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Marine Drugs May 2024Considering the lack of antiviral drugs worldwide, we investigated the antiviral potential of fucoxanthin, an edible carotenoid purified from , against zika virus (ZIKV)...
Considering the lack of antiviral drugs worldwide, we investigated the antiviral potential of fucoxanthin, an edible carotenoid purified from , against zika virus (ZIKV) infection. The antiviral activity of fucoxanthin was assessed in ZIKV-infected Vero E6 cells, and the relevant structural characteristics were confirmed using molecular docking and molecular dynamics (MD) simulation. Fucoxanthin decreased the infectious viral particles and nonstructural protein (NS)1 mRNA expression levels at concentrations of 12.5, 25, and 50 µM in ZIKV-infected cells. Fucoxanthin also decreased the increased mRNA levels of interferon-induced proteins with tetratricopeptide repeat 1 and 2 in ZIKV-infected cells. Molecular docking simulations revealed that fucoxanthin binds to three main ZIKV proteins, including the envelope protein, NS3, and RNA-dependent RNA polymerase (RdRp), with binding energies of -151.449, -303.478, and -290.919 kcal/mol, respectively. The complex of fucoxanthin with RdRp was more stable than RdRp protein alone based on MD simulation. Further, fucoxanthin bonded to the three proteins via repeated formation and disappearance of hydrogen bonds. Overall, fucoxanthin exerts antiviral potential against ZIKV by affecting its three main proteins in a concentration-dependent manner. Thus, fucoxanthin isolated from is a potential candidate for treating zika virus infections.
Topics: Antiviral Agents; Zika Virus; Animals; Molecular Docking Simulation; Sargassum; Chlorocebus aethiops; Xanthophylls; Vero Cells; Molecular Dynamics Simulation; Zika Virus Infection
PubMed: 38921558
DOI: 10.3390/md22060247 -
World Journal of Microbiology &... Jun 2024Sesquiterpenes and tetraterpenes are classes of plant-derived natural products with antineoplastic effects. While plant extraction of the sesquiterpene, germacrene A,... (Review)
Review
Sesquiterpenes and tetraterpenes are classes of plant-derived natural products with antineoplastic effects. While plant extraction of the sesquiterpene, germacrene A, and the tetraterpene, lycopene suffers supply chain deficits and poor yields, chemical synthesis has difficulties in separating stereoisomers. This review highlights cutting-edge developments in producing germacrene A and lycopene from microbial cell factories. We then summarize the antineoplastic properties of β-elemene (a thermal product from germacrene A), sesquiterpene lactones (metabolic products from germacrene A), and lycopene. We also elaborate on strategies to optimize microbial-based germacrene A and lycopene production.
Topics: Lycopene; Sesquiterpenes, Germacrane; Antineoplastic Agents; Humans; Carotenoids; Sesquiterpenes; Biosynthetic Pathways
PubMed: 38916754
DOI: 10.1007/s11274-024-04057-0 -
Journal of Acquired Immune Deficiency... Aug 2024An effective vaccine is required to end the HIV pandemic. We evaluated the safety and immunogenicity of a DNA (DNA-HIV-PT123) vaccine with low- or high-dose bivalent... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
An effective vaccine is required to end the HIV pandemic. We evaluated the safety and immunogenicity of a DNA (DNA-HIV-PT123) vaccine with low- or high-dose bivalent (TV1.C and 1086.C glycoprotein 120) subtype C envelope protein combinations, adjuvanted with MF59 or AS01B.
METHODS
HIV Vaccine Trials Network (HVTN)108 was a randomized, placebo-controlled, double-blind, phase 1/2a trial conducted in the United States and South Africa. HIV-negative adults were randomly assigned to 1 of 7 intervention arms or placebo to assess DNA prime with DNA/protein/adjuvant boosts, DNA/protein/adjuvant co-administration, and low-dose protein/adjuvant regimens. HVTN111 trial participants who received an identical regimen were also included. Outcomes included safety and immunogenicity 2 weeks and 6 months after final vaccination.
RESULTS
From June 2016 to July 2018, 400 participants were enrolled (N = 334 HVTN108, N = 66 HVTN111); 370 received vaccine and 30 received placebo. There were 48 grade 3 and 3 grade 4 reactogenicity events among 39/400 (9.8%) participants, and 32 mild/moderate-related adverse events in 23/400 (5.8%) participants. All intervention groups demonstrated high IgG response rates (>89%) and high magnitudes to HIV-1 Env gp120 and gp140 proteins; response rates for AS01B-adjuvanted groups approached 100%. V1V2 IgG magnitude, Fc-mediated functions, IgG3 Env response rates, and CD4+ T-cell response magnitudes and rates were higher in the AS01B-adjuvanted groups. The AS01B-adjuvanted low-dose protein elicited greater IgG responses than the higher protein dose.
CONCLUSIONS
The vaccine regimens were generally well tolerated. Co-administration of DNA with AS01B-adjuvanted bivalent Env gp120 elicited the strongest humoral responses; AS01B-adjuvanted regimens elicited stronger CD4+ T-cell responses, justifying further evaluation.ClinicalTrials.gov registration: NCT02915016, registered 26 September 2016.
Topics: Humans; AIDS Vaccines; Vaccines, DNA; Female; Male; Adult; Squalene; Polysorbates; HIV Envelope Protein gp120; Adjuvants, Immunologic; HIV-1; HIV Infections; HIV Antibodies; Double-Blind Method; Middle Aged; Young Adult; Adjuvants, Vaccine; South Africa; Immunogenicity, Vaccine; Adolescent; United States
PubMed: 38916429
DOI: 10.1097/QAI.0000000000003438 -
Drugs in Context 2024Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to species. , and... (Review)
Review
BACKGROUND
Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to species. , and are also emerging because of the empirical use of antifungal drugs. This updated review discusses the epidemiology of IFIs as well as antifungal drugs, dosing and potential adverse effects in critically ill children.
METHODS
A PubMed search was conducted with Clinical Queries using the key terms "antifungal", "children", "critical care" AND "paediatric intensive care unit" OR "PICU". The search strategy included clinical trials, randomized controlled trials, meta-analyses, observational studies and reviews and was limited to the English literature in paediatrics.
RESULTS
and spp. are the most prevalent fungi in paediatric IFIs, causing invasive candidiasis infections (ICIs) and invasive aspergillosis infections (IAIs), respectively. These IFIs are associated with high morbidity, mortality and healthcare costs. is the principal spp. associated with paediatric ICIs. The risks and epidemiology for IFIs vary if considering previously healthy children treated in the paediatric intensive care unit or children with leukaemia, malignancy or a severe haematological disease. The mortality rate for IAIs in children is 2.5-3.5-fold higher than for ICIs. Four major classes of antifungals for critically ill children are azoles, polyenes, antifungal antimetabolites and echinocandins.
CONCLUSIONS
Antifungal agents are highly efficacious. For successful treatment outcomes, it is crucial to determine the optimal dosage, monitor pharmacokinetics parameters and adverse effects, and individualized therapeutic monitoring. Despite potent antifungal medications, ICIs and IAIs continue to be serious infections with high mortality rates. Pre-emptive therapy has been used for IAIs. Most guidelines recommend voriconazole as initial therapy of invasive aspergillosis in most patients, with consideration of combination therapy with voriconazole plus an echinocandin in selected patients with severe disease. The challenge is to identify critically ill patients at high risks of ICIs for targeted prophylaxis. Intravenous/per os fluconazole is first-line pre-emptive treatment for spp. whereas intravenous micafungin or intravenous liposomal amphotericin B is alternative pre-emptive treatment.This article is part of the Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.
PubMed: 38915918
DOI: 10.7573/dic.2023-9-2 -
Unveiling the potential of Pseudococcomyxa simplex: a stepwise extraction for cosmetic applications.Applied Microbiology and Biotechnology Jun 2024Microalgae are gaining attention as they are considered green fabrics able to synthesize many bioactive metabolites, with unique biological activities. However, their...
Microalgae are gaining attention as they are considered green fabrics able to synthesize many bioactive metabolites, with unique biological activities. However, their use at an industrial scale is still a challenge because of the high costs related to upstream and downstream processes. Here, a biorefinery approach was proposed, starting from the biomass of the green microalga Pseudococcomyxa simplex for the extraction of two classes of molecules with a potential use in the cosmetic industry. Carotenoids were extracted first by an ultrasound-assisted extraction, and then, from the residual biomass, lipids were obtained by a conventional extraction. The chemical characterization of the ethanol extract indicated lutein, a biosynthetic derivative of α-carotene, as the most abundant carotenoid. The extract was found to be fully biocompatible on a cell-based model, active as antioxidant and with an in vitro anti-aging property. In particular, the lutein-enriched fraction was able to activate Nrf2 pathway, which plays a key role also in aging process. Finally, lipids were isolated from the residual biomass and the isolated fatty acids fraction was composed by palmitic and stearic acids. These molecules, fully biocompatible, can find application as emulsifiers and softener agents in cosmetic formulations. Thus, an untapped microalgal species can represent a sustainable source for cosmeceutical formulations. KEY POINTS: • Pseudococcomyxa simplex has been explored in a cascade approach. • Lutein is the main extracted carotenoid and has antioxidant and anti-aging activity. • Fatty acids are mainly composed of palmitic and stearic acids.
Topics: Microalgae; Cosmetics; Carotenoids; Biomass; Antioxidants; Lutein; Humans; Fatty Acids
PubMed: 38910175
DOI: 10.1007/s00253-024-13229-9 -
Methods in Molecular Biology (Clifton,... 2024Polymeric delivery systems could enable the fast- and low-side-effect transport of various RNA classes. Previously, we demonstrated that polyvinylamine (PVAm), a...
Polymeric delivery systems could enable the fast- and low-side-effect transport of various RNA classes. Previously, we demonstrated that polyvinylamine (PVAm), a cationic polymer, transfects many kinds of RNAs with high efficiency and low toxicity both in vitro and in vivo. The modification of poly lactic-co-glycolic acid (PLGA) with cartilage-targeting peptide (CAP) enhances its stiffness and tissue-specific delivery of RNA to overcome the avascular nature of articular cartilage. Here we describe the protocol to use PVAm as an RNA carrier, and further, by modifying PVAm with PLGA and CAP, the corresponding co-polymer could be applied for functional RNA delivery for osteoarthritis treatment.
Topics: Polyvinyls; Animals; Polylactic Acid-Polyglycolic Acid Copolymer; Humans; Lactic Acid; Transfection; Gene Transfer Techniques; Polyglycolic Acid; Drug Carriers; RNA, Small Interfering; Osteoarthritis
PubMed: 38907928
DOI: 10.1007/978-1-0716-3918-4_22 -
Biomedical Physics & Engineering Express Jul 2024In this study tissue equivalency of the polymeric materials was investigated by comparing with ICRP 110 Male Adult Computational Phantom tissues. For this purpose,... (Comparative Study)
Comparative Study
In this study tissue equivalency of the polymeric materials was investigated by comparing with ICRP 110 Male Adult Computational Phantom tissues. For this purpose, radiological properties of polyamide (PA), high density polyethylene (HDPE), ultra-high molecular weight polyethylene (UHMWPE), polypropylene (PP), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), polyoxymethylene (POM) and polyurethane foam (PU FOAM) were evaluated in the diagnostic energy range (15-150 keV). The radiological properties of the materials and ICRP 110 Male and Female Adult Computational Phantom tissues were calculated with Phy-X/PSD software. No major differences were seen except for sex-specific organs, and comparisons were made using an adult male phantom. To confirm the results experimentally, a chest phantom was designed with the polymeric materials. The phantom was scanned by Siemens SOMATOM Edge CT device with tube voltage of 120 kVp and Hounsfield Unit (HU) values were measured. In addition, HU values were calculated using theoretical relationships and significant agreement was obtained between measured and calculated HUs. It was determined that PA, PP, UHMWPE and HDPE were equivalent to muscle and adipose tissue, PVC and PTFE were equivalent to mineral bone, PET and POM were equivalent to spongiosa bone and PU FOAM was equivalent to lung tissue.
Topics: Phantoms, Imaging; Humans; Male; Polymers; Female; Adult; Tomography, X-Ray Computed; Materials Testing; Polyethylenes
PubMed: 38906123
DOI: 10.1088/2057-1976/ad5a9d -
Archives of Dermatological Research Jun 2024Acanthosis nigricans (AN), with an estimated prevalence of 19.4% in the U.S., presents as hyperpigmented, velvety plaques in intertriginous regions. Acanthosis... (Review)
Review
Acanthosis nigricans (AN), with an estimated prevalence of 19.4% in the U.S., presents as hyperpigmented, velvety plaques in intertriginous regions. Acanthosis Nigricans negatively affects psychological well-being and particularly impacts skin of color individuals. Addressing the underlying cause of acanthosis nigricans, as current guidelines recommend, is often challenging. This highlights the importance of skin directed treatment for acanthosis nigricans. This systematic review evaluated topical, laser, and oral treatments for acanthosis nigricans and provides evidence-based recommendations for clinical use. Adhering to PRISMA guidelines, we evaluated 19 clinical trials investigating topical, oral, and laser interventions for acanthosis nigricans. Oxford Centre for Evidence-Based Medicine guidelines were used to make clinical recommendations. We strongly recommend topical tretinoin (grade A) and endorse the appropriate use of adapalene gel, urea cream, and fractional carbon dioxide laser therapy (grade B). Further research is essential to enhance our understanding of alternative treatments to determine additional evidence-based recommendations. This review aims to guide clinicians in managing acanthosis nigricans, especially when direct treatment of underlying conditions is impractical.
Topics: Humans; Acanthosis Nigricans; Administration, Oral; Laser Therapy; Clinical Trials as Topic; Administration, Cutaneous; Evidence-Based Medicine; Dermatologic Agents; Administration, Topical; Lasers, Gas; Tretinoin; Treatment Outcome
PubMed: 38904687
DOI: 10.1007/s00403-024-02931-3 -
Stem Cell Research & Therapy Jun 2024Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other...
BACKGROUND
Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other non-cardiomyocyte cells. Retinoic acid (RA) plays an important role in regulation of the spatiotemporal development of the embryonic heart.
METHODS
CMs were derived from hiPSC (hi-PCS-CM) using different concentrations of RA (Control without RA, LRA with 0.05μM and HRA with 0.1 μM) between day 3-6 of the differentiation process. Engineered heart tissues (EHTs) were generated by assembling hiPSC-CM at high cell density in a low collagen hydrogel.
RESULTS
In the HRA group, hiPSC-CMs exhibited highest expression of contractile proteins MYH6, MYH7 and cTnT. The expression of TBX5, NKX2.5 and CORIN, which are marker genes for left ventricular CMs, was also the highest in the HRA group. In terms of EHT, the HRA group displayed the highest contraction force, the lowest beating frequency, and the highest sensitivity to hypoxia and isoprenaline, which means it was functionally more similar to the left ventricle. RNAsequencing revealed that the heightened contractility of EHT within the HRA group can be attributed to the promotion of augmented extracellular matrix strength by RA.
CONCLUSION
By interfering with the differentiation process of hiPSC with a specific concentration of RA at a specific time, we were able to successfully induce CMs and EHTs with a phenotype similar to that of the left ventricle or right ventricle.
Topics: Humans; Tretinoin; Myocytes, Cardiac; Cell Differentiation; Induced Pluripotent Stem Cells; Heart Ventricles; Myosin Heavy Chains; Cardiac Myosins; Tissue Engineering; Homeobox Protein Nkx-2.5; T-Box Domain Proteins
PubMed: 38902843
DOI: 10.1186/s13287-024-03741-0 -
Proceedings of the National Academy of... Jun 2024The photoinduced all-trans to 13-cis isomerization of the retinal Schiff base represents the ultrafast first step in the reaction cycle of bacteriorhodopsin (BR)....
The photoinduced all-trans to 13-cis isomerization of the retinal Schiff base represents the ultrafast first step in the reaction cycle of bacteriorhodopsin (BR). Extensive experimental and theoretical work has addressed excited-state dynamics and isomerization via a conical intersection with the ground state. In conflicting molecular pictures, the excited state potential energy surface has been modeled as a pure S[Formula: see text] state that intersects with the ground state, or in a 3-state picture involving the S[Formula: see text] and S[Formula: see text] states. Here, the photoexcited system passes two crossing regions to return to the ground state. The electric dipole moment of the Schiff base in the S[Formula: see text] and S[Formula: see text] state differs strongly and, thus, its measurement allows for assessing the character of the excited-state potential. We apply the method of ultrafast terahertz (THz) Stark spectroscopy to measure electric dipole changes of wild-type BR and a BR D85T mutant upon electronic excitation. A fully reversible transient broadening and spectral shift of electronic absorption is induced by a picosecond THz field of several megavolts/cm and mapped by a 120-fs optical probe pulse. For both BR variants, we derive a moderate electric dipole change of 5 [Formula: see text] 1 Debye, which is markedly smaller than predicted for a neat S[Formula: see text]-character of the excited state. In contrast, S[Formula: see text]-admixture and temporal averaging of excited-state dynamics over the probe pulse duration gives a dipole change in line with experiment. Our results support a picture of electronic and nuclear dynamics governed by the interaction of S[Formula: see text] and S[Formula: see text] states in a 3-state model.
Topics: Bacteriorhodopsins; Retinaldehyde; Terahertz Spectroscopy; Schiff Bases; Halobacterium salinarum; Isomerism
PubMed: 38900801
DOI: 10.1073/pnas.2319676121