bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Analogs to A-Type Proanthocyanidin Natural Products with Enhanced Antimicrobial Properties against Foodborne Microorganisms
Authors: Cobo Antonio , Alejo-Armijo Alfonso , Cruz Daniel , Altarejos Joaquín , Salido Sofía , Ortega-Morente Elena
Published: June 2023

Developing new types of effective antimicrobial compounds derived from natural products is of interest for the food industry. Some analogs to A-type proanthocyanidins have shown promising antimicrobial and antibiofilm activities against foodborne bacteria. We report herein the synthesis of seven additional analogs with NO2 group at A-ring and their abilities for inhibiting the growth and the biofilm formation by twenty-one foodborne bacteria. Among them, analog 4 (one OH at B-ring; two OHs at D-ring) showed the highest antimicrobial activity. The best results with these new analogs were obtained in terms of their antibiofilm activities: analog 1 (two OHs at B-ring; one OH at D-ring) inhibited at least 75% of biofilm formation by six strains at all of the concentrations tested, analog 2 (two OHs at B-ring; two OHs at D-ring; one CH3 at C-ring) also showed antibiofilm activity on thirteen of the bacteria tested, and analog 5 (one OH at B-ring; one OH at D-ring) was able to disrupt preformed biofilms in eleven strains. The description of new and more active analogs of natural compounds and the elucidation of their structure-activity relationships may contribute to the active development of new food packaging for preventing biofilm formation and lengthening the food shelf life.
The Kappa Opioid Receptor Agonist 16-Bromo Salvinorin A Has Anti-Cocaine Effects without Significant Effects on Locomotion, Food Reward, Learning and Memory, or Anxiety and Depressive-like Behaviors
Authors: van de Wetering Ross , Ewald Amy , Welsh Susan , Kornberger Lindsay , Williamson Samuel E. , McElroy Bryan D. , Butelman Eduardo R. , Prisinzano Thomas E. , Kivell Bronwyn M.
Published: June 2023

Kappa opioid receptor (KOR) agonists have preclinical antipsychostimulant effects; however, adverse side effects have limited their therapeutic development. In this preclinical study, conducted in Sprague Dawley rats, B6-SJL mice, and non-human primates (NHPs), we evaluated the G-protein-biased analogue of salvinorin A (SalA), 16-bromo salvinorin A (16-BrSalA), for its anticocaine effects, side effects, and activation of cellular signaling pathways. 16-BrSalA dose-dependently decreased the cocaine-primed reinstatement of drug-seeking behavior in a KOR-dependent manner. It also decreased cocaine-induced hyperactivity, but had no effect on responding for cocaine on a progressive ratio schedule. Compared to SalA, 16-BrSalA had an improved side effect profile, with no significant effects in the elevated plus maze, light–dark test, forced swim test, sucrose self-administration, or novel object recognition; however, it did exhibit conditioned aversive effects. 16-BrSalA increased dopamine transporter (DAT) activity in HEK-293 cells coexpressing DAT and KOR, as well as in rat nucleus accumbens and dorsal striatal tissue. 16-BrSalA also increased the early phase activation of extracellular-signal-regulated kinases 1 and 2, as well as p38 in a KOR-dependent manner. In NHPs, 16-BrSalA caused dose-dependent increases in the neuroendocrine biomarker prolactin, similar to other KOR agonists, at doses without robust sedative effects. These findings highlight that G-protein-biased structural analogues of SalA can have improved pharmacokinetic profiles and fewer side effects while maintaining their anticocaine effects.
N,N-Bis(2,4-Dibenzhydryl-6-cycloalkylphenyl)butane-2,3-diimine–Nickel Complexes as Tunable and Effective Catalysts for High-Molecular-Weight PE Elastomers
Authors: Jiang Shu , Zheng Yuting , Oleynik Irina V. , Yu Zhixin , Solan Gregory A. , Oleynik Ivan I. , Liu Ming , Ma Yanping , Liang Tongling , Sun Wen-Hua
Published: June 2023

Four examples of N,N-bis(aryl)butane-2,3-diimine–nickel(II) bromide complexes, [ArN=C(Me)-C(Me)=NAr]NiBr2 (where Ar = 2-(C5H9)-4,6-(CHPh2)2C6H2 (Ni1), Ar = 2-(C6H11)-4,6-(CHPh2)2C6H2 (Ni2), 2-(C8H15)-4,6-(CHPh2)2C6H2 (Ni3) and 2-(C12H23)-4,6-(CHPh2)2C6H2 (Ni4)), disparate in the ring size of the ortho-cycloalkyl substituents, were prepared using a straightforward one-pot synthetic method. The molecular structures of Ni2 and Ni4 highlight the variation in the steric hindrance of the ortho-cyclohexyl and -cyclododecyl rings exerted on the nickel center, respectively. By employing EtAlCl2, Et2AlCl or MAO as activators, Ni1–Ni4 displayed moderate to high activity as catalysts for ethylene polymerization, with levels falling in the order Ni2 (cyclohexyl) > Ni1 (cyclopentyl) > Ni4 (cyclododecyl) > Ni3 (cyclooctyl). Notably, cyclohexyl-containing Ni2/MAO reached a peak level of 13.2 × 106 g(PE) of (mol of Ni)−1 h−1 at 40 °C, yielding high-molecular-weight (ca. 1 million g mol−1) and highly branched polyethylene elastomers with generally narrow dispersity. The analysis of polyethylenes with 13C NMR spectroscopy revealed branching density between 73 and 104 per 1000 carbon atoms, with the run temperature and the nature of the aluminum activator being influential; selectivity for short-chain methyl branches (81.8% (EtAlCl2); 81.1% (Et2AlCl); 82.9% (MAO)) was a notable feature. The mechanical properties of these polyethylene samples measured at either 30 °C or 60 °C were also evaluated and confirmed that crystallinity (Xc) and molecular weight (Mw) were the main factors affecting tensile strength and strain at break (εb = 353–861%). In addition, the stress–strain recovery tests indicated that these polyethylenes possessed good elastic recovery (47.4–71.2%), properties that align with thermoplastic elastomers (TPEs).
Optimization of Supercritical Fluid CO2 Extraction from Yellow Horn Seed and Its Anti-Fatigue and Antioxidant Activity
Authors: Lyu Siyan , Wang Haoran , Ma Tingjun
Published: June 2023

A supercritical fluid carbon dioxide (SF-CO2) extraction method was used to obtain the optimum process for extracting yellow horn seed oil. The anti-fatigue and antioxidant properties of the extracted oil were investigated through animal experiments. The optimum process conditions for SF-CO2 extraction of the yellow horn oil were 40 MPa, 50 °C and 120 min, with an extraction yield of 31.61%. The high-dose group of yellow horn oil could significantly increase the weight-bearing swimming time, the hepatic glycogen (HG) content and decrease the lactic acid (LA) content and blood urea nitrogen (BUN) content (p < 0.05) in mice. Moreover, it improved the antioxidant ability by reducing the malondialdehyde (MDA) content (p < 0.01) and raising the glutathione reductase (GR) content and superoxide dismutase (SOD) content (p < 0.05) in mice. Yellow horn oil has the effects of being an anti-fatigue and antioxidant substance, which provides a basis for its further utilization and development.
Biological Activities of Natural Products III
Authors: Ekiert Halina Maria , Szopa Agnieszka
Published: June 2023

The search for natural products that display biological activity is invariably an attractive research area for scientific centers and teams from around the world [...]
A Comprehensive Update of Various Attempts by Medicinal Chemists to Combat COVID-19 through Natural Products
Authors: Rafiq Ayesha , Jabeen Tooba , Aslam Sana , Ahmad Matloob , Ashfaq Usman Ali , Mohsin Noor ul Amin , Zaki Magdi E. A. , Al-Hussain Sami A.
Published: June 2023

The ongoing COVID-19 pandemic has resulted in a global panic because of its continual evolution and recurring spikes. This serious malignancy is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak, millions of people have been affected from December 2019 till now, which has led to a great surge in finding treatments. Despite trying to handle the pandemic with the repurposing of some drugs, such as chloroquine, hydroxychloroquine, remdesivir, lopinavir, ivermectin, etc., against COVID-19, the SARS-CoV-2 virus continues its out-of-control spread. There is a dire need to identify a new regimen of natural products to combat the deadly viral disease. This article deals with the literature reports to date of natural products showing inhibitory activity towards SARS-CoV-2 through different approaches, such as in vivo, in vitro, and in silico studies. Natural compounds targeting the proteins of SARS-CoV-2—the main protease (Mpro), papain-like protease (PLpro), spike proteins, RNA-dependent RNA polymerase (RdRp), endoribonuclease, exoribonuclease, helicase, nucleocapsid, methyltransferase, adeno diphosphate (ADP) phosphatase, other nonstructural proteins, and envelope proteins—were extracted mainly from plants, and some were isolated from bacteria, algae, fungi, and a few marine organisms.
Association of Drinking Herbal Tea with Activities of Daily Living among Elderly: A Latent Class Analysis
Authors: Tao Liyuan , Liao Jiaojiao , Zheng Rui , Zhang Xiaoyu , Shang Hongcai
Published: June 2023

The aim of this study was to explore whether drinking herbal tea and tea would positively benefit activities of daily living (ADL) in the elderly. We used data from the Chinese longitudinal healthy longevity survey (CLHLS) to explore the association. Drinking herbal tea and drinking tea were divided into three groups using latent class analysis (LCA): frequently, occasionally, and rarely. ADL disability was measured by the ADL score. Multivariate COX proportional hazards models with competing risks were used to explore the impact of drinking herbal tea and tea on ADL disability, statistically adjusted for a range of potential confounders. A total of 7441 participants (mean age 81.8 years) were included in this study. The proportions of frequently and occasionally drinking herbal tea were 12.0% and 25.7%, respectively. Additionally, 29.6% and 28.2% of participants reported drinking tea, respectively. Multivariate COX regression showed that compared with rarely drinking, frequently drinking herbal tea could effectively reduce the incidence of ADL disability (HR = 0.85, 95% CI = 0.77–0.93, p = 0.005), whereas tea drinking had a relatively weaker effect (HR = 0.92, 95% CI = 0.83–0.99, p = 0.040). Subgroup analysis found that frequently drinking herbal tea was more protective for males under 80 years old (HR = 0.74 and 0.79, respectively), while frequently drinking tea was somewhat protective for women (HR = 0.92). The results indicate that drinking herbal tea and tea may be associated with a lower incidence of ADL disability. However, the risks associated with using Chinese herb plants still deserve attention.
Injectable Lipid Emulsion and Clinical Outcomes in Patients Exclusively Receiving Parenteral Nutrition in an ICU: A Retrospective Cohort Study Using a Japanese Medical Claims Database
Authors: Yasuda Hideto , Horikoshi Yuri , Kamoshita Satoru , Kuroda Akiyoshi , Moriya Takashi
Published: June 2023

Guidelines for the nutritional management of critically ill patients recommend the use of injectable lipid emulsion (ILE) as part of parenteral nutrition (PN). The ILE’s impact on outcomes remains unclear. Associations between prescribed ILE and in-hospital mortality, hospital readmission, and hospital length of stay (LOS) in critically ill patients in the intensive care unit (ICU) were investigated. Patients who were ≥18 years old in an ICU from January 2010 through June 2020, receiving mechanical ventilation, and fasting for >7 days, were selected from a Japanese medical claims database and divided, based on prescribed ILE during days from 4 to 7 of ICU admission, into 2 groups, no-lipid and with-lipid. Associations between the with-lipid group and in-hospital mortality, hospital readmission, and hospital LOS were evaluated relative to the no-lipid group. Regression analyses and the Cox proportional hazards model were used to calculate the odds ratios (OR) and regression coefficients, and hazard ratios (HR) were adjusted for patient characteristics and parenteral energy and amino acid doses. A total of 20,773 patients were evaluated. Adjusted OR and HR (95% confidence interval) for in-hospital mortality were 0.66 (0.62–0.71) and 0.68 (0.64–0.72), respectively, for the with-lipid group relative to the no-lipid group. No significant differences between the two groups were observed for hospital readmission or hospital LOS. The use of ILE for days 4 to 7 in PN prescribed for critically ill patients, who were in an ICU receiving mechanical ventilation and fasting for more than 7 days, was associated with a significant reduction in in-hospital mortality.
Assessment of the Concentration of 51 Elements in the Liver and in Various Parts of the Human Brain—Profiling of the Mineral Status
Authors: Baj Jacek , Kowalska Beata , Flieger Wojciech , Radzikowska-Büchner Elżbieta , Forma Alicja , Czeczelewski Marcin , Kędzierawski Paweł , Karakuła Kaja , Flieger Michał , Majerek Dariusz , Teresiński Grzegorz , Maciejewski Ryszard , Flieger Jolanta
Published: June 2023

The anthropogenic environment and diet introduce many metals into the human body, both essential and toxic. Absorption leads to systemic exposure and accumulation in body fluids and tissues. Both excess and deficiency of trace elements are health hazards. The primary aim of the present study was to evaluate the concentration of 51 elements in liver samples and 11 selected brain regions obtained at post-mortem examination from a population of adults living in south-eastern Poland (n = 15). A total of 180 analyses were performed by inductively coupled plasma mass spectrometry in two independent replicates. The collected data show very high individual variability in the content of the investigated elements. Macroelements such as sodium, magnesium, phosphorus, potassium, calcium, iron, and zinc occurred in the highest concentrations and with the greatest statistically significant variations. Although the elemental content of the brain and liver differed significantly, the strongest positive correlation between liver and polus frontalis was observed for the essential element selenium (0.9338) and the strongest negative one for manganese (−0.4316) and lanthanum (−0.5110). The brain areas studied have different requirements for phosphorus, manganese, iron, and molybdenum. In addition, males had a significantly (p < 0.05) higher brain content of lanthanides and actinides than females. The results of this study show that the inhabitants of south-eastern Poland are exposed to a fairly uniform accumulation of aluminum and vanadium in the brain, which have the highest affinity to the thalamus dorsalis. This result proves that there is environmental exposure to these elements.
Effects of Melatonin Supplementation on Lipid Metabolism and Body Fat Accumulation in Ovariectomized Rats
Authors: Hsu Ling-Wen , Chien Yi-Wen
Published: June 2023

Postmenopausal obesity is a rising problem. Melatonin (Mel) is a hormone secreted by the pineal gland that regulates the circadian rhythms and improves obesity. In this experiment, ovariectomized (OVX) rats were used as a menopause model to explore the effects of Mel supplementation on lipid metabolism, body fat accumulation, and obesity. Nine-week-old female rats underwent an OVX surgery and were assigned to the following groups: control group (C), low-dose group (L, 10 mg/kg body weight (BW) Mel), medium-dose group (M, 20 mg/kg BW Mel), and high-dose group (H, 50 mg/kg BW Mel), administered by gavage for 8 weeks. The results showed that the OVX rats supplemented with low, medium, and high doses of Mel for 8 weeks exhibited reduced BW gain, perirenal fat mass, and gonads fat mass, and an increased serum irisin level. Low and high doses of Mel induced brite/beige adipocytes in the white adipose tissues. In addition, the messenger RNA levels of the fatty acid synthesis enzymes were significantly reduced after the high-dose Mel supplementation. Thus, Mel can reduce the hepatic fatty acid synthesis and promote the browning of white adipose tissues through irisin; thereby, improving obesity and body fat accumulation in OVX rats.
Vitamin D Deficiency in Chronic Childhood Disorders: Importance of Screening and Prevention
Authors: Joshi Madhura , Uday Suma
Published: June 2023

Vitamin D plays a vital role in regulating calcium and phosphate metabolism and maintaining bone health. A state of prolonged or profound vitamin D deficiency (VDD) can result in rickets in children and osteomalacia in children and adults. Recent studies have demonstrated the pleiotropic action of vitamin D and identified its effects on multiple biological processes in addition to bone health. VDD is more prevalent in chronic childhood conditions such as long-standing systemic illnesses affecting the renal, liver, gastrointestinal, skin, neurologic and musculoskeletal systems. VDD superimposed on the underlying disease process and treatments that can adversely affect bone turnover can all add to the disease burden in these groups of children. The current review outlines the causes and mechanisms underlying poor bone health in certain groups of children and young people with chronic diseases with an emphasis on the proactive screening and treatment of VDD.
The Effects of n-3 PUFA Supplementation on Bone Metabolism Markers and Body Bone Mineral Density in Adults: A Systematic Review and Meta-Analysis of RCTs
Authors: Gao Jie , Xie Chenqi , Yang Jie , Tian Chunyan , Zhang Mai , Lu Zhenquan , Meng Xiangyuan , Cai Jing , Guo Xiaofei , Gao Tianlin
Published: June 2023

Supplemental n-3 polyunsaturated fatty acids (PUFA) on bone metabolism have yielded inconsistent results. This study aimed to examine the effects of n-3 PUFA supplementation on bone metabolism markers and bone mineral density through a meta-analysis of randomized controlled trials. A systematic literature search was conducted using the PubMed, Web of Science, and EBSCO databases, updated to 1 March 2023. The intervention effects were measured as standard mean differences (SMD) and mean differences (MD). Additionally, n-3 PUFA with the untreated control, placebo control, or lower-dose n-3 PUFA supplements were compared, respectively. Further, 19 randomized controlled trials (RCTs) (22 comparisons, n = 2546) showed that n-3 PUFA supplementation significantly increased blood n-3 PUFA (SMD: 2.612; 95% CI: 1.649 to 3.575). However, no significant effects were found on BMD, CTx-1, NTx-1, BAP, serum calcium, 25(OH)D, PTH, CRP, and IL-6. Subgroup analyses showed significant increases in femoral neck BMD in females (0.01, 95% CI: 0.01 to 0.02), people aged <60 years (0.01, 95% CI: 0.01 to 0.01), and those people in Eastern countries (0.02, 95% CI: 0.02 to 0.03), and for 25(OH)D in people aged ≥60 years (0.43, 95% CI: 0.11 to 0.74), treated with n-3 PUFA only (0.36, 95% CI: 0.06 to 0.66), and in studies lasting ≤6 months (0.29, 95% CI: 0.11 to 0.47). NTx-1 decreased in both genders (−9.66, 95% CI: −15.60 to −3.71), and serum calcium reduction was found in studies lasting >6 months (−0.19, 95% CI: −0.37 to −0.01). The present study demonstrated that n-3 PUFA supplementation might not have a significant effect on bone mineral density or bone metabolism markers, but have some potential benefits for younger postmenopausal subjects in the short term. Therefore, additional high-quality, long-term randomized controlled trials (RCTs) are warranted to fully elucidate the potential benefits of n-3 PUFA supplementation, as well as the combined supplementation of n-3 PUFA, on bone health.
Inflammation and Insulin Resistance in Diabetic Chronic Coronary Syndrome Patients
Authors: Li Tianyu , Wang Peizhi , Wang Xiaozeng , Liu Zhenyu , Zhang Zheng , Zhang Yongzhen , Wang Zhifang , Feng Yingqing , Wang Qingsheng , Guo Xiaogang , Tang Xiaofang , Xu Jingjing , Song Ying , Chen Yan , Xu Na , Yao Yi , Liu Ru , Zhu Pei , Han Yaling , Yuan Jinqing
Published: June 2023

Limited evidence exists on the combined and mediating effects of systemic inflammation on the association between insulin resistance and cardiovascular events in patients with diabetes and chronic coronary syndrome (CCS). This secondary analysis of a multicenter prospective cohort included 4419 diabetic CCS patients. Triglyceride–glucose index (TyG) and high-sensitivity C-reactive protein (hsCRP) were applied to evaluate insulin resistance and systemic inflammation, respectively. The primary endpoint was major adverse cardiac event (MACE). Associations of TyG and hsCRP with cardiovascular events were estimated using Cox regression. A mediation analysis was performed to assess whether hsCRP mediates the relationship between TyG and cardiovascular events. Within a median 2.1-year follow-up period, 405 MACEs occurred. Patients with high levels of TyG and hsCRP experienced the highest MACE risk (hazard ratio = 1.82, 95% confidence interval: 1.24–2.70, p = 0.002) compared to individuals with low levels of both markers. HsCRP significantly mediated 14.37% of the relationship between TyG and MACE (p < 0.001). In diabetic CCS patients, insulin resistance and systemic inflammation synergically increased the risk of cardiovascular events, and systemic inflammation partially mediated the association between insulin resistance and clinical outcomes. Combining TyG and hsCRP can help identify high-risk patients. Controlling inflammation in patients with insulin resistance may bring added benefits.
Maternal Diet Quality and Prenatal Depressive Symptoms: The Moderating Role of Economic Well-Being
Authors: Wang Peiyi , Yim Ilona S. , Lindsay Karen L.
Published: June 2023

Prenatal depression is prevalent and adversely impacts maternal and infant health. This study addresses a critical literature gap and investigates the association between maternal diet quality and prenatal depressive symptoms, as well as the moderating effect of economic well-being on this link. A cross-sectional design was used, including 43 healthy pregnant women in the second trimester aggregated from two research projects. Prenatal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. Dietary quality was evaluated using two non-consecutive 24 h dietary recalls, from which the Adapted Dietary Inflammatory Index (ADII) and the Healthy Eating Index (HEI)-2015 were derived. Economic well-being was indicated by the income-to-poverty ratio. A higher HEI-2015 (adherence to dietary guidelines; β = −0.53, p = 0.01) and negative ADII (anti-inflammatory diet; β = 0.40, p = 0.06) were associated with fewer prenatal depressive symp-toms. Among pregnant women with worse economic well-being, a pro-inflammatory diet was as-sociated with more prenatal depressive symptoms (b = 1.69, p = 0.004), but among those with better economic well-being, the association was not significant (b = 0.51, p = 0.09). Dietary interventions aimed at reducing dietary inflammation might hold some promise for improving mental health among pregnant women who are economically vulnerable.
Hydroethanolic Extract of Fritillariae thunbergii Bulbus Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Enhancing Intestinal Barrier Integrity
Authors: Lee Ami , Chung You Chul , Kim Kwang-Youn , Jang Chan Ho , Song Kwang Hoon , Hwang Youn-Hwan
Published: June 2023

The incidence of ulcerative colitis (UC), an inflammatory disorder of the gastrointestinal tract, has rapidly increased in Asian countries over several decades. To overcome the limitations of conventional drug therapies, including biologics for UC management, the development of herbal medicine-derived products has received continuous attention. In this study, we evaluated the beneficial effects of a hydroethanolic extract of Fritillariae thunbergii Bulbus (FTB) in a mouse model of DSS-induced UC. The DSS treatment successfully induced severe colonic inflammation and ulceration. However, the severity of colitis was reduced by the oral administration of FTB. Histopathological examination showed that FTB alleviated the infiltration of inflammatory cells (e.g., neutrophils and macrophages), damage to epithelial and goblet cells in the colonic mucosal layer, and fibrotic lesions. Additionally, FTB markedly reduced the gene expression of proinflammatory cytokines and extracellular matrix remodeling. Immunohistochemical analysis showed that FTB alleviated the decrease in occludin and zonula occludens-1 expression induced by DSS. In a Caco-2 monolayer system, FTB treatment improved intestinal barrier permeability in a dose-dependent manner and increased tight junction expression. Overall, FTB has potential as a therapeutic agent through the improvement of tissue damage and inflammation severity through the modulation of intestinal barrier integrity.
Designing Vitamin D3 Formulations: An In Vitro Investigation Using a Novel Micellar Delivery System
Authors: Du Min , Chang Chuck , Zhang Xin , Zhang Yiming , Radford Melissa J. , Gahler Roland J. , Kuo Yun Chai , Wood Simon , Solnier Julia
Published: June 2023

Vitamin D is an essential nutrient with important immunomodulatory properties. As a fat-soluble compound, Vitamin D (and its D3 form) is immiscible with water, which presents challenges to absorption. In an in vitro setting, the current study characterizes novel micellar formulations of Vitamin D3 designed to improve absorption. Techniques used to evaluate and compare the micellar formulations against a non-micellar formula include the following: cryo-SEM to determine morphology; laser diffraction to determine particle size and distribution; zeta potential to determine stability of the particles; solubility assays to determine solubility in water and gastrointestinal media; and Caco-2 cell monolayers to determine intestinal permeability. Results show advantageous features (particle size range in the low micrometres with an average zeta potential of −51.56 ± 2.76 mV), as well as significant improvements in intestinal permeability, in one optimized micellar formula (LipoMicel®). When introduced to Caco-2 cells, LipoMicel’s permeability was significantly better than the control (p < 0.01; ANOVA). Findings of this study suggest that the novel micellar form of Vitamin D3 (LipoMicel) has the potential to promote absorption of Vitamin D3. Thus, it can serve as a promising candidate for follow-up in vivo studies in humans.
Barriers with Valve Mechanisms Are Predicted to Protect Crops from Slug Carriers of Rat Lungworm Disease
Authors: Pang Genevieve C. , Hou Amy T. , Tamashiro Ryan , Mills Kristin M. , Pang Lorrin W.
Published: June 2023

Angiostrongyliasis (Rat Lungworm disease) is an emerging parasitic disease caused by the ingestion of gastropods infected with the neurotropic nematode Angiostrongylus cantonensis. The reduction of crop infestation with infected slug carriers may vary widely by protection method. We explored the application of barriers with valve mechanisms, whereby selective directional forces caused a greater number of slugs to exit than enter the protected plot, leading to decreased slug population densities at a steady state. Using field data, we constructed predictive models to estimate slug population densities at a steady state in protected plots with (1) no valve effect, (2) a valve effect, (3) no valve effect with a single breach of the barrier, (4) a valve effect with a single breach of the barrier, (5) a valve effect with a constant breach of the barrier, and (6) a repelling effect. For all scenarios, plots protected using a barrier with a valve effect had consistently lower slug densities at a steady state. Our findings support the use of barriers with valve mechanisms under different conditions, and potentially in combination with other interventions to reduce the contamination of crops by slug carriers of A. cantonensis. Improving barriers extends beyond disease mitigation to economic and cultural impacts on the local farmer and consumer communities.
Targeting Metalloenzymes: The “Achilles’ Heel” of Viruses and Parasites
Authors: Moianos Dimitrios , Prifti Georgia-Myrto , Makri Maria , Zoidis Grigoris
Published: June 2023

Metalloenzymes are central to the regulation of a wide range of essential viral and parasitic functions, including protein degradation, nucleic acid modification, and many others. Given the impact of infectious diseases on human health, inhibiting metalloenzymes offers an attractive approach to disease therapy. Metal-chelating agents have been expansively studied as antivirals and antiparasitics, resulting in important classes of metal-dependent enzyme inhibitors. This review provides the recent advances in targeting the metalloenzymes of viruses and parasites that impose a significant burden on global public health, including influenza A and B, hepatitis B and C, and human immunodeficiency viruses as well as Trypanosoma brucei and Trypanosoma cruzi.
Asiatic Acid Inhibits Nasopharyngeal Carcinoma Cell Viability and Migration via Suppressing STAT3 and Claudin-1
Authors: Pantia Supitchaya , Kangsamaksin Thaned , Janvilisri Tavan , Komyod Waraporn
Published: June 2023

Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Southeast Asia, but effective treatment options remain limited, and chemotherapy has a high resistance rate. Asiatic acid (AA), a triterpenoid found in Centella asiatica, has shown anticancer activity in various cancers. Therefore, this study aims to investigate the anticancer effects and mechanisms of AA in NPC cell lines. The effects of AA on NPC cytotoxicity, apoptosis, and migration were determined in TW-01 and SUNE5-8F NPC cell lines. Western blot analysis was performed to evaluate the protein expression levels affected by AA. The role of AA in proliferation and migration was investigated in STAT3 and claudin-1 knockdown cells. AA inhibited NPC cell viability and migration and induced cell death by increasing cleaved caspase-3 expression. Moreover, AA inhibited STAT3 phosphorylation and reduced claudin-1 expression in NPC cells. Although knockdown of STAT3 or claudin-1 slightly reduced cell viability, it did not enhance the anti-proliferative effect of AA. However, knockdown of STAT3 or claudin-1 increased the anti-migratory effect of AA in NPC cells. These results suggest that AA can be a promising candidate for drug development against NPC.
A Novel UHPLC-MS/MS Method for the Quantification of Seven Opioids in Different Human Tissues
Authors: Manca Alessandra , De Nicolò Amedeo , De Vivo Elisa Delia , Ferrara Micol , Oh Sharon , Khalili Sahar , Higgins Niamh , Deiss Robert G. , Bonora Stefano , Cusato Jessica , Palermiti Alice , Mula Jacopo , Gianella Sara , D’Avolio Antonio
Published: June 2023

Background: Opioids are considered the cornerstone of pain management: they show good efficacy as a first-line therapy for moderate to severe cancer pain. Since pharmacokinetic/pharmacodynamic information about the tissue-specific effect and toxicity of opioids is still scarce, their quantification in post-mortem autoptic specimens could give interesting insights. Methods: We describe an ultra-high-performance liquid chromatography coupled with tandem mass spectrometry method for the simultaneous quantification of methadone, morphine, oxycodone, hydrocodone, oxymorphone, hydromorphone and fentanyl in several tissues: liver, brain, kidney, abdominal adipose tissue, lung and blood plasma. The presented method has been applied on 28 autoptic samples from different organs obtained from four deceased PLWH who used opioids for palliative care during terminal disease. Results: Sample preparation was based on tissue weighing, disruption, sonication with drug extraction medium and a protein precipitation protocol. The extracts were then dried, reconstituted and injected onto the LX50 QSight 220 (Perkin Elmer, Milan, Italy) system. Separation was obtained by a 7 min gradient run at 40 °C with a Kinetex Biphenyl 2.6 µm, 2.1 × 100 mm. Concerning the analyzed samples, higher opioids concentrations were observed in tissues than in plasma. Particularly, O-MOR and O-COD showed higher concentrations in kidney and liver than other tissues (>15–20 times greater) and blood plasma (>100 times greater). Conclusions: Results in terms of linearity, accuracy, precision, recovery and matrix effect fitted the recommendations of FDA and EMA guidelines, and the sensitivity was high enough to allow successful application on human autoptic specimens from an ethically approved clinical study, confirming its eligibility for post-mortem pharmacological/toxicological studies.
CD44-Targeted Lipid Polymer Hybrid Nanoparticles Enhance Anti-Breast Cancer Effect of Cordyceps militaris Extracts
Authors: Suksiriworapong Jiraphong , Pongprasert Nutthachai , Bunsupa Somnuk , Taresco Vincenzo , Crucitti Valentina Cuzzucoli , Janurai Thitapa , Phruttiwanichakun Pornpoj , Sakchaisri Krisada , Wongrakpanich Amaraporn
Published: June 2023

This study aimed to improve the anticancer effect of Cordyceps militaris herbal extract (CME) on breast cancer cells with hyaluronic acid (HYA) surface-decorated lipid polymer hybrid nanoparticles (LPNPs) and evaluate the applicability of a synthesized poly(glycerol adipate) (PGA) polymer for LPNP preparation. Firstly, cholesterol- and vitamin E-grafted PGA polymers (PGA-CH and PGA-VE, respectively) were fabricated, with and without maleimide-ended polyethylene glycol. Subsequently, CME, which contained an active cordycepin equaling 9.89% of its weight, was encapsulated in the LPNPs. The results revealed that the synthesized polymers could be used to prepare CME-loaded LPNPs. The LPNP formulations containing Mal-PEG were decorated with cysteine-grafted HYA via thiol-maleimide reactions. The HYA-decorated PGA-based LPNPs substantially enhanced the anticancer effect of CME against MDA-MB-231 and MCF-7 breast cancer cells by enhancing cellular uptake through CD44 receptor-mediated endocytosis. This study demonstrated the successful targeted delivery of CME to the CD44 receptors of tumor cells by HYA-conjugated PGA-based LPNPs and the new application of synthesized PGA-CH- and PGA-VE-based polymers in LPNP preparation. The developed LPNPs showed promising potential for the targeted delivery of herbal extracts for cancer treatment and clear potential for translation in in vivo experiments.
The Plant Invader Alternanthera philoxeroides Benefits from Clonal Integration More than Its Native Co-Genus in Response to Patch Contrast
Authors: You Wenhua , Li Ningning , Zhang Jin , Song Ao , Du Daolin
Published: June 2023

Different connected parts of clonal plants often grow in different patches and the resource contrast between patches has an important effect on the material transfer between the connected ramets. However, it is unclear whether the effect of clonal integration differs between the invasive clonal plant and the related native species in response to patch contrast. To explore this, we grew the clonal fragment pairs of plant invader Alternanthera philoxeroides and its co-genus native species A. sessilis under high contrast, low contrast, and no contrast (control) nutrient patch environments, respectively, and with stolon connections either severed or kept intact. The results showed that, at the ramet level, clonal integration (stolon connection) significantly improved the growth of apical ramets of both species, and such positive effects were significantly greater in A. philoxeroides than in A. sessilis. Moreover, clonal integration greatly increased the chlorophyll content index of apical ramets and the growth of basal ramets in A. philoxeroides but not in A. sessilis under low and high contrast. At the whole fragment level, the benefits of clonal integration increased with increasing patch contrast, and such a positive effect was more pronounced in A. philoxeroides than in A. sessilis. This study demonstrated that A. philoxeroides possesses a stronger ability of clonal integration than A. sessilis, especially in patchy environments with a higher degree of heterogeneity, suggesting that clonal integration may give some invasive clonal plants a competitive advantage over native species, thus facilitating their invasion in patchy habitats.
Temporal Changes in the Use of Wild Medicinal Plants in Trentino–South Tyrol, Northern Italy
Authors: Mattalia Giulia , Graetz Felina , Harms Matthes , Segor Anna , Tomarelli Alessio , Kieser Victoria , Zerbe Stefan , Pieroni Andrea
Published: June 2023

Mountain regions are fragile ecosystems and often host remarkably rich biodiversity, and thus they are especially under threat from ongoing global changes. Located in the Eastern Alps, Trentino–South Tyrol is bioculturally diverse but an understudied region from an ethnobotanical perspective. We explored the ethnomedicinal knowledge of the area from a cross-cultural and diachronic perspective by conducting semi-structured interviews with 22 local inhabitants from Val di Sole (Trentino) and 30 from Überetsch–Unterland (South Tyrol). Additionally, we compared the results with ethnobotanical studies conducted in Trentino and South Tyrol over 25 years ago. The historical comparison revealed that about 75% of the plants currently in use were also used in the past in each study region. We argue that the adoption of “new” medicinal species could have occurred through printed and social media and other bibliographical sources but may also be due to limitations in conducting the comparison (i.e., different taxonomic levels and different methodologies). The inhabitants of Val di Sole and Überetsch–Unterland have shared most medicinal plants over the past few decades, yet the most used species diverge (perhaps due to differences in local landscapes), and in South Tyrol, people appear to use a higher number of medicinal plants, possibly because of the borderland nature of the area.
The Global Changes of N6-methyldeoxyadenosine in Response to Low Temperature in Arabidopsis thaliana and Rice
Authors: Mao Fei , Xie Hairong , Shi Yucheng , Jiang Shasha , Wang Shuai , Wu Yufeng
Published: June 2023

N6-methyldeoxyadenosine (6mA) is a recently discovered DNA modification involved in regulating plant adaptation to abiotic stresses. However, the mechanisms and changes of 6mA under cold stress in plants are not yet fully understood. Here, we conducted a genome-wide analysis of 6mA and observed that 6mA peaks were predominantly present within the gene body regions under both normal and cold conditions. In addition, the global level of 6mA increased both in Arabidopsis and rice after the cold treatment. The genes that exhibited an up-methylation showed enrichment in various biological processes, whereas there was no significant enrichment observed among the down-methylated genes. The association analysis revealed a positive correlation between the 6mA level and the gene expression level. Joint analysis of the 6mA methylome and transcriptome of Arabidopsis and rice unraveled that fluctuations in 6mA levels caused by cold exposure were not correlated to changes in transcript levels. Furthermore, we discovered that orthologous genes modified by 6mA showed high expression levels; however, only a minor amount of differentially 6mA-methylated orthologous genes were shared between Arabidopsis and rice under low-temperature conditions. In conclusion, our study provides information on the role of 6mA in response to cold stress and reveals its potential for regulating the expression of stress-related genes.
Identification of Quantitative Trait Loci Associated with Powdery Mildew Resistance in Spring Barley under Conditions of Southeastern Kazakhstan
Authors: Genievskaya Yuliya , Zatybekov Alibek , Abugalieva Saule , Turuspekov Yerlan
Published: June 2023

Barley (Hordeum vulgare L.) is one of the most produced cereal crops in the world. It has traditionally been used for the production of animal feed and for malting, as well as for human consumption. However, its production is highly affected by biotic stress factors, particularly the fungal pathogen Blumeria graminis (DC.) f. sp. hordei (Bgh), which causes powdery mildew (PM). In this study, a collection of 406 barley accessions from the USA, Kazakhstan, Europe, and Africa were assessed for resistance to PM over a 3-year period in southeastern Kazakhstan. The collection was grown in the field in 2020, 2021, and 2022 and was genotyped using the 9K SNP Illumina chip. A genome-wide association study (GWAS) was conducted to identify the quantitative trait loci (QTLs) associated with PM resistance. As a result, seven QTLs for PM resistance were detected on chromosomes 4H, 5H, and 7H (FDR p-values < 0.05). Genetic positions of two QTLs were similar to those of PM resistance QTLs previously reported in the scientific literature, suggesting that the five remaining QTLs are novel putative genetic factors for the studied trait. Haplotype analysis for seven QTLs revealed three haplotypes which were associated with total PM resistance and one haplotype associated with the high PM severity in the barley collection. Identified QTLs and haplotypes associated with the PM resistance of barley may be used for further analysis, trait pyramiding, and marker-assisted selection.
Antibacterial Activity of the Essential Oil of Piper tuberculatum Jacq. Fruits against Multidrug-Resistant Strains: Inhibition of Efflux Pumps and β-Lactamase
Authors: da Silva Lucas Yure Santos , Paulo Cicera Laura Roque , Moura Talysson Felismino , Alves Daniel Sampaio , Pessoa Renata Torres , Araújo Isaac Moura , de Morais Oliveira-Tintino Cícera Datiane , Tintino Saulo Relison , Nonato Carla de Fatima Alves , da Costa José Galberto Martins , Ribeiro-Filho Jaime , Coutinho Henrique Douglas Melo , Kowalska Grażyna , Mitura Przemysław , Bar Marek , Kowalski Radosław , Menezes Irwin Rose Alencar de
Published: June 2023

Antimicrobial resistance has become a growing public health concern in recent decades, demanding a search for new effective treatments. Therefore, this study aimed to elucidate the phytochemical composition and evaluate the antibacterial activity of the essential oil obtained from the fruits of Piper tuberculatum Jacq. (EOPT) against strains carrying different mechanisms of antibiotic resistance. Phytochemical analysis was performed using gas chromatography–mass spectrometry (GC/MS). The antibacterial activity of EOPT and its ability to inhibit antibiotic resistance was evaluated through the broth microdilution method. The GC-MS analysis identified 99.59% of the constituents, with β-pinene (31.51%), α-pinene (28.38%), and β-cis-ocimene (20.22%) being identified as major constituents. The minimum inhibitory concentration (MIC) of EOPT was determined to assess its antibacterial activity against multidrug-resistant strains of Staphylococcus aureus (IS-58, 1199B, K2068, and K4100). The compound showed a MIC of ≥ 1024 μg/mL, suggesting a lack of intrinsic antibacterial activity. However, when the EOPT was associated with antibiotics and EtBr, a significant decrease in antibiotic resistance was observed, indicating the modulation of efflux pump activity. This evidence was corroborated with the observation of increased fluorescent light emission by the bacterial strains, indicating the involvement of the NorA and MepA efflux pumps. Additionally, the significant potentiation of ampicillin activity against the S. aureus strain K4414 suggests the β-lactamase inhibitory activity of EOPT. These results suggest that the essential oil from P. tuberculatum fruits has antibiotic-enhancing properties, with a mechanism involving the inhibition of efflux pumps and β-lactamase in MDR S. aureus strains. These findings provide new perspectives on the potential use of EOPT against antibiotic resistance and highlight the importance of Piper species as sources of bioactive compounds with promising therapeutic activities against MDR bacteria. Nevertheless, further preclinical (in vivo) studies remain necessary to confirm these in vitro-observed results.
Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk
Authors: Obluchinskaya Ekaterina D. , Pozharitskaya Olga N. , Gorshenina Elena V. , Zakharov Denis V. , Flisyuk Elena V. , Terninko Inna I. , Generalova Yuliya E. , Shikov Alexander N.
Published: June 2023

Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed is correlated with its phenolic content. It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. We believe that our data will help to effectively use the potential of F. distichus and expand the use of this algae as a promising and safe raw material for the food and pharmaceutical industries.
Geological Substrate Effects on Teucrium montanum L. (Lamiaceae) Morphological Traits: Geometric Morphometrics Approach
Authors: Zlatić Nenad , Budečević Sanja , Stanković Milan
Published: June 2023

The shape–environment relationship in plants refers to the ways in which the physical characteristics and structures of plants are influenced by their environment. Plants have evolved a remarkable ability to adapt to their specific habitats, and their shape and form play a crucial role in determining their survival and reproductive success. This study aimed to examine differences in size and shape between morphological traits in mountain germander (Teucrium montanum L.) from different geological substrates (calcareous and serpentinite). For this study, 400 individuals of T. montanum from 20 populations (ten populations from the serpentinite and ten from the calcareous substrate) were selected. Using the geometric morphometrics approach, it was shown that the degree of phenotypic variation in the size and shape of the corolla, leaf, and stem of T. montanum depends on the type of substrate. The main differences between the populations are the narrower part of the lower lip of the corolla, the narrower leaf, and the wider central part of the vascular system stem from serpentinite populations. The results of this study will contribute to a better understanding of the morphological variability of T. montanum in relation to edaphic conditions. In addition, the results confirm that certain morphological differences play an important role in the adaptive response in relation to substrate composition, especially for substrates with increased metal content, such as serpentinite. The shape–environment relationship in plants could define diversity and complexity in plant life, and underscores the importance of shape as a key factor in their survival and success in different habitats.