Current medication therapy for leishmaniasis and trypanosomiasis remains a major challenge due to its limited efficacy, significant adverse effects, and inaccessibility. Consequently, locating ...affordable and effective medications is a pressing concern. Because of their easy-to-understand structure and high functionalization potential, chalcones are promising candidates for use as bioactive agents. Thirteen synthetic ligustrazine-containing chalcones were evaluated for their ability to inhibit the growth of leishmaniasis and trypanosomiasis in etiologic agents. The tetramethylpyrazine (TMP) analogue ligustrazine was chosen as the central moiety for the synthesis of these chalcone compounds. The most effective compound (EC
= 2.59 µM) was the chalcone derivative
, which featured a pyrazin-2-yl amino on the ketone ring and a methyl substitution. Multiple actions were observed for certain derivatives, including
,
,
, and
, against all strains tested. Eflornithine served as a positive control, and three ligustrazine-based chalcone derivatives, including
,
, and
, had a higher relative potency. Compounds
and
are particularly efficacious; even more potent than the positive control, they are therefore promising candidates for the treatment of trypanosomiasis and leishmaniasis.
Leishmaniasis, a neglected parasitic disease caused by a unicellular protozoan of the genus Leishmania, is transmitted through the bite of a female sandfly. The disease remains a major public health ...problem and is linked to tropical and subtropical regions, with an endemic picture in several regions, including East Africa, the Mediterranean basin and South America. The different causative species display a diversity of clinical presentations; therefore, the immunological data on leishmaniasis are both scarce and controversial for the different forms and infecting species of the parasite. The present review highlights the main immune parameters associated with leishmaniasis that might contribute to a better understanding of the pathogenicity of the parasite and the clinical outcomes of the disease. Our aim was to provide a concise overview of the immunobiology of the disease and the factors that influence it, as this knowledge may be helpful in developing novel chemotherapeutic and vaccine strategies.
•Immune response against Leishmania is complex and controversial.•Several immune cells and major effector molecules regulate the immune response.•Coordinated contribution occurs between active and innate immune response.
The zinc oxide (ZnO) nanostructures are highly influential material and exhibit numerous properties. Numerous physicochemical applications for instance electronic, catalyst, solar cells, hydrogen ...fuels and energy evolution. Besides the large application in various directions very few reports are available for the cytotoxic evaluations and their compression with nano particles (NPs) and nanrorods (NRs) against the breast (MCF-7) cancer cells. The ZnO-NPs and NRs were produced through solution process in a short time span and were well characterized. The cells viability was tested with MTT and NRU assays. A series of different concentrations (2 μg/mL, 5 μg/mL, 10 μg/mL, 25 μg/ mL, 50 μg/mL, 100 μg/mL and 200 μg/mL) of NRs and NPs were employed against cancer cells for to evaluate the % activity of sustained and non-sustained cells. The morphology of treated and control cells were observed via microscopy respectively. Including this, the genetic studies were also scrutinized, cell-cycle analysis express the upsurge in the apoptotic peak after a 24-h. Quantitative PCR (qPCR) data revealed that the mRNA levels of apoptotic genes such as p53, bax, and caspase-3 were upregulated, whereas bcl-2, an anti-apoptotic gene, was downregulated; therefore, apoptosis was mediated through the p53, bax, caspase-3, and bcl-2 pathways.
Three-dimensional printing has revolutionized drug manufacturing and has provided a solution to the limitations associated with the conventional manufacturing method by designing complex drug ...delivery systems with customized drug release profiles for personalized therapies. The present investigation aims to design a gastric floating tablet with prolonged gastric floating time and sustained drug release profile. In the present study, a gastro retentive floating device (GRFD) was designed and fabricated using a fused deposition modelling (FDM)-based 3D printing technique. This device acts as a multifunctional dosage form exhibiting prolonged gastric retention time and sustained drug release profile with improved oral bioavailability in the upper gastrointestinal tract. Commercial polyvinyl alcohol (PVA) and polylactic acid (PLA) filaments were used to design GRFD, which was comprised of dual compartments. The outer sealed compartment acts as an air-filled chamber that imparts buoyancy to the device and the inner compartment is filled with a commercial propranolol hydrochloride immediate-release tablet. The device is designed as a round-shaped shell with a central opening of varying size (1 mm, 2 mm, 3 mm, and 4 mm), which acts as a drug release window. Scanning electron microscope (SEM) images were used to determine morphological characterization. The in vitro buoyancy and drug release were evaluated using the USP type II dissolution apparatus. All the designed GRFDs exhibit good floating ability and sustained drug release profiles. GRFDs fabricated using PLA filament show maximum buoyancy (>24 h) and sustained drug release for up to 10 h. The floating ability and drug release from the developed devices were governed by the drug release window opening size and the filament material affinity towards the gastric fluid. The designed GRFDs show great prospects in modifying the drug release characteristics and could be applied to any conventional immediate-release product.
Cystic echinococcosis (CE), which is triggered by the parasite
, is a global zoonotic disease that is common in rural regions in which there are frequent encounters between dogs and other domestic ...animals. The disease can have devastating consequences, impacting the health of people and animals and leading to huge financial losses, especially in the agricultural industry. In the Kingdom of Saudi Arabia (KSA) and Egypt, despite the high incidence of disease, few investigations have been conducted into the genetic variation in species of the genus
.
This study sought to compare the genetic features of the hydatid cysts carried in sheep in KSA with those found in Egypt.
DNA from the protoscolices was used in a PCR targeting the mitochondrial NADH dehydrogenase 1 (
), cytochrome c oxidase subunit 1 (
), and nuclear actin II (
) genes, and the resulting amplification products of 30 KSA and Egyptian isolates were sequenced and compared.
Among the sheep in KSA, the overall prevalence of CE was 0.51%. Of the sheep cyst DNA samples, 95%, 100%, and 52% were positive for the
, and
genes, respectively. Targeting all three genes, all KSA samples belonged to the
genotype (G1), whereas all Egyptian isolates belonged to
(G1) and
(G6).
We conclude that isolates of
from the two countries shared a common origin in Arabic North Africa, with sheep and camels as common hosts.
This study aimed at developing the microwave-treated, physically cross-linked polymer blend film, optimizing the microwave treatment time, and testing for physicochemical attributes and wound healing ...potential in diabetic animals. Microwave-treated and untreated films were prepared by the solution casting method and characterized for various attributes required by a wound healing platform. The optimized formulation was tested for skin regeneration potential in the diabetes-induced open-incision animal model. The results indicated that the optimized polymer film formulation (MB-3) has significantly enhanced physicochemical properties such as high moisture adsorption (154.6 ± 4.23%), decreased the water vapor transmission rate (
) value of (53.0 ± 2.8 g/m
/h) and water vapor permeability (
) value (1.74 ± 0.08 g mm/h/m
), delayed erosion (18.69 ± 4.74%), high water uptake, smooth and homogenous surface morphology, higher tensile strength (56.84 ± 1.19 MPa), and increased glass transition temperature and enthalpy (through polymer hydrophilic functional groups depicting efficient cross-linking). The in vivo data on day 16 of post-wounding indicated that the wound healing occurred faster with significantly increased percent re-epithelialization and enhanced collagen deposition with optimized MB-3 film application compared with the untreated group. The study concluded that the microwave-treated polymer blend films have sufficiently enhanced physical properties, making them an effective candidate for ameliorating the diabetic wound healing process and hastening skin tissue regeneration.
The material extrusion fused deposition modeling (FDM) technique has become a widely used technique that enables the production of complex parts for various applications. To overcome limitations of ...PLA material such as low impact toughness, commercially available materials such as UltiMaker Tough PLA were produced to improve the parent PLA material that can be widely applied in many engineering applications. In this study, 3D-printed parts (test specimens) considering six different printing parameters (i.e., layer height, wall thickness, infill density, build plate temperature, printing speed, and printing temperature) are experimentally investigated to understand their impact on the mechanical properties of Tough PLA material. Three different standardized tests of tensile, flexural, and compressive properties were conducted to determine the maximum force and Young’s modulus. These six properties were used as responses in a design of experiment, definitive screening design (DSD), to build six regression models. Analysis of variance (ANOVA) is performed to evaluate the effects of each of the six printing parameters on Tough PLA mechanical properties. It is shown that all regression models are statistically significant (p<0.05) with high values of adjusted and predicted R2. Conducted confirmation tests resulted in low relative errors between experimental and predicted data, indicating that the developed models are adequately accurate and reliable for the prediction of tensile, flexural, and compressive properties of Tough PLA material.
Diabetes mellitus is one of the most prevalent metabolic disorders characterized by hyperglycemia due to impaired glucose metabolism. Overproduction of free radicals due to chronic hyperglycemia may ...cause oxidative stress, which delays wound healing in diabetic conditions. For people with diabetes, this impeded wound healing is one of the predominant reasons for mortality and morbidity. The study aimed to develop an
leaf extract-mediated green synthesis of titanium dioxide (TiO
) nanoparticles (NPs) and further incorporate them into 2% chitosan (CS) gel for diabetic wound healing. UV-visible spectrum analysis recorded the sharp peak at 235 and 320 nm, and this was the preliminary sign for the biosynthesis of TiO
NPs. The FTIR analysis was used to perform a qualitative validation of the biosynthesized TiO
nanoparticles. XRD analysis indicated the crystallinity of TiO
NPs in anatase form. Microscopic investigation revealed that TiO
NPs were spherical and polygonal in shape, with sizes ranging from 75 to 123 nm. The EDX analysis of green synthesized NPs showed the presence of TiO
NPs, demonstrating the peak of titanium ion and oxygen. The hydrodynamic diameter and polydispersity index (PDI) of the TiO
NPs were found to be 130.3 nm and 0.237, respectively. The developed TiO
NPs containing CS gel exhibited the desired thixotropic properties with pseudoplastic behavior. In vivo wound healing studies and histopathological investigations of healed wounds demonstrated the excellent wound-healing efficacy of TiO
NPs containing CS gel in diabetic rats.
Currently, bone fractures are commonly treated with bone fixation plates that present rigid designs and stiff biometals (e.g., Ti-6Al-4V) that increase the probability of stress shielding happening ...during bone remodeling by shielding the required stress stimuli for adequate healing. This can lead to medical implant loosening, bone resorption and possible bone refracture. In this paper, an initial custom-fit bone plate is designed to be treated based on the computer tomography imaging of a patient suffering from distal tibia spiral fracture. The initial bone plate was redesigned to reduce the risk of bone being stress shielded. Topology optimization were implemented to redesign the bone plates by minimizing the strain energy and reducing the total plate’s volume in three different cases (25%, 50% and 75%). A bone-plate construct was assembled and examined using finite element analysis considering load conditions of the patient’s gait and the tibia bone being loaded with 10% of the bodyweight. The bone stresses were evaluated in order to compare the topology optimized plates with the initial design. The findings show that with higher volume, load transfer reduction increases in the fractured area and reduces the risk of stress shielding. Topology optimization is a viable approach for building custom-fit distal tibia plates for spiral distal tibia fracture.
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