Quercetin's Restorative Properties in Male Mice with 3-Nitropropionic Acid-induced Huntington-like Symptoms: Molecular Docking, Behavioral, and Biochemical Assessment.

The neurotoxicity of 3-Nitropropionic acid (3-NP) is well known. Herein, the prophylactic versus therapeutic effects of quercetin (QCT) were investigated against 3-NP-induced behavioral anomalies and oxidative neural damage. Thirty male mice were assigned into five groups; the negative control group, the QCT group (25 mg/kg/day, p.o. for 21 days), the 3-NP group (17 days), the prophylactic group (QCT administration for 14 consecutive days, and then 3-NP was administrated), the therapeutic group (3-NP was administrated and then QCT for 21 days). At the end of the animal treatment, behavioral studies were assessed. Subsequently, the brain sample tissues were assessed for oxidative stress-related parameters and histological evaluation. Moreover, the potential interaction between 3-NP and tumor necrosis factor-alpha (TNF-α) was evaluated by using a molecular docking study. 3-NP markedly led to neurotoxicity which was indicated by behavioral deficits (motor behavior, depression-like behavior, memory dysfunction, and passive avoidance) and oxidative damage. Blind and targeted molecular docking results showed good interaction between 3-NP and TNF-α. However, the prophylactic effects of QCT were superior to the therapeutic effects for attenuating 3-NP-induced neurobehavioral and oxidative neural changes in experimental mice, which histological changes of the brain's striatum region approved our findings. Taken together, the antioxidant activity of QCT remarkably could attenuate 3-NP-induced neurobehavioral deficits and mitochondrial dysfunctions in mice.

S-3,4-DCPG, a potent orthosteric agonist for the mGlu8 receptor, facilitates extinction and inhibits the reinstatement of morphine-induced conditioned place preference in male rats.

The limbic system, particularly the NAc, shows a high concentration of metabotropic glutamate receptors (mGluRs). Recent evidence suggests the significant involvement of mGluRs in mental disorders, including substance abuse and addiction. The objective of this study was to examine the involvement of mGlu8 receptors in the NAc in the mechanisms underlying the extinction and reinstatement of conditioned place preference (CPP) induced by morphine. Male Wistar rats underwent surgical implantation of bilateral cannulas in the NAc and were assessed in a CPP protocol. In study 1 at the same time as the extinction phase, the rats were given varying doses of S-3,4-DCPG (0.03, 0.3, and 3 µg/0.5 µl). In study 2, rats that had undergone CPP extinction were given S-3,4-DCPG (0.03, 0.3, and 3 µg/0.5 µl) five minutes prior to receiving a subthreshold dose of morphine (1 mg/kg) in order to reactivate the previously extinguished morphine response. The findings demonstrated that administering S-3,4-DCPG directly into the accumbens nucleus resulted in a decrease in the duration of the CPP extinction phase. Moreover, dose-dependent administration of S-3,4-DCPG into the NAc inhibited CPP reinstatement. The observations imply that microinjection of S-3,4-DCPG as a potent orthosteric agonist with high selectivity for the mGlu8 receptor into the NAc promotes the process of extinction while concurrently exerting inhibitory effects on the reinstatement of morphine-induced CPP. This effect may be associated with the modulation of glutamate engagement within the NAc and the plasticity of reward pathways at the synaptic level.

Development of a hydrogel containing bisabolol-loaded nanocapsules for the treatment of atopic dermatitis in a Balb/c mice model.

α-Bisabolol (αBIS), a plant-derived compound with anti-inflammatory properties, is potentially a therapeutic agent for Atopic dermatitis. However, its poor water solubility and photoinstability limit its topical application. Therefore, the present study, aimed to develop cationic polymeric nanocapsules of αBIS to improve its skin delivery, photostability, and therapeutic efficacy. The αBIS-loaded nanocapsules were prepared using the solvent displacement technique. A Box-Behnken (BB) design was employed to statistically optimize formulation variables and αBIS-loaded nanocapsules characterized by particle size, surface charge and encapsulation efficiency. The optimal formulation was selected, and the spherical shape of the nanocapsules was confirmed by scanning electron microscopy (SEM). Furthermore, hydrogel containing αBIS-loaded nanocapsules was prepared by thickening of nanocapsule suspension with Carbopol 934 and evaluated for rheology, in vitro drug release and skin permeation. Furthermore, a mice model of atopic dermatitis was used to evaluate the anti-inflammatory potential of the hydrogels. The optimal formulation displayed a spherical morphology under scanning electron microscopy (SEM) with an optimum particle size of 133.00 nm, polydispersity index (PDI) of 0.12, high EE% of 93 %, and improved optical stability of αBIS in the prepared nanocapsules compared to the free drug. The nano-based hydrogels demonstrated non-Newtonian pseudoplastic behavior and an increased αBIS in vitro release profile without causing skin irritation in rabbits. Drug retention within the dermis and epidermis layers significantly surpassed that of drug-free hydrogel. Moreover, in vivo histopathological studies and myeloperoxidase (MPO) enzyme activity, revealed that hydrogel containing bisabolol nanocapsules exhibited The best anti-inflammatory effect. The results showed that hydrogels containing bisabolol nanocapsules markedly alleviated dermatitis-related inflammation and reduced skin thickness in Balb/c mice. Our findings support nanocapsules as an effective drug delivery system to enhance αBIS stability, bioavailability, and therapeutic efficacy in AD treatment.

The role of histamine H1 receptor in the anterior cingulate cortex on nociception level following acute restraint stress in male rats.

Considering the importance of pain and stress, we decided to investigate the intra-anterior cingulate cortex (ACC) microinjection of histamine and mepyramine alone and concurrently on acute pain induced by hot plate following restraint stress in male rats. 24-gauge, 10 mm stainless steel guide cannula was implanted over the ACC in the incised scalp of 4 groups. Restraint stress in healthy rats produced a significant increase (p < .05) in the pain threshold. The simultaneous microinjection of 4 µg/side histamine and 8 µg/side mepyramine as a histaminergic system inverse agonist in healthy nonrestraint animals did not affect the pain threshold. Although Histamine decreased the threshold of pain meaningfully, mepyramine elevated it in a significant manner (p < .05). In the restrained animals, intra-ACC microinjection of histamine produced no significant impact on the pain threshold. However, intra-ACC microinjection of mepyramine before histamine, significantly (p < .01) altered the result and enhanced the threshold of pain. The results of our study demonstrated that histaminergic neurons have an important role in the processing of pain in the ACC following restraint stress.

Neuroprotective effects of silymarin in 3-nitropropionic acid-induced neurotoxicity in male mice: improving behavioral deficits by attenuating oxidative stress and neuroinflammation.

3-Nitropropionic acid (3-NP) is strongly believed to be an irreversible inhibitor of mitochondrial complex II, leading to neural damage. This study aimed to investigate the neuroprotective effects of silymarin against 3-NP-induced neurotoxicity in male mice. Six-week-old mice received subacute doses of 3-NP intraperitoneally for 17 days. Mice were given silymarin (70 mg/kg/day, P.O.) for 2 weeks before 3-NP administration or for 4 weeks after 3-NP administration. At the end of the treatment schedule, animals were evaluated for behavioral alterations. Subsequently, neuronal damage in the hippocampus region of the brain tissues, oxidative stress-related parameters (lipid peroxidation, nitric oxide, superoxide dismutase, glutathione, and total antioxidant capacity), and pro-inflammatory cytokine (TNF-α, IL-17, and IL-1ß) levels were evaluated. Our results indicated that 3-NP treatment significantly (p < 0.05) tended to reduce motor coordination, memory, and neuronal antioxidant status while increasing pro-inflammatory cytokine levels. However, silymarin in both treatment and pretreatment protocols markedly (p < 0.05) attenuated the behavioral deficits, oxidative stress status, and neuroinflammation. The results of the current study suggest that the neuroprotective effect of silymarin against 3-NP-induced neurotoxicity might be due to the mitigation of oxidative stress status and provide insight into the therapeutic potential of silymarin.

Peroxisome proliferator activated receptor-gamma (PPAR-γ) ligand, pioglitazone, increases analgesic and anti-inflammatory effects of naproxen.

The aim of this study was the investigation of analgesic and anti-inflammatory activity of naproxen and pioglitazone following intra-plantar injection of carrageenan and assessment of the PPAR-γ receptor involvement in these effects. Rats were intra-plantarly injected with carrageenan (1%, 100 µl) to induce thermal hyperalgesia and paw inflammation. Different groups of rats were pre-treated intraperitoneally with naproxen (1 and 10 mg/kg) or pioglitazone (3 and 10 mg/kg) or GW9662 (a selective PPAR-γ antagonist, 100 µl/paw). The volume of the paw was evaluated using a plethysmometer, and the hot plate test was employed to assess the pain threshold in the animals. Finally, TNF-α, IL-1ß, IL-6, and myeloperoxidase (MPO) activity status were evaluated in the hind paw tissue. Naproxen and pioglitazone demonstrated analgesic and anti-inflammatory activity. Concurrent injection of an ineffective dose of naproxen (1 mg/kg) with an ineffective dose of pioglitazone (3 mg/kg) caused augmented analgesic and anti-inflammatory activity, significantly (p≤0.001 and p≤0.01, respectively). Additionally, intra-plantar injection of GW-9662 before naproxen or pioglitazone significantly suppressed their analgesic (p≤0.001) and anti-inflammatory activity (p≤0.01). Also, naproxen and pioglitazone (10 mg/kg) significantly (p≤0.001) reduced carrageenan-induced MPO activity and TNF-α, IL-6, and IL-1ß releasing. Furthermore, PPAR-γ blockade significantly prevented suppressive effects of naproxen and pioglitazone on the MPO activity and inflammatory cytokines. Pioglitazone significantly increased analgesic and anti-inflammatory effects of naproxen. This study proposes that concurrent treatment with naproxen and pioglitazone may be a substitute for overcome pain and inflammation clinically, in the future, particularly in patients with cardiovascular disorders and diabetes.

Cardioprotective effect of vitamin D3 on cisplatin-induced cardiotoxicity in male mice: role of oxidative stress.

Cisplatin (CP) is a chemotherapy drug used in a broad spectrum of cancer. The current study investigated the protective effect of vitamin D3 (vit-D3) on CP-induced cardiotoxicity. Forty-two male Balb-c mice (20-25 g) were divided into seven groups (GP), 6 per/group were included: GP1 was considered the control group, GP2 received a single dose of I.V. injection of cisplatin (10 mg/kg). Seven days before cisplatin injection on GP3 and GP4 as pre-treatment, vit-D3 was injected I.P. with the doses of 500 IU/kg and 1000 IU/kg, respectively. GP5 and GP6 were considered the treatment groups, were injected cisplatin (10 mg/kg, I.V), and 15 days later, received vit-D3 (500 IU/kg and 1000 IU/kg, I.P) for 7 days. GP7 was the positive control group, which received vit-D3 at a dose of 500 IU/kg (I.P.) for 7 days. Tissues samples and blood serum were collected for biochemical and histopathological investigations. CP injection significantly increased (p < 0.001) LDH, Troponin I, CK-MB, malondialdehyde (MDA), and nitric oxide (NO) levels, but total antioxidant capacity (TAC) levels were significantly reduced. Histological findings showed cardiac muscle rupture, myocardial fiber necrosis, edema, and pyknotic nuclei, indicating cardiac damage. In both pre-treatment and treatment protocol, vit-D3 could improve the histological and biochemical parameters and prevented from the CP toxicity. Vit-D3 significantly could prevent the CP cardiotoxicity in pre-treatment groups, and partially improve the damage of chemotherapy in treatment group. However, further research is necessary to establish the potential of vit-D3 in preventing or ameliorating cisplatin-induced cardiotoxicity.

Neuroprotective effects of coenzyme Q10 on neurological diseases: a review article.

Neurological disorders affect the nervous system. Biochemical, structural, or electrical abnormalities in the spinal cord, brain, or other nerves lead to different symptoms, including muscle weakness, paralysis, poor coordination, seizures, loss of sensation, and pain. There are many recognized neurological diseases, like epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), stroke, autosomal recessive cerebellar ataxia 2 (ARCA2), Leber's hereditary optic neuropathy (LHON), and spinocerebellar ataxia autosomal recessive 9 (SCAR9). Different agents, such as coenzyme Q10 (CoQ10), exert neuroprotective effects against neuronal damage. Online databases, such as Scopus, Google Scholar, Web of Science, and PubMed/MEDLINE were systematically searched until December 2020 using keywords, including review, neurological disorders, and CoQ10. CoQ10 is endogenously produced in the body and also can be found in supplements or foods. CoQ10 has antioxidant and anti-inflammatory effects and plays a role in energy production and mitochondria stabilization, which are mechanisms, by which CoQ10 exerts its neuroprotective effects. Thus, in this review, we discussed the association between CoQ10 and neurological diseases, including AD, depression, MS, epilepsy, PD, LHON, ARCA2, SCAR9, and stroke. In addition, new therapeutic targets were introduced for the next drug discoveries.

Effects of sesamin on Aß1-42-induced oxidative stress and LTP impairment in a rat model of Alzheimer's disease.

The present study examined the protective effect of sesamin (Ses) on ß-amyloid (Aß)-induced long-term potentiation (LTP) impairment at the PP-DG synapses in male rats. Wistar rats were randomly assigned to seven groups: control, sham, Aß; ICV Aß1-42 microinjection, Ses, Aß + Ses; first, ICV Aß injections and then receiving Ses, Ses + Aß: four weeks of pretreatment with Ses and then Aß injection, and Ses + Aß + Ses: pre (four weeks) and post (four weeks) treatment with Ses. Ses-treated groups received 30 mg/kg of Ses once a day by oral gavage for four weeks. After the treatment period, the animals were positioned in a stereotaxic device for surgery and field potential recording. The population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were evaluated in the DG region. Serum oxidative stress biomarkers (total oxidant status (TOS) and total antioxidant capacity (TAC)) were measured. Aß impaired LTP induction at the PP-DG synapses evidenced by a decrease in EPSP slope and PS amplitude of LTP. In Aß rats, Ses increased EPSP slope and PS amplitude of LTP in the DG granular cells. Also, an increase in TOS and a reduction in TAC caused by Aß were significantly corrected by Ses. Ses could prevent Aß-induced LTP impairment at the PP-DG synapses in male rats, which can be due to its preventive effects on oxidative stress.

3D-Printed Soft Membrane for Periodontal Guided Tissue Regeneration.

OBJECTIVES: The current study aimed to perform an in vivo examination using a critical-size periodontal canine model to investigate the capability of a 3D-printed soft membrane for guided tissue regeneration (GTR). This membrane is made of a specific composition of gelatin, elastin, and sodium hyaluronate that was fine-tuned and fully characterized in vitro in our previous study. The value of this composition is its potential to be employed as a suitable replacement for collagen, which is the main component of conventional GTR membranes, to overcome the cost issue with collagen. METHODS: Critical-size dehiscence defects were surgically created on the buccal surface of the roots of canine bilateral mandibular teeth. GTR treatment was performed with the 3D-printed membrane and two commercially available collagen membranes (Botiss Jason® and Smartbrane-Regedent membranes) and a group without any membrane placement was considered as the control group. The defects were submerged with tension-free closure of the gingival flaps. Histologic and histometric analyses were employed to assess the periodontal healing over an 8-week experimental period. RESULTS: Histometric evaluations confirmed higher levels of new bone formation in the 3D-printed membrane group. Moreover, in all defects treated with the membranes, the formation of periodontal tissues, bone, periodontal ligaments, and cementum was observed after 8 weeks, while in the control group, only connective tissue was found in the defect sites. There was no clinical sign of inflammation or recession of gingiva in any of the groups. SIGNIFICANCE: The 3D-printed gelatin/elastin/sodium hyaluronate membrane can be safe and effective for use in GTR for periodontal tissue regeneration therapies, with better or comparable results to the commercial collagen membranes.

Silibinin chronic treatment in a rat model of Parkinson disease: A comprehensive in-vivo evaluation and in silico molecular modeling.

BACKGROUND: Apoptosis, oxidative stress, and neuroinflammation have been linked to the onset of Parkinson's disease (PD). Although the pre-treatment effects of Silibinin on a PD model have been evaluated, in the current study we investigated the chronic therapeutic effects of Silibinin microinjection on a rat model of established parkinsonism along with behavioral and laboratory markers assessments. METHOD: Parkinsonism was induced by 6-hydroxydopamine (6-OHDA, 8 µg/2µl/rat). 21 days after that, animals were treated with Silibinin (100, 200, and 300 mg/kg for 15 consecutive days). Every two days, the bar test was used to evaluate Silibinin's anti-cataleptic properties. At the end, myeloperoxidase (MPO) activity and toll-like receptor 4 (TLR4) expression in the substantia nigra pars compacta (SNc), along with cerebrospinal fluid (CSF) levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, caspase-3, Bax and Bcl-2 levels were assessed. We used homology modeling to predict the 3D structure of TLR4. RESULT: Silibinin's Chronic treatment, dose-dependently decreased catalepsy. MPO activity and levels of TNF-α, IL-6, and IL-1ß were reduced in Silibinin-treated rats in all three doses. Silibinin decreased Bax/Bcl-2 ratio, caspase-3, and downregulated TLR4 expression. Molecular docking revealed that there were hydrophobic and hydrogen bond interactions between the studied ligand and TLR4. Silibinin formed a stable complex with both monomer and dimer forms of TLR4. CONCLUSION: In accordance with molecular modeling and alleviation of TLR4 activity with a consequent reduction in oxidative stress, restoration of CSF inflammatory cytokine, and minimization of SNc neuronal apoptosis, long-term therapy with Silibinin offers a potential opportunity for symptomatic PD treatment.

Preparation of polyvinyl alcohol hydrogel containing chlorogenic acid microspheres and its evaluation for use in skin wound healing.

Chlorogenic acid (CGA) is a phenolic compound widely found in plants. Several studies have shown that CGA possesses antioxidant, antibacterial, anti-inflammatory and wound healing properties. Because of their three-dimensional structure, good permeability, excellent biocompatibility and moisturizing properties, hydrogels are ideal candidates for wound dressing. The aim of the present study was to preparation and characterization of Polyvinyl alcohol (PVA) hydrogel containing CGA microspheres and evaluation its wound healing activity. The double-emulsion solvent evaporation technique was applied for preparing the CGA containing microspheres. The microspheres were characterized using scanning electron microscopy (SEM) and Fourier transformation infrared spectroscopy (FTIR) and subsequently incorporated in the structure of a PVA hydrogel. The effects of prepared hydrogel on NIH3T3 cell line viability were evaluated using MTT method and wound healing activity was investigated in full thickness wound model in rabbit. SEM images showed formation of homogenous CGA microspheres with diameters in the range of 1-2 µm, embedded in the porous structure of the hydrogel. Infra-red results indicated successful incorporation of CGA microspheres into PVA hydrogel. The NIH3T3 cell viability percentage in CGA 2.5% hydrogel treated group significantly (p < .05) increased after 24 h and 48 h comparing to control group. In vivo studies showed that CGA hydrogel significantly (p < .001) stimulated the rate of wounds closures. Histological studies revealed that administration of CGA hydrogel significantly increased epithelialization and production of collagen fibers compared to the control group. It can be concluded that the CGA microsphere loaded PVA hydrogel has the potential for wound healing.

Antinociceptive and anti-inflammatory actions of curcumin and nano curcumin: a comparative study.

Background and purpose: Pain and inflammation can be treated by various therapies that for the most part are not effective and can result in adverse effects. The current study was proposed to compare the antinociceptive and anti-inflammatory actions of curcumin and nano curcumin in rats. Experimental approach: Rats were randomly allocated into ten groups of six for formalin and tail-flick tests including the control group, curcumin and nano curcumin groups (20, 50, 100 mg/kg), morphine group (10 mg/kg), naloxone + 100 mg/kg curcumin group, and naloxone + 100 mg/kg nano curcumin group. There were nine groups for the carrageenan test. Groups 1-7 were the same as the previous division; groups 8 and 9 received 10 mg/kg diclofenac and 1% carrageenan, respectively. Findings/Results: All doses of nano curcumin significantly decreased the paw-licking time in both phases of the formalin test. In the tail-flick test, curcumin 100, nano curcumin 100, naloxone + curcumin 100, and naloxone + nano curcumin 100 showed significant analgesic effects compared to the control group. In the paw edema test, at 180 s after injection, curcumin (50 and 100 mg/kg) and all doses of nano curcumin significantly inhibited carrageenan-induced edema. Myeloperoxidase activity and lipid peroxidation decreased at doses of 50 and 100 mg/kg of curcumin but at three doses of nano curcumin (20, 50, and 100 mg/kg). Conclusion and implication: In conclusion, our results suggest that the nanoemulsion formulation of curcumin can be efficient in reducing pain and especially inflammation in lower doses compared to the native form of curcumin.

Post treatment with Gastrodin suppresses oxidative stress and attenuates motor disorders following 6-OHDA induced Parkinson disease.

BACKGROUND & OBJECTIVE: Researchers are currently trying to find new therapies with better symptomatic activity and fewer side effects to manage Parkinson's disease (PD). Although the protective effect of pre-treatment by Gastrodin (Gst) on a PD model has been evaluated, in the current experimental study, we investigated the symptomatic therapeutic effects of Gst microinjection in the same PD model but in the post-parkinsonism induction condition. METHODS: Parkinsonism was induced by unilateral infusion of 6- hydroxydopamine (6-OHDA; 8 µg/ 2 µl/ rat) into the central region of the substantia nigra pars compacta (SNc). After the recovery period and confirmation of parkinsonism, daily Gst treatment in three doses (20, 40, 80 µg/ 2 µ/ rat, continued for ten days with motor monitoring by bar test and rotarod examinations. Moreover, lipid peroxidation and myeloperoxidase activity were evaluated. RESULTS: In this model of 6-OHDA-induced parkinsonism, Gst treatment in all three doses showed a dose dependent symptomatic improvement in motor imbalance (P < 0.001) catalepsy (P < 0.001), decreased lipid peroxidation (P < 0.001) and SNc myeloperoxidase activity (P < 0.001). CONCLUSIONS: 6-OHDA induced parkinsonism symptomatically improved behaviorally with Gst post-induction treatment along with decreased markers of oxidative stress and microglial activation. We suggest that this agent is a candidate for symptomatic treatment of human PD.

Effects of L-carnitine supplementation in patients with mild-to-moderate COVID-19 disease: a pilot study.

BACKGROUND: The present single-center clinical trial was designed to evaluate the potential benefits of L-carnitine supplementation in patients with COVID-19 disease. METHODS AND PATIENTS: The study was conducted on 75 patients with mild-to-moderate COVID-19 hospitalized in Shahid Beheshti Hospital-Hamadan, IRAN. The participants were randomly divided into intervention (n = 32) and control groups (n = 43). The control group received their standard hospital treatment only. In addition to standard medications, the intervention group received 3000 mg oral L-carnitine daily in three divided doses for five days. The blood samples were collected and para-clinical parameters were measured at the beginning and end of the treatment. Clinical outcomes were also recorded, and data were analyzed using χ2 and t-tests. RESULTS: Higher means of O2 saturation were observed in the intervention rather than in the control group. Mean erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were significantly lower in the intervention group. Furthermore, mean alkaline phosphatase (ALP) activity and lactate dehydrogenase (LDH) were lower in the intervention group. Also, lower mean serum creatine phosphokinase (CPK) was observed in the intervention group. No significant differences were observed in terms of clinical symptoms; however, six patients (14%) in the control group died due to the complications of COVID-19, while all patients in the intervention group survived. CONCLUSION: Taken together, L-carnitine can be considered as a drug supplement in patients with COVID-19.

Silibinin-loaded nanostructured lipid carriers (NLCs) ameliorated cognitive deficits and oxidative damages in aluminum chloride-induced neurotoxicity in male mice.

Aluminum chloride (AlCl3) and its accumulation in the brain are associated with neurodegenerative disease. Recent investigations have illustrated that silibinin is known to have neuroprotective properties. The present study investigates the neuroprotective effects of silibinin-loaded nanostructured lipid carriers (Sili-NLCs) against AlCl3-induced neurotoxicity in male mice. Sili-NLCs were prepared using the emulsification-solvent evaporation method and subjected to particle size, zeta potential, and entrapment efficiency (% EE) analysis. Mice were treated with AlCl3 (100 mg/kg/day, p.o.) and with the same concentration of silibinin and Sili-NLCs (50,100, and 200 mg/kg/day, p.o.) for 30 days in different groups. After treating animals, behavioral studies were assessed. Also, the brain tissue samples were collected from all mice to evaluate oxidative damage and histological changes. The particle size, polydispersity index, zeta potential, and entrapment efficiency (% EE) of prepared Sili-NLCs found 239.7 ± 4.04 nm, 0.082 ± 0.003, - 16.33 ± 0.15 mV, and 72.65 ± 2.03 %, respectively. Brain uptake studies showed that Sili-NLCs had a 5.7-fold greater uptake in the mice brain than the free drug. The AlCl3 caused significant cognitive impairment and increased the level of lipid peroxidation accompanied by decreasing antioxidant enzyme activity in the brain tissue. These findings correlated well with the histopathological experiments. Furthermore, treatment with Sili-NLCs significantly improved the AlCl3-induced cognitive impairment, neurochemical anomalies, and histopathological changes. Given these results, silibinin, when delivered using NLCs, is potentially more effective than free silibinin in decreasing AlCl3- induced neurotoxicity.

In vivo efficacy of 3D-printed elastin-gelatin-hyaluronic acid scaffolds for regeneration of nasal septal cartilage defects.

Nasal septal cartilage perforations occur due to the different pathologies. Limited healing ability of cartilage results in remaining defects and further complications. This study sought to assess the efficacy of elastin-gelatin-hyaluronic acid (EGH) scaffolds for regeneration of nasal septal cartilage defects in rabbits. Defects (4 × 7 mm) were created in the nasal septal cartilage of 24 New Zealand rabbits. They were randomly divided into four groups: Group 1 was the control group with no further intervention, Group 2 received EGH scaffolds implanted in the defects, Group 3 received EGH scaffolds seeded with autologous auricular chondrocytes implanted in the defects, and Group 4 received EGH scaffolds seeded with homologous auricular chondrocytes implanted in the defects. After a 4-month healing period, computed tomography (CT) and magnetic resonance imaging (MRI) scans were obtained from the nasal septal cartilage, followed by histological evaluations of new tissue formation. Maximum regeneration occurred in Group 2, according to CT, and Group 3, according to both T1 and T2 images with 7.68 ± 1.36, 5.44 ± 2.41, and 8.72 ± 3.02 mm2 defect area respectively after healing. The difference in the defect size was statistically significant after healing between the experimental groups. Group 3 showed significantly greater regeneration according to CT scans and T1 and T2 images. The neocartilage formed over the underlying old cartilage with no distinct margin in histological evaluation. The EGH scaffolds have the capability of regeneration of nasal cartilage defects and are able to integrate with the existing cartilage; yet, they present the best results when pre-seeded with autologous chondrocytes.

A novel chimeric protein with enhanced cytotoxic effects on breast cancer in vitro and in vivo.

In our previous study, we reported the design and recombinant production of the p28-apoptin as a novel chimeric protein for breast cancer (BC) treatment. This study aimed to evaluate the inhibitory activity of the chimeric protein against BC cells in vitro and in vivo. We developed a novel multifunctional protein, consisting of p28, as a tumor-homing killer peptide fused to apoptin as a tumor-selective killer. The chimeric protein showed significantly higher toxicity in BC cell lines dose-dependently than in non-cancerous control cell lines. IC50 values were 1.41, 1.38, 6.13, and 264.49 µM for 4T1, MDA-MB-468, Vero, and HEK293 cells, respectively. The protein showed significantly enhanced uptake in 4T1 cancer cells compared with non-cancerous Vero cells. We also showed that the p28-apoptin chimeric protein binds significantly higher to human breast cancer tumor sections than the normal human breast tissue section. Also, significant apoptosis induction and tumor growth inhibition were observed in established tumor-bearing mice accompanied by a decreased frequency of metastases. Our results support that the chimeric protein has inhibitory activity in vitro and in vivo, making it a promising choice in targeted cancer therapy.