Explore the vast range of titles available.

We have made artificial extracellular vesicles like nanoparticles that contain biologically active Agomir (miRNA mimic)/Antagomir (miRNA inhibitor) adsorbed on magnetic ZnO particles bound by a lipid bilayer membrane from Caco-2 cells (human colorectal adenocarcinoma), which we examined for use as therapeutic nanoparticles or as delivery vehicles for therapeutic agents to the gut epithelia. Magnetic ZnO nanoparticles were synthesized using Manganese doping in both solid-state reaction (SSR) and alkaline aqueous solution methods. The SSR method exhibited ferromagnetic behavior, whereas the alkaline solution method yielded a nanorod-like morphology. Encapsulation was demonstrated using mercaptosuccinic acid. These biocompatible nanoparticles, owing to their nanorod-like morphology with larger surface area, were used to adsorb miR200c antagomir/agomir molecules as well as assemble lipid membrane fragments from Caco-2 cells. We performed various in vivo efficacy studies of Caco-2 NanoVesicles (CNVs) (Caco-2NanoVesicles) or detrimental CNV (therapeutic Caco-2 NanoVesicles (tCNVs)) loaded with miR200c Agomir that degrade occludin protein-coding mRNA as a proof of concept for clinical use of the Antagomir counterpart. There was no discernible toxicity, mortality, or systemic inflammatory or immunological responses in mice following administration of either CNVs or tCNVs. tCNV administration enhances intestinal permeability in mice. This supports their use as biological Nano-therapeutics to restore the gut barrier.

The author highlighted the dual role of Tau protein: in its normal physiological state, it serves as a protective agent against DNA damage and regulates DNA packaging, while in its pathogenic state, it induces oxidative stress, disrupts the nucleoskeleton, and triggers apoptotic cell death. Since this protein is highly conserved among orthopoxviruses, the A42R inhibitors may be widely used to also target other members of the same family. In addition to viruses that infect humans, there are several that specifically target birds, animals, and aquatic wildlife, posing significant threats to the food industry and animal farming (Meseko et al., 2023a).

As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs. Intranasal immunization of IFNAR1 −/− mice and female hamsters with TVCs generated high levels of S-specific serum IgG antibodies, broad neutralizing antibodies, and mucosal IgA antibodies as well as tissue-resident memory T cells in the lungs. The immunized female hamsters were protected from challenge with SARS-CoV-2 original WA1, B.1.617.2, and B.1.1.529 strains. The preexisting MeV and MuV immunity does not significantly interfere with the efficacy of TVC. Thus, the trivalent platform is a promising next-generation SARS-CoV-2 vaccine candidate. In this study, the authors developed intranasal measles virus and mumps virus-based trivalent vaccines, each expressing three distinct SARS-CoV-2 stabilized prefusion spike proteins. They show that the intranasal vaccines provide protection against infection of SARS-CoV-2 variants in small animal models.

Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA’s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions.

IntroductionAdjuvants added to subunit vaccines augment antigen-specific immune responses. One mechanism of adjuvant action is activation of pattern recognition receptors (PRRs) on innate immune cells. Bordetella colonization factor A (BcfA); an outer membrane protein with adjuvant function, activates TH1/TH17-polarized immune responses to protein antigens from Bordetella pertussis and SARS CoV-2. Unlike other adjuvants, BcfA does not elicit a TH2 response.MethodsTo understand the mechanism of BcfA-driven TH1/TH17 vs. TH2 activation, we screened PRRs to identify pathways activated by BcfA. We then tested the role of this receptor in the BcfA-mediated activation of bone marrow-derived dendritic cells (BMDCs) using mice with germline deletion of TLR4 to quantify upregulation of costimulatory molecule expression and cytokine production in vitro and in vivo. Activity was also tested on human PBMCs.ResultsPRR screening showed that BcfA activates antigen presenting cells through murine TLR4. BcfA-treated WT BMDCs upregulated expression of the costimulatory molecules CD40, CD80, and CD86 and produced IL-6, IL-12/23 p40, and TNF-α while TLR4 KO BMDCs were not activated. Furthermore, human PBMCs stimulated with BcfA produced IL-6. BcfA-stimulated murine BMDCs also exhibited increased uptake of the antigen DQ-OVA, supporting a role for BcfA in improving antigen presentation to T cells. BcfA further activated APCs in murine lungs. Using an in vitro TH cell polarization system, we found that BcfA-stimulated BMDC supernatant supported TFH and TH1 while suppressing TH2 gene programming.ConclusionsOverall, these data provide mechanistic understanding of how this novel adjuvant activates immune responses.

Potato biofortification is a comprehensive approach aimed at enhancing the nutritional content of potatoes, addressing widespread nutrient deficiencies and contributing to global food security. This systematic review examines the existing literature on various aspects of potato biofortification, encompassing genetic, agronomic, and biotechnological strategies. The review highlights the nutritional significance of potatoes, emphasizing their role as a staple food in many regions. Genetic approaches to biofortification involve the identification and use of natural variations in potato germplasm to develop varieties with elevated levels of essential nutrients. This includes targeting key micronutrients, such as iron, zinc, and vitamins, through traditional breeding methods. The review explores the genetic diversity within potato germplasm and the potential for breeding programs to develop nutrient-rich varieties. Agronomic practices play a crucial role in potato biofortification, with studies demonstrating the impact of tuber priming and the application of mineral fertilizers on nutrient concentrations in potatoes. The review delves into the intricacies of agronomic biofortification, emphasizing the importance of precise dosages and timing for optimal results. Biotechnological tools, including transgenic and non-transgenic approaches, are discussed in the context of potato biofortification. The review evaluates the efficiency and ethical considerations associated with the development of biofortified transgenic potatoes and emphasizes the significance of non-transgenic approaches in addressing consumer concerns and regulatory barriers. Overall, this systematic review provides a comprehensive overview of the current state of potato biofortification research. It synthesizes findings from diverse studies, offering insights into the potential of biofortified potatoes to address hidden hunger and contribute to improved nutritional outcomes. This review also identifies knowledge gaps and areas for future research, guiding the direction of efforts to harness the full potential of potato biofortification for global food and nutrition security.

Pertussis, caused by ( ), results in severe morbidity and mortality in infants. Since 2012, the tetanus, diphtheria and pertussis (Tdap) booster vaccine is recommended during every pregnancy to protect infants who are too young to be immunized. While infants of whole cell pertussis vaccine (wPV)-primed pregnant individuals are well protected from severe disease, the effectiveness of this strategy has not been assessed in acellular pertussis vaccine (aPV)-primed pregnant women. Our primary objective was to compare the cellular and humoral immune responses following Tdap booster in pregnant participants who received the wPV or aPV as infants. As a secondary objective we compared responses of pregnant women to wPV- and aPV-primed non-pregnant controls. All pertussis and non-pertussis specific serum antibody levels increased post-Tdap booster in aPV- and wPV-primed groups. Antibody avidity was higher in wPV-primed pregnant participants compared to aPV-primed pregnant women before and after Tdap booster. In contrast, antibody opsonic activity remained unchanged in either priming group. Antibody secreting cells specific for all pertussis and non-pertussis antigens increased following booster immunization. Expression of early T cell activation markers OX-40, PD-L1 and CD25 and cytokines IFNγ, IL-17 and IL-4 showed that T cell function was unaffected by Tdap booster and maintained the phenotypes elicited by the childhood priming vaccine. Secondary analysis showed that antibody and T cell responses to Tdap booster were higher in nonpregnant control participants compared to pregnant women, suggesting that responses to Tdap booster were blunted in pregnancy.

New carborane-bearing hydroxamate matrix metalloproteinase (MMP) ligands have been synthesized for boron neutron capture therapy (BNCT) with nanomolar potency against MMP-2, -9 and -13. New analogs are based on MMP inhibitor CGS-23023A, and two previously reported MMP ligands 1 (B1) and 2 (B2) were studied in vitro for BNCT activity. The boronated MMP ligands 1 and 2 showed high in vitro tumoricidal effects in an in vitro BNCT assay, exhibiting IC50 values for 1 and 2 of 2.04 × 10−2 mg/mL and 2.67 × 10−2 mg/mL, respectively. The relative killing effect of 1 to L-boronophenylalanine (BPA) is 0.82/0.27 = 3.0, and that of 2 is 0.82/0.32 = 2.6, whereas the relative killing effect of 4 is comparable to boronophenylalanine (BPA). The survival fraction of 1 and 2 in a pre-incubation boron concentration at 0.143 ppm 10B and 0.101 ppm 10B, respectively, were similar, and these results suggest that 1 and 2 are actively accumulated through attachment to the Squamous cell carcinoma (SCC)VII cells. Compounds 1 and 2 very effectively killed glioma U87 delta EGFR cells after BNCT. This study is noteworthy in demonstrating BNCT efficacy through binding to MMP enzymes overexpressed at the surface of the tumor cell without tumor cell penetration.

Background Dysmotility and postoperative ileus (POI) are frequent major clinical problems post-abdominal surgery. Erythropoietin (EPO) is a multifunctional tissue-protective cytokine that promotes recovery of the intestine in various injury models. While EPO receptors (EPOR) are present in vagal Schwann cells, the role of EPOR in POI recovery is unknown because of the lack of EPOR antagonists or Schwann-cell specific EPOR knockout animals. This study was designed to explore the effect of EPO via EPOR in vagal nerve Schwann cells in a mouse model of POI. Results The structural features of EPOR and its activation by EPO-mediated dimerization were understood using structural analysis. Later, using the Cre-loxP system, we developed a myelin protein zero (Mpz) promoter-driven knockout mouse model of Schwann cell EPOR (MpzCre-EPOR flox/flox / Mpz-EPOR-KO) confirmed using PCR and qRT-PCR techniques. We then measured the intestinal transit time (ITT) at baseline and after induction of POI with and without EPO treatment. Although we have previously shown that EPO accelerates functional recovery in POI in wild type mice, EPO treatment did not improve functional recovery of ITT in POI of Mpz-EPOR-KO mice. Conclusions To the best of our knowledge, this is the first pre-clinical study to demonstrate a novel mouse model of EPOR specific knock out on Schwan cells with an effect in the gut. We also showed novel beneficial effects of EPO through vagus nerve Schwann cell-EPOR in intestinal dysmotility. Our findings suggest that EPO-EPOR signaling in the vagus nerve after POI is important for the functional recovery of ITT.

Pregnancy is a physiological process accompanied by immuno-dynamic changes (inflammatory stages) that could influence or predict pregnancy outcomes. However, overlapping data intervals among biologically distinct conditions may hinder such differentiation. Here, a retrospective, proof-of-concept study was conducted to (a) differentiate pregnancy-related inflammatory stages, and (b) to prognosticate birth-related double risks (low birth weight and pre-term birth) based on blood tests of pregnant women. Blood samples collected from 131 Indian pregnant females (192 temporal observations) were retrospectively analyzed with: (1) a reductionist approach, which investigates cell types individually; and (2) a non-reductionist alternative, which uses a proprietary software package to explore pre-partum multicellular interactions and birth-related outcomes. Leukocyte percentages collected during the second and third trimesters were utilized to predict double risks. While the reductionist analysis failed to distinguish double risks (ambiguity was observed), the non-reductionist method differentiated four inflammatory stages, characterized by: (i) no double risk and a high phagocyte/lymphocyte (P/L) ratio (class 'A'), (ii) no double risk and a very low P/L ratio (class 'B'), (iii) 16.6% double risks and a moderately elevated phagocyte/ lymphocyte (P/L) ratio (class 'C'), and (iv) 83.3% double risks and the highest monocyte percentage (class 'D'). All double risks observations were associated with statistically higher concentrations of serum ferritin. Combined, longitudinal clinical-inflammatory and personalized data patterns inform whether a pregnancy is associated with double risks and/or when changes occur. Considering pre-partum observations anticipated birth-related outcomes, personalized and prognostic features were demonstrated. Since antenatal care involves routine blood sampling (a low-cost procedure), this methodology is inherently translational. Because construct, internal, external, and statistical validity were supported, if corroborated with prospective studies, this method may assist United Nations' 2023 goals toward reducing infant mortality.