Urtica pilulifera L. seed extract promotes folliculogenesis and alleviates the diminished ovarian reserve in the Balb/c mice model: An experimental study.

Background: Urtica pilulifera L. seed (UPS) is a Persian traditional medicine prescription that positively affects female infertility. Objective: This study aimed to evaluate the beneficial effects of UPS on a diminished ovarian reserve (DOR) model induced by cyclophosphamide in Balb/c mice. Materials and Methods: A single intraperitoneal (75 mg/kg) of cyclophosphamide was administered to establish a DOR model. 25 female Balb/c mice (6-8 wk, 25 ± 2 gr) were randomly divided into 5 groups (n = 5/each), including control (normal saline), model (DOR), DOR+50, DOR+100, and DOR+200 (mg/kg UPS, gavage) groups for 14 days. The levels of follicle-stimulating hormone, luteinizing hormone, estradiol, malondialdehyde, superoxide dismutases, apoptosis, and histopathological alterations were analyzed. Gas chromatography-mass spectrometry analysis was performed to identify the phytochemicals of the UPS. Results: It was observed that the UPS extract reduced malondialdehyde concentration and apoptosis in the DOR model as well as enhanced superoxide dismutases activity in the ovaries in a dose-dependent manner. Moreover, it exerted a modulatory effect on steroidal hormones such as follicle-stimulating hormone, luteinizing hormone, and estradiol. The histopathological analysis revealed the therapeutic potential of the UPS extract. The main chemical components of UPS were linoleic acid (59.25%), n-hexadecanoic acid (10.36%), and oleic acid (8.29%). Conclusion: The results indicated that the UPS extract has therapeutic potential in the DOR model. This potential is attributed to the reduction of oxidative stress, modulation of apoptosis, and regulation of steroidal hormones that may be associated with the observed beneficial effects of fatty acids on fertility improvement.

Do typologies of pesticide risk knowledge influence the adoption of IPM strategies? Evidence from rice farmers' behavior in northern Iran.

BACKGROUND: The active participation of farmers in adopting eco-friendly practices is vital to mitigate the environmental and health risks linked to pesticide usage. Farmers' awareness of these risks significantly influences their adoption of integrated pest management (IPM) methods over traditional pesticide applications. This study sought to explore the range of understanding on pesticide effects, categorize IPM strategies employed in pest management, and examine the correlation between knowledge levels and IPM strategy choices. Data was gathered through structured questionnaires from 391 rice farmers in Sari County, Mazandaran province, Northern Iran. RESULTS: Exploratory factor analysis revealed three distinct dimensions of pesticide risk knowledge: personal risk of pesticide, environmental risk of pesticide, and community risk of pesticide. Furthermore, the study identified three primary categories of IPM strategies: high familiarity, intermediate familiarity, and low familiarity. The results of the regression analysis indicated that the personal risk of pesticides (ß = 0.556; P < 0.01) and the environmental risk of pesticides (ß = 0.262; P < 0.01) are significantly correlated with the adoption of high familiarity IPM strategies. Furthermore, the study revealed that there was no significant statistical evidence to support the notion that different types of pesticide risk knowledge had any influence on the adoption of intermediate and low familiarity strategies. CONCLUSION: The findings of this study imply the critical importance for agricultural extension programs to focus on enhancing farmers' knowledge of pesticide risks and various IPM strategies. © 2024 Society of Chemical Industry.

The Effect of Physical Exercise Pretreatment on Spatial Memory and Learning and Function of Mitochondria in the Brain in Type 2 Diabetic Rats.

Background: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide, and this issue is one of the major concerns in the pending years. T2DM causes numerous complications, including cognition, learning, and memory impairments. The positive effect of physical exercise as a popular approach has been shown in many chronic diseases. Further, the improvement effects of exercise on cognition and memory impairment have been noticed. Objectives: This study examines the possible preventative effects of physical exercise on spatial memory attenuation and brain mitochondrial dysfunction caused by T2DM. Methods: Male Wistar rats received treadmill exercise (30 min per day, five days per week for two or four weeks). Then, T2DM was induced by a high-fat diet and an injection of streptozotocin (30 mg/kg). Spatial learning and memory were assessed by the Morris water maze test. Further, brain mitochondrial function, including reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), mitochondrial swelling, outer membrane damage, cytochrome c release, and ADP/ATP ratio, were measured. Results: Impaired spatial memory in T2DM rats was observed. Furthermore, brain mitochondrial dysfunction was demonstrated proved by increased ROS generation, MMP collapse, mitochondrial swelling, outer membrane damage, cytochrome c release, and ADP/ATP ratio. Conversely, physical exercise, before diabetes onset, significantly ameliorated spatial memory impairment and brain mitochondrial dysfunction. Conclusions: This study reveals that physical exercise could prevent diabetes-induced spatial memory impairment. Moreover, it could ameliorate brain mitochondrial dysfunction as one of the possible underlying mechanisms of spatial memory impairment in T2DM.

ChAdOx1 nCoV-19 Vaccine and Thrombosis with Thrombocytopenia Syndrome among Adults: A Systematic Review.

Several vaccine-induced thrombotic thrombocytopenia syndrome (VITTS) cases have been reported after the ChAdOx1 nCov-19 vaccination. The current study systematically reviewed the reported post-ChAdOx1 nCoV-19 vaccination thrombotic thrombocytopenia cases. Their laboratory and clinical features, as well as the diagnostic and therapeutic measures, were investigated. Online databases were searched until 25 August 2021. Studies reporting post-ChAdOx1 nCov-19 vaccination thrombotic thrombocytopenia syndrome (TTS) were included. Overall, 167 cases (21-77 years old) from 53 publications were included showing a female dominance of 1.75 times. About 85% of the cases exhibited the primary symptoms within the first two weeks post-vaccination. Headache was the most common initial symptom (>44.2%), and hemorrhage/thrombotic problems (22.46%), as well as discoordination/weakness/numbness/ hemiparesis/cyanotic toes (19.6%), were the most prevalent uncommon initial symptoms. Prothrombin time (PT), D-dimers, and C-reactive protein were the most remarkable increased laboratory parameters in 50.6%, 99.1%, and 55.6% of cases, respectively. In comparison, platelet and fibrinogen were the most remarkable decreased laboratory parameters in 92.7% and 50.5% of cases, respectively. Most VITT cases presented with cerebral venous thrombosis/cerebral venous sinus thrombosis, supraventricular tachycardia, transverse sinus/cerebral thrombosis, pulmonary embolism, and cerebral hemorrhage. Anti-PF4 antibody measurement through immunoassays and functional assays were positive in 86.2% and 73% of cases, respectively. About 31% of the cases died. Early diagnosis and proper therapeutic measures are important in ChAdOx1 nCov-19 vaccine-induced VITTS patients. Therefore, experts are recommended to know the corresponding clinical and laboratory features, as well as diagnostic methods. Elucidation of the pathophysiologic mechanism of ChAdOx1 nCov-19 vaccine-induced TTS deserves further investigation.

Design of experiments approach for the development of a validated method to determine the exenatide content in poly(lactide-co-glycolide) microspheres.

Due to the lack of pharmacopeia guidelines for injectable microspheres based on poly (D, L-lactide-co-glycolide) (PLGA), an internal method validation is a critical prerequisite for quality assurance. One of the essential issues of developing peptide-based drugs loaded PLGA microspheres is the precise determination of the amount of peptide drug entrapped in the microspheres. The aim of this study is the development and optimization of a method for measuring the drug content loading of PLGA microspheres using exenatide as a model peptide drug. Exenatide-loaded PLGA microspheres were prepared by a double emulsion solvent evaporation method. The extraction method to determine exenatide content in microspheres was optimized using Design of Experiments (DoE) approach. After the initial screening of six factors, using Fractional Factorial design (FFD), four of them, including type of organic solvent, buffer/organic solvent ratio (v/v), shaking time and pH, exhibited significant effects on the response, namely the exenatide loading, and a Box-Behnken design (BBD) was subsequently applied to obtain its optimum level. The optimum level for organic solvent volume, buffer/organic solvent ratio, shaking time, and pH were 4 ml, 1, 5.6 hrs, and pH 6, respectively. The exenatide content in microspheres under these conditions was 6.4 ± 0.0 (%w/w), whereas a value of 6.1% was predicted by the derived equation. This excellent agreement between the actual and the predicted value demonstrates that the fitted model can thus be used to determine the exenatide content.

In Situ Cross-Linkable Hyaluronic-Ferulic Acid Conjugate Containing Bucladesine Nanoparticles Promotes Neural Regeneration after Spinal Cord Injury.

Dysfunctional clinical outcomes following spinal cord injury (SCI) result from glial scar formation, leading to the inhibition of new axon growth and impaired regeneration. Nevertheless, nerve regeneration after SCI is possible, provided that the state of neuron development in the injured environment is improved. Hence, biomaterial-based therapy would be a promising strategy to endow a desirable environment for tissue repair. Herein, we designed a novel multifunctional injectable hydrogel with antioxidant, neuroprotective, and neuroregenerative effects. Bucladesine-encapsulated chitosan nanoparticles (BCS NPs) were first prepared and embedded in a matrix of thiol-functionalized hyaluronic acid modified with ferulic acid (HASH-FA). The target hydrogel (HSP-F/BCS) was then created through Michael-type addition between HASH-FA containing BCS NPs and four-arm polyethylene glycol-maleimide (4-Arm-PEG-Mal). The obtained hydrogel with shear thinning behavior showed viscoelastic and mechanical properties similar to the normal nerve tissue. FA conjugation significantly improved the antioxidant activity of HA, and suppressed intracellular ROS formation. In situ injection of the HSP-F/BCS hydrogel in a rat contusion model of SCI inhibited glial scar progression, reduced microglia/macrophage infiltration, promoted angiogenesis, and induced myelinated axon regeneration. As a result, a significant improvement in motor performance was observed compared to other experimental groups. Taken together, the HSP-F/BCS hydrogel developed in this study could be a promising system for SCI repair.

Alpha pyrrolidinovalerophenone (α-PVP) administration impairs spatial learning and memory in rats through brain mitochondrial dysfunction.

Novel psychoactive substances (NPS) consumption has increased in recent years, thus NPS-induced cognitive decline is a current source of concern. Alpha-pyrrolidinovalerophenone (α-PVP), as a member of NPS, is consumed throughout regions like Washington, D.C., Eastern Europe, and Central Asia. Mitochondrial dysfunction plays an essential role in NPS-induced cognitive impairment. Meanwhile, no investigations have been conducted regarding the α-PVP impact on spatial learning/memory and associated mechanisms. Consequently, our study investigated the α-PVP effect on spatial learning/memory and brain mitochondrial function. Wistar rats received different α-PVP doses (5, 10, and 20 mg/kg) intraperitoneally for 10 sequential days; 24 h after the last dose, spatial learning/memory was evaluated by the Morris Water Maze (MWM). Furthermore, brain mitochondrial protein yield and mitochondrial function variables (Mitochondrial swelling, succinate dehydrogenase (SDH) activity, lipid peroxidation, Mitochondrial Membrane Potential (MMP), Reactive oxygen species (ROS) level, brain ADP/ATP proportion, cytochrome c release, Mitochondrial Outer Membrane (MOM) damage) were examined. α-PVP higher dose (20 mg/kg) significantly impaired spatial learning/memory, mitochondrial protein yield, and brain mitochondrial function (caused reduced SDH activity, increased mitochondrial swelling, elevated ROS generation, increased lipid peroxidation, collapsed MMP, increased cytochrome c release, elevated brain ADP/ATP proportion, and MOM damage). Moreover, the lower dose of α-PVP (5 mg/kg) did not alter spatial learning/memory and brain mitochondrial function. These findings provide the first evidence regarding impaired spatial learning/memory following repeated administration of α-PVP and the possible role of brain mitochondrial dysfunction in these cognitive impairments.

Improved infectious burn wound healing by applying lyophilized particles containing probiotics and prebiotics.

Lactiplantibacillus plantarum cells were encapsulated in a mixture of cationic and anionic polymers, with the final composition stabilized through freeze-drying. A D-optimal design was used to examine the effects of different polymer concentrations as well as adding prebiotics on the probiotic viability and swelling behavior of the formulations. Scanning electron micrographs revealed stacked particles capable of rapidly absorbing significant amounts of water. These images corresponded to initial swelling percentages of around 2000% for the optimal formulation. The optimized formula had a viability percentage of more than 82%, with the stability studies suggesting that the powders should be stored at refrigerated temperatures. The physical characteristics of the optimized formula were examined to ensure compatibility with its application. According to antimicrobial evaluations, the difference in pathogen inhibition between formulated and fresh probiotics was less than a logarithm. The final formula was tested in vivo and showed improved wound healing indicators. The optimized formula resulted in a higher rate of wound closure and infection clearance. Furthermore, the molecular studies for oxidative stress indicated that the formula could modify wound inflammatory responses. In histological investigations, the probiotic-loaded particles functioned exactly as efficaciously as silver sulfadiazine ointment did.

Metal-organic frameworks: A promising option for the diagnosis and treatment of Alzheimer's disease.

Beta-amyloid (Aß) peptide is one of the main characteristic biomarkers of Alzheimer's disease (AD). Previous clinical investigations have proposed that unusual concentrations of this biomarker in cerebrospinal fluid, blood, and brain tissue are closely associated with the AD progression. Therefore, the critical point of early diagnosis, prevention, and treatment of AD is to monitor the levels of Aß. In view of the potential of metal-organic frameworks (MOFs) for diagnosing and treating the AD, much attention has been focused in recent years. This review discusses the latest advances in the applications of MOFs for the early diagnosis of AD via fluorescence and electrochemiluminescence (ECL) detection of AD biomarkers, fluorescence detection of the main metal ions in the brain (Zn2+, Cu2+, Mn2+, Fe3+, and Al3+) in addition to magnetic resonance imaging (MRI) of the Aß plaques. The current challenges and future strategies for translating the in vitro applications of MOFs into in vivo diagnosis of the AD are discussed.

Isolation, characterization, and genomic analysis of vB_PaeS_TUMS_P81, a lytic bacteriophage against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic human pathogen that can lead to nosocomial infections which are in turn life threatening. The increase in antibiotic resistance, at an alarming rate, has resulted in a pressing need for alternative therapeutic approaches such as phage therapy, which hold promise according to several studies. This study featured the isolation and characterization of vB_PaeS_TUMS_P81, a new lytic Pseudomonas phage. The whole-genome sequencing indicated that it has a genome of 73,167 bp containing 93 predicted coding sequences. Genes involved in virulence or lysogeny pathway were nowhere to be found in the genome, so it is potentially safe when it comes to therapeutic applications. Genomic and phylogenetic analysis indicated that vB_PaeS_TUMS_P81 is a member of the genus Litunavirus, belonging to Schitoviridae family. The present study lays the groundwork for further research on treatment of P. aeruginosa infections.

Isolation, characterization, and genomic analysis of vB_PaeP_TUMS_P121, a new lytic bacteriophage infecting Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic human pathogen that can cause life-threatening nosocomial infections. The alarming increase in antibiotic resistance has led to an urgent need for alternative therapeutic approaches, such as phage therapy, which has shown promising results in many studies. In this study, P121, a new lytic Pseudomonas phage, was isolated and characterized. Whole-genome sequencing showed that it has a genome of 73,001 bp that contains 91 predicted coding sequences. No genes involved in virulence or lysogeny were found in the genome, thus making it potentially safe for therapeutic applications. Genomic and phylogenetic analysis indicated that P121 is a member of the genus Litunavirus, family Schitoviridae. The present study provides some basic information for further research on treatment of P. aeruginosa infections.

Adsorption Behavior of a Gd-Based Metal-Organic Framework toward the Quercetin Drug: Effect of the Activation Condition.

A carboxylate gadolinium-based metal-organic framework (Gd-MOF) is an exceptional candidate for magnetic resonance imaging agents, but its low drug adsorption capacity hinders this MOF from being used as a theragnostic agent. In this work, the Gd-MOF was synthesized by a simple solvothermal method. Then, different activation situations, including various solvents over different time periods, were applied to enhance the specific surface area of the synthesized MOF. Different characterization analyses such as X-ray diffraction and Brunauer-Emmett-Teller along with experimental quercetin adsorption tests were done to study the crystalline and physical properties of various activated MOFs. In the following, the MOF activated by ethanol for 3 days (3d-E) was chosen as the best activated MOF due to its crystallinity, highest specific surface area, and drug adsorption capacity. More explorations were done for the selected MOF, including the drug adsorption isotherm, thermodynamics, and pH effect of adsorption. The results show that the activation process substantially affects the crystallinity, morphology, specific surface area, and drug adsorption capacity of Gd-MOFs. An optimized activation condition is proposed in this work, which shows an impressive enhancement of the specific surface area of Gd-MOFs just by simple solvent exchange method employment.

Anticonvulsant effects of ivermectin on pentylenetetrazole- and maximal electroshock-induced seizures in mice: the role of GABAergic system and KATP channels.

Introduction: Ivermectin (IVM) is an antiparasitic medicine that exerts its function through glutamate-gated chloride channels and GABAA receptors predominantly. There is paucity of information on anti-seizure activity of IVM. Moreover, the probable pharmacological mechanisms underlying this phenomenon have not been identified. Materials and methods: In this study, pentylenetetrazole (PTZ)-induced clonic seizures and maximal electroshock (MES)-induced tonic-clonic seizure models, respectively in mice was utilized to inquire whether IVM could alter clonic seizure threshold (CST) and seizure susceptibility. To assess the underlying mechanism behind the anti-seizure activity of IVM, we used positive and negative allosteric modulators of GABAA (diazepam and flumazenil, respectively) as well as KATP channel opener and closer (cromakalim and glibenclamide, respectively). Data are provided as mean ± S.E.M. After the performance of the variance homogeneity test, a one-way and two-way analysis of variance was used. Fisher's exact test was performed in case of MES. P-value less than 0.05 considered statistically significant. Results: and Discussion: Our data showed that IVM (0.5, 1, 5, and 10 mg/kg, i.p.) increased CST. Furthermore, flumazenil 0.25 mg/kg, i.p. and glibenclamide 1 mg/kg, i.p., could inhibit the anticonvulsant effects of IVM. Supplementary, an ineffective dose of diazepam 0.02 mg/kg, i.p. or cromakalim 10 µg/kg, i.p. were able to enhance the anticonvulsant effects of IVM. Besides, we figure out that the IVM (1 and 5 mg/kg, i.p.) could delay the onset of first clonic seizure and also might decrease the frequency of clonic seizures induced by PTZ (85 mg/kg, i.p.). Finally, IVM could prevent the incidence and death in MES-induced tonic-clonic seizures. Conclusion: Based on the obtained results, it can be concluded that IVM may exert anticonvulsant effects against PTZ- and MES-induced seizures in mice that might be mediated by GABAA receptors and KATP channels.

The electrocardiographic, hemodynamic, echocardiographic, and biochemical evaluation of treatment with edaravone on acute cardiac toxicity of aluminum phosphide.

Aluminum phosphide (AlP) poisoning can be highly fatal due to its severe toxicity to the heart. Based on the evidence, edaravone (EDA) has protective effects on various pathological conditions of the heart. This research aimed to examine the potential protective effects of EDA on AlP-induced cardiotoxicity in rats. The rats were divided into six groups, including almond oil (control), normal saline, AlP (LD50), and AlP + EDA (20, 30, and 45 mg/kg). Thirty minutes following AlP poisoning, the electrocardiographic (ECG), blood pressure (BP), and heart rate (HR) parameters were examined for 180 min. The EDA was injected 60 min following the AlP poisoning intraperitoneally. Also, 24 h after poisoning, echocardiography was carried out to evaluate the ejection fraction (EF), stroke volume (SV), and cardiac output (CO). The biochemical and molecular parameters, such as the activities of the mitochondrial complexes, reactive oxygen species (ROS), apoptosis and necrosis, and troponin I and lactate levels, were also examined after 12 and 24 h in the heart tissue. According to the results, AlP-induced ECG abnormalities, decrease in blood pressure, heart rate, SV, EF%, and CO were significantly improved with EDA at doses of 30 and 45 mg/kg. Likewise, EDA significantly improved complex I and IV activity, apoptosis and necrosis, ROS, troponin I, and lactate levels following AlP-poisoning (p < 0.05). Also, the mean survival time was increased following EDA treatment, which can be attributed to the EDA's protective effects against diverse underlying mechanisms of phosphine-induced cardiac toxicity. These findings suggest that EDA, by ameliorating heart function and modulating mitochondrial activity, might relieve AlP-induced cardiotoxicity. Nonetheless, additional investigations are required to examine any potential clinical advantages of EDA in this toxicity.

Transferrin decorated-nanostructured lipid carriers (NLCs) are a promising delivery system for rapamycin in Alzheimer's disease: An in vivo study.

Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by progressive cognitive impairment and memory loss. The mammalian target of rapamycin (mTOR) signaling pathway could regulate learning and memory. The effect of rapamycin (Rapa) on mTOR activity could slow or prevent the progression of AD by affecting various essential cellular processes. Previously, we prepared transferrin (Tf) decorated-nanostructured lipid carriers (NLCs) for rapamycin (150 ± 9 nm) to protect the drug from chemical and enzymatic degradation and for brain targeted delivery of rapamycin. Herein, the effect of Tf-NLCs compared to untargeted anionic-NLCs and free rapamycin, were studied in amyloid beta (Aß) induced rat model of AD. Behavioral test revealed that the Rapa Tf-NLCs were able to significantly improve the impaired spatial memory induced by Aß. Histopathological studies of hippocampus also showed neural survival in Rapa Tf-NLCs treated group. The immunosuppressive, and delayed wound healing adverse effects in the rapamycin solution treated group were abolished by incorporating the drug into NLCs. The Aß induced oxidative stress was also reduced by Rapa Tf-NLCs. Molecular studies on the level of Aß, autophagy (LC3) and apoptotic (caspase-3) markers, and mTOR activity revealed that the Rapa Tf-NLCs decreased the Aß level and suppressed the toxic effects of Aß plaques by modulating the mTOR activity and autophagy, and decreasing the apoptosis level. As a conclusion, the designed Tf-NLCs could be an appropriate and a safe brain delivery system for rapamycin and make this drug more efficient in AD for improving memory and neuroprotection.

A Review of Virus-Like Particle-Based SARS-CoV-2 Vaccines in Clinical Trial Phases.

The Coronavirus disease 2019 (COVID-19) pandemic has affected more than 269 million worldwide, with more than five million deaths as of early December 2021. The main concerns in this pandemic include the asymptomatic nature of COVID-19, leading to the infection of many healthy people, the infectious nature of the pathogen, and its high spreading rate. The disease features have highlighted the importance of controlling this pandemic via vaccines. There has been a worldwide race to produce better, more protective, and efficacious vaccines. Simultaneously, different new variants of the virus are emerging. Therefore, there is a concern about the efficacy of the vaccines against new variants. The platform used for COVID-19 vaccine development needs to be flexible enough to enable the manufacturer to react suitably to new virus variants. We performed a comprehensive search in the online databases of PubMed, Scopus, Google Scholar, clinicaltrials.gov, WHO, ICTRP, and Cochrane until December 10th, 2021. There are 331 candidate vaccines in clinical development, with 194 in the preclinical stage and 137 in different clinical phases. Eleven platforms have been used for the development of COVID-19 vaccines, including inactivated/live attenuated virus, protein subunit, virus-like particle (VLP), non-replicating/replicating viral vectors (VVnr or VVr), VVr or VVnr plus antigen-presenting cell, bacterial antigen-spore expression vector, DNA, and RNA. The VLP-based vaccine platform is a safe, highly immunogenic, and flexible platform for developing vaccines. This review focuses on VLP-based vaccine platforms and explicitly discusses the six VLP-based COVID-19 vaccines in clinical trial phases.

Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing.

Wound healing is one of the most complex biological processes. Studies show that Matrixyl (MTI), known as a cosmetic peptide, can lead to a faster healing process. The contribution of MTI to collagen formation during wound healing also depends on its mode of delivery and its release over time. Here, we investigate two modes of MTI-delivery system, the influence of MTI patch for wound healing application in comparison with MTI cream. In this study, animals were randomly divided into seven groups and studied for 21 days: patches containing two different concentrations of MTI (P-MTI-0.1 mg and P-MTI-1 mg), a cream containing MTI (C-MTI-1 mg), a patch (P-MTI-0), a cream with no MTI (C-MTI-0), a positive control (Comfeel), and a negative control (sham) group. To study the wound healing process, the change in collagen density, angiogenesis, epitheliogenesis, histopathology, immunohistochemical analysis, and wound area through imaging was monitored and measured. The macroscopic results showed that wound healing was improved from 63.5 up to 81.81% in treatment groups compared to that in the negative control group (P < 0.05 and P < 0.001). In addition, C-MTI-1 and P-MTI-1 had a larger impact on wound healing compared to that in the positive control group (Comfeel, P < 0.05). In hematoxylin and eosin (H&E) staining analysis, the rejuvenation of skin appendage was visible in both groups of cream and patches with MTI. According to the obtained results, the re-epithelialization had a higher range for the patch with MTI in comparison with cream containing MTI and positive control.

LipoxinA4 as a Potential Prognostic Marker of COVID-19.

This pilot study aimed to determine early changes of LXA4 levels among the hospitalized patients confirmed as COVID-19 cases following the clinical management and its correlation with commonly used inflammatory markers, including erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and ferritin. Thirty-one adult hospitalized patients infected with the non-severe COVID-19 were included. LXA4 levels were measured at the baseline and 48-72 hours after hospitalization. Accordingly, ESR and CRP levels were collected on the first day of hospitalization. Moreover, the maximum serum ferritin levels were determined during the five days. LXA4 levels significantly increased at 48-72 hours compared to the baseline. ESR, CRP, and ferritin levels were positively correlated with the increased LXA4. In contrast, aging was shown to negatively correlate with the increased LXA4 levels. LXA4 may be known as a valuable marker to assess the treatment response among non-elderly patients with non-severe COVID-19. Furthermore, LXA4 could be considered as a potential treatment option under inflammatory conditions. Further studies are necessary to clarify LXA4 role in COVID-19 pathogenesis, as well as the balance between such pro-resolving mediators and inflammatory parameters.

Novel Coumarin-Pyridine Hybrids as Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer's Disease.

In this research, a series of coumarin-based scaffolds linked to pyridine derivatives via a flexible aliphatic linkage were synthesized and assessed as multifunctional anti-AD agents. All the compounds showed acceptable acetylcholinesterase (AChE) inhibition activity in the nanomolar range (IC50 = 2-144 nM) and remarkable butyrylcholinesterase (BuChE) inhibition property (IC50 = 9-123 nM) compared to donepezil as the standard drug (IC50 = 14 and 275 nM, respectively). Compound 3f as the best AChE inhibitor (IC50 = 2 nM) showed acceptable BuChE inhibition activity (IC50 = 24 nM), 100 times more active than the standard drug. Compound 3f could also significantly protect PC12 and SH-SY5Y cells against H2O2-induced cell death and amyloid toxicity, respectively, superior to the standard drugs. It could interestingly reduce ß-amyloid self and AChE-induced aggregation, more potent than the standard drug. All the results suggest that compound 3f could be considered as a promising multi-target-directed ligand (MTDL) against AD.

Polysaccharide-based hydrogels containing herbal extracts for wound healing applications.

Development of an ideal wound dressing with effective function for healing various types of wounds is the ultimate desire of the researchers. Natural-based compounds such as polysaccharides and phytochemicals offer useful properties making them perfect candidates for wound management. Polysaccharides-based hydrogels with an interconnected three-dimensional network, and desired properties have great potential as a carrier for delivery of different herbal extracts for oral and topical applications. Herbal extracts are extensively used for wound healing purposes, individually or in combination with other active agents. This study summarizes the current knowledge acquired on the preparation, functionalizing, and application of different kinds of polysaccharide-based hydrogels enriched by herbal extracts for different wound healing applications. The structural, biological, and functional impact of the polysaccharides and herbal extracts on the final hydrogel characteristics, as well as their influence on the different phases of the wound healing process have been discussed.