Thermosensitive and mucoadhesive gels containing solid lipid nanoparticles loaded with fluconazole and niosomes loaded with clindamycin for the treatment of periodontal diseases: a laboratory experiment.

BACKGROUND: Periodontal diseases may benefit more from topical treatments with nanoparticles rather than systemic treatments due to advantages such as higher stability and controlled release profile. This study investigated the preparation and characterization of thermosensitive gel formulations containing clindamycin-loaded niosomes and solid lipid nanoparticles (SLNs) loaded with fluconazole (FLZ), as well as their in vitro antibacterial and antifungal effects in the treatment of common microorganisms that cause periodontal diseases. METHODS: This study loaded niosomes and SLNs with clindamycin and FLZ, respectively, and assessed their loading efficiency, particle size, and zeta potential. The particles were characterized using a variety of methods such as differential scanning calorimetry (DSC), dynamic light scattering (DLS), and Transmission Electron Microscopy (TEM). Thermosensitive gels were formulated by combining these particles and their viscosity, gelation temperature, in-vitro release profile, as well as antibacterial and antifungal effects were evaluated. RESULTS: Both types of these nanoparticles were found to be spherical (TEM) with a mean particle size of 243.03 nm in niosomes and 171.97 nm in SLNs (DLS), and respective zeta potentials of -23.3 and -15. The loading rate was 98% in niosomes and 51% in SLNs. The release profiles of niosomal formulations were slower than those of the SLNs. Both formulations allowed the release of the drug by first-order kinetic. Additionally, the gel formulation presented a slower release of both drugs compared to niosomes and SLNs suspensions. CONCLUSION: Thermosensitive gels containing clindamycin-loaded niosomes and/or FLZ-SLNs were found to effectively fight the periodontitis-causing bacteria and fungi.

Comparison of Perioperative Pregabalin and Duloxetine for Pain Management After Total Knee Arthroplasty: A Double-Blind Clinical Trial.

Background: Chronic residual pain after total knee arthroplasty (TKA) is one of the challenges of postoperative pain management. Duloxetine, by controlling neuropathic pain, and pregabalin, by affecting nociceptors, can effectively manage postoperative pain. Objectives: This study aimed to compare the effect of perioperative oral duloxetine and pregabalin in pain management after knee arthroplasty. Methods: In this clinical trial, 60 patients scheduled for TKA under spinal anesthesia were randomly assigned to one of three groups A (pregabalin 75 mg), B (duloxetine 30 mg), and C (placebo). Drugs were administered 90 minutes before, 12, and 24 hours after surgery. The visual analog scale (VAS) score for pain, the first analgesic request time, postoperative analgesic consumption (i.v. paracetamol), and WOMAC score six months after surgery were recorded. Results: The VAS score and analgesic consumption 48 hours after TKA in groups A and B significantly decreased compared to the placebo (P < 0.05). The first analgesic request time was longer in groups A and B than in group C (P < 0.05). While the differences were statistically significant, they are most likely not clinically significant. The WOMAC score before and six months after arthroplasty did not differ between the groups (P > 0.05). Conclusions: Perioperative oral pregabalin and duloxetine similarly reduce pain and the need for analgesic consumption within 48 hours after TKA but do not affect knee mobility status.

Evaluation of the Expression Levels of miR-21-5p and miR-429 Genes in Biopsy Samples from Patients with Oral Squamous Cell Carcinoma.

INTRODUCTION: MicroRNAs (miRs) are a group of endogenous, non-coding, 18-24 nucleotide length single-strand RNAs that mediate gene expression at the post-transcriptional level through mRNA degradation or translational repression. They are involved in regulating diverse cellular biological processes such as cell cycle, differentiation, and apoptosis. The deregulation of miRs affects normal biological processes, leading to malignancies, including oral squamous cell carcinoma (OSCC). This study evaluates the expression level of miR-21-5p and miR-429 genes in biopsy samples from patients with OSCC and performs a comparison with controls. MATERIALS AND METHODS: In this study, tissue samples were obtained from 40 individuals (20 OSCC patients and 20 healthy controls) to determine miR-21-5p and miR-429 expression using the ΔCT method and analyzed by the Mann-Whitney test. RESULTS: The mean age of subjects in the control and patient groups was 47.15 and 53.8 years, respectively. According to the Mann-Whitney test, significant differences were observed in miR-21-5p (p < 0.0001) and miR-429 (p = 0.0191) expression levels between the two groups (p < 0.05). CONCLUSIONS: The expression of miR-21-5p, miR-429, and combined miRNAs in the OSCC group was significantly higher compared to the control group. As a result, changes in the expression of these biomarkers in cancerous tissues could potentially be considered as a marker for the early diagnosis of OSCC.

Polyphyllin D-loaded solid lipid nanoparticles for breast cancer: Synthesis, characterization, in vitro, and in vivo studies.

Polyphyllin D (PD), a steroidal saponin in Paris polyphylla, induces apoptosis via the intrinsic apoptotic pathway in different cancer types. However, emerging evidence has shown that the primary issue with PD is its structure's hemolysis and cytotoxicity. This study aimed to develop and optimize PD-loaded SLN formulation and evaluate its efficacy in breast cancer cell lines. Apoptosis, as the mechanism of cell death, was confirmed by flow cytometry following Annexin V/propidium iodide staining and western blot analysis. In in vivo studies, tumor inhibitory efficacy was compared with different doses of PD-loaded SLN on 4T1-implanted BALB/c mice. The half-maximal inhibitory concentration (IC50) of PD- loaded SLN was calculated to be 33.25 and 35.74 µg/mL for MCF7 and MDA-MB-231 cells, respectively. Flow cytometry analysis further confirmed a significant increase in apoptosis after treatment with PD- loaded SLN. When both cell lines were treated with PD-loaded SLN, Bcl2 and HSP70 proteins were down regulated, while Bax, Bad, P53, Apaf-1, p-p53 and Noxa proteins were upregulated. This effect was also confirmed by test performed on BALB/c mice in vivo. Based on results, PD-loaded SLN may be a promising breast cancer treatment, without recognizable side effects.

The association between wood dust exposure and respiratory disorders and oxidative stress among furniture workers.

BACKGROUND: This study was undertaken to determine the effect of wood dust on the respiratory system and oxidative stress in furniture workers and to determine whether any associations exist between respiratory parameters and oxidative stress. METHODS: This cross-sectional study was performed on 45 furniture workers and 45 office workers as a reference group in Iran. The NIOSH method 0600 was used to determine the concentration of particulates. The prevalence of respiratory symptoms was estimated via the European Community Respiratory Health Survey (ECRHS) questionnaire. Oxidative stress biomarkers and respiratory parameters were also measured. RESULTS: The mean concentrations of respirable and non-respirable dust were found to be 1.51 mg/m3 and 1.23 mg/m3, respectively. Pulmonary function parameters, including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC, and antioxidant capacity biomarkers such as total antioxidant capacity (TAC) and superoxide dismutase (SOD) were significantly lower, while the prevalence of respiratory symptoms, and malondialdehyde (MDA) levels, were significantly higher in the furniture workers than in the reference group. There were significant positive associations between FVC and FEV1 with SOD and TAC. CONCLUSION: The present study results indicated that exposure to wood dust significantly increased respiratory disorders and confirmed the association between lung function parameters and oxidative stress.

Evaluation of the Expression of miR-486-3p, miR-548-3p, miR-561-5p and miR-509-5p in Tumor Biopsies of Patients with Oral Squamous Cell Carcinoma.

BACKGROUND AND OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy. Expression patterns of microRNAs (miRNAs) can direct us in identifying valuable biomarkers for the prognosis of different neoplasms. Inappropriate regulation of miRNAs during physiological procedures can result in malignancies including OSCC. The aim of the present study was to evaluate the expression of miR-486-3p, miR-561-5p, miR-548-3p, and miR-509-5p in tissue biopsy samples with and without OSCC. MATERIALS AND METHODS: This case-control study was conducted on 17 healthy and 17 OSCC tissue biopsy samples. The expression of miRNAs was assessed using quantitative real-time PCR (q-RT-PCR) after RNA extraction from normal and cancer tissues and cDNA synthesis. RESULTS: The means of miRNA-486-3p, miR-561-5p, and miR-548-3p expression were significantly different between OSCC and control groups (p < 0.001), but there was no significant difference in means of miR-509-5p expression between OSCC and control groups (p = 0.179). CONCLUSIONS: The findings of this study revealed that the expression of miR-486-3p and miR-561-5p was significantly lower in cancer samples compared to normal tissue samples. On the other hand, miR-548-3p expression increased in the OSCC group compared to the control group.

Postoperative Pain Management: Efficacy of Caudal Tramadol in Pediatric Lower Abdominal Surgery: A Randomized Clinical Study.

BACKGROUND: One of the methods of pain control after pediatric surgical procedures is regional techniques, including caudal block, despite their limitations. OBJECTIVES: In this study, the pain score and complications of caudal tramadol were evaluated in pediatrics following lower abdominal surgery. METHODS: In this study, 46 children aged 3 to 10 years were allocated into two equal groups (R and TR) for performing caudal analgesia after lower abdominal surgery. The injectate contained 0.2% ropivacaine 1 mL/kg in the R group (control group) and tramadol (2 mg/kg) and ropivacaine in the TR group. The pain score, duration of pain relief, amount of paracetamol consumption, hemodynamic alterations, and possible complications at specific times (1, 2, and 6 hours) were evaluated in both groups. RESULTS: No considerable difference was observed in the pain score between the groups in the first and second hours (P > 0.05). However, in the sixth hour, the TR group had a significantly lower pain score than the R group (P < 0.05). Compared to the R group, the TR group had a longer period of analgesia and lower consumption of analgesic drugs (P < 0.05). Heart rate and blood pressure differences were not significant between the two groups (P > 0.05). Similarly, the duration of operation and recovery time were not remarkably different between the two groups (P > 0.05). Complications had no apparent differences between these two groups, as well (P > 0.05). CONCLUSIONS: In this study, the addition of tramadol to caudal ropivacaine in pediatric lower abdominal surgery promoted pain relief without complications.

A retrospective study on mandibular reconstruction using iliac crest free flap.

PURPOSE: To assess the availability, success rate and complications of microvascular iliac crest free flap for reconstruction of mandibular segmental defects. METHODS: In this retrospective-descriptive study, we report patients who had undergone segmental mandibular resection for pathologic lesions and received reconstruction with iliac crest microvascular free flap between 2016 and 2019. Clinical and demographic data of all the cases were collected. Success was regarded as complete consolidation of the bone graft in panoramic radiograph. Postoperative complications were defined as major or minor based on the need for intervention. T-test, Kolomogorov_Smirnov, and multivariate analysis were used and the p-value<0.05 was considered to be statistically significant. RESULTS: Of all 30 patients, 16 were women and 14 were men with an average age of 27.2 years (range 14-40). Patients were followed for 12-60 month (mean: 38.4). One flap was lost due to unsalvageable venous thrombosis. Six other cases had post-op complications while smoking and diabetes were associated with more complications (P = 0.036). Twenty-three patients received primary reconstruction which was more successful than secondary ones (P = 0.003). Osteogenic sarcoma was associated with greater risk of complications (P < 0.01). CONCLUSIONS: The results of this study suggest that iliac crest microvascular free flap serves as a promising option for the reconstruction of mandibular defects, providing excellent contour and acceptable success rate with low donor site morbidity. Future studies will focus on the role of systemic diseases in post-op complications and flap failures.

Performance evaluation of developed dedicated breast PET scanner and improvement of the spatial resolution by wobbling: a Monte Carlo study.

PURPOSE: Molecular imaging, particularly PET scanning, has become an important cancer diagnostic tool. Whole-body PET is not effective for local staging of cancer because of their declining efficiency in detecting small lesions. The preliminary results of the performance evaluation of designed dedicated breast PET scanner presented. METHODS AND MATERIALS: A new scanner is based on LYSO crystals coupled with SiPM, and it consists of 14 compact modules with a transaxial FOV of 180 mm in diameter. In this study, initial GATE simulation studies were performed to predict the spatial resolution, absolute sensitivity, noise equivalent count rate (NECR) and scatter fraction (SF) of the new design. Spatial wobbling acquisitions were also implemented. Finally, the obtained projections were reconstructed using analytical and iterative algorithms. RESULTS: The simulation results indicate that absolute sensitivity is 1.42% which is appropriate than other commercial breast PET systems. The calculated SF and NECR in our design are 20.6% and 21.8 kcps. The initial simulation results demonstrate the potential of this design for breast cancer detection. A small wobble motion to improve spatial resolution and contrast. CONCLUSION: The performance of the dedicated breast PET scanner is considered to be reasonable enough to support its use in breast cancer imaging.

Association of TGFß1 and SMAD4 variants in the etiology of keloid scar in the Malay population.

Keloid is a complex condition with environmental and genetic risk-contributing factors. Two candidate genes, TGFß1 and SMAD4, located in the same signaling pathway are highly expressed in the keloid fibroblast cells. In a case-control design, TGFß1 haplotypes showed association with the risk of keloid in the present study. The CC haplotype, composed of both c.29C>T and -509T>C variants, was observed more frequently among cases (Corrected p = 0.037, OR = 2.07, 95 % CI = 0.87-4.93), showing a 4.5-fold increased risk for keloid. The AG genotype of the SMAD4 c.5131A>G variant showed a trend of significance (p = 0.0573, OR = 1.75, 95 % CI = 0.99-3.13). Taken together, either of these variants is most probably causative at the expression level or is in linkage disequilibrium with other causative variants in a complex pattern together with the environmental factors that contribute to the condition. To the best of our knowledge, there is only one documented report on a relationship between TGFß1 and keloid with no association within the Caucasian population, while there have not been any reports for SMAD4. Therefore, the present study is likely the first research showing a significant association between TGFß1 variants and keloids in the Malay population.

Keloid scarring: understanding the genetic basis, advances, and prospects.

Keloid disease is a fibroproliferative dermal tumor with an unknown etiology that occurs after a skin injury in genetically susceptible individuals. Increased familial aggregation, a higher prevalence in certain races, parallelism in identical twins, and alteration in gene expression all favor a remarkable genetic contribution to keloid pathology. It seems that the environment triggers the disease in genetically susceptible individuals. Several genes have been implicated in the etiology of keloid disease, but no single gene mutation has thus far been found to be responsible. Therefore, a combination of methods such as association, gene-gene interaction, epigenetics, linkage, gene expression, and protein analysis should be applied to determine keloid etiology.