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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]

Background: Propolis is a natural resinous product from a variety of plants and combines it with beeswax and salivary enzymes to create bee glue. Its potentials have been employed in the treatment of many diseases and conditions for centuries. This study, therefore, aims to determine the anti-Acanthamoeba properties of the propolis extract, eye drops coupled to some mechanisms such as inhibition of encystation and excystation. Methods: The minimum inhibitory concentrations (MICs) of the most active propolis extract were assessed in trophozoites and cysts of Acanthamoeba triangularis (A. triangularis) at 0.256 and 1 mg/mL, respectively. Results: Active eye drops inhibited trophozoites and cysts with a MIC value of 100%. At concentrations lower than their MICs values (1/2--1/16 MIC), propolis and eye drops revealed inhibition of encystation. In addition, at 1/2 MIC, both the propolis extract and eye drops showed potential inhibition of excystation. In combined sets of propolis extract and eye drops, they showed slightly increasing inhibition of encystation and excystation. Surprisingly, the MIC of chlorhexidine decreased when combined with the propolis and eye drops. SEM and TEM images displayed morphological changes in A. triangularis treated with combined sets of propolis extract and eye drops. Conclusion: From this study, a new combined eye drop solution with propolis extract was found to be helpful in reducing encystation and excystation in A. triangularis. Therefore, this combination is an alternative for the treatment of eye diseases in early stages along with reducing the entry into the cyst stage of Acanthamoeba. The results of this study revealed new anti-Acanthamoeba inhibitors with promising combined alternative therapeutic potential for the treatment of Acanthamoeba keratitis. [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]

Introduction. The research aimed to study the intensity of arm swing exercise (ASE) with different tempi of music-movement synchrony in untrained young adults and to investigate the effect of different music tempi on heart rate and oxygen consumption. Methods. Participants were 30 healthy volunteers (15 males and 15 females), 20.67 ± 1.37 years and low-to-moderate physical activity. They performed ASE synchronised with music at a tempo of 60 and 140 bpm with a random sequence. They were measured for heart rate and oxygen consumption using a Quark SPIRO (COSMED) before and after the ASE for 6 minutes of each tempo. They rested for at least 15 minutes between music tempi during the ASE. The intensity of ASE with music-movement synchrony of each tempo was calculated as a percentage of maximum heart rate (%HRmax) and percentage maximum oxygen consumption (%VO2max). Results. The %HRmax of all participants post-ASE at 60 and 140 bpm were 58.64 ± 8.82 and 60.12 ± 8.95%, respectively. The %VO2max of all participants post-ASE at 60 and 140 bpm were 38.65 ± 11.36 and 40.17 ± 10.71%, respectively. There was no significant difference in HR and VO2 of ASE between music tempi. Conclusions. The ASE with music-movement synchrony at 60 and 140 bpm is a low-intensity aerobic exercise, so is a suitable choice for people with low physical activity. Furthermore, the faster tempo did not significantly alter the intensity, therefore, we recommend selecting the slower music tempo at 60 bpm to avoid repetitive shoulder joint injury. [ABSTRACT FROM AUTHOR]

Garcinia mangostana L., also known as the mangosteen tree, is a native medicinal plant in Southeast Asia having a wide variety of pharmacologically active compounds, including xanthonoid mangostin. In this study, we examined the pharmacological activities of the selected semi-synthetic mangostin derivative, namely, amoebicidal activity, encystation inhibition, excystation activity, and removal capacity of adhesive Acanthamoeba from the surface of contact lens (CL). Among the three derivatives, C1 exhibited promising anti-Acanthamoeba activity against Acanthamoeba triangularis WU19001 trophozoites and cysts. SEM images displayed morphological changes in Acanthamoeba trophozoites, including the loss of acanthopodia, pore formation in the cell membrane, and membrane damage. In addition, the treated cyst was shrunken and adopted an irregular flat cyst shape. Under a fluorescence microscope, acridine orange and propidium iodide (AO/PI) staining revealed C1 induced condensation of cytoplasm and chromatin with the loss of cell volume in the treated trophozoites, while calcofluor white staining demonstrated the leakage of cell wall in treated cysts, leading to cell death. Interestingly, at the concentration ranges in which C1 showed the anti-Acanthamoeba effects (IC50 values ranging from 0.035-0.056 mg/mL), they were not toxic to Vero cells. C1 displayed the highest inhibitory effect on A. triangularis encystation at 1/16×MIC value (0.004 mg/mL). While C1 demonstrated the excystation activity at 1/128×MIC value with a high rate of 89.47%. Furthermore, C1 exhibited the removal capacity of adhesive Acanthamoeba from the surface of CL comparable with commercial multipurpose solutions (MPSs). Based on the results obtained, C1 may be a promising lead agent to develop a therapeutic for the treatment of Acanthamoeba infections and disinfectant solutions for CL. [ABSTRACT FROM AUTHOR]