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Background: Dendritic cells (DCs) loaded with HIV-1 antigens have been explored as a promising therapeutic approach to overcome HIV-1 infection. Heat shock proteins (Hsps) can improve cross-presentation of linked antigens by DCs. Our aim was a comprehensive in silico, in vitro, and in vivo evaluation of fusion proteins comprising the N- and C-terminal regions of Hsp70 (i.e., NT-Hsp70 and CT-Hsp70) as an adjuvant linked to HIV-1 Nef antigen in development of DCs-based vaccine candidates., Methods: Computational analyses of the NT-Hsp70-Nef and CT-Hsp70-Nef fusion constructs were performed, and their structural features and docking ability with toll-like or endocytic receptors were evaluated. The effectiveness of DCs loaded with the fusion proteins in eliciting immunity was assessed in mice. Cytokine secretion levels from splenocytes exposed to single-cycle replicable (SCR) HIV-1 were also measured in vitro., Results: The DCs pulsed with the fusion constructs induced robust cellular and humoral immune responses in mice and infected splenocytes. The CT-Hsp70 region showed better docking scores with immune receptors and superior adjuvanticity for inducing Nef-specific immune responses (Th1 and CTL activity) compared to the NT-Hsp70 region in DC-based immunization., Conclusions: The CT-Hsp70-Nef protein demonstrated promising results in both computational and experimental analyses compared to the NT-Hsp70-Nef protein., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2025 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Purpose of Review: Fusobacterium nucleatum (F. nucleatum), an anaerobic, gram-negative microbe, commonly found in human dental biofilm and the gut flora. It has long been known to have a higher concentration in periodontal disease and has recently been implicated in both oral and distant cancers such as colorectal, gastrointestinal, esophageal, breast, pancreatic hepatocellular, and genitourinary cancers. However, the mechanism of its involvement in the development of cancer has not been fully discussed. This review aims to cover biological molecular and clinical aspects of F. nucleatum and cancers., Recent Findings: Studies indicate F. nucleatum promotes tumor development through chronic inflammation, immune evasion, cell proliferation activation, and direct cell interactions, as in oral squamous cell carcinoma (OSCC). In colorectal cancer (CRC), F. nucleatum contributes to tumorigenesis through β-catenin signaling and NF-κB activation. It also induces autophagy, leading to chemoresistance in CRC and esophageal cancers, and enhances tumor growth and metastasis in breast cancer by reducing T-cell infiltration. F. nucleatum is linked to carcinogenesis and increased bacterial diversity in OSCC, with improved oral hygiene potentially preventing OSCC. F. nucleatum triggers cancer by causing mutations and epigenetic changes through cytokines and reactive oxygen species. It also promotes chemoresistance in CRC. F. nucleatum may potentially serve as a diagnostic tool in various cancers, with non-invasive detection methods available. Further investigation is needed to discover its potential in the diagnosis and treatment of OSCC and other cancers., Competing Interests: Declarations. Ethical Approval: Not applicable. Informed Consent: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. Crown.)

Background: Heat shock proteins (HSPs) as an adjuvant induce antigen-specific immunity through facilitating antigen presentation and stimulating T cells. In this study, the immunostimulatory properties of two major fragments of Hsp70 (N-Hsp70 (aa 1-387) with ATPase property and C-Hsp70 (aa 508-641) with peptide-binding capacity) and the full length of Hsp27 as vaccine adjuvants were evaluated to boost HIV-1 Nef antigen-specific immunity in both in vitro and in vivo experiments., Methods: At first, the nanoparticles harbouring DNA fusion constructs (i.e. N-Hsp70-Nef, C-Hsp70-Nef and Hsp27-Nef) complexed with HIV Rev (34-50) cell-penetrating peptide were generated to deliver DNA into the cells. Then, the recombinant Nef, Hsp27-Nef, N-Hsp70-Nef and C-Hsp70-Nef proteins were generated in E.coli expression system. Next, the immunostimulatory properties of these fusion constructs were evaluated in both in vitro and in vivo studies. Finally, the secretion of main cytokines from single-cycle replicable (SCR) HIV-1 virion-exposed splenocytes was investigated., Results: Our data showed that the stable and non-toxic DNA/Rev nanoparticles could successfully deliver the genes of interest into the cells. Moreover, higher secretion of antibodies and cytokines was detected in mice receiving the Hsp-Nef constructs than in mice receiving Nef antigen. The C-Hsp70 was also superior for inducing Nef-specific Th1 and CTL immunity compared with N-Hsp70 and Hsp27. The T-cell activity was maintained in the SCR-exposed splenocytes, especially the splenocytes of mice receiving the C-Hsp70-Nef regimen., Conclusion: Altogether, these findings demonstrate the significance of Hsps as enhancers of antigen-specific immunity. Notably, the C-Hsp70 region showed better adjuvant properties for inducing cellular immunity in the improvement of HIV-1 therapeutic vaccines., (© 2023 British HIV Association.)

High-risk human papillomaviruses (HR-HPVs) cause various malignancies in the anogenital and oropharyngeal regions. About 70% of cervical and oropharyngeal cancers are caused by HPV types 16 and 18. Notably, some viruses including herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus along with various bacteria often interact with HPV, potentially impacting its replication, persistence, and cancer progression. Thus, HPV infection can be significantly influenced by co-infecting agents that influence infection dynamics and disease progression. Bacterial co-infections (e.g., Chlamydia trachomatis) along with bacterial vaginosis-related species also interact with HPV in genital tract leading to viral persistence and disease outcomes. Co-infections involving HPV and diverse infectious agents have significant implications for disease transmission and clinical progression. This review explores multiple facets of HPV infection encompassing the co-infection dynamics with other pathogens, interaction with the human microbiome, and its role in disease development., (© 2023 Wiley Periodicals LLC.)

Heat shock proteins (HSPs) improve cross-presentation of linked tumor antigens, thus they can be exploited in therapeutic vaccine design. Herein, in silico analyses of different vaccine constructs were performed based on human papillomavirus (HPV)-16 E7 protein linked to Homo sapiens/Mus musculus Hsp27 or Hsp70 in multiepitope and whole sequence forms. Then, computational comparison between different orientations of Hsp/E7 was carried out in both forms. Finally, molecular docking was performed between the designed constructs and signaling (TLRs) or endocytic (CD14, LOX-1 and SREC-1) receptors. Our data represented the high-ranked T-cell epitopes and the potential B-cell epitopes of Homo sapiens/Mus musculus Hsp27 and Hsp70. Moreover, molecular docking showed that whole sequence of Hsp27 had better interaction with all receptors than whole sequence of Hsp70 suggesting likely stronger stimulation of innate and adaptive immunity. All designed Homo sapiens/Mus musculus Hsp27/E7 constructs had better docking scores with the endocytic receptors especially SREC-1 than all designed Homo sapiens/Mus musculus Hsp70/E7 constructs in both orientations. Generally, the multiepitope-/whole sequence-based Homo sapiens/Mus musculus Hsp27-E7 fusion constructs showed more conservancy and immunogenicity than other designed constructs. These fusion constructs were non-allergenic, non-toxic and stable suggesting them as promising vaccine candidates against HPV-related cancers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Despite the success of Antiretroviral Therapy (ART) in preventing HIV-1-associated clinical progression to AIDS, it is unable to eliminate the viral reservoirs and eradicate the HIV-1 infection. Therapeutic vaccination is an alternative approach to alter the HIV-1 infection course. It can induce effective HIV-1-specific immunity to control viremia and eliminate the need for lifelong ART. Immunological data from spontaneous HIV-1 controllers have shown that cross-reactive T-cell responses are the key immune mechanism in HIV-1 control. Directing these responses toward preferred HIV-1 epitopes is a promising strategy in therapeutic vaccine settings. Designing novel immunogens based on the HIV-1 conserved regions containing a wide range of critical T- and B-cell epitopes of the main viral antigens (conserved multiepitope approaches) supplies broad coverage of global diversity in HIV-1 strains and Human Leukocyte Antigen (HLA) alleles. It can also prevent immune induction to undesirable decoy epitopes theoretically. The efficacy of different novel HIV-1 immunogens based on the conserved and/or functional protective site of HIV-1 proteome has been evaluated in multiple clinical trials. Most of these immunogens were generally safe and able to induce potent HIV-1-specific immunity. However, despite these findings, several candidates have demonstrated limited efficacy in viral replication control. In this study, we used the PubMed and ClinicalTrial.gov databases to review the rationale of designing curative HIV-1 vaccine immunogens based on the conserved favorable site of the virus. Most of these studies evaluate the efficacy of vaccine candidates in combination with other therapeutics and/or with new formulations and immunization protocols. This review briefly describes the design of conserved multiepitope constructs and outlines the results of these vaccine candidates in the recent clinical pipeline., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Therapeutic human immunodeficiency virus (HIV) vaccines can boost the anti-HIV host immunity to control viral replication and eliminate viral reservoirs in the absence of anti-retroviral therapy. In this study, two computationally designed multiepitope Gag-Pol-Env-Nef-Rev and Hsp70-Gag-Pol-Env-Nef-Rev constructs harboring immunogenic and highly conserved HIV T cell epitopes were generated in E. coli as polypeptide vaccine candidates. Furthermore, the multiepitope gag-pol-env-nef-rev and hsp70-gag-pol-env-nef-rev DNA vaccine constructs were prepared and complexed with MPG cell-penetrating peptide. The immunogenicity of the multiepitope constructs were evaluated using the homologous and heterologous prime/boost strategies in mice. Moreover, the secretion of IFN-γ was assessed in infected lymphocytes in vitro. Our data showed that the homologous polypeptide regimens could significantly induce a mixture of IgG1 and IgG2a antibody responses, activate T cells to secret IFN-γ, IL-5, IL-10, and generate Granzyme B. Moreover, IFN-γ secretion was significantly enhanced in single-cycle replicable (SCR) HIV-1 virions-infected splenocytes in these groups compared to uninfected splenocytes. The linkage of heat shock protein 70 (Hsp70) epitopes to Gag-Pol-Env-Nef-Rev polypeptide in the homologous regimen increased significantly cytokines and Granzyme B levels, and IFN-γ secretion in virions-infected splenocytes. Briefly, both designed constructs in the homologous regimens can be used as a promising vaccine candidate against HIV infection., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Objectives: Epitope-driven vaccines carrying highly conserved and immunodominant epitopes have emerged as promising approaches to overcome human immunodeficiency virus-1 (HIV-1) infection., Methods: Two multiepitope DNA constructs encoding T cell epitopes from HIV-1 Gag, Pol, Env, Nef and Rev proteins alone and/or linked to the immunogenic epitopes derived from heat shock protein 70 (Hsp70) as an immunostimulatory agent were designed. In silico analyses were applied including MHC-I and MHC-II binding, MHC-I immunogenicity and antigen processing, population coverage, conservancy, allergenicity, toxicity and hemotoxicity. The peptide-MHC-I/MHC-II molecular docking and cytokine production analyses were carried out for predicted epitopes. The selected highly immunogenic T-cell epitopes were then used to design two multiepitope fusion constructs. Next, prediction of the physicochemical and structural properties, B cell epitopes, and constructs-toll-like receptors (TLRs) molecular docking were performed for each construct. Finally, the eukaryotic expression plasmids harboring totally 12 cytotoxic T Lymphocyte (CTL) and 10 helper T lymphocytes (HTL) epitopes from HIV-1 proteins (i.e., pEGFP-N1-gag-pol-env-nef-rev), and linked to 2 CTL and 2 HTL epitopes from Hsp70 (i.e., pEGFP-N1-hsp70-gag-pol-env-nef-rev) were generated and transfected into HEK-293 T cells for evaluating the percentage of multiepitope peptides expression using flow cytometry and western blotting., Results: The designed DNA constructs could be successfully expressed in mammalian cells. The expression rates of Gag-Pol-Env-Nef-Rev-GFP and Hsp70-Gag-Pol-Env-Nef-Rev-GFP were about 56-60% as the bands of ~ 63 and ~ 72 kDa confirmed in western blotting, respectively., Conclusion: The combined in silico/in vitro methods indicated two multiepitope constructs can be produced and used as probable effective immunogens for HIV-1 vaccine development.

Hydrogels are a three-dimensional and crosslinked network of hydrophilic polymers. They can absorb a large amount of water or biological fluids, which leads to their swelling while maintaining their 3D structure without dissolving (Zhu and Marchant, Expert Rev Med Devices 8:607-626, 2011). Among the numerous polymers which have been utilized for the preparation of the hydrogels, polysaccharides have gained more attention in the area of pharmaceutics; Sodium alginate is a non-toxic, biocompatible, and biodegradable polysaccharide with several unique physicochemical properties for which has used as delivery vehicles for drugs (Kumar Giri et al., Curr Drug Deliv 9:539-555, 2012). Owing to their high-water content and resembling the natural soft tissue, hydrogels were studied a lot as a scaffold. The formation of hydrogels can occur by interactions of the anionic alginates with multivalent inorganic cations through a typical ionotropic gelation method. However, those applications require the control of some properties such as mechanical stiffness, swelling, degradation, cell attachment, and binding or release of bioactive molecules by using the chemical or physical modifications of the alginate hydrogel. In the current review, an overview of alginate hydrogels and their properties will be presented as well as the methods of producing alginate hydrogels. In the next section of the present review paper, the application of the alginate hydrogels will be defined as drug delivery vehicles for chemotherapeutic agents. The recent advances in the application of the alginate-based hydrogels will be describe later as a wound dressing and bioink in 3D bioprinting., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Synthetic antioxidants can reduce postharvest losses, but consumers are concerned about chemical residues in the product. There is a growing interest in using natural compounds for the preservation of foods. In this study, the efficiency of juices or extracts obtained from three fruit species with high antioxidant activity as browning inhibitors was measured and then compared with that obtained from pomegranate by-product (PBP). The aim was to offer the most significant contributions concerning fresh-cut fruit preservation, using 'Shahmive' pear as the fruit model. Slices of pear were dipped in pomegranate juice (PJ) or extract (PE), kiwifruit juice (KJ) or extract (KE), grape juice (GJ) or extract (GE), PBP and chitosan before being stored at 4 °C. The total phenolic content of solutions ranged from 11 to 127.5 mg gallic acid/100 mL. Extracts of pomegranate peel and grape had the uppermost and the lowermost antioxidant activity (%DPPH), respectively. In comparison with other treatments including the control one, the minimum peroxidase (POD) activity, the maximum ascorbic acid content and the retention of firmness were seen in the fruit which was treated with kiwifruit extract. PJ + GJ treatment decreased POD and polyphenol oxidase activity and improved L* and a* values in the slices. The use of fruit juice or extracts had no adverse effect on the sensory quality of slices, with the exception of samples subjected to PJ or GJ + KJ treatments. Improving antioxidant capacity of fresh cut pear treated with KE and PJ + GJ would have a big advantage of preventing enzymatic browning.