Around the world, polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic condition that typically affects 6–20% of females. Our study’s major goal was to examine how chlorogenic acid (CGA) affected mice with endocrine and metabolic problems brought on by letrozole-induced PCOS. Group I served as the control for 81 days; Group II was given Letrozole (LETZ) orally at a dose of 6 mg/kg bw for 21 days to induce PCOS; Group III was given LETZ (6 mg/kg) for 21 days, followed by treatment with CGA (50 mg/kg bw daily) for 60 days. The study indicated that LETZ-treated mice displayed symptoms of PCOS, such as dyslipidemia, hyperinsulinemia, elevated testosterone, increases in inflammatory markers and malonaldehyde, and a decline in antioxidants (Ar, lhr, fshr, and esr2) in the ovaries. These alterations were affected when the mice were given CGA and were associated with reduced levels of adiponectin. Adiponectin showed interactions with hub genes, namely MLX interacting protein like (MLXIPL), peroxisome proliferator-activated receptor gamma Coactivator 1- alpha (PPARGC1), peroxisome proliferator-activated receptor gamma (Pparg), and adiponectin receptor 1 (Adipor1). Lastly, the gene ontology of adiponectin revealed that adiponectin was highly involved in biological processes. The findings from our research suggest that adiponectin has direct impacts on metabolic and endocrine facets of PCOS.
Major epigenetic alterations, such as chromatin modifications, DNA methylation, and miRNA regulation, have gained greater attention and play significant roles in oncogenesis, representing a new paradigm in our understanding of cancer susceptibility. These epigenetic changes, particularly aberrant promoter hypermethylation, abnormal histone acetylation, and miRNA dysregulation, represent a set of epigenetic patterns that contribute to inappropriate gene silencing at every stage of cancer progression. Notably, the cancer epigenome possesses various HDACs and DNMTs, which participate in the histone modifications and DNA methylation. As a result, there is an unmet need for developing the epigenetic inhibitors against HDACs and DNMTs for cancer therapy. To date, several epigenetically active synthetic inhibitors of DNA methyltransferases and histone deacetylases have been developed. However, a growing body of research reports that most of these synthetic inhibitors have significant side effects and a narrow window of specificity for cancer cells. Targeting tumor epigenetics with phytocompounds that have the capacity to modulate abnormal DNA methylation, histone acetylation, and miRNAs expression is one of the evolving strategies for cancer prevention. Encouragingly, there are many bioactive phytochemicals, including organo-sulfur compounds that have been shown to alter the expression of key tumor suppressor genes, oncogenes, and oncogenic miRNAs through modulation of DNA methylation and histones in cancer. In addition to vitamins and microelements, dietary phytochemicals such as sulforaphane, PEITC, BITC, DADS, and allicin are among a growing list of naturally occurring anticancer agents that have been studied as an alternative strategy for cancer treatment and prevention. Moreover, these bioactive organo-sulfur compounds, either alone or in combination with other standard cancer drugs or phytochemicals, showed promising results against many cancers. Here, we particularly summarize and focus on the impact of specific organo-sulfur compounds on DNA methylation and histone modifications through targeting the expression of different DNMTs and HDACs that are of particular interest in cancer therapy and prevention.
Heart failure is a major cause of death worldwide with insufficient treatment options. In the search for pathomechanisms, we found up-regulation of an enzyme, stearoyl-CoA desaturase 1 (Scd1), in different experimental models of heart failure induced by advanced atherosclerosis, chronic pressure overload, and/or volume overload. Because the pathophysiological role of Scd1/SCD in heart failure is not clear, we investigated the impact of cardiac SCD upregulation through the generation of C57BL/6-Tg(MHCSCD)Sjaa mice with myocardium-specific expression of SCD. Echocardiographic examination showed that 4.9-fold-increased SCD levels triggered cardiac hypertrophy and symptoms of heart failure at an age of eight months. Tg-SCD mice had a significantly reduced left ventricular cardiac ejection fraction of 25.7 ± 2.9% compared to 54.3 ± 4.5% of non-transgenic B6 control mice. Whole-genome gene expression profiling identified up-regulated heart-failure-related genes such as resistin, adiponectin, and fatty acid synthase, and type 1 and 3 collagens. Tg-SCD mice were characterized by cardiac lipid accumulation with 1.6- and 1.7-fold-increased cardiac contents of saturated lipids, palmitate, and stearate, respectively. In contrast, unsaturated lipids were not changed. Together with saturated lipids, apoptosis-enhancing p53 protein contents were elevated. Imaging by autoradiography revealed that the heart-failure-promoting and membrane-spanning angiotensin II AT1 receptor protein of Tg-SCD hearts was significantly up-regulated. In transfected HEK cells, the expression of SCD increased the number of cell-surface angiotensin II AT1 receptor binding sites. In addition, increased AT1 receptor protein levels were detected by fluorescence spectroscopy of fluorescent protein-labeled AT1 receptor-Cerulean. Taken together, we found that SCD promotes cardiac dysfunction with overload of cardiotoxic saturated lipids and up-regulation of the heart-failure-promoting AT1 receptor protein.
Plant fractions have a diversity of biomolecules that can be used to make complicated reactions for the bioactive fabrication of metal nanoparticles (NPs), in addition to being beneficial as antioxidant medications or dietary supplements. The current study shows that Urtica dioica (UD) and biologically synthesized silver nanoparticles (AgNPs) of UD have antibacterial and antioxidant properties against bacteria (Escherichia coli and Pseudomonas putida) and Drosophila melanogaster (Oregon R+). According to their ability to scavenge free radicals, DPPH, ABTS, TFC, and TPC initially estimated the antioxidant potential of UD and UD AgNPs. The fabricated AgNPs were analyzed (UV‒Vis, FTIR, EDS, and SEM) to determine the functional groups (alcohol, carboxylic acids, phenol, proteins, and aldehydes) and to observe the shape (agglomerated crystalline and rod-shaped structure). The disc diffusion method was used to test the antimicrobial properties of synthesized Ag-NPs against E. coli and P. putida. For 24 to 120 h, newly enclosed flies and third instar larvae of Drosophila were treated with UD and UD AgNPs. After exposure, tests for biochemical effects (acetylcholinesterase inhibition and protein estimation assays), cytotoxicity (dye exclusion), and behavioral effects (jumping and climbing assays) were conducted. The results showed that nanoparticles were found to have potent antimicrobial activity against all microbial strains tested at various concentrations. In this regard, ethno-medicinal characteristics exhibit a similar impact in D. melanogaster, showing (p < 0.05) significantly decreased cellular toxicity (trypan blue dye), enhanced biochemical markers (AChE efficacy and proteotoxicity), and improved behavioral patterns in the organism treated with UD AgNPs, especially in comparison to UD extract. The results of this study may help in the utilization of specific plants as reliable sources of natural antioxidants that may have been beneficial in the synthesis of metallic NPs, which aids in the production of nanomedicine and other therapeutic applications.
Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future.
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