Infected Rats Research Articles

Proliferative arrest induces neuron differentiation and innate immune responses in control and Creutzfeldt-Jakob Disease agent infected rat septal neurons.

Rat post-mitotic septal (SEP) neurons, engineered to conditionally proliferate at 33°C, differentiate when arrested at 37.5°C and can be maintained for weeks without cytotoxic effects. Nine independent cDNA libraries were made to follow arrest-induced neural differentiation and innate immune responses in normal (Nl) uninfected and CJ agent infected SEP cells. Proliferating Nl versus latently infected (CJ-) cells showed few RNA-seq differences. However arrest induced major changes. Normal cells displayed a plethora of anti-proliferative transcripts. Additionally, known neuron differentiation transcripts, e.g., Agtr2, Neuregulin-1, GDF6, SFRP4 and Prnp were upregulated. These Nl neurons also displayed many activated IFN innate immune genes, e.g., OAS1, RTP4, ISG20, GTB4, CD80 and cytokines, complement, and clusterin (CLU) that binds to misfolded proteins. In contrast, arrested highly infectious CJ+ cells (10 logs/gm) downregulated many replication controls. Furthermore, arrested CJ+ cells suppressed neuronal differentiation transcripts, including Prnp which is essential for CJ agent infection. CJ+ cells also enhanced IFN stimulated pathways, and analysis of the 342 CJ+ unique transcripts revealed additional innate immune and anti-viral-linked transcripts, e.g., Il17, ISG15, and RSAD2 (viperin). These data show: 1) innate immune transcripts are produced by normal neurons during differentiation; 2) CJ infection can enhance and expand anti-viral responses; 3) latent CJ infection epigenetically imprints many proliferative pathways to thwart complete arrest. CJ+ brain microglia, white blood cells and intestinal myeloid cells with shared transcripts may be stimulated to educe latent CJD infections that can be clinically silent for >30 years.

Noscapine shows antimalarial activity against Plasmodium falciparum 3D7, its clinical isolate Pf140/SS, and Plasmodium berghei ANKA

Objective: To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain (Pf3D7), its clinical isolate (Pf140/SS), and Plasmodium berghei ANKA (PbA). Methods: Using ring-stage survival assay, phenotypic assessments, and SYBR-green-based fluorescence assay, the antimalarial activities of noscapine were assessed compared with dihydroartemisinin (DHA) in in vivo and in vitro studies. In addition, hemolysis and cytotoxicity tests were carried out to evaluate its safety. RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2 (PfFP-2). Results: The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA, with IC50 values of (7.68±0.88) and (5.57±0.74) nM/mL, respectively, and >95% inhibition of PbA infected rats. Noscapine also showed a safe profile, as evidenced by low hemolysis and cytotoxicity even at high concentrations. Moreover, PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS (P<0.01). Conclusions: Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles, which may be further explored as a therapeutic candidate for the treatment of malaria.

Inhalable tobramycin EEG powder formulation for treating Pseudomonas aeruginosa-induced lung infection

Pulmonary delivery of antibiotics is an effective strategy in treating bacterial lung infection for cystic fibrosis patients, by achieving high local drug concentrations and reducing overall systemic exposure compared to systemic administration. However, the inherent anatomical lung defense mechanisms, formulation characteristics, and drug-device combination determine the treatment efficacy of the aerosol delivery approach. In this study, we prepared a new tobramycin (Tobi) dry powder aerosol using excipient enhanced growth (EEG) technology and evaluated the in vitro and in vivo aerosol performance. We further established a Pseudomonas aeruginosa-induced lung infection rat model using an in-house designed novel liquid aerosolizer device. Notably, novel liquid aerosolizer yields comparable lung infection profiles despite administering 3-times lower P. aeruginosa CFU per rat in comparison to the conventional intratracheal administration. Dry powder insufflator (e.g. Penn-Century DP-4) to administer small powder masses to experimental animals is no longer commercially available. To address this gap, we developed a novel rat air-jet dry powder insufflator (Rat AJ DPI) that can emit 68–70 % of the loaded mass for 2 mg and 5 mg of Tobi-EEG powder formulations, achieving a high rat lung deposition efficiency of 79 % and 86 %, respectively. Rat AJ DPI can achieve homogenous distribution of Tobi EEG powder formulations at both loaded mass (2 mg and 5 mg) over all five lung lobes in rats. We then demonstrated that Tobi EEG formulation delivered by Rat AJ DPI can significantly decrease CFU counts in both trachea and lung lobes at 2 mg (p < 0.05) and 5 mg (p < 0.001) loaded mass compared to the untreated P. aeruginosa-infected group. Tobi EEG powder formulation delivered by the novel Rat AJ DPI showed excellent efficiencies in substantially reducing the P. aeruginosa-induced lung infection in rats.

Collagen Synthesis During Wound Repair in Infected Albino Rats Using Ciprofloxacin-Loaded Gelatin Microspheres Incorporated into a Collagen Scaffold: A Histological Approach Using Masson’s Trichrome Staining

The production of collagen fibers is essential for wound healing because it creates a scaffold of collagen on which new cells may move and proliferate. It indicates cellular activity and improves strength and flexibility. Collagen synthesis is influenced by a number of factors, including age, health, infection, and diet. Collagen dressings often have the ability to increase the production of collagen. Collagen production can be adversely affected by infected cutaneous wounds, which can result in a delayed healing process, a higher risk of scarring, weakened tissue, and functional impairment. For this reason, in order to speed up wound healing, antimicrobial agents have been added to the collagen scaffold. Furthermore, the prolonged delivery of antimicrobial agent-loaded gelatin microspheres to infected wounds promotes quicker wound healing and effective collagen synthesis in the granulated tissue. These scaffolds may make superior wound dressings in clinical settings in light of this relationship.

In vitro, in vivo and in silico antiplasmodial profiling of the aqueous extract of Hibiscus asper HOOK F. Leaf (Malvaceae)

Ethnopharmacological relevancePlasmodium resistance to antimalarial drugs raises the urgent need to seek for alternative treatments. Aqueous extract of Hibiscus asper leaves is currently used in malaria management but remains less documented.Aim of the study: The study aims to evaluate antimalarial effects of the aqueous extract of Hibiscus asper. UHPLC/MS, was used to identify some likely compounds present in the plant that were thereafter docked to some malaria parasite proteins. Study designIn vitro anti-plasmodium and antioxidant, UHPLC/Ms analysis, in vivo antimalarial of the plant extract, and in silico molecular docking prediction of some identified compounds were performed to investigate the pharmacological effects of H. asper. Material and methodsThe in vitro antiplasmodial activity of the extract was carried out on Plasmodium falciparum strains using SYBR-green dye; then, the curative antimalarial activity was conducted on Plasmodium berghei NK65-infected male Wistar rats. The UHPLC/MS analysis was used to identify plant compounds, followed by interactions (docking affinity) between some compounds and parasitic enzymes such as P. falciparum purine nucleoside phosphorylase (2BSX) and 6-phosphogluconate dehydrogenase (6FQY) to explore potential mechanisms of action at the molecular level. ResultsNo hemolysis effect of the extract was observed at concentrations up to 100 mg/mL. In vitro test of the aqueous leaves extract of H. asper showed inhibitory activity against P. falciparum Dd2 and 3D7 strains with IC50 values of 19.75 and 21.97 μg/mL, respectively. The curative antimalarial test of the H. asper extract in infected rats exhibited significant inhibition of the parasite growth (p < 0.001) with inhibition percentage of 95.11%, 97.68% and 95.59% at all the doses (50, 100 and 200 mg/kg) respectively. The extract corrected major physiological alterations such as liver and kidney impairments, oxidative stress and architectural disorganization in liver, spleen and kidneys tissues. The UHPLC/MS analysis identified 7 compounds, namely chlorogenic acid, azulene, quercetin, rhodine, 1-ethyl-2,4-dimethyl benzene and phthalan. Out of seven compounds identified in the extract quercetin and phthalan showed higher in silico inhibitory activity against P. falciparum purine nucleoside phosphorylase and Plasmodium falciparum 6-phosphosgluconate dehydrogenase parasite enzymes. ConclusionThese findings indicate that H. asper could be a promising complementary medicine to manage malaria. Meanwhile, the affinity of annoted compounds with these enzymes should be further confirmed.

Antihistamines H1 as Potential Anthelmintic Agents against the Zoonotic Parasite Angiostrongylus cantonensis.

Infections caused by parasitic helminths pose significant health concerns for both humans and animals. The limited efficacy of existing drugs underscores the urgent need for novel anthelmintic agents. Given the reported potential of antihistamines against various parasites, including worms, this study conducted a screening of clinically available antihistamines against Angiostrongylus cantonensis-a nematode with widespread implications for vertebrate hosts, including humans. Twenty-one anti-H1 antihistamines were screened against first-stage larvae (L1) of A. cantonensis obtained from the feces of infected rats. Standard anthelmintic drugs ivermectin and albendazole were employed for comparative analysis. The findings revealed four active compounds (promethazine, cinnarizine, desloratadine, and rupatadine), with promethazine demonstrating the highest potency (EC50 = 31.6 μM). Additionally, morphological analysis showed that antihistamines induced significant changes in larvae. To understand the mechanism of action, antimuscarinic activities were reported based on average pK i values for human muscarinic receptor (mAChR) subtypes of the evaluated compounds. Furthermore, an analysis of the physicochemical and pharmacodynamic properties of antihistamines revealed that their anthelmintic activity does not correlate with their activity at H1 receptors. This study marks the first documentation of antihistamines' activity against A. cantonensis, offering a valuable contribution to the quest for novel agents effective against zoonotic helminths.

PH‑responsive nanozyme cascade catalysis: A strategy of BiVO4 application for modulation of pathological wound microenvironment

Persistent inflammation and bacterial infection commonly occur during the wound healing process, necessitating urgent development of effective strategies for treating drug-resistant bacterial infections. In this study, bismuth vanadate (BiVO4) was successfully synthesized as an antibacterial agent that promotes wound healing. Through In vitro antibacterial experiments, it was observed that the prepared BiVO4 exhibited excellent performance in catalyzing H2O2 to produce hydroxyl radicals (OH) at a lower concentration (0.2 mg mL−1), resulting in significant antibacterial effects against Gram-negative Extended-Spectrum β-Lactamases-Producing Escherichia coli (ESBL-E. coli) strains. Furthermore, biosafety tests, cell scratch experiments, and ESBL-E. coli infected wound rat model experiments demonstrated high biocompatibility of BiVO4 with a cell survival rate exceeding 85 %. Additionally, BiVO4 promoted the production of vascular endothelial growth factors and fibroblasts migration while contributing to collagen production, effectively facilitating immune reconstruction at the wound site. By integrating peroxidase (POD)-like under acidic conditions (pH 4) and catalase (CAT)-like catalytic activities at under neutral conditions (pH 7), BiVO4 exhibited the ability to activate free radical sterilization and accelerate wound healing by activating O2. Therefore, our findings provide evidence for a dual enzyme regulatory mechanism involving antibacterial properties and promotion of wound tissue reconstruction for potential application in both antibacterial treatment and wound healing.

Targeted treatment for biofilm-based infections using PEGylated tobramycin

Chronic infections often involve biofilm-based bacteria, in which the biofilm results in significant resistance against antimicrobial agents and prevents eradication of the infection. The physicochemical barrier presented by the biofilm matrix is a major impediment to the delivery of many antibiotics. Previously, PEGylation has been shown to improve antibiotic penetration into biofilms in vitro. In these studies, PEGylating tobramycin was investigated both in vitro and in vivo. Two distinct PEGylated tobramycin molecules were synthesized (mPEG-SA-Tob and mPEG-AA-Tob). Then, in a P. aeruginosa biofilm in vitro model, we found that mPEG-SA-Tob can operate as a prodrug and showed 7 times more effectiveness than tobramycin (MIC80: 14 μM vs.100 μM). This improved biofilm eradication is attributable to the fact that mPEG-SA-Tob can aid tobramycin to penetrate through the biofilm and overcome the alginate-mediated antibiotic resistance. Finally, we used an in vivo biofilm-based chronic pulmonary infection rat model to confirm the therapeutic impact of mPEG-SA-Tob on biofilm-based chronic lung infection. mPEG-SA-Tob has a better therapeutic impact than tobramycin in that it cannot only stop P. aeruginosa from multiplying in the lungs but can also reduce inflammation caused by infections and prevent a recurrence infection. Overall, our findings show that PEGylated tobramycin is an effective treatment for biofilm-based chronic lung infections.

Imiquimod Reverses Chronic Toxoplasmosis-Associated Behavioral and Neurocognitive Anomalies in a Rat Model.

Toxoplasma gondii is the etiologic agent of toxoplasmosis, a highly prevalent parasitosis. Toxoplasma gondii (T. gondii) transits in the brain from acute (AT) to chronic toxoplasmosis (CT), under host immune control. In immunocompromised patients, reactivation of CT is potentially life-threatening. Behavioral and neurological complications have been associated with CT. Furthermore, an effective treatment targeting CT is still lacking. We previously reported the efficacy of imiquimod against CT. Here, we demonstrate the molecular effects of imiquimod or imiquimod followed by the clinically used combination of sulfadiazine and pyrimethamine (SDZ + PYR) on CT-associated behavior in a rat model. Imiquimod decreased the number of cysts in the brains of chronically infected rats due to an induced reactivation of bradyzoites into tachyzoites. Importantly, this decrease was more pronounced in rats treated with imiquimod followed by SDZ + PYR. Rats chronically infected with T. gondii exhibited an anxiety-like behavior. Notably, treatment with imiquimod reversed this behavior aberrancy, with even a more pronounced effect with imiquimod followed by SDZ/PYR. Similarly, rats chronically infected with T. gondii exhibited learning deficits, and imiquimod alone or followed by SDZ/PYR reversed this behavior. Our results enhance our knowledge of the implications of CT on behavioral aberrancies and highlight the potency of imiquimod followed by SDZ + PYR on these CT-associated complications.

SrTiO3 Nanotube-Based "Pneumatic Nanocannon" for On-Demand Delivery of Antibacterial and Sustained Osseointegration Enhancement.

Infection and aseptic loosening caused by bacteria and poor osseointegration remain serious challenges for orthopedic implants. The advanced surface modification of implants is an effective strategy for addressing these challenges. This study presents a "pneumatic nanocannon" coating for titanium orthopedic implants to achieve on-demand release of antibacterial and sustained release of osteogenic agents. SrTiO3 nanotubes (SrNT) were constructed on the surface of Ti implants as "cannon barrel," the "cannonball" (antibiotic) and "propellant" (NH4HCO3) were codeposited into SrNT with assistance of mussel-inspired copolymerization of dopamine and subsequently sealed by a layer of polydopamine. The encapsulated NH4HCO3 within the nanotubes could be thermally decomposed into gases under near-infrared irradiation, propelling the on-demand delivery of antibiotics. This coating demonstrated significant efficacy in eliminating typical pathogenic bacteria both in planktonic and biofilm forms. Additionally, this coating exhibited a continuous release of strontium ions, which significantly enhanced the osteogenic differentiation of preosteoblasts. In an implant-associated infection rat model, this coating demonstrated substantial antibacterial efficiency (>99%) and significant promotion of osseointegration, along with alleviated postoperative inflammation. This pneumatic nanocannon coating presents a promising approach to achieving on-demand infection inhibition and sustained osseointegration enhancement for titanium orthopedic implants.

Sequential Regulation of Local Reactive Oxygen Species by Ir@Cu/Zn-MOF Nanoparticles for Promoting Infected Wound Healing.

Most antimicrobials treat wound infections by an oxidation effect, which is induced by the generation of reactive oxygen species (ROS). However, the potential harm of the prolonged high level of ROS should not be ignored. In this study, we presented a novel cascade-reaction nanoparticle, Ir@Cu/Zn-MOF, to effectively regulate the ROS level throughout the healing progress of the infected wound. The nanoparticles consisted of a copper/zinc-modified metal-organic framework (Cu/Zn-MOF) serving as the external structure and an inner core composed of Ir-PVP NPs, which were achieved through a process known as "bionic mineralization". The released Cu2+ and Zn2+ from the shell structure contributed to the production of ROS, which acted as antimicrobial agents during the initial stage. With the disintegration of the shell, the Ir-PVP NP core was gradually released, exhibiting the property of multiple antioxidant enzyme activities, thereby playing an important role in clearing excessive ROS and alleviating oxidative stress. In a full-layer infected rat wound model, Ir@Cu/Zn-MOF nanoparticles presented exciting performance in promoting wound healing by clearing the bacteria and accelerating neovascularization as well as collagen deposition. This study provided a promising alternative for the repair of infected wounds.

In vitro anthelmintic efficacy of Ferulic and Sinapic acid against zoonotic cestode Hymenolepis diminuta (Rudolphi, 1819).

The present study is aimed to investigate potential in vitro anthelmintic efficacy of two phenolic compounds Ferulic acid and Sinapic acid against the parasite H. diminuta. Adult parasites collected from infected rat's intestine (maintained in our laboratory) were treated with 1, 2.5, 5, 10 and 20mg/mL concentrations of both the compounds in RPMI-1640 media containing 1% Tween 20. Further, one group was treated in Praziquantel as a reference drug and another group of parasites were kept as control. The efficacy was evaluated on the basis of motility and mortality of the parasites. The paralyzed worms were further processed for the morphological and ultrastructural studies and observed through light and scanning electron microscopy. A significant dose-dependent efficacy was found in all treatment and decrease in relative movability value was also recorded in all the concentrations of two compounds treated parasites. The time taken for paralysis in 5mg/mL of Ferulic acid and 10mg/mL of Sinapic acid were 1.47 ± 0.04h and 0.88 ± 0.03h respectively which is accorded with the standard concentration of Praziquantel. Morphological micrographs revealed pronounced distortion and altered topography of scolex and tegument while histological study showed loss of uniform tegumental integrity with folds and cracks in the treated parasites. Further, extensive alteration in the scolex and irrevocable disruption all over the body surface with loss of trapezoid shape, shrinkage of tegument and sloughing off microtriches were observed in electron microscopic study. The study indicated that both the compounds possess strong activity against H. diminuta and further studies are required to understand their detailed mode of action to exploit them as potential alternative candidates for curing helminthiases.

A hydrogel dressing loaded with tea tree oil nanoemulsion accelerates methicillin-resistant Staphylococcus aureus-infected wound healing

Drug-resistant bacterial infections can easily lead to delayed wound healing and pose a serious threat to patients' health. Therefore, it was imperative to develop wound dressings to solve this problem. Herein, we developed a hydrogel based on laponite and polyacrylamide (PAAG/LAP) and loaded with tea tree oil nano-emulsion (nanoTTO) by a simple one-step mixing method via the principle of photopolymerization and its potential use and safety for MRSA-infected skin wounds. The evaluation showed that the PAAG/LAP/nanoTTO30 % hydrogel exhibited excellent compressive resistance (∼85 kPa), good biocompatibility, and great antibacterial properties against MRSA in vitro and in vivo (over 90 %). Cell migration results showed that the relative wound area ratio of the PAAG/LAP/nanoTTO30 % hydrogel treatment group (∼55.18 %) was significantly lower than that of the control group (∼68.89 %). The results of the in vivo infection rat model showed that compared with other control groups, the PAAG/LAP/nanoTTO30 % hydrogel treatment group had the lowest relative wound area ratio (8.78 %) within 12 days. Moreover, the results showed the PAAG/LAP/nanoTTO30 % hydrogel could promote MRSA-infected wound healing by directly killing bacteria and promoting angiogenesis. In conclusion, our study provided an antibacterial hydrogel dressing that does not require loading antibiotics for wounds infected by drug-resistant bacteria, expecting to achieve infected wound healing.

Cu-MOF loaded chitosan based freeze-dried highly porous dressings with anti-biofilm and pro-angiogenic activities accelerated Pseudomonas aeruginosa infected wounds healing in rats

Metal–organic frameworks (MOFs)-based therapy opens a new area for antibiotic-drug free infections treatment. In the present study, chitosan membranes (CS) loaded with two concentrations of copper-MOF 10 mg/20 ml (Cu-MOF10/CS) & 20 mg/20 ml (Cu-MOF20/CS) were prepared by a simple lyophilization procedure. FTIR spectra of Cu-MOF10/CS and Cu-MOF20/CS dressings confirmed absence of any undesirable chemical changes after loading Cu-MOF. The SEM images of the synthesized materials (CS, Cu-MOF10/CS & Cu-MOF20/CS) showed interconnected porous structures. Cytocompatibility of the materials was confirmed by fibroblasts cells culturing and the materials were hemocompatible, with blood clotting index <5 %. Cu-MOF20/CS showed comparatively higher effective antibacterial activity against the tested strains; E. coli (149.2 %), P. aeruginosa (165 %) S. aureus (117.8 %) and MRSA (142 %) as compared to Amikacin, CS and Cu-MOF10/CS membranes. Similarly, Cu-MOF20/CS dressing significantly eradicated the biofilms; P. aeruginosa (37 %) and MRSA (52 %) respectively. In full thickness infected wound rat model, on day 23, Cu-MOF10/CS and Cu-MOF20/CS promoted wound healing up to 87.7 % and 82 % respectively. H&E staining of wounded tissues treated with Cu-MOF10/CS & Cu-MOF20/CS demonstrated enhanced neovascularization and re-epithelization along-with reduced inflammation, while trichrome staining exhibited increased collagen deposition. Overall, this study declares Cu-MOFs loaded chitosan dressings a multifunctional platform for the healing of infected wounds.

Modulation of the rat intestinal microbiota in the course of Anisakis pegreffii infection.

Anisakis are globally distributed, marine parasitic nematodes that can cause human health problems, including symptoms such as vomiting, acute diarrhea, and allergic reactions. As parasitic nematodes that primarily affect the patient's digestive tract, intestinal helminths can interact directly with the host microbiota through physical contact, chemicals, or nutrient competition. It is widely accepted that the host microbiota plays a crucial role in the regulation of immunity. Nematodes collected from the abdominal cavity of marine fish were identified by molecular biology and live worms were artificially infected in rats. Infection was determined by indirect ELISA based on rat serum and worm extraction. Feces were collected for 16S rDNA-based analysis of microbiota diversity. Molecular biology identification based on ITS sequences identified the collected nematodes as A. pegreffii. The success of the artificial infection was determined by indirect ELISA based on serum and worm extraction from artificially infected rats. Microbiota diversity analysis showed that a total of 773 ASVs were generated, and PCoA showed that the infected group was differentiated from the control group. The control group contained five characterized genera (Prevotellaceae NK3B31 group, Turicibacter, Clostridium sensu stricto 1, Candidatus Stoquefichus, Lachnospira) and the infected group contained nine characterized genera (Rodentibacter, Christensenella, Dubosiella, Streptococcus, Anaeroplasma, Lactococcus, Papillibacter, Desulfovibrio, Roseburia). Based on the Wilcoxon test, four processes were found to be significant: bacterial secretion system, bacterial invasion of epithelial cells, bacterial chemotaxis, and ABC transporters. This study is the first to analyze the diversity of the intestinal microbiota of rats infected with A. pegreffii and to determine the damage and regulation of metabolism and immunity caused by the infection in the rat gut. The findings provide a basis for further research on host-helminth-microbe correlationships.

Antiproliferative activity &lt;i&gt;in vitro&lt;/i&gt; of &lt;i&gt;Trichinella spiralis&lt;/i&gt; larval extracts depending on the infection stage following experimental infection of rats

Relevance.The aim is evaluation in vitro antiproliferative activity of T. spiralis larvae extracts obtained from experimentally infected rats, depending on the duration of infection.Methods. The experiment was carried out on outbred male rats infected with T. spiralis larvae at the rate of 10 larvae per 1 g of body weight. The antiproliferative activity of larval extracts obtained 40 days, 3 and 12 months after infection was determined on tumor cells of the A549 line (human lung carcinoma) using an MTT test during cultivation for 24, 48 and 72 hours in concentrations from 32 to 1000 micrograms/ml. Antiproliferative activity was expressed as % inhibition and IC50.Results. There was direct dependence of Trichinella extract antiproliferative effects on time of cultivation with A549 cells and protein concentration in extracts. At all stages of invasion, the antiproliferative activity of the extract increased from 24 to 72 hours. at a protein concentration of 250 to 1000 mcg/ml. The extract antiproliferative activity expressed in tumor cell % inhibition and IC50 increased from day 40 to month 12. The most intense dynamics was observed between day 40 and month 3. The possible reason of enhancement in extract antiproliferative effect at months 3 and 12 is alteration in quantitative and qualitative composition of proteins comprised the extracts.

Exploring the mechanism of Huanglian ointment in alleviating wound healing after anal fistula surgery through metabolomics and proteomics

Anal fistula is a common anal and intestinal disease. The wound of anal fistula surgery is open and polluting, which is the most difficult to heal among all surgical incisions. To investigate the mechanism of Huanglian ointment (HLO) on wound healing after anal fistula incision. The S. aureus infected wound in SD rats were used to imitate poor healing wound after anal fistula surgery. SD rats with wound sites (n = 24) were randomly divided into four groups (Control group, Model group, Potassium permanganate (PP) treatment group, and HLO treatment group). The wound healing rate was evaluated, HE staining was used to evaluate the pathological changes of each group, ELISA was used to detect the secretion of inflammatory factors in each group, and the mechanism was explored through metabolomics and proteomics in plasma rat. Compared to other groups, the rate of wound healing in the HLO group was higher on days 7 and 14. Histological analysis showed that collagen and fibroblast in HLO rats were significantly increased, inflammatory cells were reduced, and vascular endothelial permeability was increased. ELISA results showed that the secretion of inflammatory factors in HLO rats was significantly lower. Significant proteins and metabolites were identified in the wound tissues of the infected rats and HLO-treated rats, which were mainly attributed to Cdc42, Ctnnb1, Actr2, Actr3, Arpc1b, Itgam, Itgb2, Cttn, Linoleic acid metabolism, d-Glutamine and d-glutamate metabolism, Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism, alpha-Linolenic acid metabolism, and Ascorbate and aldarate metabolism. In conclusion, this study showed that HLO can promote S. aureus infected wound healing, and the data provide a theoretical basis for the treatment of wounds after anal fistula surgery with HLO.

Formulation and evaluation of azithromycin-loaded silver nanoparticles for the treatment of infected wounds

Infected wounds pose a significant challenge in healthcare, requiring innovative therapeutic strategies. Therefore, there is a critical need for innovative pharmaceutical materials to improve wound healing and combat bacterial growth. This study examined the efficacy of azithromycin-loaded silver nanoparticles (AZM-AgNPs) in treating infected wounds. AgNPs synthesized using a green method with Quinoa seed extract were loaded with AZM. Characterization techniques, including X-ray Powder Diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and Uv-Vis analysis were utilized. The agar diffusion assay and determination of the MIC were used to assess the initial antibacterial impact of the formulations on both MRSA and E. coli. In addition, the antimicrobial, wound-healing effects and histological changes following treatment with the AZM-AgNPs were assessed using an infected rat model. The nanoparticles had size of 24.9 ± 15.2 nm for AgNPs and 34.7 ± 9.7 nm for AZM-AgNPs. The Langmuir model accurately characterized the adsorption of AZM onto the AgNP surface, indicating a maximum loading capacity of 162.73 mg/g. AZM-AgNPs exhibited superior antibacterial properties in vivo and in vitro compared to controls. Using the agar diffusion technique, AZM-AgNPs showed enhanced zones of inhibition against E. coli and MRSA, which was coupled with decreased MIC levels. In addition, in vivo studies showed that AZM-AgNP treated rats had the best outcome characterized by improved healing process, lower bacterial counts and superior epithelialization, compared to the control group. In conclusion, AZM-AgNPs can be synthesized using a green method with Quinoa seed with successful loading of azithromycin onto silver nanoparticles. In vitro and in vivo studies suggest the promising use of AZM-AgNPs as an effective therapeutic agent for infected wounds.

Biochemical and Haematological Effects of Aqueous Leaf Extract of Sida cordifolia in Plasmodium beighei Infected Wistar Rats

Assessment of haematological and biochemical parameters can be predictive of the adverse effects resulting from ingesting foreign substances. Thus, the aim of this study was to evaluate the biochemical and haematological indices in Plasmodium beighei infected wistar rats. Freshly harvested leaves of Sida cordifolia were washed and dried at room temperature, after which they were ground to fine powder and subsequently extracted. Twenty-five adult Wistar rats were divided into five groups of five rats each. Group I was the normal control and was administered 2 ml of distilled of water. Group II was infected without treatment, while Group III and IV were infected and afterwards administered 200 and 400 mg/kg of aqueous extract of Sida cordifolia respectively. Group V was administered the standard drug. Biochemical and haematological indices were determined using standard procedures. The Packed Cell Volume (PCV) reported for group II (negative) control was significantly (P&lt;0.05) lower than that reported for the normal control. However, oral administration of 200 and 400 mg/kg of Sida cordifolia leaf extract significantly (P&lt;0.05) increased it, though to a level which was significantly (P&lt;0.05) lower than that reported for the normal control. Similar observation was made on Haemoglobin Concentration (Hb) and Red Blood Cell (RBC). However, a contrary observation was made on the white blood cell. Urea and creatinine reported for the negative control were significantly (P&lt;0.05) higher than those reported for the normal control. However, the aforementioned parameters were significantly (P&lt;0.05) reduced following oral administration of Sida cordifolia. In conclusion, it can be deduced from this study that Sida cordifolia leaf extract has the ability to restore distorted haematological and biochemical status resulting from P. berghei infection.

Efficacy of X-Ray Phytosanitary Irradiation on the Infectivity and Reproduction of Angiostrongylus cantonensis in Experimentally Infected Rats.

Angiostrongylus cantonensis is a globally distributed nematode and the leading cause of eosinophilic meningitis in humans. As a global hotspot for this disease, Hawaii's agricultural exports may be contributing to the spread of A. cantonensis. Phytosanitary irradiation doses of 150 or 400 Gy provide quarantine security against multiple insect pests. We evaluated the invitro and invivo effects of phytosanitary irradiation on infectious, third-stage, A. cantonensis larvae. In vitro experiments directly exposed larvae to irradiation doses ranging from 200 to 1,000 Gy. Results showed low mortality and no dose response across all treatments 27 days post-irradiation. In vivo studies isolated larvae from wild-caught Parmarion martensi after exposure to x-ray irradiation at doses of 0, 150, and 400 Gy and infected them into laboratory rats. Fourteen rats were assigned to each treatment and infected with 50 larvae from their assigned irradiation dose. Results at 3 and 6 weeks post-infection demonstrated a significant negative dose response in regard to the number of larvae that migrated to the brain and adults found in the pulmonary artery. No irradiated larvae that grew into adults were able to produce eggs. These findings indicate that x-ray irradiation does not result in the direct mortality of A. cantonensis larvae; however, it does affect the infectivity and reproduction of A. cantonensis within its definitive host, the rat. Phytosanitary irradiation at doses ≥150 Gy appears to be an effective means of preventing the establishment of viable populations of A. cantonensis, thus reducing the potential for global spread due to agricultural exports from Hawaii.