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Leishmaniasis is a tropical infectious disease caused by Leishmania parasites. The disease can be spread by the bite of an infected sand fly. Currently, five chemotherapeutic drugs are available in leishmaniasis treatment. However, these drugs exhibit toxicity and serious adverse effects on infected individuals, necessitating alternative treatment strategies. One such strategy involves using combinations of existing antileishmanial drugs. In this study, we evaluated the interaction between artesunate (AS) and three antileishmanial drugs—amphotericin B (AmB), miltefosine (MF), and paromomycin (PM) against Leishmania infantum. This evaluation marks the first time such an assessment has been conducted. The Chou–Talalay combination index method was employed to analyze the drug interaction. The findings revealed that the interaction between AS and AmB ranged from antagonistic to synergistic, while the interaction between AS and MF showed moderate to strong synergism. In contrast, the interaction between AS and PM resulted in an antagonistic interaction, which differs from the combinations with AmB or MF. This study provides valuable insights for developing novel drug regimens for leishmaniasis treatment, emphasizing the potential of AS and its combination with existing antileishmanial drugs. Further research is necessary to optimize drug combinations and minimize adverse effects, leading to more effective therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Exposure to pesticides poses a significant threat to male fertility by compromising crucial cells involved in spermatogenesis. Although aminocarb is a widely used carbamate insecticide, little is known about its impact on male fertility and, consequently, on sustentacular Sertoli cells. In this study, we investigated the effects of increasing concentrations of aminocarb on a mouse Sertoli cell line, TM4. Assessments included analyses of cellular proliferation and viability, membrane integrity, mitochondrial biogenesis and membrane potential and expression and the activity of apoptotic proteins, as well as oxidative stress. Our findings revealed a dose-dependent reduction in the proliferation and viability of TM4 cells following exposure to aminocarb. Moreover, exposure to 5 μM of aminocarb induced depolarization of mitochondria membrane potential, and a decrease in the ratio of phosphorylated eIF2α to total eIF2α, suggesting heightened endoplasmic reticulum stress via the activation of the eIF2α pathway. An elevation in both caspase-3 protein levels and activity was also observed for the cells under this same aminocarb concentration, thus indicating an apoptotic induction. Altogether, our results demonstrate that aminocarb serves as an apoptotic inducer for mouse sustentacular Sertoli cells in vitro, suggesting its potential to modulate independent pathways of the apoptotic cascade. Exposure to pesticides, poses a significant threat to male fertility by compromising crucial cells involved in spermatogenesis. Aminocarb, is a widely used carbamate insecticide, although its detrimental effects on the male reproductive system, especially on sustentacular Sertoli cells, pivotal for spermatogenesis, remains poorly understood. In this study, we investigated the effects of escalating concentrations of aminocarb on a mouse Sertoli cell line, TM4. Assessments included cytotoxic analysis, mitochondrial biogenesis and membrane potential, expression of apoptotic proteins, caspase-3 activity, and oxidative stress evaluation. Our findings revealed a dose-dependent reduction in the proliferation and viability of TM4 cells following exposure to increasing concentrations of aminocarb. Notably, exposure to 5 μM of aminocarb induced depolarization of mitochondria membrane potential, and a significant decrease in the ratio of phosphorylated eIF2α to total eIF2α, suggesting heightened endoplasmic reticulum stress via the activation of the eIF2α pathway. Moreover, the same aminocarb concentration was demonstrated to increase both caspase-3 protein levels and activity, indicating an apoptotic induction. Collectively, our results demonstrate that aminocarb serves as an apoptotic inducer for mouse sustentacular Sertoli cells in vitro, suggesting its potential to modulate independent pathways of the apoptotic cascade. These findings underscore the deleterious impact of aminocarb on spermatogenic performance and male fertility, highlighting the urgent need for further investigation into its mechanisms of action and mitigation strategies to safeguard male fertility. [ABSTRACT FROM AUTHOR]

Leydig cells (LCs) play a pivotal role in male fertility, producing testosterone. Chromium (III) picolinate (CrPic3), a contentious supplement with antidiabetic and antioxidant properties, raises concerns regarding male fertility. Using a rodent LC line, we investigated the cytotoxicity of increasing CrPic3 doses. An insulin resistance (IR) model was established using palmitate (PA), and LCs were further exposed to CrPic3 to assess its antioxidant/antidiabetic activities. An exometabolome analysis was performed using 1H-NMR. Mitochondrial function and oxidative stress were evaluated via immunoblot. Steroidogenesis was assessed by quantifying androstenedione through ELISA. Our results uncover the toxic effects of CrPic3 on LCs even at low doses under IR conditions. Furthermore, even under these IR conditions, CrPic3 fails to enhance glucose consumption but restores the expression of mitochondrial complexes CII and CIII, alleviating oxidative stress in LCs. While baseline androgen production remained unaffected, CrPic3 promoted androstenedione production in LCs in the presence of PA, suggesting that it promotes cholesterol conversion into androgenic intermediates in this context. This study highlights the need for caution with CrPic3 even at lower doses. It provides valuable insights into the intricate factors influencing LCs metabolism and antioxidant defenses, shedding light on potential benefits and risks of CrPic3, particularly in IR conditions. [ABSTRACT FROM AUTHOR]

L-Carnitine, a natural antioxidant found in mammals, plays a crucial role in the transport of long-chain fatty acids across the inner mitochondrial membrane. It is used as a nutritional supplement by professional athletes, improving performance and post-exercise recovery. Additionally, its therapeutic applications, including those in male infertility, have been investigated, as it may act as a defense mechanism against the excessive production of reactive oxygen species (ROS) in the testis, a process that can lead to sperm damage. This effect is achieved by enhancing the expression and activity of enzymes with antioxidant properties. Nevertheless, the mechanisms underlying the benefits of L-Carnitine remain unknown. This review aims to consolidate the current knowledge about the potential benefits of L-Carnitine and its role in male (in)fertility. Considering in vitro studies with Sertoli cells, pre-clinical studies, and investigations involving infertile men, a comprehensive understanding of the effects of L-Carnitine has been established. In vitro studies suggest that L-Carnitine has a direct influence on somatic Sertoli cells, improving the development of germ cells. Overall, evidence supports that L-Carnitine can positively impact male fertility, even at a relatively low dose of 2 g/day. This supplementation enhances sperm parameters, regulates hormone levels, reduces ROS levels, and subsequently improves fertility rates. However, further research is needed to elucidate the underlying mechanisms and establish optimal doses. In conclusion, the role of L-Carnitine in the field of male reproductive health is highlighted, with the potential to improve sperm quality and fertility. [ABSTRACT FROM AUTHOR]

The WHO declared coronavirus disease 2019 (COVID-19) a pandemic in March 2020, which was caused by novel coronavirus severe acute respiratory coronavirus 2 (SARS-CoV-2). SARS-CoV-2 made its first entry into the world in November 2019, and the first case was detected in Wuhan, China. Mutations in the SARS-CoV-2 genome distressed life in almost every discipline by the extended production of novel viral variants. In this article, authorized SARS-CoV-2 vaccines including mRNA vaccines, DNA vaccines, subunit vaccines, inactivated virus vaccines, viral vector vaccine, live attenuated virus vaccines and mix and match vaccines will be discussed based on their mechanism, administration, storage, stability, safety and efficacy. The information was collected from various journals via electronic searches including PubMed, Science Direct, Google Scholar and the WHO platform. This review article includes a brief summary on the pathophysiology, epidemiology, mutant variants and management strategies related to COVID-19. Due to the continuous production and unsatisfactory understanding of novel variants of SARS-CoV-2, it is important to design an effective vaccine along with long-lasting protection against variant strains by eliminating the gaps through practical and theoretical knowledge. Consequently, it is mandatory to update the literature through previous and ongoing trials of vaccines tested among various ethnicities and age groups to gain a better insight into management strategies and combat complications associated with upcoming novel variants of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Simple Summary: Parasitosis of the digestive tract by worms and protozoa in livestock is a veterinary health and economic concern as parasitic infections can cause deterioration of animal welfare and reduced productivity associated with delayed growth rate, weight loss, and reduced milk production. Some parasites of the digestive tract have zoonotic potential, so farm animals can act as source of human infections. This study investigated the prevalence of intestinal parasites in cattle, camels, donkeys, horse, sheep, goats, and dogs from Iranshahr County in Southeastern Iran. Our findings indicate that most animals studied were infected with at least one species of intestinal parasite. Parasitological monitoring, including testing during the rearing of free-range animals, is needed in livestock to detect carriers and shedders of parasite eggs, cysts, and oocysts. It is also recommended that villagers prevent stray dogs from entering agricultural fields and ensure the proper housing and management of animal's facilities, with special attention to their hygienic conditions. Furthermore, accurate diagnosis of parasitic infections, as well as effective monitoring and prophylaxis, are essential to keep livestock free of parasitic infections. Gastrointestinal parasites (GIP) are a major cause of disease and production loss in livestock. Some have zoonotic potential, so production animals can be a source of human infections. We describe the prevalence of GIP in domestic mammals in Southeastern Iran. Fresh fecal samples (n = 200) collected from cattle (n = 88), sheep (n = 50), goats (n = 23), camels (n = 30), donkeys (n = 5), horse (n = 1), and dogs (n = 3) were subjected to conventional coprological examination for the detection of protozoan (oo)cysts and helminth ova. Overall, 83% (166/200) of the samples were positive for one or more GIP. Helminths were found in dogs, donkeys, sheep (42%), camels (37%), goats (30%), and cattle (19%), but not in the horse. Protozoa were found in cattle (82%), goats (78%), sheep (60%), and camels (13%), but not in donkeys, dogs, or the horse. Lambs were 3.5 times more likely to be infected by protozoa than sheep (OR = 3.5, 95% CI: 1.05–11.66), whereas sheep were at higher odds of being infected by helminths than lambs (OR = 4.09, 95% CI: 1.06–16.59). This is the first study assessing the prevalence of GIP in domestic mammals in Southeastern Iran. [ABSTRACT FROM AUTHOR]

Verbena officinalis L. or vervain is an herbal medicine and dietary supplement used worldwide. It is used for antidepressant and anticonvulsant purposes, as well as to treat inflammatory disorders, skin burns, abrasions, and gastric diseases, among others. Here, we investigated the biochemical, antioxidant, and histopathological effects of vervain against chronic physical stress. Male Wistar rats were submitted to chronic physical training and oral administration of 200 mg/kg of extract for 7 weeks. Control animals were not treated with either stress or vervain. Body weight was monitored during the study. Liver, kidney, spleen, testis, epididymis, heart, skeletal muscle, and brain samples were collected. Blood cholesterol, lactate dehydrogenase (LDH), bilirubin, and creatinine kinase (CREA), among others, were studied. Glutathione peroxidase (GPox) and superoxide dismutase (SOD) antioxidant activity was analyzed in the blood, liver, and kidney. Testosterone measurements were also performed on whole testis extracts. We found significant weight ratios differences in the epididymis, brain, and heart. Animals submitted to training showed hemorrhagic livers. Kidney histology was affected by both stress and vervain. Cell disruption and vacuolization were observed in the testes and epididymis of animals submitted to stress. Hematological and biochemical markers as CREA, LDH, TP, CKI, URCA, γGT, and glucose revealed statistically significantly differences. Additionally, the activity of glutathione peroxide (GPox) and superoxide dismutase (SOD) in the blood was also impacted. Both stress and vervain have significant in vivo effects. Infusions of vervain include phenylpropanoids, iridoids, verbenalin, hastatoside, and flavonoids, amongst others, which interact synergistically to produce the preclinical effects reported here. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnO NPs) are one of the most used nanoparticles due to their unique physicochemical and biological properties. There is, however, a growing concern about their negative impact on male reproductive health. Therefore, in the present study, two different strategies were used to evaluate the recovery ability of spermatogonia cells from the first stage of spermatogenesis (GC-1 spg cell line) after being exposed to a cytotoxic concentration of ZnO NPs (20 µg/mL) for two different short time periods, 6 and 12 h. The first strategy was to let the GC-1 cells recover after ZnO NPs exposure in a ZnO NPs-free medium for 4 days. At this phase, cell viability assays were performed to evaluate whether this period was long enough to allow for cell recovery. Exposure to ZnO NPs for 6 h and 12 h induced a decrease in viability of 25% and 41%, respectively. However, the recovery period allowed for an increase in cell viability from 16% to 25% to values as high as 91% and 84%. These results strongly suggest that GC-1 cells recover, but not completely, given that the cell viability does not reach 100%. Additionally, the impact of a synthetic chalcone (E)-3-(2,6-dichlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (1) to counteract the reproductive toxicity of ZnO NPs was investigated. Different concentrations of chalcone 1 (0–12.5 µM) were used before and during exposure of GC-1 cells to ZnO NPs to mitigate the damage induced by NPs. The protective ability of this compound was evaluated through viability assays, levels of DNA damage, and cytoskeleton dynamics (evaluating the acetylated α-tubulin and β-actin protein levels). The results indicated that the tested concentrations of chalcone 1 can attenuate the genotoxicity induced by ZnO NPs for shorter exposure periods (6 h). Chalcone 1 supplementation also increased cell viability and stabilized the microtubules. However, the antioxidant potential of this compound remains to be elucidated. In conclusion, this work addressed the main cytotoxic effects of ZnO NPs on a spermatogonia cell line and analyzed two different strategies to mitigate this damage, which represent a significant contribution to the field of male fertility. [ABSTRACT FROM AUTHOR]

PCSK9 is a promising target for developing novel cholesterol-lowering drugs. We developed a recipe that combined molecular docking, GC-MS/MS, and real-time PCR to identify potential PCSK9 inhibitors for herb ratio determination. Three herbs, Carthamus tinctorius, Coscinium fenestratum, and Zingiber officinale, were used in this study. This work aimed to evaluate cholesterol-lowering through a PCSK9 inhibitory mechanism of these three herbs for defining a suitable ratio. Chemical constituents were identified using GC-MS/MS. The PCSK9 inhibitory potential of the compounds was determined using molecular docking, real-time PCR, and Oil red O staining. It has been shown that most of the active compounds of C. fenestratum and Z. officinale inhibit PCSK9 when extracted with water, and C. fenestratum has been shown to yield tetraacetyl-d-xylonic nitrile (27.92%) and inositol, 1-deoxy-(24.89%). These compounds could inhibit PCSK9 through the binding of 6 and 5 hydrogen bonds, respectively, while the active compound in Z. officinale is 2-Formyl-9-[.beta.-d-ribofuranosyl] hypoxanthine (4.37%) inhibits PCSK9 by forming 8 hydrogen bonds. These results suggest that a recipe comprising three parts C. fenestratum, two parts Z. officinale, and one part C. tinctorius is a suitable herbal ratio for reducing lipid levels in the bloodstream through a PCSK9 inhibitory mechanism. [ABSTRACT FROM AUTHOR]

The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthusmalaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been studied. Burkillanthusmalaccensis (Ridl.) Swingle may produce antibacterial and antibiotic-potentiating secondary metabolites. Hexane, chloroform, and methanol extracts of leaves, bark, wood, pericarps, and endocarps were tested against bacteria by broth microdilution assay and their antibiotic-potentiating activities. Chromatographic separations of hexane extracts of seeds were conducted to investigate effective phytochemicals and their antibacterial activities. Molecular docking studies of werneria chromene and dihydroxyacidissiminol against SARS-CoV-2 virus infection were conducted using AutoDock Vina. The methanol extract of bark inhibited the growth of Staphylococcusaureus, Escherichiacoli, and Pseudomonasaeruginosa with the minimum inhibitory concentration of 250, 500, and 250 µg/mL, respectively. The chloroform extract of endocarps potentiated the activity of imipenem against imipenem-resistant Acinetobacterbaumannii. The hexane extract of seeds increased the sensitivity of P. aeruginosa against ciprofloxacin and levofloxacin. The hexane extract of seeds and chloroform extract of endocarps were chromatographed, yielding werneria chromene and dihydroxyacidissiminol. Werneria chromene was bacteriostatic for P.aeruginosa and P.putida, with MIC/MBC values of 1000 > 1000 µg/mL. Dihydroxyacidissiminol showed the predicted binding energies of −8.1, −7.6, −7.0, and −7.5 kcal/mol with cathepsin L, nsp13 helicase, SARS-CoV-2 main protease, and SARS-CoV-2 spike protein receptor-binding domain S-RBD. Burkillanthusmalaccensis (Ridl.) Swingle can be a potential source of natural products with antibiotic-potentiating activity and that are anti-SARS-CoV-2. [ABSTRACT FROM AUTHOR]

In recent decades, an increasing incidence of male infertility has been reported. Interestingly, and considering that pesticides have been used for a long time, the high incidence of this pathological state is concomitant with the increasing use of these chemicals, suggesting they are contributors for the development of human infertility. Data from literature highlight the ability of certain pesticides and/or their metabolites to persist in the environment for long periods of time, as well as to bioaccumulate in the food chain, thus contributing for their chronic exposure. Furthermore, pesticides can act as endocrine disrupting chemicals (EDCs), interfering with the normal function of natural hormones (which are responsible for the regulation of the reproductive system), or even as obesogens, promoting obesity and associated comorbidities, like infertility. Several in vitro and in vivo studies have focused on the effects and possible mechanisms of action of these pesticides on the male reproductive system that cause sundry negative effects, even though through diverse mechanisms, but all may lead to infertility. In this review, we present an up-to-date overview and discussion of the effects, and the metabolic and molecular features of pesticides on somatic cells and germinal tissues that affect germ cell differentiation. [ABSTRACT FROM AUTHOR]

Recent years have witnessed the emergence of several viral diseases, including various zoonotic diseases such as the current pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Other viruses, which possess pandemic-causing potential include avian flu, Ebola, dengue, Zika, and Nipah virus, as well as the re-emergence of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) coronaviruses. Notably, effective drugs or vaccines against these viruses are still to be discovered. All the newly approved vaccines against the SARS-CoV-2-induced disease COVID-19 possess real-time possibility of becoming obsolete because of the development of 'variants of concern'. Flavonoids are being increasingly recognized as prophylactic and therapeutic agents against emerging and old viral diseases. Around 10,000 natural flavonoid compounds have been identified, being phytochemicals, all plant-based. Flavonoids have been reported to have lesser side effects than conventional anti-viral agents and are effective against more viral diseases than currently used anti-virals. Despite their abundance in plants, which are a part of human diet, flavonoids have the problem of low bioavailability. Various attempts are in progress to increase the bioavailability of flavonoids, one of the promising fields being nanotechnology. This review is a narrative of some anti-viral dietary flavonoids, their bioavailability, and various means with an emphasis on the nanotechnology system(s) being experimented with to deliver anti-viral flavonoids, whose systems show potential in the efficient delivery of flavonoids, resulting in increased bioavailability. [ABSTRACT FROM AUTHOR]

Through the years, many promising tools for gene editing have been developed including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), CRISPR-associated protein 9 (Cas9), and homing endonucleases (HEs). These novel technologies are now leading new scientific advancements and practical applications at an inimitable speed. While most work has been performed in eukaryotes, CRISPR systems also enable tools to understand and engineer bacteria. The increase in the number of multi-drug resistant strains highlights a necessity for more innovative approaches to the diagnosis and treatment of infections. CRISPR has given scientists a glimmer of hope in this area that can provide a novel tool to fight against antimicrobial resistance. This system can provide useful information about the functions of genes and aid us to find potential targets for antimicrobials. This paper discusses the emerging use of CRISPR-Cas systems in the fields of clinical microbiology and infectious diseases with a particular emphasis on future prospects. [ABSTRACT FROM AUTHOR]

Male reproductive tissues are strongly susceptible to several environmental and lifestyle stressors. In general, male reproductive health is highly sensitive to oxidative stress, which results in reversible and/or irreversible changes in testosterone-producing cells, spermatogenesis, and sperm quality. Chromium compounds are widely used in the +3 and +6 valence states, as food supplements, and in the industrial field, respectively. Chromium (III) compounds, i.e., Cr(III)-tris-picolinate, [Cr(pic)3], known as chromium picolinate, are used as nutritional supplements for the control of diabetes, body weight, and muscular growth. However, previous studies showed that animal models exposed to chromium picolinate experienced degenerative changes in spermatogenesis. Contradictory results are documented in the literature and deserve discussion. Furthermore, the long-term effects of chromium picolinate on the antioxidant system of treated subjects have not been properly studied. Comprehensive studies on the role of this compound will help to establish the safe and useful use of chromium supplementation. On the other hand, chromium (VI) compounds are widely used in several industries, despite being well-known environmental pollutants (i.e., welding fumes). Chromium (VI) is known for its deleterious effects on male reproductive health as toxic, carcinogenic, and mutagenic. Previous studies have demonstrated severe lesions to mouse spermatogenesis after exposure to chromium (VI). However, workers worldwide are still exposed to hexavalent chromium, particularly in electronics and military industries. Data from the literature pinpoints mechanisms of oxidative stress induced by chromium compounds in somatic and germ cells that lead to apoptosis, thus underlining the impairment of fertility potential. In this review, we analyze the benefits and risks of chromium compounds on male fertility, as well as the mechanisms underlying (in)fertility outcomes. Although supplements with antioxidant properties may maximize male fertility, adverse effects need to be investigated and discussed. [ABSTRACT FROM AUTHOR]

Croton heliotropiifolius Kunth (Euphorbiaceae), whose occurrence has already been registered in the most varied Brazilian biomes, is commonly found in the Chapada do Araripe, Ceará. The species is traditionally used to treat fungal, parasitic, and degenerative diseases. This study investigated the chemical composition and pharmacological potential (antioxidant, antifungal, antiparasitic, and cytotoxic) of an aqueous extract obtained from the roots of C. heliotropiifolius. Following a qualitative phytochemical screening, the chemical constituents were identified by ultra-efficiency liquid chromatography coupled witha quadrupole/time-of-flight system (UPLC-QTOF). The antioxidant potential was verified by thin-layer chromatography (TLC). The direct and combined antifungal activity of the extract against opportunistic Candida strains was investigated using the microdilution method. The minimal fungicidal concentration (MFC) was determined by subculture, while the modulation of the morphological transition (fungal virulence) was evaluated by light microscopy. The in vitro antiparasitic activity was analyzed using epimastigotes of Trypanosoma cruzi and promastigotes of Leishmania braziliensis and Leishmania infantum, while cytotoxicity was determined in cultures of mouse fibroblasts. The phytochemical analysis identified the presence of acids, terpenes, flavonoids, lignans, and alkaloids. Among these constituents, the presence of polar and non-polar phenolic compounds with known antioxidant action was highlighted. While the extract showed clinically ineffective antifungal effects, it could enhance the effectiveness of fluconazole, in addition to inhibiting the morphological transition associated with increased virulence in Candida strains. Although the extract showed low cytotoxicity against fibroblasts, it also had weak antiparasitic effects. In conclusion, Croton heliotropiifolius is a source of natural products with antifungal and antioxidant potential. [ABSTRACT FROM AUTHOR]

Depressive disorder is a recurrent illness that affects large numbers of the general population worldwide. In recent years, the goal of depression treatment has moved from symptomatic response to that of full remission. However, treatment-resistant depression is a major challenge in the treatment of depression or depression-related disorders. Consensus opinion, therefore, suggests that effective combined aggressive initial treatment is the most appropriate strategy. This study aimed to evaluate the effects of quercetin (QUR) and/or ascorbic acid (AA) on Phenobarbital-induced sleeping mice. QUR (50 mg/kg) and/or AA (25 mg/kg) with or without intraperitoneally pre-treated with GABA receptor agonist (diazepam: 2 mg/kg, i.p.) or antagonist (Flumazenil: 2.5 mg/kg, i.p.) to underscore the effects, as well as the possible involvement of the GABA receptor in the modulatory action of QUR and AA in sleeping mice. Additionally, an in silico study was undertaken to predict the involvement of GABA receptors in the sleep mechanism. Findings suggest that the pretreatment of QUR and AA modulated the onset and duration of action of the standard drugs in experimental animals. The acute administration of QUR and/or AA significantly (p < 0.05) reversed the DZP-mediated onset of action and slightly reversed the duration of sleep time in comparison to the vehicle (control) group. A further combination of QUR or AA with the FLU resulted in an enhancement of the onset of action while reducing the duration of action, suggesting a FLU-like effect on the test animals. In in silico studies, AA and QUR showed good to moderate binding affinities with GABAA and GABAB receptors. Both QUR and AA produced a stimulatory-like effect on mice, possibly through the GABAA and GABAB receptor interaction pathways. Further studies are necessary to verify this activity and clarify the exact mechanism of action(s) involved. [ABSTRACT FROM AUTHOR]

Metal oxide nanoparticles (MONPs) are inorganic materials that have become a valuable tool for many industrial sectors, especially in healthcare, due to their versatility, unique intrinsic properties, and relatively inexpensive production cost. As a consequence of their wide applications, human exposure to MONPs has increased dramatically. More recently, their use has become somehow controversial. On one hand, MONPs can interact with cellular macromolecules, which makes them useful platforms for diagnostic and therapeutic interventions. On the other hand, research suggests that these MONPs can cross the blood–testis barrier and accumulate in the testis. Although it has been demonstrated that some MONPs have protective effects on male germ cells, contradictory reports suggest that these nanoparticles compromise male fertility by interfering with spermatogenesis. In fact, in vitro and in vivo studies indicate that exposure to MONPs could induce the overproduction of reactive oxygen species, resulting in oxidative stress, which is the main suggested molecular mechanism that leads to germ cells' toxicity. The latter results in subsequent damage to proteins, cell membranes, and DNA, which ultimately may lead to the impairment of the male reproductive system. The present manuscript overviews the therapeutic potential of MONPs and their biomedical applications, followed by a critical view of their potential risks in mammalian male fertility, as suggested by recent scientific literature. [ABSTRACT FROM AUTHOR]

The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC50) and 90% (EC90) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent. [ABSTRACT FROM AUTHOR]

Cystic hydatid disease (CHD) is a zoonotic disease with different clinical stages caused by the larval stage of the cestode Echinococcus granulosus. It is important to highlight as a public health problem in various regions of the world. In the current study, the efficacy and apoptotic activity of the liposomal system containing juglone (5-hydroxy-1,4-naphthoquinone) were assessed against protoscoleces (PSCs) in vitro. To this aim, firstly, liposomal vesicles were prepared by the thin-film method. Their physico-chemical features were assessed using Zeta-Sizer and Scanning Electron Microscope (SEM). Subsequently, various concentrations (50, 100, 200, 400, and 800 μg/mL) of juglone nanoliposomes at different exposure times (15, 30, 60, and 120 min) were used against PSCs. Results showed that juglone nanoliposomes at all tested concentrations induced scolicidal effect, however, 800 μg/mL and 400 μg/mL of juglone nanoliposomes could reach 100% mortality in 60 and 120 min, respectively. Additionally, we found that caspase-3 mRNA expression was higher in PSCs treated with juglone nanoliposomes compared to control groups (p < 0.001). Therefore, juglone nanoliposomes are suggested to have a more potent apoptotic effect on PSCs. Generally, optimized doses of juglone nanoliposomes could display significant scolicidal effects. Moreover, further in vivo studies are required to evaluate the efficacy of this nanoliposome. [ABSTRACT FROM AUTHOR]

Human echinococcosis is a serious parasitic diseasethat still affects millions of people in many parts of the world. Since it can offer a critical threat to people's health, it is important to discover a rapid, convenient, and economical method for detection. Herein, we propose a novel point of care assay, namely, an enhanced immuno-dot-blot assay for diagnosis of cystic echinococcosis (hydatidosis). This method is based on the formation of a sandwich complex between a goldnanoprobe (chitosan–gold nanoparticleprotein A) and hydatid cyst antigen (Ag B), which holds anti-Ag B antibodies. Briefly, protein A was conjugated to chitosan–gold nanoparticles via glutaraldehyde chemistry. Then, Ag B was immobilized on the surface of a nitrocellulose membrane, which was followed by the addition of the sera sample and gold nanoprobes. The positive signals were easily detectable by naked eye. The signal intensity of this biosensor was proportional to the concentration of active anti-Echinococcus granulosus antibodies on the surface of the nanoparticles, titer of antibodies in the sera samples, and concentration of Ag B coated on the nitrocellulose membrane. The minimum concentration to use the protein A for conjugation to detect titer of anti-Echinococcus IgGand the concentration of Ag B coated in nitrocellulose membrane were 0.5 and 0.3 mg/mL, respectively. This enhanced immuno-dot-blot assay offers a simple diagnostic technique withoutthe need for expensive equipment for diagnosis of echinococcosis. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death worldwide. After diagnosis, cancer treatment may involve radiotherapy, chemotherapy, and surgery. Several of the approaches used to treat cancer also attack normal cells and, thus, there is the need for more effective treatments that decrease the toxicity to normal cells and increase the success rates of treatment. The use of beta-blockers in cancer has been studied for their antagonist action on the adrenergic system through inhibition of beta-adrenergic receptors. Besides regulating processes such as blood pressure, heart rate, and airway strength or reactivity, beta-blockers block mechanisms that trigger tumorigenesis, angiogenesis, and tumor metastasis. This study presents a literature review of the available studies addressing cancer treatments and beta-blockers. Overall, data suggest that propranolol may be used as a complement for the treatment of several types of cancer due to its ability to improve cancer outcomes by decreasing cancer cell proliferation rates. Nonetheless, additional in vitro studies should be performed to fully understand the protective role of BBs in cancer patients. [ABSTRACT FROM AUTHOR]

Zinc Oxide Nanoparticles (ZnO NPs) are a type of metal oxide nanoparticle with an extensive use in biomedicine. Several studies have focused on the biosafety of ZnO NPs, since their size and surface area favor entrance and accumulation in the body, which can induce toxic effects. In previous studies, ZnO NPs have been identified as a dose- and time-dependent cytotoxic inducer in testis and male germ cells. However, the consequences for the first cell stage of spermatogenesis, spermatogonia, have never been evaluated. Therefore, the aim of the present work is to evaluate in vitro the cytotoxic effects of ZnO NPs in spermatogonia cells, focusing on changes in cytoskeleton and nucleoskeleton. For that purpose, GC-1 cell line derived from mouse testes was selected as a model of spermatogenesis. These cells were treated with different doses of ZnO NPs for 6 h and 12 h. The impact of GC-1 cells exposure to ZnO NPs on cell viability, cell damage, and cytoskeleton and nucleoskeleton dynamics was assessed. Our results clearly indicate that higher concentrations of ZnO NPs have a cytotoxic effect in GC-1 cells, leading to an increase of intracellular Reactive Oxygen Species (ROS) levels, DNA damage, cytoskeleton and nucleoskeleton dynamics alterations, and consequently cell death. In conclusion, it is here reported for the first time that ZnO NPs induce cytotoxic effects, including changes in cytoskeleton and nucleoskeleton in mouse spermatogonia cells, which may compromise the progression of spermatogenesis in a time- and dose-dependent manner. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnO NPs) are among nanoscale materials, attracting increasing attention owing to their exceptional set of characteristics, which makes these engineered nanoparticles a great option for improving the quality and effectiveness of diagnosis and treatment. The capacity of ZnO NPs to induce reactive oxygen species (ROS) production, DNA damage, and apoptosis represents a promise for their use in both cancer therapy and microbial treatment. However, their intrinsic toxicity together with their easy entrance and accumulation in organism have raised some concerns regarding the biomedical use of these NPs. Several studies have reported that ZnO NPs might induce cytotoxic effects on the male reproductive system, compromising male fertility. Despite some advances in this area, the knowledge of the effects of ZnO NPs on male fertility is still scarce. Overall, a brief outline of the major ZnO NPs biomedical applications and promises in terms of diagnostic and therapeutic use will also be explored. Further, this review intends to discuss the effect of ZnO NPs exposure on the male reproductive system and speculate their effects on male (in)fertility. [ABSTRACT FROM AUTHOR]

Parasites may affect the dynamics of bird populations. Plasmodium , Leucocytozoon and Haemoproteus are well-known avian haematozoa that can trigger decreased productivity and high mortality in domesticated birds. In this study, we evaluated the prevalence of avian blood parasites ( Plasmodium , Leucocytozoon and Haemoproteus ) against 335 birds of 8 species in the Yazd province in central Iran. To detect blood parasites, Giemsa-stained blood smears were prepared. Of the birds, 11.64% (39/335) were infected with at least one parasite genus, particularly Haemoproteus (32.6%; 23/335). The total prevalence values for Plasmodium , Haemoproteus and Leucocytozoon were 1.7, 6.8 and 2.9%, respectively. Plasmodium had lower prevalence rates of 1.7% (6/335). Among birds, pigeons, hens and ducks have the highest prevalence of Haemoproteus , Leucocytozoon and Plasmodium parasites at 1.7%, 6.8% and 2.9%, respectively. Results from this research extend our knowledge on the incidence of avian blood parasites in domesticated birds living in central Iran. The overall low incidence of avian blood parasites in birds was found in the Yazd province, Iran.