Search Results (9)

Background/Objectives: Pteridine reductase 1 (PTR1) has been one of the prime targets for discovering novel antileishmanial therapeutics in the fight against Leishmaniasis. This enzyme catalyzes the NADPH-dependent reduction of pterins to their tetrahydro forms. While chemotherapy remains the primary treatment, its effectiveness is constrained by drug resistance, unfavorable side effects, and substantial associated costs. Methods: This study addresses the urgent need for novel, cost-effective drugs by employing in silico techniques to identify potential lead compounds targeting the PTR1 enzyme. A library of 1463 natural compounds from AfroDb and NANPDB, prefiltered based on Lipinski’s rules, was used to screen against the LmPTR1 target. The X-ray structure of LmPTR1 complexed with NADP and dihydrobiopterin (Protein Data Bank ID: 1E92) was identified to contain the critical residues Arg17, Leu18, Ser111, Phe113, Pro224, Gly225, Ser227, Leu229, and Val230 including the triad of residues Asp181-Tyr194-Lys198, which are critical for the catalytic process involving the reduction of dihydrofolate to tetrahydrofolate. Results: The docking yielded 155 compounds meeting the stringent criteria of −8.9 kcal/mol instead of the widely used −7.0 kcal/mol. These compounds demonstrated binding affinities comparable to the known inhibitors; methotrexate (−9.5 kcal/mol), jatrorrhizine (−9.0 kcal/mol), pyrimethamine (−7.3 kcal/mol), hardwickiic acid (−8.1 kcal/mol), and columbamine (−8.6 kcal/mol). Protein–ligand interactions and molecular dynamics (MD) simulation revealed favorable hydrophobic and hydrogen bonding with critical residues, such as Lys198, Arg17, Ser111, Tyr194, Asp181, and Gly225. Crucial to the drug development, the compounds were physiochemically and pharmacologically profiled, narrowing the selection to eight compounds, excluding those with potential toxicities. The five selected compounds ZINC000095486253, ZINC000095486221, ZINC000095486249, 8alpha-hydroxy-13-epi-pimar-16-en-6,18-olide, and pachycladin D were predicted to be antiprotozoal (Leishmania) with Pa values of 0.642, 0.297, 0.543, 0.431, and 0.350, respectively. Conclusions: This study identified five lead compounds that showed substantial binding affinity against LmPTR1 as well as critical residue interactions. A 100 ns MD combined with molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations confirmed the robust binding interactions and provided insights into the dynamics and stability of the protein–ligand complexes. Full article

Zygophyllum propinquum (Decne.) is a leaf succulent C₄ perennial found in arid saline areas of southern Pakistan and neighboring countries, where it is utilized as herbal medicine. This study investigated how growth, water relations, ion content, chlorophyll fluorescence, and antioxidant system of Z. propinquum change as salinity levels increase (0, 150, 300, 600, and 900 mM NaCl). Salinity increments inhibited total plant fresh weight, whereas dry weight remained constant at moderate salinity and decreased at high salinity. Leaf area, succulence, and relative water content decreased as salinity increased. Similarly, the sap osmotic potential of both roots and shoots declined as NaCl concentrations increased. Except for a transitory increase in roots at 300 mM NaCl, sodium concentrations in roots and shoots increased constitutively to more than five times higher under saline conditions than in non-saline controls. Root potassium increased briefly at 300 mM NaCl but did not respond to NaCl treatments in the leaf. Photosynthetic pigments increased with 300 and 600 mM NaCl compared to non-saline treatments, although carotenoids appeared unaffected by NaCl treatments. Except for very high NaCl concentration (900 mM), salinity showed no significant effect on the maximum efficiency of photosystem II photochemistry (Fv/Fm). Light response curves demonstrated reduced absolute (ETR^*) and maximum electron transport rates (ETR_max) for the 600 and 900 mM NaCl treatments. The alpha (α), which indicates the maximum yield of photosynthesis, decreased with increasing NaCl concentrations, reaching its lowest at 900 mM NaCl. Non-photochemical quenching (NPQ) values were significantly higher under 150 and 300 mM NaCl treatments than under non-saline and higher NaCl treatments. Electrolyte leakage, malondialdehyde (MDA), and hydrogen peroxide (H₂O₂) peaked only at 900 mM NaCl. Superoxide dismutase and glutathione reductase activities and glutathione content in both roots and shoots increased progressively with increasing salinity. Hence, growth reduction under low to moderate (150–600 mM NaCl) salinity appeared to be an induced response, while high (900 mM NaCl) salinity was injurious. Full article

The porcine bulbourethral glands produce a gel-type secretion. Although the role of these contributions to reproductive success remains murky, the bulbourethral glands are major accessory sex glands in this species. Isometric growth in the early neonatal interval is followed by allometric growth in the late juvenile interval (6 to 11 weeks of age), while circulating endogenous steroids are low. The rate of allometric growth increases during the peripuberal interval (16 to 20 weeks of age) when systemic testosterone is relatively high. Gene expression for androgen receptor (AR) and for the steroid 5 alpha-reductase 2 (SRD5A2) enzyme that synthesizes the more potent androgen dihydrotestosterone from its precursor was evaluated by qPCR analyses of bulbourethral gland tissue. Tissues were collected from control boars (2 weeks to 40 weeks of age) and from littermates of these boars treated with letrozole to suppress endogenous estrogen synthesis. Gene expression for these two key proteins in androgen signaling was quite low during the initial allometric growth in the late juvenile and prepuberal intervals, suggesting that this initial growth was not primarily stimulated by androgens. These observations are consistent with a more direct estrogen-mediated inhibition of growth via GPER previously proposed, with the sensitivity extending into the late juvenile interval when estrogens as well as androgens are normally relatively low. Full article

Enterocytozoon hepatopenaei (EHP) causes slow growth syndrome in shrimp, resulting in huge economic losses for the global shrimp industry. Despite worldwide reports, there are no effective therapeutics for controlling EHP infections. In this study, five potential druggable targets of EHP, namely, aquaporin (AQP), cytidine triphosphate (CTP) synthase, thymidine kinase (TK), methionine aminopeptidase2 (MetAP2), and dihydrofolate reductase (DHFR), were identified via functional classification of the whole EHP proteome. The three-dimensional structures of the proteins were constructed using the artificial-intelligence-based program AlphaFold 2. Following the prediction of druggable sites, the ZINC15 and ChEMBL databases were screened against targets using docking-based virtual screening. Molecules with affinity scores ≥ 7.5 and numbers of interactions ≥ 9 were initially selected and subsequently enriched based on their ADMET properties and electrostatic complementarities. Five compounds were finally selected against each target based on their complex stabilities and binding energies. The compounds CHEMBL3703838, CHEMBL2132563, and CHEMBL133039 were selected against AQP; CHEMBL1091856, CHEMBL1162979, and CHEMBL525202 against CTP synthase; CHEMBL4078273, CHEMBL1683320, and CHEMBL3674540 against TK; CHEMBL340488, CHEMBL1966988, and ZINC000828645375 against DHFR; and CHEMBL3913373, ZINC000016682972, and CHEMBL3142997 against MetAP2.The compounds exhibited high stabilities and low binding free energies, indicating their abilities to suppress EHP infections; however, further validation is necessary for determining their efficacy. Full article

Background: Benign prostatic hyperplasia (BPH) is commonly responsible for lower urinary tract symptoms (LUTS) in men aged 50 or over. Sexual dysfunctions, such as ejaculatory disorders (EjD), go along with LUTS but are frequently overlooked in the initial evaluation. This review aimed to detail BPH-related EjD, as well as their modifications by medical, surgical, and interventional treatments. Methods: We conducted a narrative review looking for publications between 1990 and 2020, regarding physiopathology, epidemiology, evaluation, and therapeutic management (medical, surgical, and interventional) of BPH-related EjD. Results: Sixty-five articles were included in our final analysis. Forty-six percent of men presenting with LUTS reported EjD. If the prevalence increases with age and LUTS severity, the functional impairment is not correlated with age. Several self-questionnaires evaluated the sexual function, but only four approaches are specific to EjD. Medical therapies were exposed to anejaculation, rather than retrograde ejaculation (RE) (4–30% (alpha-blockers), 4–18% (5-alpha-reductase inhibitors)). Regarding surgical therapies, trans-urethral resection of the prostate (TURP) and incision of the prostate (TUIP) are associated with 50–70% and 21–35% of RE. The RE rate is important after open simple prostatectomy but can be reduced with robotic approaches and urethral sparing techniques (19%). Anatomic endoscopic enucleation of the prostate (AEEP) with or without a laser source is associated with an 11–36% RE rate, according to supramontanal preservation. Recent surgical techniques (Rezum©, Aquablation©, or Urolift©) were developed to preserve antegrade ejaculation with promising short-term results. Regardless of the surgical approach, anatomic studies suggest that the preservation of peri-montanal tissue (7.5 mm laterally; 10 mm proximally) is primordial to avoid post-operative RE. Finally, prostate artery embolization (PAE) limits the RE rate but exposes it to a 12 months 10% re-intervention rate. Conclusion: EjD concerns almost half of the patients presenting BPH-related LUTS. Initial evaluation of EjD impairment is primordial before medical or surgical therapy. Peri-montanal tissue preservation represents a key point for antegrade ejaculation preservation, regardless of the surgical option. Full article

The present study aimed to evaluate the muscle fiber metabolism and assess the presence and distribution of both procollagen and collagen type III in pectoralis major muscles affected by white striping (WS), wooden breast (WB), and spaghetti meat (SM), as well as in those with macroscopically normal appearance (NORM). For this purpose, 20 pectoralis major muscles (five per group) were selected from the same flock of fast-growing broilers (Ross 308, males, 45-days-old, 3.0 kg live weight) and were used for histochemical (nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) and alpha-glycerophosphate dehydrogenase (α-GPD)) and immunohistochemical (procollagen and collagen type III) analyses. When compared to NORM, we found an increased proportion (p < 0.001) of fibers positively stained to NADH-TR in myopathic muscles along with a relevant decrease (p < 0.001) in the percentage of those exhibiting a positive reaction to α-GPD. In addition, an increased proportion of fibers exhibiting a positive reaction to both stainings was observed in SM, in comparison with NORM (14.3 vs. 7.2%; p < 0.001). After reacting to NADH-TR, SM exhibited the lowest (p < 0.001) cross-sectional area (CSA) of the fibers (−12% with respect to NORM). On the other hand, after reacting to α-GPD, the CSA of WS was found to be significantly larger (+10%) in comparison with NORM (7480 vs. 6776 µm²; p < 0.05). A profound modification of the connective tissue architecture involving a different presence and distribution of procollagen and collagen type III was observed. Intriguingly, an altered metabolism and differences in the presence and distribution of procollagen and collagen type III were even observed in pectoralis major muscle classified as NORM. Full article

The objective of this study was to investigate the effects of dietary bamboo leaf extract (BLE) on antioxidant status and cholesterol metabolism in broilers. One-day-old male Arbor Acres (576) broilers were randomly divided into six groups. A control group was fed a basal diet, while five experimental groups were supplemented with 1.0, 2.0, 3.0, 4.0, and 5.0g BLE per kg feed in their basal diets. The result indicated that BLE supplementation linearly improved eviscerated yield and decreased abdominal fat (p < 0.05). A significant decrease of serum triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c) content was observed with BLE supplementation (p < 0.05). BLE supplementation linearly improved the total antioxidant capacity and catalase activity in both serum and liver (p < 0.05). Glutathione peroxidase was quadratically increased in serum and linearly increased in the liver with BLE supplementation (p < 0.05). The malonaldehyde content in liver showed a linear and quadratic decrease with BLE supplementation (p < 0.05). BLE supplementation up-regulated the mRNA expression of cholesterol 7- alpha hydroxylase and low-density lipoprotein receptor and downregulated 3-hydroxy3-methyl glutamates coenzyme A reductase mRNA expression in the liver. The antioxidant enzyme mRNA expressions were all up-regulated by BLE supplementation in the liver. In conclusion, supplemental BLE improved antioxidant status and cholesterol metabolism in broilers, which eventually led to a decrease of serum TG, LDL-c content, and abdominal fat deposition. Full article

The mechanism of hepatoprotective compounds is usually related to its antioxidant or anti-inflammatory effects. Black garlic is produced from garlic by heat treatment and its anti-inflammatory activity has been previously reported. Therefore, the aim of this study was to investigate the hepatoprotective effect of five different extracts of black garlic against carbon tetrachloride (CCl₄)-induced acute hepatic injury (AHI). In this study, mice in the control, CCl₄, silymarin, and black garlic groups were orally administered distilled water, silymarin, and different fraction extracts of black garlic, respectively, after CCl₄ was injected intraperitoneally to induce AHI. The results revealed that the n-butanol layer extract (BA) and water layer extract (WS) demonstrated a hepatoprotective effect by reducing the levels of alanine aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and hepatic malondialdehyde (MDA). Furthermore, the BA and WS fractions of black garlic extract increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), tumor necrosis factor alpha (TNF-α), and the interleukin-1 (IL-1β) level in liver. It was concluded that black garlic exhibited significant protective effects on CCl₄-induced acute hepatic injury. Full article

This study was done to identify the content compounds of Achillea wilhelmsii (A. wilhelmsii) and to evaluate its hypoglycemic and anti-hypercholesterolemic activity and effect on inflammatory mediators. The extracts and fractions of A. wilhelmsii were thoroughly analyzed using high performance liquid chromatography (HPLC), and the total content of phenols and flavonoids was determined. The hypoglycemic activity was evaluated in vivo using alloxan-induced diabetic mice. The effect upon inflammatory mediators was evaluated in vitro using the human monocytic leukemia cell line (THP-1). The anti-hypercholesterolemic activity was evaluated in vitro using the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase assay kit. The water extract (WE)-treated group showed the highest reduction in the fasting blood glucose levels (FBGL). The chloroform fraction (CF) and ethyl acetate fraction (EAF) both showed a significant ability to reduce the secretion of tumor necrosis factor alpha (TNF-α). The EAF, however, also attenuated the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The CF showed the most significant 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibition activity. The five main compounds in the CF were isolated and identified. Out of the five compounds in the CF, 1β,10β-epoxydesacetoxymatricarin (CP1) and leucodin (CP2) showed the highest anti-hypercholesterolemic potential. A molecular docking study provided corresponding results. Full article