Nanofabrication of chitosan-based dressing to treat the infected wounds: in vitro and in vivo evaluations.

Aim: Here, an innovative kind of antibacterial nanocomposite film is developed by incorporating graphene oxide and zinc oxide into chitosan matrix. Materials & methods: Our dressing was fabricated using the solution casting method. Fourier transform infrared spectra and TGA-DTG clearly confirmed the structure of film dressing. Results & conclusion: Our results showed the tensile strength and elongation at the break of the films were 20.1 ± 0.7 MPa and 36 ± 10%, respectively. Our fabricated film could absorb at least three-times the fluid of its dry weight while being biocompatible, antibacterial, non-irritant and non-allergic. In addition, it accelerated the healing process of infected wounds by regulating epithelium thickness and the number of inflammatory cells, thus it may be useful for direct application to damaged infected wounds.

In this study, an innovative kind of antibacterial nanocomposite film is developed by incorporating graphene oxide and zinc oxide into chitosan matrix. Our antibacterial wound dressing was fabricated using the solution casting method. Our fabricated film could absorb at least three-times the fluid of its dry weight while being biocompatible, antibacterial, non-irritant and non-allergic. In addition, our film accelerated the healing process of infected wounds by regulating epithelium thickness and the number of inflammatory cells. thus it may be useful for direct application to damaged infected wounds.

Chitosan-Aloe Vera Composition Loaded with Zinc Oxide Nanoparticles for Wound Healing: In Vitro and In Vivo Evaluations.

Global concerns due to the negative impacts of untreatable wounds, as well as the growing population of these patients, emphasize the critical need for advancements in the wound healing materials and techniques. Nanotechnology offers encouraging avenues for improving wound healing process. In this context, nanoparticles (NPs) and certain natural materials, including chitosan (CS) and aloe vera (AV), have demonstrated the potential to promote healing effects. The objective of this investigation is to assess the effect of novel fabricated nanocomposite gel containing CS, AV, and zinc oxide NPs (ZnO NPs) on the wound healing process. The ZnO NPs were synthesized and characterized by X-ray diffraction and electron microscopy. Then, CS/AV gel with different ratios was prepared and loaded with ZnO NPs. The obtained formulations were characterized in vitro based on an antimicrobial study, and the best formulations were used for the animal study to assess their wound healing effects in 21 days. The ZnO NPs were produced with an average 33 nm particle size and exhibited rod shape morphology. Prepared gels were homogenous with good spreadability, and CS/AV/ZnO NPs formulations showed higher antimicrobial effects against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The wound healing findings showed significant wound area reduction in the CS/AV/ZnO NPs group compared to negative control at day 21. Histopathological assessment revealed the advantageous impact of this formulation across various stages of the wound healing process, including collagen deposition (CS/AV/ZnO NPs (2 : 1), 76.6 ± 3.3 compared to negative control, 46.2 ± 3.7) and epitheliogenesis (CS/AV/ZnO NPs (2 : 1), 3 ± 0.9 compared to negative control, 0.8 ± 0.8). CS/AV gel-loaded ZnO NPs showed significant effectiveness in wound healing and would be suggested as a promising formulation in the wound healing process. Further assessments are warranted to ensure the robustness of our findings.

Chitosan and its amphiphilic derivative nanoparticles loaded with Minoxidil for induction of hair growth: In vitro and in vivo evaluation.

Minoxidil is widely used for treating Androgenic Alopecia, but its low hydrophilicity promotes the use of co-solvents in commercial formulations, which could then cause skin irritations. Nano-drug delivery systems have been developed to improve the solubility of lipophilic molecules and increase the concentration of drugs in hair follicles, thereby minimizing side effects. Chitosan (CS) and Methylated Aminobenzyl Carboxymethyl Chitosan (MCS) nanoparticles containing Minoxidil were prepared and evaluated for their physicochemical properties, drug release profile, skin permeation, cytotoxicity, and animal hair growth. The results showed that MCS nanoparticles had a 60 % drug release compared to CS nanoparticles, with almost complete release in 2 h. MCS nanoparticles also showed a 20 % drug permeation from skin compared to 70 % for CS nanoparticles in 24 h. In 48 and 72 h, CS and MCS nanoparticles didn't exhibit any significant cytotoxicity. Animal study revealed a significant increase in hair growth from MCS nanoparticles compared to the commercial formulation in fourteen days. However, MCS nanoparticles were less efficient compared to CS nanoparticles. The use of MCS in nano-drug delivery systems is expected to continue to gain importance due to its ability to enhance the solubility of hydrophobic drugs, particularly in the treatment of skin diseases.

Climate-related subsidies for CO2 absorption and fuel substitution: Effects on optimal forest management decisions.

This study investigates rational ways to optimize stand-level management decisions from an economic perspective to adjust alternative subsidies, aiming to reduce the CO2 level in the atmosphere and consequently, to mitigate the global warming impacts. An objective function consisting of two parts is used to maximize the current production value that forests represent and the value of forests under the effects of different types of subsidies intended to reduce CO2 levels. The optimal ways of adjusting stand-level management decisions are determined using a general comparative statics analysis, which takes into account alternative forms of climate-related subsidies. The optimal changes to stand-level management decisions are functions of the initial conditions of the stand of trees on which the decision will be made. The results have shown that there are one or two of the alternative forms of CO2 subsidies increase: if the initially optimal values of the stock level after harvesting {V1} is lower than the stock level that maximizes the sustainable yield {VMSY}, and the time interval between harvests {t} is sufficiently short, then the initially optimal value of V1 and t increase; if the initially optimal value of V1 is lower than VMSY, and t is sufficiently long, then the initially optimal values of V1 and t may vary or stay unchanged; if the initially optimal value of V1 is equal to VMSY, and t is very short, then V1 and t are not changed; if the initially optimal value of V1 is higher than VMSY, and/or t is sufficiently long, then the initially optimal values of V1 and t decrease. Our approach of providing decisions at the stand-level can be extended to the broader scales at forest landscapes to address the related challenges.

Chitosan nanoparticle loaded by epidermal growth factor as a potential protein carrier for wound healing: In vitro and in vivo studies.

Epidermal growth factor (EGF) can be efficiently used in wound healing process; but the main obstacle of its clinical use is its susceptibility to proteolysis and maintaining its effective concentration in the site of action. In this study, chitosan nanoparticles containing EGF is formulated using a simple method to increase its stability in physiological pH as well as protect its biological activity and effectiveness in wound healing process. Nanoparticles with different ratios of chitosan/EGF were prepared and evaluated in vitro and in vivo. Obtained results showed nanoparticles with 2:1 ratio of chitosan/EGF were able to release 80% of encapsulated protein after 12 h. Cell proliferation study demonstrated that prepared nanoparticles could protect EGF functionality in physiological pH. In vivo results showed that nanoparticles with 2:1 ratio of chitosan/EGF could significantly accelerate the wound closure-rate, re-epithelialisation and collagen deposition. In conclusion, the designed nanoparticles in optimal ratio can be considered as a potential vehicle for EGF delivery to wounds with the aim of improving healing process.

The Sensitivity of Tau Tracers for the Discrimination of Alzheimer's Disease Patients and Healthy Controls by PET.

Hyperphosphorylated tau aggregates, also known as neurofibrillary tangles, are a hallmark neuropathological feature of Alzheimer's disease (AD). Molecular imaging of tau by positron emission tomography (PET) began with the development of [18F]FDDNP, an amyloid ß tracer with off-target binding to tau, which obtained regional specificity through the differing distributions of amyloid ß and tau in AD brains. A concerted search for more selective and affine tau PET tracers yielded compounds belonging to at least eight structural categories; 18F-flortaucipir, known variously as [18F]-T807, AV-1451, and Tauvid®, emerged as the first tau tracer approved by the American Food and Drug Administration. The various tau tracers differ concerning their selectivity over amyloid ß, off-target binding at sites such as monoamine oxidase and neuromelanin, and degree of uptake in white matter. While there have been many reviews of molecular imaging of tau in AD and other conditions, there has been no systematic comparison of the fitness of the various tracers for discriminating between AD patient and healthy control (HC) groups. In this narrative review, we endeavored to compare the binding properties of the various tau tracers in vitro and the effect size (Cohen's d) for the contrast by PET between AD patients and age-matched HC groups. The available tracers all gave good discrimination, with Cohen's d generally in the range of two-three in culprit brain regions. Overall, Cohen's d was higher for AD patient groups with more severe illness. Second-generation tracers, while superior concerning off-target binding, do not have conspicuously higher sensitivity for the discrimination of AD and HC groups. We suppose that available pharmacophores may have converged on a maximal affinity for tau fibrils, which may limit the specific signal imparted in PET studies.

Spermidine reduced neuropathic pain in chronic constriction injury-induced peripheral neuropathy in rats.

Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into three groups: sham, CCI and CCI+SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done four times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than in the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P < 0.01, P < 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of superoxide dismutase (SOD), glutathione (GPx), and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress and improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model.

Statistical modelling of COVID-19 and drug data via an INAR(1) process with a recent thinning operator and cosine Poisson innovations.

In this paper, we propose the first-order stationary integer-valued autoregressive process with the cosine Poisson innovation, based on the negative binomial thinning operator. It can be equi-dispersed, under-dispersed and over-dispersed. Therefore, it is flexible for modelling integer-valued time series. Some statistical properties of the process are derived. The parameters of the process are estimated by two methods of estimation and the performances of the estimators are evaluated via some simulation studies. Finally, we demonstrate the usefulness of the proposed model by modelling and analyzing some practical count time series data on the daily deaths of COVID-19 and the drug calls data.

Integrating graphene oxide into layers of PVDF/PVDF@cross-linked sodium alginate/polyamide membrane for efficiently enhancing desalination performances.

The membrane modules of the water treatment system are faced costly damages; thereby executing pre-desalination units based on Nanofiltration (NF) could prevent these suffers, and improve the permeated water flux (PWF) and salt rejection (SR). Hence, we focused on the construction of a novel ternary-layer NF membrane through "electrospinning Polyvinylidene Fluoride (PVDF) (as bottom layer)", "generating middle layer by electrospinning PVDF along with, the implementation cross-linking after electrospraying Sodium Alginate", and "synthesizing Polyamide (as top layer) through interfacial polymerization". More importantly, it anticipated that the Taguchi statistical method can expeditiously optimize the effects of Graphene Oxide nano-sheets (GOns) on water-dependent properties, such as PWF and SR. Astonishingly, the desalination capabilities significantly improved, when the top, middle, and bottom layers simultaneously had 1, 0.1, and 0.1 wt.% of GOns, respectively. Overall, comparing the performances between the optimized sample containing low-dosage and without GOns demonstrated the PWF ameliorated from 6.68 to 20.36 L/m2 h; also, the SR ability remained on an incremental basis as NaCl < MgCl2 < MgSO4 under 6 bar pressure. Manifestly, these authentic results denoted promising, innovative, and large-scaling insights when effectual PWF and SR be necessary.

Clinical and Laboratory Predictors of COVID-19-Related In-hospital Mortality; a Cross-sectional Study of 1000 Cases.

Introduction: Identifying patients at risk for mortality and using appropriate treatment for each patient based on their situation could be an effective strategy in improving their outcome. This study aimed to evaluated the predictors of COVID-19 in-hospital mortality. Methods: This descriptive cross-sectional study was conducted on all adult COVID-19 patients who were managed in Imam-Reza and Sina Hospitals, Tabriz, Iran, from November 2020 until December 2021. The demographic, clinical, and laboratory characteristics of patients were evaluated and predictors of in-hospital mortality were identified using logistic regression model. Results: 1000 patients with the mean age of 56.34 ± 18.00 years were studied (65.7% male). There were significant associations between COVID-19 in-hospital mortality and hospitalization above five days (p = 0.001), white blood cell count (WBC) > 4000 Cells*103/mL (p < 0.01), aspartate aminotransferase (AST) above 40 IU/L (p = 0.001), alanine transaminase (ALT) above 40 IU/L (p = 0.001), creatinine above 1.4 mg/dL (p = 0.007), urea above 100 mg/dL (p = 0.024), and SaO2 below 80% (p = 0.001). Hospital stay above five days (OR: 3.473; 95%CI: 1.272 - 9.479; p = 0.15), AST above 40 IU/L (OR: 0.269, 95%CI: 0.179 - 0.402; p = 0.001), creatinine above 1.4 mg/dL (OR: 0.529; 95%CI: 0.344 - 0.813; p = 0.004), urea above 100 mg/dL (OR: 0.327, 95%CI: 0.189 - 0.567; p = 0.001), and SaO2 below 80% (OR: 8.754, 95%CI: 5.413 - 14.156; p = 0.001) were among the independent predictors of COVID-19 in-hospital mortality. Conclusion: The mortality rate of patients with COVID-19 in our study was 29.9%. Hospitalization of more than five days, AST above 40 IU/L, creatinine above 1.4 mg/dL, urea above 100 mg/dL and SaO2 < 80% were independent risk factors of in-hospital mortality among patients with COVID-19.

The neural effects of oxytocin administration in autism spectrum disorders studied by fMRI: A systematic review.

PURPOSE: Oxytocin (OXT) is a hypothalamic neuropeptide that is released from the posterior pituitary gland and at specific targets in the central nervous system (CNS). The prosocial effects of OXT acting in the CNS present it as a potential therapeutic agent for the treatment of aspects of autism spectrum disorder (ASD). In this article, we systematically review the functional MRI (fMRI) literature that reports task-state and resting-state fMRI (rsfMRI) studies of the neural effects of single or multiple dose intranasal OXT (IN-OXT) administration in individuals with ASD. METHOD: We searched four databases for relevant documents (PubMed, Web of Science, Scopus, and Google Scholar) using the keywords "autism spectrum disorder", "Asperger Syndrome", "oxytocin", and "fMRI". Moreover, we made a manual search to assess the quality of our automatic search. The search was confined to English language articles published in the interval February 2013 until March 2021. RESULTS: The search yielded 12 fMRI studies with OXT intervention, including 288 individuals with ASD (age 8-55 years) enrolled in randomized, double-blind, placebo-controlled, parallel designs, within-subject-crossover experimental OXT trials. Studies reporting activation task and rsfMRI were summarized with region of interest (ROI) or whole-brain voxel wise analysis. The systematic review of the 12 studies supported the proposition that IN-OXT administration alters brain activation in individuals with ASD. The effects of IN-OXT interacted with the type of the task and the overall results did not indicate restoration of normal brain activation in ASD signature regions albeit the lack of statistical evidence. CONCLUSION: A large body of evidence consistently indicates that OXT alters activation to fMRI in brain networks of individuals with ASD, but with uncertain implications for alleviation of their social deficits.

The effect of the EX-PLISSIT model-based psychosexual counseling on improving sexual function and sexual quality of life in gynecologic cancer survivors: a randomized controlled clinical trial.

PURPOSE: Psychosexual support has received considerable attention in the improvement of sexuality in gynecologic cancer survivors. The current study was conducted to examine the effect of EX-PLISSIT model-based psychosexual counseling on improving sexual function and sexual quality of life in this group of patients. METHODS: One hundred ten eligible women with the most common gynecologic cancers were randomized 1:1 to intervention (EX-PLISSIT-based counseling sessions for 4 weeks) and control groups. Sexual function and sexual quality of life were assessed via FSFI and SQOL-F self-reported questionnaires at baseline and 8 weeks post-intervention. RESULTS: One hundred fifty patients were registered; 110 were equally randomized to the intervention and control groups (55 each). Ninety-nine patients completed both questionnaires at baseline and 8 weeks post-intervention. There were no significant differences in the FSFI and SQOL-F scores between the study arms compared to baseline using the independent t-test (P > 0.05). Positive changes in FSFI and SQOL-F scores were observed in patients in both arms at 8 weeks. However, the mean difference was higher in the intervention arm but was statistically significant only in the domains of sexual desire, lubrication, orgasm, pain, overall sexual function, and sexual and relationship satisfaction subscale of SQOL-F (P < 0.05). CONCLUSIONS: Based on our findings, by facilitating communication, the EX-PLISSIT-based psychosexual counseling resulted in positive changes in sexual function and sexual quality of life in gynecologic cancer survivors. Therefore, we recommend this type of counseling in combination with other therapeutic and rehabilitative services for survivors of gynecologic cancers. TRIAL REGISTRATION: This study was registered in Iran's Clinical Trial Registry under registration code IRCT20160808029255N6 on 29 June 2019.

Modeling Medical Data by Flexible Integer-Valued AR(1) Process with Zero-and-One-Inflated Geometric Innovations.

In this paper, we introduce a new stationary first-order integer-valued autoregressive process (INAR) with zero-and-one-inflated geometric innovations that is useful for modeling medical practical data. Basic probabilistic and statistical properties of the model are discussed. Conditional least squares and maximum likelihood estimators are proposed to estimate the model parameters. The performance of the estimation methods is assessed by some Monte Carlo simulation experiments. The zero-and-one-inflated INAR process is subsequently applied to analyze two medical series that include the number of new COVID-19-infected series from Barbados and Poliomyelitis data. The proposed model is compared with other popular competing zero-inflated and zero-and-one-inflated INAR models on the basis of some goodness-of-fit statistics and selection criteria, where it shows to provide better fitting and hence can be considered as another important commendable model in the class of INAR models.

Tissue presentation of human pegivirus infection in liver transplanted recipients.

Human pegivirus-1 (HPgV-1) is known for its protective role in HIV co-infected individuals. This immunomodulatory effect raised questions concerning the possible role of HPgV-1 infection and the risk of rejection in liver transplanted patients. We aimed to evaluate the possible protective effect of HPgV-1 on graft outcome of liver transplanted patients. A total of 283 patients were recruited. Formalin-fixed paraffin-embedded tissue samples were collected from the explanted liver. HBV-DNA, HCV-RNA, and HPgV-1-RNA were determined using PCR and multiplex RT-PCR assays. The clinical course of patients including the occurrence of acute cellular rejection was compared between HPgV-1-infected vs. uninfected patients. HBV-DNA, HCV-RNA and HPgV-1-RNA were detected in 42.6%, 4.9%, and 7.8% of samples, respectively. None of the HPgV-1-infected patients experienced graft rejection. Group LASSO logistic regression revealed that HPgV-1 infection was the only factor which significantly reduced the odds of graft rejection (OR = 0.5, 95% CI = 0.29-0.89). No significant association was found between the presence of HPgV-1 with HBV and HCV infections. The lack of graft rejection in HPgV-1-infected liver transplanted patients might indicate a possible role of this virus for graft surveillance. Since these are still preliminary findings, prospective studies should further elucidate the role of HPgV-1 in liver transplantation outcomes.

Chitosan as a machine for biomolecule delivery: A review.

The major role of biomolecules in treatment of different diseases has been proven by several studies. However, the main drawback in successful treatment by these molecules is designing of efficient delivery systems to fulfill all of the delivery purposes. In this regard, many polymeric vehicles have been introduced for protecting and delivery of biomolecules to the target site. Chitosan as a unique biopolymer with special properties has been widely used for biomolecule delivery. Several research groups have focused on developing and applying of chitosan as a versatile machine in biomolecule delivery. In this review the unique properties of chitosan have been discussed at first and then its application as a delivery machine for different types of biomolecules include protein and peptides, nucleic acids and vaccines has been considered. Furthermore, the targeting approach by conjugation of various ligands to the chitosan and also the current challenges for development of chitosan vehicles will be discussed for biomolecule delivery.

Chitosan-Raloxifene nanoparticle containing doxorubicin as a new double-effect targeting vehicle for breast cancer therapy.

BACKGROUND: treatment of breast cancer as one of the most common cancers in the world remains an important area of drug development based on nanoparticulate systems. Effective targeted therapy of affected cells based on ligand conjugate biocompatible polymeric nanoparticles is an attractive perspective in this context. OBJECTIVE: In this study, a novel double effect nanoparticle based on Chitosan-Raloxifene conjugate was prepared for adjuvant therapy (hormone and chemo therapy) and drug targeting to breast cancer cells via estrogen receptor (ER). METHODS: Chitosan-raloxifene conjugate was synthesized. Related nanoparticles containing doxorubicin (DOX) were prepared and characterized. Experimental design study was performed to determine the optimum levels of variables in the preparation of nanoparticle. Drug loading, release, nanoparticle stability, and the effect of nanoparticles on cell viability were evaluated. Further, inhibition tests were performed to demonstrate that the function of these novel nanoparticles is mediated via ER. RESULTS: Chitosan-raloxifene conjugate was successfully synthesized. The prepared nanoparticles showed sizes within 25-35 nm, more than 95% drug loading, about 60% of drug release and desired stability after 24 h. XTT assay on MCF-7 cell line illustrated that these nanoparticles could inhibit the cellular growth up to 60%. The results from inhibition tests revealed that prepared nanoparticles can inhibit cell growth via ER blocking. CONCLUSION: This study introduced chitosan-raloxifene nanoparticles containing doxorubicin as a novel targeting agent for adjuvant therapy of breast cancer. Graphical abstract.

Thiolated chitosan-lauric acid as a new chitosan derivative: Synthesis, characterization and cytotoxicity.

Chitosan as a biopolymer is an attractive vehicle for biomedical applications due to its unique characteristics. In order to improve chitosan's physicochemical features, chemical modification has been carried out to make it more suitable for such approaches. The aim of this study was to prepare and evaluate thiolated chitosan-lauric acid as a new chitosan derivative for biomedical use. Lauric acid was introduced to chitosan via stable amide bond between carboxylic acid group of fatty acid and the amine in the chitosan and thiolation was carried out using thioglycolic acid. Resulted polymers were characterized by FTIR, 1H NMR and TGA. Moreover, cell viability assessment of new derivative was performed using MTT method. FTIR and 1H NMR results showed that both substitution reactions were successfully completed. Furthermore, new synthesized polymer had no significant cytotoxicity against normal gingiva human cells (HGF1-PI 1).These findings confirm that this new derivative can be introduced as a suitable polymer for biomedical purposes such as mucosal drug delivery.

Novel chitosan based nanoparticles as gene delivery systems to cancerous and noncancerous cells.

The present study aimed to investigate in vitro DNA transfection efficiency of three novel chitosan derivatives: thiolated trimethyl chitosan (TMC-Cys), methylated 4-N,N dimethyl aminobenzyl N,O carboxymethyl chitosan(MABCC) and thiolated trimethyl aminobenzyl chitosan(MABC-Cys). After polymer synthesis and characterization, nanoparticles were prepared using these polymers and their size, zeta potential and DNA condensing ability were measured. After that, cytotoxicity and transfection efficiency of nanocomplexes were carried out in three different cells. The results showed that all polymers could condense DNA plasmid strongly from N/P 2 and nanocomplexes had eligible sizes and zeta potentials. Moreover, the nanocomplexes had negligible cytotoxicity and MABC-Cys was the most effective vehicle for gene delivery in HEK-293T cells. In the two other cell lines, SKOV-3 and MCF-7, TMC-Cys exhibited the highest transfection efficiency. This study indicated that chemical structure of these novel chitosan derivatives in the interaction with the cell type can lead to successful gene delivery.

Effects of silymarin, cabergoline and letrozole on rat model of endometriosis.

OBJECTIVE: Silymarin as an herbal drug has potent antioxidant effects that could make it a good choice for endometriosis therapy. The aim of the current study was to determine the effects of silymarin as an herbal drug on induced endometrial lesion in rat model of endometriosis. MATERIALS AND METHODS: A total of 32 mature, female Sprague-Dawley rats were allocated into 4 experimental groups. The duration of study was about 6 months. Endometriosis implants were surgically prepared and autografted into 32 rats. Three weeks after endometriosis induction, animals were randomly allocated into four groups: Group 1 received cabergoline (CAB group); Group 2 received letrozole (LET group); Group 3 received silymarin (SIL group) and Group 4 received no medication (CONT group). Experimental groups were treated for 3 weeks and then were sacrificed for volume and histopathological evaluation of implants and biochemical assessment. Serum and peritoneal levels of vascular endothelial growth factor (VEGF), total antioxidant activity (TAC) and tumor necrosis (TNF)-α were measured. RESULTS: Mean volume of the implants decreased significantly in silymarin (p < 0.001), letrozole (p < 0.001) and cabergoline (p < 0.001) groups compared to the control. Histopathologic score was significantly lower in silymarin (p: 0.039), letrozole (p: 0.017) and cabergoline (p < 0.001) groups compared to the control. Those receiving silymarin had significantly higher serum TAC compared to control after 21 days of therapy (p < 0.001). CONCLUSION: Silymarin, Letrozole, and Cabergoline administration resulted in decreased size and histopathologic grade of the induced endometrial lesions in a rat model. Silymarin appears to be a virtual novel therapeutic agent for treatment of endometriosis.

Biocompatible electrospinning chitosan nanofibers: A novel delivery system with superior local cancer therapy.

In this study, an electrospinning technique was used for the fabrication of novel biomedicated nanofibers which are applied for preventing wound infections and local chemotherapy. CURs containing nanofibers with a crosslinking agent (Si-O-Si network) have been produced through functionalization of graphene oxide with APTES. In vitro drug release profile results showed the novel nanofibers could limit the drug's initial burst release and provide better sustainability in comparison with the blend nanofibers without modified GO. The novel delivery vehicle can inhibit the growth of MRSA and S. epidermidis up to 94% and 88%. Also in vitro cell toxicity experiments which were performed by XTT method on MCF-7, HEP G2 and L929 cell lines showed that anticancer activity of CUR remained intact even after loading into nanofibers. This result suggested that the fGO-Si-CUR including nanofibers were a promising candidate for postoperative chemotherapy.