https://digital.csic.es/bitstream/10261/170827/4/ProgLipResPostprint.pdf

A global perspective on carotenoids: Metabolism, biotechnology, and benefits for nutrition and health

Carotenoids in human nutrition and health

This review gives an updated picture of each class of phenolic compounds and their properties. The most common classification implies the subdivision of phenolics in two main groups: flavonoids (e.g., anthocyanins, flavanols, flavanones, flavonols, flavonones, and isoflavones) and non-flavonoids (e.g., phenolic acids, xanthones, stilbens, lignans, and tannins) polyphenols. The great interest in polyphenols is associated with their high potential application for food preservation and for therapeutic beneficial use. The relationship between polyphenol intake and human health has been exploited with special reference to cardiovascular diseases, hypertension, diabetes, metabolic syndrome, obesity, and cancer. The use of current existing databases of bioactive compounds including polyphenols is described as key tools for human health research.

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Polyphenols: A concise overview on the chemistry, occurrence, and human health

Methylation of arginine residues by protein arginine methyltransferases (PRMTs) is involved in the regulation of fundamental cellular processes, including transcription, RNA processing, signal transduction cascades, the DNA damage response and liquid-liquid phase separation. Recent studies have provided considerable advances in the development of experimental tools and the identification of clinically relevant PRMT inhibitors. In this review, we discuss the regulation of PRMTs, their various cellular roles and the clinical relevance of PRMT inhibitors for the therapy of neurodegenerative diseases and cancer.

The regulation, functions and clinical relevance of arginine methylation.

Nanoencapsulation of carotenoids within lipid-based nanocarriers.

Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation‐related proteins, retinoid‐like receptors, antioxidant response element, nuclear receptors, AP‐1 transcriptional complex, the Wnt/β‐catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B‐ and T‐lymphocytes, the activity of macrophages and cytotoxic T‐cells, effector T‐cell function and the production of cytokines. Recently, the beneficial effects of carotenoid‐rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β‐carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time‐ and dose‐dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.13625

Carotenoids: biochemistry, pharmacology and treatment

Heat-shock proteins (HSPs) have been involved in different functions including chaperone activity, protein folding, apoptosis, autophagy and immunity. The HSP families have powerful effects on the stimulation of innate immune responses through Toll-like receptors and scavenger receptors. Moreover, HSP-mediated phagocytosis directly enhances the processing and presentation of internalized antigens via the endocytic pathway in adaptive immune system. These properties of HSPs have been used for development of prophylactic and therapeutic vaccines against infectious and noninfectious diseases. Several studies also demonstrated the relationship between HSPs and drug resistance as well as their use as a novel biomarker for detecting tumors in patients. The present review describes different roles of HSPs in biology and medicine especially biochemical and immunological aspects.

Heat-shock proteins in diagnosis and treatment: an overview of different biochemical and immunological functions.

Background Hepatitis C (HCV) is known as a serious blood-borne disease that infects millions of people globally. NS3 is a conserved non-structural sequence of hepatitis C virus which has a major role in activating specific CTL responses. As known, there is no effective vaccine against HCV infection, thus it is required to design a specific regimen of vaccination. Recently, the strong immunological properties of Heat shock proteins (Hsps) led to their use as immunomodulators and an antigen carrier for subunit vaccine candidates. In the current study, the role of Hsp20 was evaluated as a HCV NS3 gene carrier in mammalian cell line. Methods At first, the recombinant plasmids of pEGFP-Hsp20, pEGFP-NS3, and pEGFP-Hsp20-NS3 were constructed and their accuracy was confirmed by digestion and sequencing. Then, all recombinant plasmids were transfected into HEK293T cells by Lipofectamine and TurboFect gene delivery systems. Finally, the expression of proteins was assessed by fluorescent microscopy, western blotting, and flow cytometry. Results In western blotting, the 47, 59, and 79 kDa bands were detected for pEGFP-Hsp20, pEGFP-NS3, and pEGFP-Hsp20-NS3, respectively. The percentage of NS3-Hsp20-GFP protein expression was ∼67% by TurboFect and ∼50% by Lipofectamine indicating high potency of TurboFect delivery system. Furthermore, the expression of Hsp20 (∼83%) was higher than NS3 (∼58%) in the cells transfected by TurboFect using flow cytometry analysis. This result was confirmed in the expression of Hsp20-NS3 fusion (∼67%) in which Hsp20 increased the delivery of HCV NS3 in vitro. The same data were obtained by Lipofectamine transfection reagent. Conclusion Briefly, our data confirmed the role of Hsp20 as a suitable antigen carrier for DNA vaccine design.

/pdf/the-distinct-role-of-small-heat-shock-protein-20-on-hcv-ns3-31sefljxeh.pdf

The Distinct Role of Small Heat Shock Protein 20 on HCV NS3 Expression in HEK-293T Cell Line.

Background Hepatitis C Virus (HCV) is a major cause of chronic liver disease in the world. Many studies showed that T-cell responses to HCV Nonstructural Protein 3 (NS3) play an important role in clearing acute HCV infections, thus NS3 can be considered as a suitable candidate antigen for development of a HCV therapeutic vaccine. Objective We used Hp91 peptide and small heat shock protein 20 as an adjuvant for enhancement of NS3-specific humoral and cellular immunity in mice. Method In this study, various NS3 DNA and protein constructs were generated in eukaryotic and prokaryotic expression systems, and their potency in eliciting humoral and cellular immune responses was compared using small Heat shock protein 20 (Hsp20), the High Mobility Group Box 1 protein (HMGB1)-derived peptide (Hp91), and Freund's adjuvant in a BALB/c mouse model. Results Our results indicated that both the Hsp20 conjugated with NS3 protein and Hp91 significantly enhanced the levels of IgG2a, IgG2b and IFN-γ directed toward Th1 responses compared to other groups. Moreover, the immunostimulatory properties of Hp91 were significantly higher than Hsp20 and Freund's adjuvant in various immunization strategies. Mice immunized by NS3 protein formulated with Freund's adjuvant, and also mixed with Hp91 peptide showed higher secretion of Granzyme B than other groups. Conclusion Hp91 peptide could develop NS3-specific B- and T-cell immune responses as a promising HCV therapeutic vaccine candidate in future.

Development of HCV Therapeutic Vaccines Using Hp91 Peptide and Small Heat Shock Protein 20 as an Adjuvant

Both prokaryotes and eukaryotes tolerate different stress conditions (e.g., metabolic, environmental and pathophysiological stress) by up-regulating the expression of heat shock proteins (HSPs). These proteins are divided into six main families such as Hsp100, Hsp90, Hsp70, Hsp60, Hsp40 and small heat shock proteins (sHsps) based on their molecular weights (MW) and sequence homology [1, 2]. Among them, sHsps (MW: 12-43 kDa) including Hsp27, αAand αB-crystallin are distinguished by the presence of a highly conserved sequence (80-100 amino acids) called as the “α-crystallin domain” (ACD) [3-5]. The studies showed that Hsps are targets of the host immune responses (e.g., Hsp60 in bacterial infections) [6] and play a significant role as a biomarker in infectious diseases. For example, women with pre-existing antibody responses to chlamydial Hsp60 (CHsp60) indicated a high risk of developing pelvic inflammatory disease (PID) during a new chlamydial infection as compared to women without CHsp60 antibody [7]. Hsps can elicit strong humoral and cellular immune responses in various infectious diseases [8], [9]. For instance, antibody and T cell responses specific for Hsp60 were induced in leprosy and tuberculosis (TB) patients as well as in individuals vaccinated with Mycobacterium bovis BCG [8, 10-12]. In contrast, Hsp70 has an important role in viral infections such as rabies virus infection [13].

Marzieh Basirnejad

Papers

Carotenoids: biochemistry, pharmacology and treatment

Heat-shock proteins in diagnosis and treatment: an overview of different biochemical and immunological functions.

The Distinct Role of Small Heat Shock Protein 20 on HCV NS3 Expression in HEK-293T Cell Line.

Development of HCV Therapeutic Vaccines Using Hp91 Peptide and Small Heat Shock Protein 20 as an Adjuvant

HSP Roles as Biomarkers and Antigens in Bacterial and Viral Infections