Advances in Targeting Drug Biological Carriers for Enhancing Tumor Therapy Efficacy.

Chemotherapy drugs continue to be the main component of oncology treatment research and have been proven to be the main treatment modality in tumor therapy. However, the poor delivery efficiency of cancer therapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. The recent integration of biological carriers and functional agents is expected to camouflage synthetic biomimetic nanoparticles for targeted delivery. The promising candidates, including but not limited to red blood cells and their membranes, platelets, tumor cell membrane, bacteria, immune cell membrane, and hybrid membrane are typical representatives of biological carriers because of their excellent biocompatibility and biodegradability. Biological carriers are widely used to deliver chemotherapy drugs to improve the effectiveness of drug delivery and therapeutic efficacy in vivo, and tremendous progress is made in this field. This review summarizes recent developments in biological vectors as targeted drug delivery systems based on microenvironmental stimuli-responsive release, thus highlighting the potential applications of target drug biological carriers. The review also discusses the possibility of clinical translation, as well as the exploitation trend of these target drug biological carriers.

Manifestaciones oculares producidas por la larva del Culex quinquefaciatus / Ocular manifestations produced by the larva of Culex quinquefaciatus

Las enfermedades transmitidas por vectores registran altas tasas de morbilidad y mortalidad para las personas. Los vectores biológicos son aquellos organismos capaces de transportar y transmitir un patógeno a otro organismo animal u hombre. Los más comunes son los insectos. El Culex quinquefaciatus es un vector de importantes enfermedades. Tiene un amplio desarrollo en nuestro país por las condiciones favorables climatológicas para su reproducción. El objetivo de este estudio fue presentar un caso portador de una larva de mosquito. Se describen las características más importantes del cuadro clínico, su diagnóstico, manejo. Las manifestaciones oculares secundarias a la infección por el mosquito C. quiquefasciatus en nuestro país son poco frecuentes, gracias a la campaña de erradicación del Aedes Aegiyptis en Cuba. En nuestro caso, se debió a las malas condiciones higiénicas del paciente y a la mala disposición de los desechos líquidos. Tal ambiente favoreció el depósito del huevo del mosquito en el ojo del paciente y que se desarrollara hasta la larva en el espacio subconjuntival del mismo(AU)

Vector-borne diseases have high morbidity and mortality rates for people. Biological vectors are those organisms capable of transporting and transmitting a pathogen to another animal organism or man, the most common being insects. Culex quinquefaciatus is a vector of important diseases, it is widely developed in our country due to the favorable weather conditions for its reproduction. A case carrying a mosquito larva is presented. The most important characteristics of the clinical picture, its diagnosis and management are described. Ocular manifestations secondary to infection by the Cx quiquefasciatus mosquito in our country are rare. Thanks to the campaign to eradicate Aedes Aegiyptis in Cuba. In our case, it was due to poor hygienic conditions of the patient and poor disposal of liquid waste. What favored the deposit of the mosquito egg in the patient's eye and that it developed into a larva in its subconjunctival space(AU)

Detection of Wolbachia in Mosquitoes (Diptera: Culicidae) in the State of Maranhão, Brazil.

Recently, the endobacteria Wolbachia has emerged as a biological tool for the control of arboviruses. Thus, we investigated the rate of natural infection by Wolbachia in Culicidae species from Maranhão, Brazil. For this, we amplified the Wolbachia surface protein gene (wsp) from mosquitoes collected in six localities of Maranhão, and positive samples were subjected to new analysis using group-specific primers. In total, 448 specimens comprising 6 genera and 18 species of mosquitoes were analyzed. Wolbachia DNA was PCR-detected in 7 species, three of which are new records: Aedes scapularis (Rondani, 1848), Coquillettidia juxtamansonia (Chagas, 1907) and Cq. venezuelensis (Theobald, 1912), in addition to Ae. albopictus (Skuse, 1894) and Culex quinquefasciatus Say, 1823, which are commonly described as permissive to maintain this bacterium in natural environments, and two species of the subgenera Anopheles (Nyssorhynchus) Blanchard, 1902 and Culex (Melanoconion) Theobald, 1903 which could not be identified at species level. The infection rate of all species ranged from 0 to 80%, and the average value was 16.5%. This study increases the knowledge about the prevalence of Wolbachia in the culicid fauna and may help in selecting strains for biological control purposes.

[Application of tetrahedral framework nucleic acids in the treatment of osteoarthritis].

Objective: To introduce the characteristics of tetrahedral framework nucleic acids (tFNA), focusing on its application in the treatment of osteoarthritis (OA) and relationship with microRNA (miRNA), and prospect the application of tFNA in the treatment of OA and the new idea of constructing miR-tFNA functional complex to treat OA. Methods: Recent studies were extensively reviewed to analyze the mechanism of tFNA and its relationship with OA and miRNA. Results: tFNA, a new type of new carrier, can not only play an indirect role in the treatment of OA as a small molecular carrier with therapeutic effect, but also play a direct role through the regulation of chondrocytes. It can bind with the miRNA that can regulate OA. The therapeutic effect of constructing tFNA functional complex loaded with miRNA has been verified in various diseases, and tFNA has advantages compared with other vectors. Conclusion: tFNA, a novel framework nucleic acid structure, plays an important role in the treatment of OA. Constructing miR-tFNA functional complex may be an innovative idea in the treatment of OA.

Maintenance and Productivity of a Lutzomyia longipalpis (Diptera: Psychodidae) Colony from an Area Endemic for Visceral and Cutaneous Leishmaniasis in Northeastern Brazil.

Studies on experimental sand fly infection require the availability of colonies and laboratory conditions. In Brazil, Lutzomyia longipalpis (Diptera: Psychodidae) (Lutz and Neiva 1912) is responsible for the highest infection rates by Leishmania spp. and this species is one of the most suitable species for laboratory colonization. In this study, we describe a method for growing Lu. longipalpis in laboratory conditions (10 generations) from natural populations sampled from a region of high endemicity for visceral leishmaniasis in the state of Maranhão, Northeastern Brazil. Using two methods (individualized or grouped females), the colony's highest productivity occurred in the first four generations, where all stages presented with high frequency. Nonviable eggs represented more than 50% of the total eggs produced by engorged females, while pupae were more resistant to fungal contamination, with a mortality rate of only 2%. In both methods, there was a predominance of female emergence; however, the ratio between males and females did not show significant differences, IF (P = 0.8023) and GF (P = 0.1831). Using the method of individualized females, the F4 generation took the longest to appear (234 d; 64 ± 57 d); by grouped females, F3 took the longest to appear (102 d; 47 ± 20 d). This method provides sufficient numbers of insects to perform vector competence tests for Leishmania spp. that cause the cutaneous form of leishmaniasis, usually found in Lu. longipalpis sampled from the study location.

Toxorhynchites Species: A Review of Current Knowledge.

The increasing global incidence of mosquito-borne infections is driving a need for effective control methods. Vector populations have expanded their geographical ranges, while increasing resistance to chemical insecticides and a lack of effective treatments or vaccines has meant that the development of vector control methods is essential in the fight against mosquito-transmitted diseases. This review will focus on Toxorhynchites, a non-hematophagous mosquito genus which is a natural predator of vector species and may be exploited as a biological control agent. Their effectiveness in this role has been strongly debated for many years and early trials have been marred by misinformation and incomplete descriptions. Here, we draw together current knowledge of the general biology of Toxorhynchites and discuss how this updated information will benefit their role in an integrated vector management program.

Biological larviciding against malaria vector mosquitoes with Bacillus thuringiensis israelensis (Bti) - Long term observations and assessment of repeatability during an additional intervention year of a large-scale field trial in rural Burkina Faso.

The first line of malaria vector control to date mainly relies on the use of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). For integrated vector management, targeting the vector larvae with biological larvicides such as Bacillus thuringiensis israelensis (Bti) can be an effective additional mainstay. This study presents data from the second intervention year of a large-scale trial on biological larviciding with Bti that was carried out in 127 rural villages and a semi-urban town in Burkina Faso. Here we present the reductions in malaria mosquitoes that were achieved by continuing the initial interventions for an additional year, important to assess sustainability and repeatability of the results from the first intervention year. Larviciding was performed applying two different larviciding choices ((a) treatment of all environmental breeding sites, and (b) selective treatment of those that were most productive for Anopheles larvae indicated by remote sensing based risk maps). Adult Anopheles spp. mosquito abundance was reduced by 77.4% (full treatment) and 63.5% (guided treatment) compared to the baseline year. The results showed that malaria vector abundance can be dramatically reduced using biological larviciding and that this effect can be achieved and maintained over several consecutive transmission seasons.

Effect of vertebrate feces on the attraction of Culicoides (Diptera: Ceratopogonidae) in an Amazonian mangrove.

Biting midges are of interest to public health because they play an important role as vectors of disease-causing pathogens, as well as being a biting nuisance to humans and domestic animals. Although these insects are common in mangrove areas, they have not yet been studied in this ecosystem in the state of Maranhão (MA), Brazil. The objective of this study was to characterize the Culicoides community structure found in a mangrove swamp and verify if the use of vertebrate feces as bait interferes with their composition, richness, abundance, or seasonality. CDC light traps with vertebrate (chicken, ox, control, donkey, capuchin monkey and pig) feces baits were used to capture biting midges in a mangrove area of the Island of São Luís, MA. A total of 4,087 individuals representing 22 species of Culicoides were captured, the most abundant being C. (Oecacta) furens Poey (23.46%), C. (gr. Fluviatilis) leopoldoi Ortiz (21.58%), C. (Hoffmania) ignacioi Forattini (16.98%), C. (Hoffmania) maruim Lutz (13.85%), C. (Diphaomyia) iriartei Fox (10.57%), C. (Hoffmania) insignis Lutz (7.07%), and C. (gr. Limai) limai Barreto (3.03%). Species richness and abundance were higher when baits of capuchin monkey (15 species; 26.84% of the individuals) and pig (15; 25.3%) feces were used. The least attractive baits were donkey (12 species; 9.3%) and ox (nine species; 11.52%) feces. Biting midges were more abundant in the rainy season (67%), but richness was higher in the dry season (19 species). These results show that vertebrate feces may serve as olfactory cues and increase the attraction of biting midges to traps.

Effects of forest degradation on the sand fly communities of northeast Brazil.

The richness and abundance of sand fly species were studied in northeastern Brazil in areas of leishmaniasis transmission. The study was carried out in two forest areas with different deforestation times for agricultural and livestock activities: one modified by long-term settlement (more than 50 years of occupation) and another less impacted by short-term settlement (10 years). The sand flies were captured with CDC light traps from 18:00 to 06:00 for three consecutive nights, once a month, from May, 2012 to April, 2014. The study captured 21,708 specimens and also 33 species of Lutzomyia and two of Brumptomyia. Species richness and abundance were higher in the more conserved area of short-term occupation (31 species; 61.7%) than in the more degraded area with long-term occupation (17 species; 38.3%). In the most conserved area, the species richness was higher in the forest fragment than in the rural settlement, whereas in the degraded area the richness was higher in the peri-domicile than in the forest. The diversity was higher in the degraded area forest. There were significant statistical differences when comparing the means of total abundance with the intra-domicile, peri-domicile, and forest environments. The average abundance was statistically higher in the peri-domicile compared to the forest (p = 0.009), but there were no statistically significant differences between intra-domicile-peri-domicile (p = 0.11) and forest-intra-domicile (p = 0.87). In conclusion, a change in vegetation cover negatively affects the richness and abundance of sand flies in the natural environment.

Current Challenges in the Development of Vaccines and Drugs Against Emerging Vector-borne Diseases.

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.

The seaweed fly (Coelopidae) can facilitate environmental survival and transmission of E. coli O157 at sandy beaches.

The sustainable management of recreational beaches is essential for minimising risk of human exposure to microbial pathogens whilst simultaneously maintaining valuable ecosystem services. Decaying seaweed on public beaches is gaining recognition as a substrate for microbial contamination, and is a potentially significant reservoir for human pathogens in close proximity to beach users. Closely associated with beds of decaying seaweed are dense populations of the seaweed fly (Coelopidae), which could influence the spatio-temporal fate of seaweed-associated human pathogens within beach environments. Replicated mesocosms containing seaweed inoculated with a bioluminescent strain of the zoonotic pathogen E. coli O157:H7, were used to determine the effects of two seaweed flies, Coelopa frigida and C. pilipes, on E. coli O157:H7 survival dynamics. Multiple generations of seaweed flies and their larvae significantly enhanced persistence of E. coli O157:H7 in simulated wrack habitats, demonstrating that both female and male C. frigida flies are capable of transferring E. coli O157:H7 between individual wrack beds and into the sand. Adult fly faeces can contain significant concentrations of E. coli O157:H7, which suggests they are capable of acting as biological vectors and bridge hosts between wrack habitats and other seaweed fly populations, and facilitate the persistence and dispersal of E. coli O157:H7 in sandy beach environments. This study provides the first evidence that seaweed fly populations inhabiting natural wrack beds contaminated with the human pathogen E. coli O157:H7 have the capacity to amplify the hazard source, and therefore potential transmission risk, to beach users exposed to seaweed and sand in the intertidal zone. The risk to public health from seaweed flies and decaying wrack beds is usually limited by human avoidance behaviour; however, seaweed fly migration and nuisance inland plagues in urban areas could increase human exposure routes beyond the beach environment.

Evaluation of the involvement of mice (Mus musculus) in the epidemiology of porcine proliferative enteropathy.

The aim of this study was to evaluate the fecal-oral transmission of L. intracellularis between mice and pigs. The study was divided into two parts. The first part aimed to determine whether mice could be infected by feces from pigs that are experimentally infected with L. intracellularis. Thirty-four Swiss mice received L. intracellularis PCR-positive feces from experimentally infected pigs (M1) for four consecutive days. Twelve other mice received swine negative feces (M2). Pools of mice feces were collected on alternating days post-exposure (dpe). The second part of the study aimed to test whether pigs could be infected when exposed to L. intracellularis PCR-positive feces from experimentally infected mice. Twelve 5-week-old pigs received feed mixed with L. intracellularis PCR-positive mice feces (P1), while the other two pigs received PCR-negative mice feces (P2) for four consecutive days. In the first study, the amount of L. intracellularis provided to M1 boxes per day was between 106 and 108. Mice shed, an average of 104 bacterial units every collection day. Three mice from M1 were positive for L. intracellularis by immunohistochemistry (IHC) at the end of the study. In the second part of the study, pigs in P1 received an average of 105 bacterial units per day. Ten pigs were infected by L. intracellularis based on positive qPCR and/or immunohistochemistry and serology results. These pigs shed an average of 104L. intracellularis/g of feces. Mice and pigs experimentally infected with L. intracellularis can infect each other, therefore, rodents should be considered players in the epidemiology of this disease in pig farms.

Implications of guppy (Poecilia reticulata) life-history phenotype for mosquito control.

Guppies (Poecilia reticulata) are frequently introduced to both natural and artificial water bodies as a mosquito control. Laboratory studies have demonstrated that guppies can consume large numbers of larval mosquitoes. Our study investigates how intraspecific variability in guppy phenotype affects their importance as a mosquito biocontrol and how habitat conditions (natural ponds vs. water storage containers) may influence insect biomass and guppy feeding. Using a blocked experimental design, we established stream-side mesocosm ponds with half receiving gravel substrate to simulate pond-bottom habitat. To provide realistic diet choices and insect abundances, we allowed the mesocosms to colonize naturally with aquatic insect larvae for 1 month before introducing guppies. We tested two distinct guppy phenotypes (from high- and low-predation streams) alongside fish-free controls. After 1 month, we measured insect biomass in the mesocosms and examined guppy gut contents to document direct predation. While overall insect biomass was not significantly different across the three fish treatments, we observed a significant reduction in mosquito biomass in fish treatments compared to fish-free controls, as well as intraspecific differences in feeding. Overall insect biomass was significantly higher in mesocosms without gravel, while habitat condition had no effect on mosquito biomass. As guppy phenotype responds to changes in their environments, it is an important consideration for biocontrol policy to anticipate potential ecosystem effects. We close by relating our findings to other studies and by discussing the implications and potential risks of using guppies to control mosquitoes.

The influence of environmental management and animal shelters in vector control of Culicoides (Diptera, Ceratopogonidae) in northeastern Brazil.

We investigated whether biting midges in peridomestic environments are affected by environmental management practices and the presence of domestic animals. We used CDC light traps to collect midges in 112 residences across 24 locations along tourism routes of Maranhão, Brazil. The collection areas were characterized as follows: i) peridomestic area with domestic animals and without management (dirty); ii) peridomestic with domestic animals and management (clean); iii) peridomestic without animals and with management (clean); iv) peridomestic without animals and without management (dirty). The first two treatments had higher biting midge species richness and abundance, respectively. Generalized linear models indicated a positive correlation between the presence of domestic animals and midge abundance, with an approximate four-fold increase in Culicoides (Diptera: Ceratopogonidae) abundance in peridomestic areas with animals. The same model showed that domestic animals have no influence on richness. Environmental management does not appear to influence species richness or abundance of biting midges.

Detection of Leishmania amazonensis and Leishmania braziliensis in Culicoides (Diptera, Ceratopogonidae) in an endemic area of cutaneous leishmaniasis in the Brazilian Amazonia.

Biting midges in the genus Culicoides act as vectors of arboviruses throughout the world and as vectors of filariasis in Latin America, the Caribbean, and parts of Africa. Although Culicoides spp. are currently not considered to be vectors of Leishmania protozoa, the high abundance of biting midges in areas with active cutaneous leishmaniasis transmission points to the possibility of Culicoides infection by these pathogens. We used PCR to test captured Culicoides species for natural infection with Leishmania spp. We tested 450 Culicoides females, divided into 30 pools of 15 individuals each, as follows: nine pools of C. foxi (135 specimens), seven pools of C. filariferus (105), seven pools of C. insignis (105), five pools of C. ignacioi (75), and two pools of C. flavivenula (30). PCR confirmed the presence of Leishmania braziliensis DNA in C. ignacioi (0.14%), C. insignis (0.14%), and C. foxi (0.11); and Le. amazonensis DNA in C. filariferus (0.14%) and C. flavivenula (0.50%). We conclude that these Culicoides species can be naturally infected, but vector competence and transmission capability must be confirmed in future studies. Our results warrant further investigation into the role of these biting midge species in the leishmaniasis epidemiological cycle.

In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector.

The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response. New antigens associated with pneumococcal disease virulence were used to test the delivery and adjuvant capabilities of a hybrid biological-biomaterial vector consisting of a bacterial core electrostatically coated with a cationic polymer. The hybrid design provides (i) passive and active targeting of antigen-presenting cells, (ii) natural and multicomponent adjuvant properties, (iii) dual intracellular delivery mechanisms, and (iv) a simple formulation mechanism. In addition, the hybrid format enables device-specific, or in situ, antigen production and consolidation via localization within the bacterial component of the vector. This capability eliminates the need for dedicated antigen production and purification before vaccination efforts while leveraging the aforementioned features of the overall delivery device. We present the first disease-specific utilization of the vector toward pneumococcal disease highlighted by improved immune responses and protective capabilities when tested against traditional vaccine formulations and a range of clinically relevant Streptococcus pneumoniae strains. More broadly, the results point to similar levels of success with other diseases that would benefit from the production, delivery, and efficacy capabilities offered by the hybrid vector.

Infestation of Brazilian Peridomiciliary Areas by Culicoides (Diptera: Ceratopogonidae) in Humid and Semihumid Climates.

This study investigates Culicoides infestation in peridomestic environments in two villages in Maranhão, one with hot and humid climate and the other with semihumid climate. We evaluated the composition, richness, abundance, and seasonality of species. We captured insects using CDC light traps installed in animal shelters once a month, from 6 pm to 6 am, for 24 mo (May 2012 to April 2014). In this study, 17 species were found. Of these, 10 occurred simultaneously in two areas; six were found only in hot and humid area, while one occurred only in the semihumid area. Species richness was higher in the hot and humid climate (16 species) than in the semihumid (11 species). The rank of abundance was uneven across areas: C. foxi, C. insignis, C. filariferus, C. ignacioi, and C. flavivenula were dominant in the hot and humid area, and C. ignacioi, C. foxi, C. filariferus, C. insignis, and C. boliviensis in the semihumid. Midges were more abundant in the rainy season in both areas. This result reveals a diversified fauna of midges, with variable abundance of rank according to the area, prevailing in the rainy season and in the Amazon area. It also highlights the need for health monitoring in order to contain the infestation by these insects in peridomestic environments, taking into account that some species can be effective vectors of arboviruses in the Amazon and northeastern Maranhão.

Bioaccumulation and effects of metals and trace elements from aquatic disposal of coal combustion residues: recent advances and recommendations for further study.

Advances have been made recently in assessing accumulation and effects of coal combustion residues (CCR). I provide a brief review of recent advancements, provide a tabulated summary of results of recent work, and put forth recommendations for future studies. One advancement is that mercury accumulation has begun to receive (limited) attention, whereas it had rarely been considered in the past. Additionally, some constituents of CCR have been shown to be accumulated by adults and transferred to offspring, sometimes compromising offspring health. Studies have demonstrated that amphibians, possessing complex life cycles, may accumulate and transfer some contaminants to terrestrial systems. Some study has been given to molecular and cellular effects of CCR exposure, although these studies have been limited to invertebrates. Population models have also been applied to CCR affected systems and have shown that CCR may affect animal populations under some conditions. In light of these advancements, there are several topics that require further assessment. First, more attention to Hg and its dynamics in CCR affected systems is warranted. Hg can be highly accumulative and toxic under some conditions and may interact with other components of CCR (notably Se), perhaps altering accumulation and effects of the contaminant mixtures. Second, further investigation of maternal transfer and effects of CCR contaminants need to be conducted. These studies could benefit from incorporation of quantitative models to project impacts on populations. Finally, more attention to the organic constituents of CCR (PAHs) is required, as a focus on inorganic compounds only may restrict our knowledge of contaminant dynamics and effects as a whole. While further studies will shed light on some chemical and biological nuances of exposure and effect, information available to date from numerous study sites implicates CCR as a bulk effluent that presents risks of bioaccumulation and effects on organisms in aquatic systems.