bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Therapeutic Potential of Royal Jelly in Metabolic Disorders and Gastrointestinal Diseases
Authors: El-Seedi Hesham R. , Salama Suzy , El-Wahed Aida A. Abd , Guo Zhiming , Di Minno Alessandro , Daglia Maria , Li Chuan , Guan Xiao , Buccato Daniele Giuseppe , Khalifa Shaden A. M. , Wang Kai
Published: January 2024

Metabolic disorders, encompassing diabetes mellitus, cardiovascular diseases, gastrointestinal disorders, etc., pose a substantial global health threat, with rising morbidity and mortality rates. Addressing these disorders is crucial, as conventional drugs often come with high costs and adverse effects. This review explores the potential of royal jelly (RJ), a natural bee product rich in bioactive components, as an alternative strategy for managing metabolic diseases. RJ exhibits diverse therapeutic properties, including antimicrobial, estrogen-like, anti-inflammatory, hypotensive, anticancer, and antioxidant effects. This review’s focus is on investigating how RJ and its components impact conditions like diabetes mellitus, cardiovascular disease, and gastrointestinal illnesses. Evidence suggests that RJ serves as a complementary treatment for various health issues, notably demonstrating cholesterol- and glucose-lowering effects in diabetic rats. Specific RJ-derived metabolites, such as 10-hydroxy-2-decenoic acid (10-HDA), also known as the “Queen bee acid,” show promise in reducing insulin resistance and hyperglycemia. Recent research highlights RJ’s role in modulating immune responses, enhancing anti-inflammatory cytokines, and suppressing key inflammatory mediators. Despite these promising findings, further research is needed to comprehensively understand the mechanisms underlying RJ’s therapeutic effects.
Genetic and Biochemical Characterization of AXC-2 from Achromobacter ruhlandii
Authors: Papalia Mariana , González-Espinosa Francisco , Castedo Fátima Quiroga , Gutkind Gabriel , Ramírez María Soledad , Power Pablo , Radice Marcela
Published: January 2024

Achromobacter spp. are intrinsically resistant to multiple antibiotics and can also acquire resistance to those commonly used for the treatment of respiratory infections, especially in patients with cystic fibrosis. The aim of this study was to perform the genetic and biochemical characterization of AXC-2 from A. ruhlandii and to analyze all available AXC variants. Steady-state kinetic parameters were determined on a purified AXC-2 enzyme. It exhibited higher catalytic efficiencies towards amino-penicillins and older cephalosporins, while carbapenems behaved as poor substrates. Phylogenetic analysis of all blaAXC variants available in the NCBI was conducted. AXC was encoded in almost all A. ruhlandii genomes, whereas it was only found in 30% of A. xylosoxidans. AXC-1 was prevalent among A. xylosoxidans. AXC variants were clustered in two main groups, correlating with the Achromobacter species. No association could be established between the presence of blaAXC variants and a specific lineage of A. xylosoxidans; however, a proportion of AXC-1-producing isolates corresponded to ST 182 and ST 447. In conclusion, this study provides valuable insights into the genetic context and kinetic properties of AXC-2, identified in A. ruhlandii. It also provides a thorough description of all AXC variants and their association with Achromobacter species and various lineages.
Characterizing Indicators of Engagement in HIV-Associated Healthcare and Clinical Outcomes among People with HIV and Mpox in Washington, DC: A Nested Case-Control Study of the DC Cohort
Authors: O’Connor Lauren F. , Byrne Morgan , Baskaran Anuja , Andersen Elisabeth W. , Horberg Michael A. , Benator Debra A. , Lucar Jose , Denyer Rachel V. , Lee Rachel , Castel Amanda D. , Monroe Anne K.
Published: January 2024

The high proportion of people with HIV (PWH) in the 2022–2023 mpox outbreak has raised questions surrounding the association between HIV and mpox. The objectives of this study were to evaluate the association between engagement in HIV-associated healthcare and mpox diagnosis, as well as to characterize cases of mpox among PWH. The DC Cohort is a longitudinal cohort of PWH in Washington, DC. We conducted a 5:1 (controls:cases) nested case-cohort study on male participants, matching age and care site. Cases were participants with an identified mpox diagnosis. Conditional logistic regression was used to assess the impact of indicators of engagement in HIV-associated healthcare on mpox diagnosis. We identified 70 cases of mpox in DC Cohort participants randomly matched to 323 controls, for a total of 393 participants included in the analysis. Study participants were primarily non-Hispanic Black (72.3%) with a median age of 41 (IQR: 36, 50). There was no association between engagement in care and mpox diagnosis; however, low CD4 was associated with increased odds of mpox diagnosis (aOR: 4.60 (95% CI: 1.23, 17.11)). Among a cohort of PWH, engagement in care was not associated with mpox diagnosis, suggesting that the overrepresentation of PWH among mpox cases is not due to surveillance bias.
Clostridioides difficile Infection: Diagnosis and Treatment Challenges
Authors: Markantonis John E. , Fallon John T. , Madan Rajat , Alam Md Zahidul
Published: January 2024

Clostridioides difficile is the most important cause of healthcare-associated diarrhea in the United States. The high incidence and recurrence rates of C. difficile infection (CDI), associated with high morbidity and mortality, pose a public health challenge. Although antibiotics targeting C. difficile bacteria are the first treatment choice, antibiotics also disrupt the indigenous gut flora and, therefore, create an environment that is favorable for recurrent CDI. The challenge of treating CDI is further exacerbated by the rise of antibiotic-resistant strains of C. difficile, placing it among the top five most urgent antibiotic resistance threats in the USA. The evolution of antibiotic resistance in C. difficile involves the acquisition of new resistance mechanisms, which can be shared among various bacterial species and different C. difficile strains within clinical and community settings. This review provides a summary of commonly used diagnostic tests and antibiotic treatment strategies for CDI. In addition, it discusses antibiotic treatment and its resistance mechanisms. This review aims to enhance our current understanding and pinpoint knowledge gaps in antimicrobial resistance mechanisms in C. difficile, with an emphasis on CDI therapies.
Gut Microbiota of Apis mellifera at Selected Ontogenetic Stages and Their Immunogenic Potential during Summer
Authors: Maigoro Abdulkadir Yusif , Lee Jeong-Hyeon , Kim Hyunjee , Frunze Olga , Kwon Hyung-Wook
Published: January 2024

Honeybees (Apis mellifera) are pollinating agents of economic importance. The role of the gut microbiome in honeybee health has become increasingly evident due to its relationship with immune function, growth, and development. Although their dynamics at various developmental stages have been documented, their dynamics during the era of colony collapse disorder and immunogenic potential, which are connected to the antagonistic immune response against pathogens, need to be elucidated. Using 16S rRNA gene Illumina sequencing, the results indicated changes in the gut microbiota with the developmental stage. The bacterial diversity of fifth stage larva was significantly different among the other age groups, in which Fructobacillus, Escherichia-Shigella, Bombella, and Tyzzerella were unique bacteria. In addition, the diversity of the worker bee microbiome was distinct from that of the younger microbiome. Lactobacillus and Gilliamella remained conserved throughout the developmental stages, while Bifidobacterium colonized only worker bees. Using an in silico approach, the production potential of lipopolysaccharide-endotoxin was predicted. Forager bees tend to have a higher abundance rate of Gram-negative bacteria. Our results revealed the evolutionary importance of some microbiome from the larval stage to the adult stage, providing insight into the potential dynamics of disease response and susceptibility. This finding provides a theoretical foundation for furthering the understanding of the function of the gut microbiota at various developmental stages related to probiotic development and immunogenic potential.
Immune Mediators Important for a Protective Secondary Response to Babesia microti
Authors: Conti Joseph , Gagliardi Thomas , Arnaboldi Paul M. , Hale Synthia J. , Skariah Sini , Sultan Ali A. , Mordue Dana G.
Published: January 2024

Babesia microti (B. microti) is a tick-transmitted protozoan parasite that invades red blood cells. It is the primary cause of human babesiosis in the US. The severity of babesiosis caused by B. microti infection can range from asymptomatic to fatal. Risk factors for severe disease include general immune suppression, advanced age (>50) and lack of a spleen. However, severe disease can occur in the absence of any known risk factors. The degree to which tick-transmitted B. microti infection confers protection from subsequent exposure is largely unexplored. This is an important question as both the prevalence and geographic range of tick-transmitted B. microti infection continues to increase and individuals in endemic regions may have multiple exposures over their lifetime. In the current study we used a mouse model to evaluate the degree to which primary infection with B. microti protected against secondary challenge with the same parasite strain. We show that CD4 T cells, and to a lesser extent B cells, contribute to protection. However, mice exhibited significant protection from secondary parasite challenge even in the absence of either CD4 T cells or B cells. The protection mediated by CD4 T cells did not depend on their production of IFN-γ as mice with a targeted gene deletion for the IFN-γ receptor remained fully protected against secondary challenge. Other factors including inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88, important for toll-like receptors, IL-18 and IL-1 signaling, were not important for protection against primary or secondary challenge with B. microti. Thus, our study shows that resolution of primary infection with B. microti results in robust protection against secondary challenge with parasites, at least in the short term. Further studies are needed to evaluate the length of protection and the degree to which protection is impacted by parasite heterogeneity. Although we show an important role for CD4 T cells in protection against secondary challenge, our results suggest that no single aspect of the immune system is solely responsible for adequate protection against secondary challenge with B. microti.
Mpox Awareness, Risk Reduction, and Vaccine Acceptance among People with HIV in Washington, DC
Authors: Andersen Elisabeth W. , Kulie Paige , Castel Amanda D. , Lucar Jose , Benator Debra , Greenberg Alan E. , Monroe Anne
Published: January 2024

People with HIV (PWH) are disproportionally affected by mpox and at risk of severe complications. We assessed mpox knowledge, adoption of preventive behaviors, and vaccination attitudes among PWH enrolled in a longitudinal HIV cohort in Washington, DC, the DC Cohort. We conducted uni- and multivariable analyses comparing participants by vaccination status and HIV risk group, and multinomial regression to identify factors associated with vaccine acceptance. Among 430 PWH, 378 (87.9%) were aware of mpox. Among 373 participants with vaccination status data, 101 (27.1%) were vaccinated, 129 (34.6%) planned to vaccinate, and 143 (38.3%) did not plan to vaccinate. The three vaccination groups differed significantly by age, race, education, HIV risk group, recent STI status, and level of mpox worry (all p < 0.05). A higher proportion of men who have sex with men (MSM) reported limiting their number of sexual partners compared to non-MSM (p < 0.0001). Multinomial regression models comparing vaccinated to unvaccinated PWH found age, education, mode of HIV transmission/gender, and survey period were significantly associated with vaccination status (all p < 0.05). High levels of mpox awareness were observed among this cohort of PWH with more MSM employing risk reduction behaviors and being vaccinated. Ensuring that PWH, regardless of gender, sexual orientation, or age, understand the risks of mpox may improve vaccination uptake.
Influenza Virus Host Restriction Factors: The ISGs and Non-ISGs
Authors: Husain Matloob
Published: January 2024

Influenza virus has been one of the most prevalent and researched viruses globally. Consequently, there is ample information available about influenza virus lifecycle and pathogenesis. However, there is plenty yet to be known about the determinants of influenza virus pathogenesis and disease severity. Influenza virus exploits host factors to promote each step of its lifecycle. In turn, the host deploys antiviral or restriction factors that inhibit or restrict the influenza virus lifecycle at each of those steps. Two broad categories of host restriction factors can exist in virus-infected cells: (1) encoded by the interferon-stimulated genes (ISGs) and (2) encoded by the constitutively expressed genes that are not stimulated by interferons (non-ISGs). There are hundreds of ISGs known, and many, e.g., Mx, IFITMs, and TRIMs, have been characterized to restrict influenza virus infection at different stages of its lifecycle by (1) blocking viral entry or progeny release, (2) sequestering or degrading viral components and interfering with viral synthesis and assembly, or (3) bolstering host innate defenses. Also, many non-ISGs, e.g., cyclophilins, ncRNAs, and HDACs, have been identified and characterized to restrict influenza virus infection at different lifecycle stages by similar mechanisms. This review provides an overview of those ISGs and non-ISGs and how the influenza virus escapes the restriction imposed by them and aims to improve our understanding of the host restriction mechanisms of the influenza virus.
Ehrlichia canis and Rickettsia conorii Infections in Shelter Dogs: Seropositivity and Implications for Public Health
Authors: Afonso Paulo , Lopes Ana Patrícia , Quintas Hélder , Cardoso Luís , Coelho Ana Cláudia
Published: January 2024

A cross-sectional study was conducted to gain insight into the epidemiology of canine ehrlichiosis and rickettsiosis in northern Portugal. Specific IgG antibodies to Ehrlichia canis were analysed using a commercial enzyme-linked immunosorbent assay (ELISA), and antibodies to Rickettsia conorii were analysed using a commercial indirect immunofluorescence antibody test (IFAT). A total of 113 dogs from two different shelters were sampled, and seroprevalence values of 0.9% (95% confidence (CI): 0.2–4.8%) for E. canis and 9.7 (95% CI: 5.5–16.6%) for R. conorii were found. Multiple logistic regression investigated risk factors for seropositivity. The odds ratios (ORs) of R. conorii seropositivity were higher for female dogs (OR = 6.429; 95% CI: 1.201–34.407). Dogs seropositive for co-infection (E. canis + R. conorii) were more frequently observed among females (OR = 7.606; CI 95%: 1.478–39.132) and in Shelter 2 (OR = 18.229; 95% CI: 2.190–151.756). These findings show that shelter dogs in northern Portugal are exposed to E. canis and R. conorii, which can affect both canines and humans. It is imperative to adopt a One Health approach to educate the public about the hazards of canine zoonoses and develop legislation and procedures to control their spread and preserve public health.
De Novo Drug Design Using Transformer-Based Machine Translation and Reinforcement Learning of an Adaptive Monte Carlo Tree Search
Authors: Ang Dony , Rakovski Cyril , Atamian Hagop S.
Published: January 2024

The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researchers to explore innovative methods that harness the power of deep learning and reinforcement learning techniques. Here, we introduce a novel drug design approach called drugAI that leverages the Encoder–Decoder Transformer architecture in tandem with Reinforcement Learning via a Monte Carlo Tree Search (RL-MCTS) to expedite the process of drug discovery while ensuring the production of valid small molecules with drug-like characteristics and strong binding affinities towards their targets. We successfully integrated the Encoder–Decoder Transformer architecture, which generates molecular structures (drugs) from scratch with the RL-MCTS, serving as a reinforcement learning framework. The RL-MCTS combines the exploitation and exploration capabilities of a Monte Carlo Tree Search with the machine translation of a transformer-based Encoder–Decoder model. This dynamic approach allows the model to iteratively refine its drug candidate generation process, ensuring that the generated molecules adhere to essential physicochemical and biological constraints and effectively bind to their targets. The results from drugAI showcase the effectiveness of the proposed approach across various benchmark datasets, demonstrating a significant improvement in both the validity and drug-likeness of the generated compounds, compared to two existing benchmark methods. Moreover, drugAI ensures that the generated molecules exhibit strong binding affinities to their respective targets. In summary, this research highlights the real-world applications of drugAI in drug discovery pipelines, potentially accelerating the identification of promising drug candidates for a wide range of diseases.
The Antimicrobial Potential of the Hop (Humulus lupulus L.) Extract against Staphylococcus aureus and Oral Streptococci
Authors: Khaliullina Alyona , Kolesnikova Alyona , Khairullina Leysan , Morgatskaya Olga , Shakirova Dilyara , Patov Sergey , Nekrasova Polina , Bogachev Mikhail , Kurkin Vladimir , Trizna Elena , Kayumov Airat
Published: January 2024

Plant extracts are in the focus of the pharmaceutical industry as potential antimicrobials for oral care due to their high antimicrobial activity coupled with low production costs and safety for eukaryotic cells. Here, we show that the extract from Hop (Humulus lupulus L.) exhibits antimicrobial activity against Staphylococcus aureus and Streptococci in both planktonic and biofilm-embedded forms. An extract was prepared by acetone extraction from hop infructescences, followed by purification and solubilization of the remaining fraction in ethanol. The effect of the extract on S. aureus (MSSA and MRSA) was comparable with the reference antibiotics (amikacin, ciprofloxacin, and ceftriaxone) and did not depend on the bacterial resistance to methicillin. The extract also demonstrated synergy with amikacin on six S. aureus clinical isolates, on four of six isolates with ciprofloxacin, and on three of six isolates with ceftriaxone. On various Streptococci, while demonstrating lower antimicrobial activity, an extract exhibited a considerable synergistic effect in combination with two of three of these antibiotics, decreasing their MIC up to 512-fold. Moreover, the extract was able to penetrate S. aureus and S. mutans biofilms, leading to almost complete bacterial death within them. The thin-layer chromatography and LC-MS of the extract revealed the presence of prenylated flavonoids (2′,4′,6′,4-tetrahydroxy-3′-geranylchalcone) and acylphloroglucides (cohumulone, colupulone, humulone, and lupulone), apparently responsible for the observed antimicrobial activity and ability to increase the efficiency of antibiotics. Taken together, these data suggest an extract from H. lupulus as a promising antimicrobial agent for use both as a solely antiseptic and to potentiate conventional antimicrobials.
Bioavailability of Oral Curcumin in Systematic Reviews: A Methodological Study
Authors: Bučević Popović Viljemka , Karahmet Farhat Esma , Banjari Ines , Jeličić Kadić Antonia , Puljak Livia
Published: January 2024

Curcumin is a natural compound found in turmeric that exhibits diverse biological activities. However, its poor bioavailability limits its therapeutic application, which has led to the development of various bioavailability-improved formulations. In this methodological study, we analyzed whether systematic reviews on curcumin considered the bioavailability of systemic oral curcumin formulations when synthesizing evidence from human clinical trials. A total of 171 systematic reviews published between 2003 and 2022 were included in the study. From the included studies, we extracted data on study characteristics; type of curcumin; methods; and reporting regarding bioavailability, funding, and conflict of interest. Our results show that systematic reviews rarely consider the variable bioavailability of tested curcumin formulations. Relevant statistical subgroup and/or sensitivity analyses were reported in the methods and results of only 3.5% and 6.4% of reviews, respectively. However, more reviews mentioned bioavailability in their discussion (57%) or conclusion (13%). The detailed analysis of the included systematic reviews suggests that there is broad recognition of product bioavailability as a crucial factor affecting the health effects of curcumin, which is not accompanied by adequate evidence synthesis. Therefore, the results of most systematic reviews on orally administered curcumin should be taken with caution.
Synergistic Anti-Inflammatory Activity of Apolipoprotein A-I and CIGB-258 in Reconstituted High-Density Lipoproteins (rHDL) against Acute Toxicity of Carboxymethyllysine in Zebrafish and Its Embryo
Authors: Cho Kyung-Hyun , Kim Ji-Eun , Kang Dae-Jin , Dominguez-Horta Maria del Carmen , Martinez-Donato Gillian
Published: January 2024

CIGB-258 is a 3 kDa altered peptide ligand from heat shock protein (HSP) 60 that exhibits anti-inflammatory activity against the acute toxicity of carboxymethyllysine (CML) with antioxidant and anti-glycation activities via protection of high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I). It is necessary to test a synergistic interaction between apoA-I and CIGB-258 in reconstituted high-density lipoproteins (rHDL). Several rHDLs were synthesized containing palmitoyloleoyl phosphatidylcholine (POPC), cholesterol, apoA-I, and CIGB-258 at molar ratios of 95:5:1:0, 95:5:1:0.1, 95:5:1:0.5, and 95:5:1:1 for rHDL-(1:0), rHDL-(1:0.1), rHDL-(1:0.5), and rHDL-(1:1), respectively. As the CIGB-258 content in rHDL was increased, the particle size of rHDL was 1.4-times higher than rHDL-(1:0) to rHDL-(1:1), from 60 nm to 83 nm, respectively. As the CIGB-258 content was increased, the rHDL showed the most resistance to isothermal denaturation by a urea treatment, and rHDL-(1:1) exhibited the highest structural stability and the strongest antioxidant ability against LDL oxidation. Co-treatment of rHDL-(1:0), rHDL-(1:0.5), and rHDL-(1:1) resulted in up to 10%, 24%, and 34% inhibition of HDL glycation, inhibition of HDL glycation, which was caused by the CML, with protection of apoA-I. Microinjection of each rHDL into zebrafish embryos in the presence of CML showed that a higher CIGB-258 content in rHDL was associated with higher survivability with the least inflammation and apoptosis. Furthermore, an intraperitoneal injection of rHDL and CML showed that a higher CIGB-258 content in rHDL was also associated with higher survivability of zebrafish and faster recovery of swimming ability. The rHDL-(1:1) group showed the lowest triglyceride, AST, and ALT serum levels with the least production of interleukin-6, oxidized product, and neutrophil infiltration in hepatic tissue. In conclusion, CIGB-258 could bind well to phospholipids and cholesterol to stabilize apoA-I in the rHDL structure against denaturation stress and larger particle sizes. The rHDL containing CIGB-258 enhanced the in vitro antioxidant ability against LDL oxidation, the anti-glycation activity to protect HDL, and the in vivo anti-inflammatory activity against CML toxicity in zebrafish adults and embryos. Overall, incorporating apoA-I and CIGB-258 in rHDL resulted in a synergistic interaction to enhance the structural and functional correlations in a dose-dependent manner of CIGB-258.
[18F]Fluspidine—A PET Tracer for Imaging of σ1 Receptors in the Central Nervous System
Authors: Ludwig Friedrich-Alexander , Laurini Erik , Schmidt Judith , Pricl Sabrina , Deuther-Conrad Winnie , Wünsch Bernhard
Published: January 2024

σ1 receptors play a crucial role in various neurological and neurodegenerative diseases including pain, psychosis, Alzheimer’s disease, and depression. Spirocyclic piperidines represent a promising class of potent σ1 receptor ligands. The relationship between structural modifications and σ1 receptor affinity and selectivity over σ2 receptors led to the 2-fluoroethyl derivative fluspidine (2, Ki = 0.59 nM). Enantiomerically pure (S)-configured fluspidine ((S)-2) was prepared by the enantioselective reduction of the α,β-unsaturated ester 23 with NaBH4 and the enantiomerically pure co-catalyst (S,S)-24. The pharmacokinetic properties of both fluspidine enantiomers (R)-2 and (S)-2 were analyzed in vitro. Molecular dynamics simulations revealed very similar interactions of both fluspidine enantiomers with the σ1 receptor protein, with a strong ionic interaction between the protonated amino moiety of the piperidine ring and the COO- moiety of glutamate 172. The 18F-labeled radiotracers (S)-[18F]2 and (R)-[18F]2 were synthesized in automated syntheses using a TRACERlab FX FN synthesis module. High radiochemical yields and radiochemical purity were achieved. Radiometabolites were not found in the brains of mice, piglets, and rhesus monkeys. While both enantiomers revealed similar initial brain uptake, the slow washout of (R)-[18F]2 indicated a kind of irreversible binding. In the first clinical trial, (S)-[18F]2 was used to visualize σ1 receptors in the brains of patients with major depressive disorder (MDD). This study revealed an increased density of σ1 receptors in cortico-striato-(para)limbic brain regions of MDD patients. The increased density of σ1 receptors correlated with the severity of the depressive symptoms. In an occupancy study with the PET tracer (S)-[18F]2, the selective binding of pridopidine at σ1 receptors in the brain of healthy volunteers and HD patients was shown.
Synthesis, Characterization, and Toxicity Assessment of Zinc Oxide-Doped Manganese Oxide Nanoparticles in a Macrophage Model
Authors: Alsaleh Nasser B. , Aljarbou Anas M. , Assal Mohamed E. , Assiri Mohammed A. , Almutairi Mohammed M. , As Sobeai Homood M. , Alshamrani Ali A. , Almudimeegh Sultan , Hatshan Mohammad R. , Adil Syed F.
Published: January 2024

The doping of engineered nanomaterials (ENMs) is a key tool for manipulating the properties of ENMs (e.g., electromagnetic, optical, etc.) for different therapeutic applications. However, adverse health outcomes and the cellular biointeraction of doped ENMs, compared to undoped counterparts, are not fully understood. Previously, we have shown that doping manganese oxide nanoparticles with ZnO (ZnO-MnO2 NPs) improved their catalytic properties. In this study, we assessed the toxicity of ZnO-MnO2 NPs in Raw 264.7 cells. NPs were prepared via an eco-friendly, co-precipitation method and characterized by several techniques, including transmission and scanning electron microscopy, X-ray diffraction, and Fourier transform infrared. The physicochemical properties of ZnO-MnO2 NPs, including size, morphology, and crystalline structure, were almost identical to MnO2 NPs. However, ZnO-MnO2 NPs showed slightly larger particle aggregates and negative charge in cell culture media. Exposure to ZnO-MnO2 NPs resulted in lower toxicity based on the cell viability and functional assay (phagocytosis) data. Exposure to both NPs resulted in the activation of the cell inflammatory response and the generation of reactive oxygen species (ROS). Despite this, exposure to ZnO-MnO2 NPs was associated with a lower toxicity profile, and it resulted in a higher ROS burst and the activation of the cell antioxidant system, hence indicating that MnO2 NP-induced toxicity is potentially mediated via other ROS-independent pathways. Furthermore, the cellular internalization of ZnO-MnO2 NPs was lower compared to MnO2 NPs, and this could explain the lower extent of toxicity of ZnO-MnO2 NPs and suggests Zn-driven ROS generation. Together, the findings of this report suggest that ZnO (1%) doping impacts cellular biointeraction and the consequent toxicological outcomes of MnO2 NPs in Raw 264.7 cells.
Evaluation of the Antibacterial Activity of New Dermaseptin Derivatives against Acinetobacter baumannii
Authors: Haddad Houda , Mejri Radhia , Zaïri Amira
Published: January 2024

Nosocomial infections represent one of the biggest health problems nowadays. Acinetobacter baumannii is known as an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived infection. It is known that in recent years, more and more bacteria have become multidrug-resistant (MDR) and, for this reason, the development of new drugs is a priority. However, these products must not affect the human body, and therefore, cytotoxicity studies are mandatory. In this context, antimicrobial peptides with potential antibacterial proprieties could be an alternative. In this research, we describe the synthesis and the bioactivity of dermaseptins and their derivatives against Acinetobacter baumannii. The cytotoxicity of these compounds was investigated on the HEp-2 cell line by MTT cell viability assay. Thereafter, we studied the morphological alterations caused by the action of one of the active peptides on the bacterial membrane using atomic force microscopy (AFM). The cytotoxicity of dermaseptins was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibited antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 3.125 to 12.5 μg/mL and Minimum Bactericidal Concentrations (MBCs) ranging from 6.25 to 25 μg/mL. Microscopic images obtained by AFM revealed morphological changes on the surface of the treated bacteria caused by K4S4(1-16), as well as significant surface alterations. Overall, these findings demonstrate that dermaseptins might constitute new lead structures for the development of potent antibacterial agents against Acinetobacter baumannii infections.
Optimization of Pramipexole-Loaded In Situ Thermosensitive Intranasal Gel for Parkinson’s Disease
Authors: Trivedi Rushi , Minglani Vahid Vikram , El-Gazzar Ahmed M. , Batiha Gaber El-Saber , Mahmoud Mohamed H. , Patel Mitesh , Patel Meenakshi
Published: January 2024

The objective of the present work was to develop and optimize an intranasal in situ gel of Pramipexole dihydrochloride for enhanced drug delivery, better patient acceptability, and possible proper treatment of Parkinson’s disease. Preliminary studies were performed to select formulation components and identify key variables affecting the formulation. The optimization of the in situ gelling system of Pramipexole dihydrochloride was achieved by applying 32 full factorial design using Design-Expert® software (Stat-Ease 9.0.6 version) and taking concentrations of Poloxamer 407 (X1) and HPMC K4M (X2) as independent variables. The gelling temperature, gel strength, and percentage of drug diffused after 8 h were taken as dependent variables. The software provided an optimized formulation, with 16.50% of X1 and 0.2% of X2 with the highest desirability. An in vivo drug retention time study was performed for the optimized formulation in Wistar rats. The results of the optimization process demonstrated that the selected gel formulation exhibited desirable characteristics, including gelation near body temperature, good gel strength, suitable viscosity, and sustained drug release. The optimized formulation displayed significantly higher drug retention, lasting about 5 h, versus the plain poloxamer gel formulation. Hence, it was concluded that the optimized formulation will remain affixed at the site of application for a significant time after intranasal administration and consequently sustain the release of the drug. The optimized formulation was found to be stable during the stability studies. The developed dosage form may improve patient compliance, enhance nasal drug residence, and offer sustained drug release. However, further clinical studies are necessary to validate these findings.
PEG–Lipid–PLGA Hybrid Particles for Targeted Delivery of Anti-Inflammatory Drugs
Authors: Ismail Jana , Klepsch Lea C. , Dahlke Philipp , Tsarenko Ekaterina , Vollrath Antje , Pretzel David , Jordan Paul M. , Rezaei Kourosh , Czaplewska Justyna A. , Stumpf Steffi , Beringer-Siemers Baerbel , Nischang Ivo , Hoeppener Stephanie , Werz Oliver , Schubert Ulrich S.
Published: January 2024

Hybrid nanoparticles (HNPs) were designed by combining a PLGA core with a lipid shell that incorporated PEG–Lipid conjugates with various functionalities (-RGD, -cRGD, -NH2, and -COOH) to create targeted drug delivery systems. Loaded with a neutral lipid orange dye, the HNPs were extensively characterized using various techniques and investigated for their uptake in human monocyte-derived macrophages (MDMs) using FC and CLSM. Moreover, the best-performing HNPs (i.e., HNP-COOH and HNP-RGD as well as HNP-RGD/COOH mixed) were loaded with the anti-inflammatory drug BRP-201 and prepared in two size ranges (dH ~140 nm and dH ~250 nm). The HNPs were examined further for their stability, degradation, MDM uptake, and drug delivery efficiency by studying the inhibition of 5-lipoxygenase (5-LOX) product formation, whereby HNP-COOH and HNP-RGD both exhibited superior uptake, and the HNP-COOH/RGD (2:1) displayed the highest inhibition.
Designing Advanced Drug Delivery Systems: Core-Shell Alginate Particles through Electro-Fluid Dynamic Atomization
Authors: Cruz-Maya Iriczalli , Schiavone Carmine , Ferraro Rosalia , Renkler Nergis Zeynep , Caserta Sergio , Guarino Vincenzo
Published: January 2024

Innovations in drug delivery systems are crucial for enhancing therapeutic efficiency. Our research presents a novel approach based on using electro-fluid dynamic atomization (EFDA) to fabricate core-shell monophasic particles (CSMp) from sodium alginate blends of varying molecular weights. This study explores the morphological characteristics of these particles in relation to material properties and process conditions, highlighting their potential in drug delivery applications. A key aspect of our work is the development of a mathematical model that simulates the release kinetics of small molecules, specifically sodium diclofenac. By assessing the diffusion properties of different molecules and gel formulations through transport and rheological models, we have created a predictive tool for evaluating the efficiency of these particles in drug delivery. Our findings underscore two critical, independent parameters for optimizing drug release: the external shell thickness and the diffusivity ratios within the dual layers. This allows for precise control over the timing and intensity of the release profile. This study advances our understanding of EFDA in the fabrication of CSMp and offers promising avenues for enhancing drug delivery systems by tailoring release profiles through particle characteristic manipulation.
Regional Variations in Peucedanum japonicum Antioxidants and Phytochemicals
Authors: Uy Neil Patrick , Kim Hoon , Ku Jajung , Lee Sanghyun
Published: January 2024

Peucedanum japonicum has long been a staple in East Asian cuisine. In the context of traditional medicine, various members of the Peucedanum genus have been investigated for potential medicinal properties. In laboratory settings, some compounds derived from this plant have shown antioxidant and anti-inflammatory properties—characteristics often associated with potential medicinal applications. This study aimed to determine which part of the P. japonicum plants cultivated on two Korean islands contains the most antioxidant compounds. This determination was made through assessments of total polyphenol content and total flavonoid content, coupled with evaluation of antioxidant activity via DPPH and ABTS assays. The results showed that the aerial parts contain a richer array of bioactive compounds and demonstrate superior antioxidant activity compared to their root counterparts in the plants from both islands. To characterize the phytochemicals underpinning this bioactivity, LC-MS/MS and HPLC analyses were carried out. These methods detected varying amounts of chlorogenic acid, peucedanol 7-O-glucoside, rutin, and peucedanol, with good separation and retention times. This study addresses the lack of research on the antioxidant activity of different parts of P. japonicum. The findings hold significance for traditional medicine, dietary supplements, and the development of functional foods. Understanding antioxidant distribution aids in the development of medicinal and nutritional applications, influences agricultural practices, and contributes to regional biodiversity-conservation efforts. The study’s geographical scope provides insights into how location impacts the concentration of bioactive compounds in plants. Overall, the results contribute valuable data for future research in plant biology, biochemistry, and related fields.
Morphophysiological Characterisation of Guayule (Parthenium argentatum A. Gray) in Response to Increasing NaCl Concentrations: Phytomanagement and Phytodesalinisation in Arid and Semiarid Areas
Authors: Di Baccio Daniela , Lorenzi Aurora , Scartazza Andrea , Rosellini Irene , Franchi Elisabetta , Barbafieri Meri
Published: January 2024

Water and soil salinity continuously rises due to climate change and irrigation with reused waters. Guayule (Parthenium argentatum A. Gray) is a desert perennial shrub native to northern Mexico and the southwestern United States; it is known worldwide for rubber production and is suitable for cultivation in arid and semiarid regions, such as the Mediterranean. In the present study, we investigated the effects of high and increasing concentrations of sodium chloride (NaCl) on the growth and the morphophysiological and biochemical characteristics of guayule to evaluate its tolerance to salt stress and suitability in phytomanagement and, eventually, the phytodesalinisation of salt-affected areas. Guayule originates from desert areas, but has not been found in salt-affected soils; thus, here, we tested the potential tolerance to salinity of this species, identifying the toxicity threshold and its possible sodium (Na) accumulation capacity. In a hydroponic floating root system, guayule seedlings were subjected to salinity-tolerance tests using increasing NaCl concentrations (from 2.5 to 40 g L−1 and from 43 to 684 mM). The first impairments in leaf morphophysiological traits appeared after adding 15 g L−1 (257 mM) NaCl, but the plants survived up to the hypersaline conditions of 35–40 g L−1 NaCl (about 600 mM). The distribution of major cell cations modulated the high Na content in the leaves, stems and roots; Na bioconcentration and translocation factors were close to one and greater than one, respectively. This is the first study on the morphophysiological and (bio)chemical response of guayule to different high and increasing levels of NaCl, showing the parameters and indices useful for identifying its salt tolerance threshold, adaptative mechanisms and reclamation potential in high-saline environments.
Overexpression of a Ramie (Boehmaeria nivea L. Gaud) Group I WRKY Gene, BnWRKY49, Increases Drought Resistance in Arabidopsis thaliana
Authors: Bao Yaning , Zou Yifei , An Xia , Liao Yiwen , Dai Lunjin , Liu Lijun , Peng Dingxiang , Huang Xing , Wang Bo
Published: January 2024

Plants face multiple stresses in their natural habitats. WRKY transcription factors (TFs) play an important regulatory role in plant stress signaling, regulating the expression of multiple stress-related genes to improve plant stress resistance. In this study, we analyzed the expression profiles of 25 BnWRKY genes in three stages of ramie growth (the seedling stage, the rapid-growth stage, and the fiber maturity stage) and response to abiotic stress through qRT-PCR. The results indicated that 25 BnWRKY genes play a role in different growth stages of ramie and were induced by salt and drought stress in the root and leaf. We selected BnWRKY49 as a candidate gene for overexpression in Arabidopsis. BnWRKY49 was localized in the nucleus. Overexpression of BnWRKY49 affected root elongation under drought and salt stress at the Arabidopsis seedling stage and exhibited increased tolerance to drought stress. Further research found that BnWRKY49-overexpressing lines showed decreased stomatal size and increased cuticular wax deposition under drought compared with wild type (WT). Antioxidant enzyme activities of SOD, POD, and CAT were higher in the BnWRKY49-overexpressing lines than the WT. These findings suggested that the BnWRKY49 gene played an important role in drought stress tolerance in Arabidopsis and laid the foundation for further research on the functional analysis of the BnWRKYs in ramie.
Absorption and Biotransformation of Selenomethionine and Selenomethionine-Oxide by Wheat Seedlings (Triticum aestivum L.)
Authors: Wang Qi , Huang Siyu , Huang Qingqing , Yu Yao , Li Huafen , Wan Yanan
Published: January 2024

An in-depth understanding of Se uptake and metabolism in plants is necessary for developing Se biofortification strategies. Thus, hydroponic experiments were conducted to investigate the associated processes and mechanisms of organic Se (selenomethionine (SeMet) and selenomethionine-oxide (SeOMet)) uptake, translocation, transformation and their interaction in wheat, in comparison to inorganic Se. The results showed that Se uptake by the roots and the root-to-shoot translocation factor under the SeMet treatment were higher than those under the selenite, selenate and SeOMet treatments. The uptake and translocation of SeMet were higher than those of SeOMet within 72 h, although the differences gradually narrowed with time. The uptake of SeMet and SeOMet was also sensitive to the aquaporin inhibitor: AgNO3 addition resulted in 99.5% and 99.9% inhibitions of Se in the root in the SeMet and SeOMet treatments, respectively. Once absorbed by the root, they rapidly assimilated to other Se forms, and SeMet and Se-methyl-selenocysteine (MeSeCys) were the dominant species in SeMet- and SeOMet-treated plants, while notably, an unidentified Se form was also found in the root and xylem sap under the SeMet treatment. In addition, within 16 h, SeOMet inhibited the uptake and translocation of SeMet, while the inhibition was weakened with longer treatment time. Taken together, the present study provides new insights for the uptake and transformation processes of organic Se within plants.
Onion Fusarium Basal Rot Disease Control by Arbuscular Mycorrhizal Fungi and Trichoderma harzianum
Authors: Yağmur Abdulaziz , Demir Semra , Canpolat Sirel , Rezaee Danesh Younes , Farda Beatrice , Djebaili Rihab , Pace Loretta , Pellegrini Marika
Published: January 2024

Soilborne pathogens reduce 60% of the yield of onion crops. A common fungal pathogen causing wilt disease and severe losses is Fusarium basal rot (FBR). In this study, the combination of Arbuscular Mycorrhizal Fungi (AMF) with Trichoderma harzianum was investigated against FBR. Onion samples were collected from the Ankara–Polatlı region. Among the isolates, isolate S6 was identified as F. oxysporum f. sp. cepae (FOC) using morphological and molecular methods and pathogenicity tests. Different combinations of AMF (Funneliformis mosseae pure strain and the commercial AMF) and T. harzianum were inoculated on susceptible onion cultivars (Seç, Gence, and Şampiyon). The effects of the treatments on FOC biocontrol were studied under growth chamber conditions. The results showed that Şampiyon was the most resistant, while Gence was the most susceptible to basal rot disease. Different colonization rates (8.91–24%), spore densities (16.4–50.4 spore/10 g soil), and the extent to which a plant needs mycorrhizal conditions to grow to its maximum potential (i.e., mycorrhizal dependencies—18.3–51.9%) were recorded by treatment. Both single and combined applications of AMF and Trichoderma applications suppressed FOC. Suppressive effects were more pronounced when the F. mosseae pure strain was used alone (when F. mosseae was used, disease severity decreased from 90 to 68%, p < 0.05). The F. mosseae pure strain also showed the best plant growth promotion and phosphorus content release. The results indicate an interesting potential use of F. mosseae and the combination of AMF with T. harzianum in the management of FOC in onions.
Telomere Length Variation in Model Bryophytes
Authors: Valeeva Liia R. , Sannikova Anastasia V. , Shafigullina Nadiya R. , Abdulkina Liliia R. , Sharipova Margarita R. , Shakirov Eugene V.
Published: January 2024

The ends of linear chromosomes of most eukaryotes consist of protein-bound DNA arrays called telomeres, which play essential roles in protecting genome integrity. Despite general evolutionary conservation in function, telomeric DNA is known to drastically vary in length and sequence between different eukaryotic lineages. Bryophytes are a group of early diverging land plants that include mosses, liverworts, and hornworts. This group of ancient land plants recently emerged as a new model for important discoveries in genomics and evolutionary biology, as well as for understanding plant adaptations to a terrestrial lifestyle. We measured telomere length in different ecotypes of model bryophyte species, including Physcomitrium patens, Marchantia polymorpha, Ceratodon purpureus, and in Sphagnum isolates. Our data indicate that all analyzed moss and liverwort genotypes have relatively short telomeres. Furthermore, all analyzed ecotypes and isolates of model mosses and liverworts display evidence of substantial natural variation in telomere length. Interestingly, telomere length also differs between male and female strains of the dioecious liverwort M. polymorpha and dioecious moss C. purpureus. Given that bryophytes are extraordinarily well adapted to different ecological niches from polar to tropical environments, our data will contribute to understanding the impact of natural telomere length variation on evolutionary adaptations in this ancient land plant lineage.