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Viruses May 2024The viral interferon regulatory factors (vIRFs) of KSHV are known to dysregulate cell signaling pathways to promote viral oncogenesis and to block antiviral immune...
The viral interferon regulatory factors (vIRFs) of KSHV are known to dysregulate cell signaling pathways to promote viral oncogenesis and to block antiviral immune responses to facilitate infection. However, it remains unknown to what extent each vIRF plays a role in gene regulation. To address this, we performed a comparative analysis of the protein structures and gene regulation of the four vIRFs. Our structure prediction analysis revealed that despite their low amino acid sequence similarity, vIRFs exhibit high structural homology in both their DNA-binding domain (DBD) and IRF association domain. However, despite this shared structural homology, we demonstrate that each vIRF regulates a distinct set of KSHV gene promoters and human genes in epithelial cells. We also found that the DBD of vIRF1 is essential in regulating the expression of its target genes. We propose that the structurally similar vIRFs evolved to possess specialized transcriptional functions to regulate specific genes.
Topics: Humans; Interferon Regulatory Factors; Herpesvirus 8, Human; Epithelial Cells; Viral Proteins; Gene Expression Regulation, Viral; Promoter Regions, Genetic; Transcription, Genetic; Genome, Viral; Cell Line
PubMed: 38932139
DOI: 10.3390/v16060846 -
Viruses May 2024The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple... (Review)
Review
The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.
Topics: SARS-CoV-2; Humans; COVID-19; Animals; Spike Glycoprotein, Coronavirus; Mice; Post-Acute COVID-19 Syndrome; Angiotensin-Converting Enzyme 2; Peptides; Antiviral Agents; COVID-19 Drug Treatment
PubMed: 38932130
DOI: 10.3390/v16060838 -
Pharmaceutics May 2024Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids...
Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids extracted from The primary aim of this study was to investigate the exceptional stability of archaeosomes as potential carriers for oral drug delivery, with a focus on powdered formulations. The archaeosomes were negatively charged with a size of approximately 100 nm and a low polydispersity index. To assess their suitability for oral delivery, the archaeosomes were loaded with two model drugs: calcein, a fluorescent compound, and insulin, a peptide hormone. The archaeosomes demonstrated high stability in simulated intestinal fluids, with only 5% of the encapsulated compounds being released after 24 h, regardless of the presence of degrading enzymes or extremely acidic pH values such as those found in the stomach. In a co-culture cell model system mimicking the intestinal barrier, the archaeosomes showed strong adhesion to the cell membranes, facilitating a slow release of contents. The archaeosomes were loaded with insulin in a single-step procedure achieving an encapsulation efficiency of approximately 35%. These particles have been exposed to extreme manufacturing temperatures during freeze-drying and spray-drying processes, demonstrating remarkable resilience under these harsh conditions. The fabrication of stable dry powder formulations of archaeosomes represents a promising advancement toward the development of solid dosage forms for oral delivery of biological drugs.
PubMed: 38931818
DOI: 10.3390/pharmaceutics16060694 -
Nutrients Jun 2024The immune system is affected by the dietary products humans intake. Immune system regulation by nutrition has uses in the clinical context, but it can also benefit... (Randomized Controlled Trial)
Randomized Controlled Trial
Prospective, Randomized, Double-Blind Parallel Group Nutritional Study to Evaluate the Effects of Routine Intake of Fresh vs. Pasteurized Yogurt on the Immune System in Healthy Adults.
The immune system is affected by the dietary products humans intake. Immune system regulation by nutrition has uses in the clinical context, but it can also benefit healthy populations by delaying or preventing the emergence of immune-mediated chronic illnesses. In this study, the purpose was to describe and compare the modulator effects on the immune system of the routine ingestion of fresh vs. pasteurized yogurt. A unicentral, prospective, randomized, double-blind, parallel group 8-week nutritional study was carried out comparing the ingestion of 125 g of the products in healthy adults three times a day. A complete battery of in vitro tests on the activity of the immune system, processes and phenomena was performed. Exclusive immune-modulatory effects of fresh yogurt with respect to base line were found in terms of increased systemic IgM (primary immune responses), increased synthesis of IFN-gamma upon stimulation (Th1) and increased peripheral T cells (mainly "naive" CD4s). In the three interventions, we observed an increased phagocytic activity and burst test in granulocytes, together with increased secretion of IL-6, IL-1 β and IL-8 (pro-inflammatory) and increased CD16 expression (FcR favoring phagocytosis) in granulocytes. Overall, it is concluded that regardless of bacteria being alive or thermally inactivated, yogurt has common effects on the innate system, but the presence of live bacteria is necessary to achieve a potentiating effect on the specific immune response.
Topics: Yogurt; Humans; Double-Blind Method; Adult; Male; Female; Prospective Studies; Pasteurization; Phagocytosis; Cytokines; Young Adult; Immunoglobulin M; Interferon-gamma; Middle Aged; Granulocytes; Immune System; Receptors, IgG
PubMed: 38931322
DOI: 10.3390/nu16121969 -
Nutrients Jun 2024Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection,...
Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection, and the study of anti-adenoviral drugs has far-reaching clinical implications. Elemental selenium can play a specific role as an antioxidant in the human immune cycle by non-specifically binding to the amino acid methionine in body proteins. Methods: The antiviral mechanism of selenomethionine was explored by measuring cell membrane status, intracellular DNA status, cytokine secretion, mitochondrial membrane potential, and ROS production. Conclusions: Selenomethionine improved the regulation of ROS-mediated apoptosis by modulating the expression of Jak1/2, STAT3, and BCL-XL, which led to the inhibition of apoptosis. It is anticipated that selenomethionine will offer a new anti-adenoviral therapeutic alternative.
Topics: Humans; Selenomethionine; Apoptosis; Signal Transduction; Reactive Oxygen Species; STAT3 Transcription Factor; Janus Kinases; Antiviral Agents; Membrane Potential, Mitochondrial; A549 Cells
PubMed: 38931321
DOI: 10.3390/nu16121966 -
Nutrients Jun 2024Liver-expressed antimicrobial peptide-2 (LEAP-2) has mutual antagonism with ghrelin, which evokes food intake under a freely fed state. Nevertheless, the impact of...
Liver-expressed antimicrobial peptide-2 (LEAP-2) has mutual antagonism with ghrelin, which evokes food intake under a freely fed state. Nevertheless, the impact of LEAP-2 on ghrelin under time-restricted feeding (TRF), which has benefits in the context of metabolic disease, is still unknown. This study aims to explore the impact of central administration of LEAP-2 on the ingestion behavior of rats, which was evaluated using their cumulative food intake in the TRF state. Before intracerebroventricular (ICV) administration of -octanoylated ghrelin (0.1 nmol/rat), as a food-stimulatory model, the rats received various doses of LEAP-2 (0.3, 1, 3 nmol/rat, ICV). Cumulative food intake was recorded at 1, 2, 4, 8, 12, and 24 h after ICV injection under 12 h freely fed and TRF states in a light phase. In 12 h freely fed and TRF states, central administration of ghrelin alone induced feeding behavior. Pre-treatment with LEAP-2 (1 and 3 nmol/rat, ICV) suppressed ghrelin-induced food intake in a dose-dependent manner in a 12 h freely fed state instead of a TRF state, which may have disturbed the balance of ghrelin and LEAP-2. This study provides neuroendocrine-based evidence that may explain why TRF sometimes fails in fighting obesity/metabolic dysfunction-associated steatotic liver disease in clinics.
Topics: Animals; Ghrelin; Male; Rats; Eating; Feeding Behavior; Injections, Intraventricular; Antimicrobial Cationic Peptides; Rats, Sprague-Dawley; Consciousness; Blood Proteins
PubMed: 38931301
DOI: 10.3390/nu16121946 -
Nutrients Jun 2024In recent years, there has been a notable surge in the popularity of beetroot-based dietary supplements, driven by their rich nitrate composition. Several types of... (Randomized Controlled Trial)
Randomized Controlled Trial
In recent years, there has been a notable surge in the popularity of beetroot-based dietary supplements, driven by their rich nitrate composition. Several types of beetroot-based dietary supplements can be found in markets worldwide; however, ensuring the safety of dietary supplements is a crucial consideration, as there is limited evidence on their safety, especially for older populations. Therefore, the purpose of the current study was to evaluate the safety and tolerability of a nitrate-rich beetroot extract in older participants taking supplements over 12 weeks. The participants were randomly assigned to receive 20 g daily of beetroot extract or a matching placebo. The safety and tolerability of the supplementation were evaluated as the occurrence of adverse events and anthropometric, biochemical, and hemodynamic parameters were measured. No serious adverse events were reported in any group. Anthropometric, biochemical, and hemodynamic parameter changes between the baseline and the end of the study were not statistically significant in either group. However, interestingly, the group receiving beetroot extract supplementation exhibited a notable increase in plasma nitrate levels ( = 0.076, = 0.50) and showed a decrease in insulin levels ( = 0.026, = 0.59). In conclusion, we found that 20 g of beetroot extract supplementation for 12 weeks was safe and well tolerated in older participants.
Topics: Humans; Dietary Supplements; Beta vulgaris; Plant Extracts; Aged; Male; Female; Nitrates; Plant Roots; Double-Blind Method; Insulin; Middle Aged
PubMed: 38931296
DOI: 10.3390/nu16121942 -
Nutrients Jun 2024Corn peptide (CP) is a short, naturally occurring, and physiologically active peptide generated from corn-protease-catalyzed hydrolysis. CP plays a role in preventing...
Corn peptide (CP) is a short, naturally occurring, and physiologically active peptide generated from corn-protease-catalyzed hydrolysis. CP plays a role in preventing obesity-related disorders, but its impact on reducing inflammation is unknown. Hence, this study examined the possible protective effects of corn peptide powder (CPP) against the harmful effects of lipopolysaccharide (LPS), with a particular emphasis on reducing oxidative damage and inflammation in adipocytes. Hence, mature 3T3-L1 adipocytes underwent exposure to 10 ng/mL LPS, with or without CPP (10 and 20 μg/mL). LPS stimulation increased reactive oxygen species and superoxide anion generation. However, this effect was reduced in a dose-dependent manner by pretreatment with CPP. CPP treatment elevated the mRNA expressions of the antioxidant enzymes manganese superoxide dismutase (mnSOD) and glutathione peroxidase 1 (Gpx1) while reducing the mRNA expressions of the cytosolic reactive oxygen species indicators p40 and p67 (NADPH oxidase 2). In addition, CPP inhibited the monocyte chemoattractant protein-1, tumor necrosis factor-alpha, Toll-like receptor 4, and nuclear factor kappa B mRNA expressions induced by LPS. These findings demonstrate that CPP may ameliorate adipocyte dysfunction by suppressing oxidative damage and inflammatory responses through a new mechanism known as Toll-like receptor 4/nuclear factor kappa B-mediated signaling.
Topics: Animals; Mice; 3T3-L1 Cells; Adipocytes; Lipopolysaccharides; Zea mays; Reactive Oxygen Species; Inflammation; Toll-Like Receptor 4; Oxidative Stress; Superoxide Dismutase; Powders; Peptides; Glutathione Peroxidase; NF-kappa B; Antioxidants; Glutathione Peroxidase GPX1; Signal Transduction; Chemokine CCL2; Tumor Necrosis Factor-alpha; Anti-Inflammatory Agents
PubMed: 38931278
DOI: 10.3390/nu16121924 -
Nutrients Jun 2024Influenza, a severe respiratory disease caused by the influenza virus, has long been a prominent threat to human health. An increasing number of studies have...
Influenza, a severe respiratory disease caused by the influenza virus, has long been a prominent threat to human health. An increasing number of studies have demonstrated that oral administration with probiotics may increase the immune response to lung infection via the gut-lung axis leading to the alleviation of the pulmonary disease. In this study, we evaluated the effects of oral administration of MIANGUAN2 (MIANGUAN2) on influenza infection in a mouse model. Our results showed that oral administration of MIANGUAN2 significantly improved weight loss, lung index, and lung pathology, and decreased lung viral load of influenza-infected mice. Additionally, MIANGUAN2-treated mice showed significantly lower levels of TNF-α, IL-1β, IFN-γ, and IL-12p70 and higher production of IL-4 in the lung. In accordance with this, the transcriptome analysis of the lung indicated that MIANGUAN2-treated mice had reduced expression of inflammation markers, such as TNF, apoptosis, and the NF-Kappa B pathway. Furthermore, the administration of MIANGUAN2 restored the SCFAs profiles through regulating the gut microbiota. SCFA-producing bacteria, such as p_Firmicutes, f_Lachnospiraceae, and f_Ruminococcaceae, were enriched in the MIANGUAN2-treated group compared with PBS-treated group. Consistently, the concentrations of SCFAs in the MIANGUAN2 group were significantly higher than those in the PBS-treated group. In addition, the concentrations of SCFAs were positively correlated with SCFA-producing bacteria, such as , while being negatively correlated with the virial titers and proinflammatory cytokines. In conclusion, this animal study suggests that MIANGUAN2 may alleviate the influenza infection by altering the gut microbiota composition and increasing the levels of gut microbiota-derived SCFAs.
Topics: Animals; Gastrointestinal Microbiome; Pediococcus pentosaceus; Fatty Acids, Volatile; Mice; Probiotics; Lung; Orthomyxoviridae Infections; Disease Models, Animal; Cytokines; Male
PubMed: 38931277
DOI: 10.3390/nu16121923 -
Nutrients Jun 2024Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived...
Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived from marine animal proteins show promise as safe and effective anti-obesity agents by regulating adipocyte differentiation through the AMPK signaling pathway. Therefore, this study aims to investigate the anti-obesity and anti-diabetic effects of bioactive compounds derived from a Protamex enzymatic hydrolysate (MLP) fraction (≤1 kDa) through a 6-week treatment (150 mg/kg or 300 mg/kg, administered once daily) in leptin receptor-deficient mice. The MLP treatment significantly decreased the body weight, serum total cholesterol, triglycerides, and LDL-cholesterol levels while also exhibiting a beneficial effect on hepatic and serum marker parameters in mice. A histological analysis revealed a reduction in hepatic steatosis and epididymal fat following MLP treatment. Furthermore, poor glucose tolerance was improved, and hepatic antioxidant enzyme activities were elevated in MLP-treated mice compared to control mice. Western blot analysis showed an increased expression of the AMPK protein after MLP treatment. In addition, the expression of lipogenic genes decreased in mice. These findings indicate that bioactive peptides, which are known to regulate blood glucose levels, lipid metabolism, and adipogenesis, could be beneficial functional food additives and pharmaceuticals.
Topics: Animals; Obesity; Mice; Male; Peptides; Anti-Obesity Agents; Protein Hydrolysates; Liver; Blood Glucose; Hypoglycemic Agents; Lipid Metabolism; AMP-Activated Protein Kinases; Mice, Inbred C57BL; Receptors, Leptin; Adipogenesis; Body Weight
PubMed: 38931268
DOI: 10.3390/nu16121913