Arthropod-Borne Disease Control at a Glance: What’s New on Drug Development?

Discovering and validating effective drugs to manage arthropod-borne diseases (ABD) is a timely and important research challenge with major impacts on real-world control programs at the time of quick resistance development in the targeted pathogens. This editorial highlights major research advances in the development of drugs for the control of vector-borne diseases, with a significant focus on malaria, Chagas disease, dengue, human African trypanosomiasis, leishmaniasis, and Zika. Broad reviews providing new insights on ABD recently published in Molecules have also been covered in “The Editors’ pick” section

An Innovative Simulation Agent-Based Model for the Combined Sea-Road Transport as a DSS

This research proposes an innovative approach to evaluate modal shift from the road-only to the combined sea-road transport in order to implement new policies and introduce a Decision Support System (DSS) for the transportation planner's decision. The impact of these is carried out by using an innovative simulation tool which has the capability to simulate the real choice process of all stakeholders involved, specifically modelling the freight forwarder's point of view. The model runs as a single-agent based simulation which uses a multimodal network with detailed zoning. The simulation tool, capable of simulating the assignment of the whole network simultaneously, consists of a path choice model and a mode choice model for each o/d pair considered, establishing o/d pairs suitable and not suitable for modal shift. Three policies have been designed and tested through the simulation tool with an application in the Italian context: (1) internalization of the external costs of heavy vehicles; (2) introduction of a bonus for shipping companies; (3) design of new Ro-Ro services. The most affecting policy concerns an increase of speed of some Ro-Ro services to 22 kn, proposing a good balance between the navigation costs and the potential demand attracted

Editorial for Special Issue "Antiprotozoal Activity of Natural Products"

Neglected tropical diseases (NTDs), a group of diverse infectious diseases, repre-sent the leading cause of morbidity and mortality among the world's low-income pop-ulations. These diseases are often referred to as "neglected" due to their historical lack of attention from the global health agenda and research investment, with the excep-tion of some important support from the Bill & Melinda Gates Foundation. According to the World Health Organization (WHO), over 1.5 billion people are affected by at least one NTD, causing around 500,000 deaths yearly, social discrimination, and phys-ical suffering. Although NTDs can be found worldwide, they are most prevalent in tropical areas, where factors such as limited access to clean water, favorable environ-mental conditions, and inadequate sanitation expedite their transmission. Among a core group of 20 NTDs and conditions, the infections caused by single-celled protozoan parasites, such as Human African Trypanosomiasis (sleeping sickness or HAT), Chagas disease, Leishmaniasis, and Malaria, are regarded as therapeutically challenging be-cause of their elevated fatality rates and limited treatment options. Even though Malaria is not included in the NTDs’ list, it remains a significant public health issue in many NTD-endemic regions, and it is frequently considered within the framework of initiatives aimed at managing and eradicating NTDs

Adenosine receptors as promising targets for the management of ocular diseases

The ocular drug discovery arena has undergone a significant improvement in the last few years culminating in the FDA approvals of 8 new drugs. However, despite a large number of drugs, generics, and combination products available, it remains an urgent need to find breakthrough strategies and therapies for tackling ocular diseases. Targeting the adenosinergic system may represent an innovative strategy for discovering new ocular therapeutics. This review focused on the recent advance in the field and described the numerous nucleoside and non-nucleoside modulators of the four adenosine receptors (ARs) used as potential tools or clinical drug candidates

Oviposition inhibitory activity of the Mexican sunflower Tithonia diversifolia (Asteraceae) polar extracts against the two-spotted spider mite Tetranychus urticae (Tetranychidae)

The Mexican sunflower (Tithonia diversifolia, Asteraceae) is an invasive shrub of agricultural and non-agricultural lands in tropical countries. Besides extensive utilizations in the traditional medicine, mainly to treat malaria, the plant is believed to have a great potential in agriculture of developing countries as a green biomass to produce fertilizer, fodder and biopesticides. The plant is known to produce tagitinins, which are sesquiterpene lactones with a bitter taste endowed with toxicity against several insects such as mosquitoes, aphids, and beetles. Here, we evaluated the potential of T. diversifolia against the two-spotted spider mite Tetranychus urticae (Tetranychidae), which is one of the most economically important arthropod pests worldwide. The leaf methanolic extract and its ethyl acetate fraction were tested for acute and chronic toxicity and for oviposition inhibitory effects. The chemical composition of the extracts was analyzed by HPLC-MSn and NMR. The main constituents were flavonoid derivatives, phenylpropanoids and sesquiterpene lactones. Among the latter, tagitinin C and tagitinin A were the major compounds. In acute toxicity assays, mortality did not exceed 50% even for the highest tested dose of 150 \u3bcg cm-3. However, in chronic toxicity assays, on day 5 from application, the methanolic extract LD50 was 41.3 \u3bcg cm-3 while LD90 was 98.7 \u3bcg cm-3. Furthermore, both T. diversifolia extracts inhibited oviposition in T. urticae. The ethyl acetate extract was the most active oviposition inhibitor, with an ED50 value of 44.3 \u3bcg cm-3 and an ED90 of 121.5 \u3bcg cm-3. Overall, the good yield rate of the extract and the high crop yield highlighted good prospects of using the extract from this plant for the development of oviposition inhibitors against mite

CHEMICAL COMPOSITION OF TEN ESSENTIAL OILS FROM CALOPHYLLUM INOPHYLLUM LINN AND THEIR TOXICITY AGAINST ARTEMIA SALINA

Essential oils from ten different parts of Calophyllum inophyllum were analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) to study their chemical compositions. The yields were between 0.219 and 0.506 %. A total of 102 compounds were identified in the ten C. inophyllum essential oils, which are mostly monoterpenes, sesquiterpenes and their oxygenated derivatives. The numbers and percentages of identified compounds varied in the different parts of the plant: leaf (71, 54.94%), leaf stalk (22, 79.55%), flower (25, 51.24%), seed (25, 89.39%), seed-coat (69, 73.80%) fruit-pulp (15, 46.10%), stem wood (55, 59.40%), stem bark (9, 69.38%) root wood (51, 58.73%), and root bark (24, 74.66%). High content of cymene, terpinene, and limonene in the oils may be responsible for the vast ethno-medicinal applications of the plant. Toxicity experiments show that the oils were fairly toxic. Each part after 24 hours of exposure against Artemia salina gave the following LC50 values in μg/mL: leaf (68.8740 μg/mL), leaf-stalk (102.5692 μg/mL), flower (114.4410 μg/mL), seed (132.2324 μg/mL), seed coat (137.1206 μg/mL), fruit-pulp (135.0350 μg/mL) stem wood (126.1410 μg/mL), stem bark (149.7237 μg/mL), root wood (110.6539 μg/mL) and root bark (110.6539 μg/mL). The chemical compositions and toxicity levels of these ten Calophyllum inophyllum essential oils are reported for the first time in literature

Quantification of 17 Endogenous and Exogenous Steroidal Hormones in Equine and Bovine Blood for Doping Control with UHPLC-MS/MS

A simple and fast analytical method able to simultaneously identify and quantify 17 endogenous and exogenous steroidal hormones was developed in bovine and equine blood using UHPLC-MS/MS. A total amount of 500 µL of sample was deproteinized with 500 µL of a mixture of methanol and zinc sulfate and evaporated. The mixture was reconstituted with 50 µL of a solution of 25% methanol and injected in the UHPLC-MS/MS triple quadrupole. The correlation coefficients of the calibration curves of the analyzed compounds were in the range of 0.9932-0.9999, and the limits of detection and quantification were in the range of 0.023-1.833 and 0.069-5.5 ppb, respectively. The developed method showed a high sensitivity and qualitative aspects allowing the detection and quantification of all steroids in equine and bovine blood. Moreover, the detection limit of testosterone (50 ppt) is half of the threshold admitted in plasma (100 ppt). Once validated, the method was used to quantify 17 steroid hormones in both bovine and equine blood samples. The primary endogenous compounds detected were corticosterone (range 0.28-0.60 ppb) and cortisol (range 0.44-10.00 ppb), followed by androstenedione, testosterone and 11-deoxycortisol

Investigating the phytotoxic potential of Carlina acaulis essential oil against the weed Bidens pilosa through a physiological and metabolomic approach

Essential oils (EOs) are widely studied as possible candidates for new eco-friendly herbicides for weed management due to their phytotoxicity. In this study we tested the phytotoxic potential of the EO obtained from the roots of Carlina acaulis L. (Apiaceae) against the weed Bidens pilosa L. This EO, containing 98% of the polyacetylene carlina oxide, showed strong phytotoxic effects on the plant metabolism, such as leaf necrosis, reduction of relative water content and total leaf area, and an increase in the dry weight/fresh weight ratio, suggesting a water status alteration. The EO also damaged the photosynthetic machinery, as evidenced by the significant reduction of the effective quantum yield of photosystem II (ΦII) and the maximum quantum yield of photosystem II (Fv/Fm). In addition, the non-photochemical quenching (ΦNPQ) significantly increased after spraying with C. acaulis EO. Damage to photosystem II was further demonstrated through the reduction of manganese and calcium concentrations, possibly due to an alteration in the correct functionality of the Mn4Ca cluster of the PSII. Metabolomics analysis revealed an accumulation of branched-chain amino acids, such as isoleucine and valine, which is commonly related to osmotic alterations under drought stress situations and a general reduction in sugar content (fructose, glucose, mannose, among others), suggesting reduction of the photosynthetic efficiency too. Overall, these findings suggest C. acaulis EO as a promising natural product with phytotoxic potential against weeds that deserves further investigation

Lethal and sublethal effects of carlina oxide on Tetranychus urticae (Acari: Tetranychidae) and Neoseiulus californicus (Acari: Phytoseiidae)

BACKGROUND: Tetranychus urticae Koch, is a polyphagous and damaging pest, presenting several resistant populations world- wide. Among new and more environmentally friendly control tools, botanical pesticides represent a valuable alternative to syn- thetic ones within integrated pest management strategies. Accordingly, we investigated the lethal and sublethal effects of carlina oxide isolated from Carlina acaulis (Asteraceae) roots on T. urticae and its natural enemy, the predatory mite, Neoseiulus californicus (McGregor). RESULTS: Carlina oxide (98.7% pure compound) was used for acaricidal tests on eggs, nymphs, and adult females of T. urticae (concentrations of 312.5, 625, 1250, 2500 and 5000 !L L!1), and eggs and females of N. californicus (1250 and 5000 !L L!1 on eggs and females, respectively). Behavioral two-choice tests were also conducted on phytoseiid females. Carlina oxide toxicity was higher on T. urticae females than nymphs (median lethal dose 1145 and 1825 !L L!1, respectively), whereas egg mortality and mean hatching time were signi!cantly affected by all tested concentrations. A decreasing daily oviposition rate for T. urticae was recorded with concentrations ranging from 625 to 5000 !L L!1, whereas negative effects on the population growth rate were recorded only with the three higher concentrations (1250, 2500 and 5000 !L L!1). No toxic effect on N. californicus females was found, but a strong repellent activity lasting for 48 h from application was recorded. CONCLUSION: Carlina oxide reduced longevity and fecundity of T. urticae adults, but not of N. californicus. This selective prop- erty allows us to propose it as a novel active ingredient of ecofriendly acaricides for T. urticae management

5'-C-ethyl-tetrazolyl-N 6-substituted adenosine and 2-chloro-adenosine derivatives as highly potent dual acting A1 adenosine receptor agonists and A3 adenosine receptor antagonists

A series of N(6)-substituted-5'-C-(2-ethyl-2H-tetrazol-5-yl)-adenosine and 2-chloro-adenosine derivatives was synthesized as novel, highly potent dual acting hA1AR agonists and hA3AR antagonists, potentially useful in the treatment of glaucoma and other diseases. The best affinity and selectivity profiles were achieved by N(6)-substitution with a 2-fluoro-4-chloro-phenyl- or a methyl- group. Through an in silico receptor-driven approach, the molecular bases of the hA1- and hA3AR recognition and activation of this series of 5'-C-ethyl-tetrazolyl derivatives were explained