and the effects of several other DPP III mutations on the stability of KEAP1-DPP III complex using an interdisciplinary approach combining biochemical, biophysical and molecular biology methods with computational studies. We determined the affinity of the DPP III variants for the Kelch domain experimentally and by molecular modeling, as well as the effects of the R623W on the expression of several NRF2-controlled genes. We confirmed that the R623W variant upregulates NQO1 expression at the transcriptional level. This supports the hypothesis from our previous study that the increased affinity of the R623W variant for KEAP1 leads to upregulation of the KEAP1-NRF2 pathway. These results provide a new perspective on the involvement of DPP III in cancer progression and prognosis

Chronic high fat diet intake impairs hepatic metabolic parameters in ovariectomized Sirt3 KO mice

High fat diet (HFD) is an important factor in the development of metabolic diseases, with liver as metabolic center being highly exposed to its influence. However, the effect of HFD-induced metabolic stress with respect to ovary hormone depletion and sirtuin 3 (Sirt3) is not clear. Here we investigated the effect of Sirt3 in liver of ovariectomized and sham female mice upon 10 weeks of feeding with standard-fat diet (SFD) or HFD. Liver was examined by Folch, gas chromatography and lipid hydroperoxide analysis, histology and oil red staining, RT-PCR, Western blot, antioxidative enzyme and oxygen consumption analyses. In SFD-fed WT mice, ovariectomy increased Sirt3 and fatty acids synthesis, maintained mitochondrial function, and decreased levels of lipid hydroperoxides. Combination of ovariectomy and Sirt3 depletion reduced pparα, Scd-1 ratio, MUFA proportions, CII-driven respiration, and increased lipid damage. HFD compromised CII-driven respiration and activated peroxisomal ROS scavenging enzyme catalase in sham mice, whereas in combination with ovariectomy and Sirt3 depletion, increased body weight gain, expression of NAFLD- and oxidative stress-inducing genes, and impaired response of antioxidative system. Overall, this study provides evidence that protection against harmful effects of HFD in female mice is attributed to the combined effect of female sex hormones and Sirt3, thus contributing to preclinical research on possible sex-related therapeutic agents for metabolic syndrome and associated diseases

Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells

Estrogen (E2) is a major risk factor for the initiation and progression of malignancy in estrogen receptor (ER) positive breast cancers, whereas sirtuin 3 (Sirt3), a major mitochondrial NAD+-dependent deacetylase, has the inhibitory effect on the tumorigenic properties of ER positive MCF-7 breast cancer cells. Since it is unclear if this effect is mediated through the estrogen receptor alpha (ERα) signaling pathway, in this study, we aimed to determine if the tumor-suppressive function of Sirt3 in MCF-7 cells interferes with their response to E2. Although we found that Sirt3 improves the antioxidative response and mitochondrial fitness of the MCF-7 cells, it also increases DNA damage along with p53, AIF, and ERα expression. Moreover, Sirt3 desensitizes cells to the proliferative effect of E2, affects p53 by disruption of the ERα–p53 interaction, and decreases proliferation, colony formation, and migration of the cells. Our observations indicate that these tumor-suppressive effects of Sirt3 could be reversed by E2 treatment only to a limited extent which is not sufficient to recover the tumorigenic properties of the MCF-7 cells. This study provides new and interesting insights with respect to the functional role of Sirt3 in the E2-dependent breast cancers