Esterase Levels Research Articles

Comparing the frequency, antifungal susceptibility, and enzymatic profiles of the oral fungal composition in patients with and without Alzheimer's disease admitted to a neurology clinic

BackgroundStudies have shown that changes in the frequency of oral microorganisms may play a key role in the development of Alzheimer's disease (AD). However, no research has been conducted on the oral fungal composition in AD-patients. The present study aimed to investigate the changes in the frequency of oral fungal composition, the antifungal susceptibility, and the enzymatic profiles of oral fungal composition in patients suffering from AD compared to non-AD individuals.Materials and methodsIn the present analytical cross-sectional study during 12 months, 76 hospitalized patients with AD were matched with 76 individuals without AD. A sterile serum physiology-moistened cotton-tipped swab was used to sample the mouth area. All swabs were cultured on Sabouraud Chloramphenicol Agar. Fungal identified were confirmed through the PCR-sequencing techniques. Enzyme activity index (EAI) for important pathogenic factors including proteinase, esterase and hemolysin was measured using relevant protocols. The susceptibility to 8 antifungal agents (nystatin, voriconazole, itraconazole, fluconazole, posaconazole, amphotericin B, 5-fluorocytosine, and caspofungin) against fungal strains obtained from AD-patients was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-A2 for filamentous fungi, and document M27-A4 for yeasts.ResultsThe results showed that compared to the non-AD individuals, the prevalence of oral fungal composition in AD group was 1.6 times higher. Candida albicans was the most common fungal species isolated from oral swab samples of AD group (n=53, 80%) and non-AD group (n=28, 40%), and the diversity of the oral fungal composition in AD-patients were lower than non-AD individuals. Among the 3 investigated virulence factors, a statistically significant difference was shown in terms of hemolysin activity level between the two studied groups (p<0.05) and the activity level of esterase and proteinase enzymes did not show a significant difference in the two studied groups (p>0.05). The results showed that almost all of the tested isolates were susceptible to nystatin, the most widely prescribed antifungal to treat superficial infections, and only 1.69 % (2/118) of the Candida isolates were resistant to this antifungal drug.ConclusionUnderstanding the changes in the frequency of oral fungal composition the antifungal susceptibility, and the enzymatic profiles of oral fungal composition in patients suffering from AD compared to non-AD individuals makes it possible to better understand the etiology of this disease.

Herniarin ameliorates acrylamide-induced neurotoxicity in rat: involvement of neuro-inflammation and acetylcholinesterase

This study aimed to investigate the protective effects of herniarin against acrylamide neuro-toxicity. Rats were administered 50 mg/kg of acrylamide (Acr) along with oral doses of herniarin at 50, 100, and 200 mg/kg for 11 days. After treatment, the animals were sacrificed and biochemical markers including superoxide dismutase (SOD), catalase activity, malondialdehyde (MDA), nitric oxide (NO), thiols and acetylcholine esterase (AChE) level were evaluated. Moreover, mRNA expression of neuro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 were measured using qRT-PCR method. As results, Acr increased MDA with subsequent reduction in SOD, catalase, and thiols content. In contrast, administration of herniarin remarkably normalised the antioxidants and decreased lipid peroxidation. Furthermore, it downregulated mRNA expression of TNF-α, IL-1β, and IL-6 (p < 0.001) as well as decreased NO (p < 0.01) and AchE levels (p < 0.001) in the Acr-injured brains. Herniarin ameliorated Acr-induced brain injury via modulating redox hemostasis, cholinergic function, as well as inhibiting neuro-inflammation in rats.

Design and synthesis of phyto-Saxagliptin conjugates: Targeting DPP IV, AChE, and β-amyloid in cognitive impairment

Cognitive impairment is a major secondary consequence of Type II diabetes mellitus. The present investigation is designed to enhance the efficacy of an antidiabetic drug (Saxagliptin/SXG) against diabetes-induced cognitive impairment in rats. SXG has limited blood-brain barrier (BBB) permeability due to its hydrophilic nature. Phytochemical-based carboxylic acid conjugates enhance the lipophilicity and anti-oxidant properties of the drugs. Virtually SXG was conjugated with 10 different carboxylic acids and evaluated for drug-likeness, pre-ADMET, Molecular docking, and HUMO-LUMO study. Based on the molecular weight, log P value, docking score, and toxicity profile; three carboxylic acids were selected. Gallic acid (GA), Isonicotinic acid (INA), and Caffeic acid (CA) conjugates of SXG were synthesized and characterized by FTIR, and NMR studies. Diabetes-induced cognitive impairment was induced in the rats by administration of STZ, 45 mg kg-1 i.p. Learning and memory were evaluated by assessing spontaneous alternation behavior (SAB), number of correct responses, and transfer latency using Y-maze, radial arm maze, and elevated plus maze respectively. The antioxidant activity, nitrite levels, acetylcholine esterase level, and Aβ42 content in the rat brain was also evaluated. Histopathology of the hippocampal area was also done. The carboxamides of SXG have improved the efficacy of SXG against diabetes-induced cognitive impairment. This neuroprotective effect of carboxamides of SXG may be attributed to anti-oxidant activity, cholinergic activity, and anti-amyloid β activity.

In vivo neuroprotective effect of Guaiacum officinale leaf extracts in scopolamine-induced cognitive impairment model

ABSTRACT The phytochemical composition and neuroprotective potential of the ethanolic extract of Guaiacum officinale leaves against scopolamine-induced amnesia were investigated. Spatial memory was evaluated through the Morris water maze, while the entire brain was assessed for acetylcholinesterase (AchE), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. The presence of glycosides, alkaloids, steroids, terpenoids, flavonoids, and saponins was detected in the ethanolic extract through phycological analysis. The findings suggested that the ethanolic extract alleviated scopolamine-induced spatial memory impairments caused by scopolamine and decreased the AchE activity. The study also detailed MDA, SOD, transfer latency periods, and acetylcholine esterase levels in both normal and extract-treated groups.

Dose-Dependent Attenuation of the Efficacy of Clitoria ternatea by Cobalt Oxide Nanoparticles Against Diabetes-Induced Cognitive Impairment.

Diabetes mellitus is a metabolic disorder caused by insulin deficiency, insulin resistance, genetic alterations, and oxidative stress. The high glucose levels may impair the functioning of nerve cells, leading to neurodegenerative diseases, including cognitive impairment. Clitoria ternatea has various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic, and neuroprotective effects. The present study evaluates the efficacy of fresh flower aqueous extract of Clitoria ternatea against diabetes-induced cognitive impairment. The challenges in delivering drugs targeting the brain possess the limitations of crossing the blood-brain barrier. Metal nanoparticles are considered the most reliable brain drug delivery systems. Considering the neurotoxicity of cobalt oxide, whether it can be used to improve brain delivery is also evaluated. Cobalt oxide nanoparticles (Co3O4 NPs) of fresh flower aqueous extract of Clitoria ternatea are prepared by green synthesis and characterized. The effect of these nanoparticles is compared with Clitoria ternatea extract against Streptozotocin (STZ)-induced cognitive impairment. The behavioral, biochemical, in vivo antioxidant, total thiol content, estimation of proinflammatory cytokines, acetylcholine esterase, and nitrite levels in the brain of STZ-induced diabetic rats revealed that cobalt oxide nanoparticles showed neurotoxicity, whereas C. ternatea showed neuroprotective effect and also improved the cognitive function. The lower dose of cobalt oxide nanoparticles of C. ternatea (2mg/kg) exhibited a neuroprotective and cognition improvement effect. However, the higher dose (4mg/kg) of cobalt oxide nanoparticles of C. ternatea showed a neurotoxic effect. Since Co3O4 NPs are neuroprotective at low doses, they can be used for neuroprotective actions. However, dose optimization studies are required.

Fluorescent cyclopropyl ester probes are efficiently cleaved by endogenous carboxylesterase in mouse blood: implications for preclinical fluorescence imaging

ABSTRACT Prior studies have shown that fluorescent molecular probes based on cyclopropyl esters are good substrates for butyrylcholine esterase (BChE), which is a biomarker of several human diseases. We tested two fluorescent cyclopropyl ester derivatives as BChE-activated fluorogenic probes. One was a known fluorescein probe, and the other was a newly designed near-infrared probe based on a heptamethine cyanine dye. As expected, both probes were good substrates for BChE, but they were also good substrates for carboxylesterase (CE). The probes were efficiently cleaved in mouse blood and serum which contains high levels of CE, but they were not cleaved in human serum which contains negligible CE. There are two major implications of these results. One is a cautionary note that esterase levels in different organisms can vary substantially. Researchers developing fluorescent cyclopropyl ester probes for BChE imaging should anticipate high levels of background signal in preclinical mouse models due to ester cleavage by the abundant CE in mouse blood. However, there is very little cleavage of fluorescent cyclopropyl ester probes in human blood, which contains low levels of CE. Therefore, fluorescent cyclopropyl ester probes should be viable in humans as imaging agents that identify disease sites with overexpressed levels of CE or BChE.

Acute exposure to environmentally relevant concentrations of pharmaceutical pollutants induces neurobehavioral toxicity in zebrafish (Danio rerio)

Pharmaceutical waste from point and non-point sources enters, persists, or disseminates in the environment and is known as environmentally persistent pharmaceutical pollutants. Understanding the impacts of pharmaceutical pollutants on the environment and health is essential. This study investigates the behavioral impacts of pharmaceutical pollutants on aquatic organisms and delineates the possible nexus of oxidative stress. The male zebrafish were exposed to four major representative pharmaceutical pollutants, viz., acetaminophen, carbamazepine, metformin, and trimethoprim at environmentally relevant concentrations individually as well as in a mixture for seven days. Substantial alterations in social interaction, aggressive nature, novel tank exploration, and light and dark zone preferences were recorded and the degree varied to different pharmaceutical pollutants. The activity of oxidative stress markers, superoxide dismutase, glutathione-S-transferase, and catalase, was found to be suppressed to 66–20%, 42–25%, and 59–20% respectively with the elevated malondialdehyde generation (180–260%) compared to control. The activity level of acetylcholine esterase was found to be increased to 200–500% across all treatment groups. Despite the synergistic impacts of pharmaceutical pollutants on the whole system that could not be ascertained, this comprehensive study highlights their toxicity nature to induce neurobehavioral toxicity in zebrafish through oxidative stress mechanisms and altered cholinergic systems.

Microplastics Biofragmentation and Degradation Kinetics in the Plastivore Insect Tenebrio molitor.

The insect Tenebrio molitor possesses an exceptional capacity for ultrafast plastic biodegradation within 1 day of gut retention, but the kinetics remains unknown. Herein, we investigated the biofragmentation and degradation kinetics of different microplastics (MPs), i.e., polyethylene (PE), poly(vinyl chloride) (PVC), and poly(lactic acid) (PLA), in T. molitor larvae. The intestinal reactions contributing to the in vivo MPs biodegradation were concurrently examined by utilizing aggregated-induced emission (AIE) probes. Our findings revealed that the intestinal biofragmentation rates essentially followed the order of PLA > PE > PVC. Notably, all MPs displayed retention effects in the intestine, with PVC requiring the longest duration for complete removal/digestion. The dynamic rate constant of degradable MPs (0.2108 h-1 for PLA) was significantly higher than that of persistent MPs (0.0675 and 0.0501 h-1 for PE and PVC, respectively) during the digestive gut retention. Surprisingly,T. molitor larvae instinctively modulated their internal digestive environment in response to in vivo biodegradation of various MP polymers. Esterase activity and intestinal acidification both significantly increased following MPs ingestion. The highest esterase and acidification levels were observed in the PLA-fed and PVC-fed larvae, respectively. High digestive esterase activity and relatively low acidification levels inT. molitor larvae may, to some extent, contribute to more efficient MPs removal within the plastic-degrading insect. This work provided important understanding of MPs biofragmentation and intestinal responses to in vivo MPs biodegradation in plastic-degrading insects.

Dietary Moringa oleifera mitigates Fluconazole-Induced immunological and spleen-histological alterations in Catfish (Clarias gariepinus)

Fluconazole (FCZ), an antifungal from the azole family, causes several detrimental effects in fish. In recent times, there has been a notable surge in interest regarding the utilization of Moringa oleifera (Mo) as a dietary antioxidant. This research aimed to evaluate the potential protective effects of dietary Moringa oleifera (MO) against the adverse impacts of fluconazole in the African catfish (Clarias gariepinus). The fish were allocated into four groups as follows: a control group fed a basal diet, an FCZ - exposed (200 ng/L) fed basal diet, 1% MO fed through basal diet, and an FCZ-exposed (200 ng/L) and 1% MO fed through basal diet fed group. The results showed that FCZ exposure decreased superoxide dismutase, total antioxidant capacity, and acetylcholine esterase levels. On the other hand, FCZ exposure increased malonaldehyde and cortisol levels as compared to control (P < 0.05). FCZ caused immunosuppressive effects in C. gariepinus as revealed by lower immunity indices (lysozyme and phagocytic activity and immunoglobulin level) and increased cytokine levels (IL-6 IL-1β). Histological examination of the spleen from fish exposed to FCZ showed several splenic changes. We conclude that dietary MO supplementation has the potential to alleviate the oxidative stress, restore immune response balance, and mitigate histological damage induced by FCZ exposure, thus positioning MO as an immunostimulant in C. gariepinus when administered alongside FCZ.

Impact of Single Blast Exposure on Neuronal Damage and Protein Levels in the Rat Brain at Varying Pressures

Abstract Introduction Brain injuries from blasts are increasingly common in both civilian and war settings. The impact of blast injuries at different pressure levels remains unclear, and their long-term effects are not well understood. This study investigates how varying blast pressures affect the rat brain over time. Materials and Methods Forty adult Sprague-Dawley rats were randomized into four groups of 10. Three groups were exposed to blasts, while one served as a control and was only subjected to blast sounds. Each group received a single blast at different pressures, followed by neuropsychological tests. After 28 and 84 days, the rats were sacrificed to measure tau protein and acetylcholine esterase levels and to conduct histological examinations of brain tissues. Results A single blast exposure did not significantly impact visuospatial memory or recall. Despite the lack of noticeable cognitive deficits, histopathological and biochemical analyses revealed reduced tau protein levels, indicating ongoing neuronal damage. Conclusion While a single blast did not significantly impair visuospatial memory or recall in this rat model, there were decreases in tau protein and acetylcholine esterase levels, along with histological signs of neuronal damage.

Deciphering the biocontrol and immunomodulatory potential of Metarhabditis amsactae (Nematoda: Rhabditidae) against Corcyra cephalonica (Lepidoptera: Pyralidae)

ABSTRACT In the present work, laboratory assays were performed to appraise the biocontrol potential of Metarhabditis amsactae, a Rhabditid nematode, against fifth instar larvae of Corcyra cephalonica. Virulence was tested at four different doses, i.e. 20, 40, 80 and 160 IJs/L (infective juveniles per larva) and mortality was documented from 24 up to 96 h of nematode treatment. Concentration and time-based enhancement in larval mortality was observed with 100% mortality recorded at 160 IJs/L after 96 h. Even at 20 IJs/L concentration, 60% and 76.7% larval mortality was recorded after 72 and 96 h, respectively. At 80 IJs/L, the mortality increased from 33.3% at 48 h to more than 90% at 96 h of nematode inoculation. Whereas, at 40 IJs/L, it enhanced from 16.7% at 48 h to 83.3% at 96 h. The effect of M. amsactae infection on the immune system of C. cephalonica was also evaluated at a dose of 100 IJs/L after 12, 24, 36 and 48 h time intervals. Insect larvae displayed augmented levels of antioxidant and detoxifying enzymes. The peak activities of superoxide dismutase, catalase, ascorbate peroxidase, phenol oxidase and glutathione-S-transferase in infected larvae were observed after 36 h, whereas acetylcholine esterase levels peaked after 48 h, as compared to control. Malondialdehyde content was also increased post nematode infection. Thus the current study is the first report that depicts the significant bioefficacy and immunomodulatory effects of M. amsactae against C. cephalonica under laboratory conditions. However, further research to assess its efficiency under field conditions is required.

Oral administration of encapsulated catechin in chitosan-alginate nanoparticles improves cognitive function and neurodegeneration in an aluminum chloride-induced rat model of Alzheimer's disease.

The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl3)-induced rat model of Alzheimer's disease (AD). The Catechin-loaded Chitosan-Alginate nanocarriers were synthesized through ionotropic gelation (IG) method. Physio-chemical characterization was conducted with the Zetasizer Nano system, the scanning electron microscope, and the Fourier transform infrared spectroscopy. The experiments were performed over 21 days on six groups of male Wistar rats. The control group, AlCl3 treated group, Catechin group, nanocarrier group, treatment group 1 (AlCl3 + Catechin), and treatment group 2 (AlCl3 + nanocarrier). A behavioral study was done by the Morris water maze (MWM) test. In addition, the level of oxidative indices and acetylcholine esterase (AChE) activity was determined by standard procedures at the end of the study. AlCl3 induced a significant increase in AChE activity, along with a significant decrease in the level of Catalase (CAT) and total antioxidant capacity (TAC) in the hippocampus. Moreover, the significant effect of AlCl3 was observed on the behavioral parameters of the MWM test. Both forms of Catechin markedly improved AChE activity, oxidative biomarkers, spatial memory, and learning. The present study indicated that the administration of Catechin-loaded Chitosan-Alginate NPs is a beneficial therapeutic option against behavioral and chemical alteration of AD in male Wistar rats.

Formulation and Characterization of Silibinin Entrapped Nano-Liquid Crystals for Activity against Aβ1-42 Neurotoxicity in In-Vivo Model.

Silibinin (SIL) Encapsulated Nanoliquid Crystalline (SIL-NLCs) particles were prepared to study neuroprotective effect against amyloid beta (Aβ1-42) neurotoxicity in Balb/c mice model. Theses NLCs were prepared through hot emulsification and probe sonication technique. The pharmacodynamics was investigatigated on Aβ1-42 intracerebroventricular (ICV) injected Balb/c mice. The particle size, zeta potential and drug loading were optimized to be 153 ± 2.5nm, -21mV, and 8.2%, respectively. Small angle X-ray (SAXS) and electron microscopy revealed to crystalline shape of SIL-NLCs. Thioflavin T (ThT) fluroscence and circular dichroism (CD) techniquewere employed to understand monomer inhibition effect of SIL-NLCs on Aβ1-4. In neurobehavioral studies, SIL-NLCs exhibited enhanced mitigation of memory impairment induced on by Aβ1-42 in T-maze and new object recognition test (NORT). Whereas biochemical and histopathological estimation of brain samples showed reduction in level of Aβ1-42 aggregate, acetylcholine esterase (ACHE) and reactive oxygen species (ROS). SIL-NLCs treated animal group showed higher protection against Aβ1-42 toxicity compared to free SIL and Donopezil (DPZ). Therefore SIL-NLCs promises great prospect in neurodegenerative diseases such as Alzheimer's disease.

Reduced preoperative serum choline esterase levels and fecal peritoneal contamination as potential predictors for the leakage of intestinal sutures after source control in secondary peritonitis

BackgroundThe high rate of stoma placement during emergency laparotomy for secondary peritonitis is a paradigm in need of change in the current fast-track surgical setting. Despite growing evidence for the feasibility of primary bowel reconstruction in a peritonitic environment, little data substantiate a surgeons’ choice between a stoma and an anastomosis. The aim of this retrospective analysis is to identify pre- and intraoperative parameters that predict the leakage risk for enteric sutures placed during source control surgery (SCS) for secondary peritonitis.MethodsBetween January 2014 and December 2020, 497 patients underwent SCS for secondary peritonitis, of whom 187 received a primary reconstruction of the lower gastro-intestinal tract without a diverting stoma. In 47 (25.1%) patients postoperative leakage of the enteric sutures was directly confirmed during revision surgery or by computed tomography. Quantifiable predictors of intestinal suture outcome were detected by multivariate analysis.ResultsLength of intensive care, in-hospital mortality and failure of release to the initial home environment were significantly higher in patients with enteric suture leakage following SCS compared to patients with intact anastomoses (p < 0.0001, p = 0.0026 and p =0.0009, respectively). Reduced serum choline esterase (sCHE) levels and a high extent of peritonitis were identified as independent risk factors for insufficiency of enteric sutures placed during emergency laparotomy.ConclusionsA preoperative sCHE < 4.5 kU/L and generalized fecal peritonitis associate with a significantly higher incidence of enteric suture insufficiency after primary reconstruction of the lower gastro-intestinal tract in a peritonitic abdomen. These parameters may guide surgeons when choosing the optimal surgical procedure in the emergency setting.

Immunostimulatory effects of dietary verjuice (Vitis vinifera) on immune response and transcription of immune-related genes in juvenile rainbow trout (Oncorhynchusmykiss)

The development of green aquaculture practices has led to the supplementation of fish diets with natural immunostimulants such as organic acids. This study aimed to assess the dietary effects of verjuice (VJ; unfermented unripe grapes; Vitis vinifera) on hematological parameters, skin mucosal immunity, transcriptional immune responses, and antibacterial serum activity against Aeromonas hydrophila in rainbow trout. The fish (51.0 ± 2.4 g) were randomly distributed into 15 tanks and fed ad-libitum thrice daily with diets containing different levels of VJ including 0 (control; VJ-0), 3 (VJ-3), 6 (VJ-6), 9 (VJ-9), and 12 (VJ-12) mL/kg VJ for 56 d. Results showed that immuno-hematological parameters (total white blood cells, neutrophils, and monocytes) were improved in VJ-added groups (P < 0.05). In addition, dietary VJ (9 mL/kg) modulated serum immunological parameters. Skin mucus immunology exhibited a notable increase in alkaline phosphatase, lysozyme activity, alkaline protease, total protein, total immunoglobulin, and esterase levels in VJ-9 group compared with those in the control group (P < 0.05). The mRNA expression of interleukin-1β, interleukin-6, interleukin-8, and immunoglobulin M were significantly higher in VJ-9 group than in the control (P < 0.05). Furthermore, the results of the antibacterial evaluation showed that A. hydrophila growth was significantly inhibited in the serum samples from VJ-3 to VJ-9 groups after the 56th day and in all VJ-treated groups after the 70th (P < 0.05). In conclusion, dietary VJ is a novel immunostimulant and the optimal dietary supplementation level of 6.65–7.46 mL/kg can effectively improve immune responses in rainbow trout.

Vitamin e succinate-glycol chitosan modified copper ferrite nanocomposites for lung cancer: Targeted oxidative stress regulation induces cuproptosis and ferroptosis

Although platinum-based drugs continue to be the mainstay of chemotherapy for non-small cell lung cancer (NSCLC), drug toxicity and resistance have caused considerable clinical problems. Copper species may overcome cisplatin-induced resistance, have a wider activity range, and be less toxic than platinum-based drugs. Despite the strong potential of copper-based nanomaterials to trigger cuproptosis and ferroptosis for the treatment of NSCLC, effectively targeting cancer cell death remains challenging. The copper ferrite nanocomposite (CF-GV-LBL) was designed to specifically induce tumor cell death by the responsiveness of vitamin E succinate-glycol chitosan (GV) polymers to cellular esterase levels, the protonation action of GV polymers and polylysine (PL) amino acids, and the active targeting of human serum albumin. Copper ferrite (CF) released iron and copper ions, increasing intracellular oxidative stress, depleting cellular glutathione, and initiating cuproptosis and ferroptosis. Because oxidative stress plays a crucial role in the processes of cuproptosis and ferroptosis, this work focuses on selectively regulating oxidative stress levels in intercellulars. In normal cells, GV degraded and produces the antioxidant vitamin E, which decreases cellular oxidative stress and subsequent damage. In cancer cells, GV generated reactive oxygen species, further promoting the occurrence of cuproptosis and ferroptosis. The CF-GV-LBL nanocomposite demonstrated greater anti-tumor efficacy and biocompatibility than carboplatin. Increased oxidative stress may activate the p53 signaling pathway, thus inhibiting tumor cell growth. Significantly, after 15 days of treatment, CF-GV-LBL efficiently suppressed the development of subcutaneous A549 tumors in the nude mice. Overall, this study focuses on providing insights for the treatment of NSCLC.

Sonchus maritimus Extract-Loaded Niosomes Bioconjugated by Linoleic Acid in Hepatic Encephalopathy Induced by High-Fructose Diet in Albino Wistar Rats.

One of the major roles of nanotechnology in the pharmaceutical field is to provide a facility to improve drug delivery systems and design smart nanocarriers with the potential to deliver specific biomolecules to the target site for treatment. This study evaluated Sonchus maritimus-loaded niosomes (SmE-N) in hepatic encephalopathy induced by a high-fructose diet (HFD) in rats. High-performance liquid chromatography (HPLC) analysis of Sonchus maritimus extracts (SmE), the synthesis of niosomes, and their characterization were performed. For the in vivo study, 24 male rats were haphazardly divided into 4 groups (n=6) control, HFD (35%), HFD+SmE-N (50 mg/kg/day), and HFD+metformin (50 mg/kg/day). Clinical behaviors and biological markers were assessed for all groups. The in vitro results of the chromatographic analysis revealed that Sonchus maritimus contains important phenolic acids, including gallic acid, vanillic acid, chlorogenic acid, and caffeic acid, as well as diverse flavonoids, including quercetin, rutin, and naringin bioactive compounds. The niosome formulation, characterized by the encapsulation efficiency of SmE, reached up to 61.40%. The in vivo results of the HFD showed a significant change in behavior parameters, liver glycogen, transaminase enzymes, brain protein, and acetylcholine esterase levels. In addition, there was a significant increase in malondialdehyde levels and a decrease in glutathione, superoxide dismutase, and glutathione peroxidase activities in the HFD group compared to the control group. Furthermore, the histopathological observation recorded a profound modification in the liver and brain tissues of the HFD group. In contrast, the treatment with SmE-N and metformin assured a partial amelioration in the noticed parameters compared to the HFD group, but SmE-N led to a better improvement than metformin compared to the control group. In conclusion, the use of SmE-N bioconjugated by linoleic acid seems powerful in treating the complications of fructose-induced metabolic disorders due to its hepato-neuroprotective abilities.

Glucose and leukocyte esterase levels are possible biomarkers for bacterial septic arthritis

Glucose and leukocyte esterase levels are possible biomarkers for bacterial septic arthritis

Molecular networking-guided investigation of the secondary metabolome of four Morus species and their in vivo neuroprotective potential for the mitigation of Alzheimer's disease.

Alzheimer's Disease (AD) is a fatal age-related neurodegenerative condition with a multifactorial etiology contributing to 70% of dementia globally. The search for a multi-target agent to hit different targets involved in the pathogenesis of AD is crucial. In the present study, the neuroprotective effects of four Morus extracts were assessed in LPS-induced AD in mice. Among the studied species, M. macroura exhibited a profound effect on alleviating the loss of cognitive function, improved the learning ability, restored the acetylcholine esterase (AChE) levels to normal, and significantly reduced the tumor necrosis factor alpha (TNF-α) brain content in LPS-treated mice. To investigate the secondary metabolome of the studied Morus species, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-HRMS/MS), aided with feature-based molecular networking, was employed. Among the annotated features, aryl benzofurans and prenylated flavonoids were suggested as being responsible for the observed neuroprotective effect. Furthermore, some of the detected metabolites were proposed as new natural products such as moranoline di-O-hexoside (1), isomers of trimethoxy-dihydrochalcone-O-dihexoside (59 & 76), (hydroxy-dimethoxyphenyl)butenone-O-hexoside (82), and O-methylpreglabridin-O-sulphate (105). In conclusion, our findings advocate the potential usage of M. macroura leaves for the management of AD, yet after considering further clinical trials.

Metabolic Resistance Mechanisms Evident in Generations of Anopheles gambiae (Kisumu) Adults Exposed to Sub-lethal Concentrations of Permethrin Insecticide

Background: Anopheles gambiae mosquitoes are one of the best-known of the genus Anopheles because of their predominant role in transmitting the most dangerous malaria parasite species (to humans), Plasmodium falciparum. Unfortunately, An. gambiae mosquitoes have grown resistant to the most popular and widely used insecticides, particularly Permethrin, spreading across Africa. The current study sought to determine the lowest Permethrin concentrations that could be a selection pressure for metabolic resistance development in the renowned adult An. gambiae (Kisumu) mosquito population. Methods: Established, insectary-reared, and fully susceptible strains of Kisumu populations were reared, and exposed for mortality assay and Lowest Sub-lethal Concentrations (LSLCs) determination at the adult stage. Various exposure concentrations were achieved by slightly modifying the Centre for Disease Control (CDC) protocol. Adult Kisumu mosquitoes exposed to the same LSLC over generations were compared with unexposed control populations by way of resistance status and correlating levels of esterase, monooxygenase, and Glutathione-S -transferases (GST) metabolic enzymes. Information obtained was analysed using SPSS 16.0 and Analysis of Variance at P=0.05 with the aid of Graph-Pad prism 8. Results: The LSLCs of Permethrin with mortality rates not significantly (P&gt; 0.05) different from control Kisumu strains (0.00) were 0.2μg (0.00) and 0.4μg (0.00) per CDC bottle, i.e., LSLC 1 and LSLC 2 respectively. The LSLC 1 exposure lasted five generations (f0-f4), during which resistance statuses were consistently below 1.00±0.82 (4.0%) after 1 hour. There was no significant difference (P&gt;0.05) in the levels of esterase across generations, while monooxygenase and GST levels were significantly up-regulated (P&lt;0.05) in subsequent generations of LSLC 1-treated mosquitoes. However, there was a consistent and progressive increase in GST level with advancing generations. Conclusion: It may be concluded that the P450 monooxygenase enzyme mechanism is a prelude to the overexpression of the GST enzyme. Hence, if the development of the GST resistance enzyme can be inhibited or stopped in An. gambiae mosquito vector populations, multiple resistance and cross-resistance mechanisms in malaria vectors could be effectively regulated.