Doxorubicin-loaded liposome-like particles embedded in chitosan/hyaluronic acid-based hydrogels as a controlled drug release model for local treatment of glioblastoma.

Glioblastoma (GBM) resection and medication treatment are limited, and local drug therapies are required. This study aims to create a hybrid system comprising liposome-like particles (LLP-DOX) encapsulated in chitosan/hyaluronic acid/polyethyleneimine (CHI/HA/PEI) hydrogels, enabling controlled local delivery of doxorubicin (DOX) into the resection cavity for treating GBM. CHI/HA/PEI hydrogels were characterized morphologically, physically, chemically, mechanically, and thermally. Findings revealed a high network and compact micro-network structure, along with enhanced physical and thermal stability compared to CHI/HA hydrogels. Simultaneously, drug release from CHI/HA/PEI/LLP-DOX hydrogels was assessed, revealing continuous and controlled release up to the 148th hour, with no significant burst release. Cell studies showed that CHI/HA/PEI hydrogels are biocompatible with low genotoxicity. Additionally, LLP-DOX-loaded CHI/HA/PEI hydrogels significantly decreased cell viability and gene expression levels compared to LLP-DOX alone. It was also observed that the viability of GBM spheroids decreased over time when interacting with CHI/HA/PEI/LLP-DOX hydrogels, accompanied by a reduction in total surface area and an increase in apoptotic tendencies. In this study, we hypothesized that creating a hybrid drug delivery system by encapsulating DOX-loaded LLPs within a CHI/HA/PEI hydrogel matrix could achieve sustained drug release, improve anticancer efficacy via localized treatment, and effectively mitigate GBM progression for 3D microtissues.

The Impact of COVID-19 Pandemic Restrictions on Musculoskeletal Pathology Services.

BACKGROUND AND OBJECTIVES:  The COVID-19 pandemic has had a negative impact on healthcare in musculoskeletal pathology. There is no standard protocol for pathology services during a pandemic. The study aimed to assess the impact of COVID-19 restrictions on the workload of the musculoskeletal pathology service and the hurdles faced in collaboration with the orthopedic oncology unit in a tertiary reference center in a developing country. MATERIALS AND METHODS:  The pathology reports from mid-March to mid-June 2019, 2020, and 2021 were retrospectively reviewed. RESULTS:  Significant differences were found between the pandemic period (2020) and the non-pandemic periods (2019-2021) in benign bone and soft tissue lesions, resection surgeries, and soft tissue tumors, which were more prevalent in the non-pandemic periods. However, there was no significant decrease in biopsy procedures. Conclusion: During the pandemic period, the biopsy procedure appears to be feasible for bone and soft tissue lesions without the need for anesthesia.

Melatonin has favorable preventive effects on experimental chronic pancreatitis rat model.

BACKGROUND: Currently, there is not any specific treatment for chronic pancreatitis (CP). It was aimed to investigate the effects of melatonin administration on endoplasmic reticulum (ER) stress, oxidative stress, fibrosis, biochemical and histopathological parameters, and Abcc2,Abcc5, and Abcg2 gene levels in an experimental rat CP model. METHODS: Forty rats were randomized into five groups: Sham, CP, CP+25 mg/kg melatonin, CP+50 mg/kg melatonin, and CP+placebo. In all rats, except the sham group, a model of chronic pancreatitis was accomplished with intraperitoneal caerulein administration. In treatment groups, melatonin was used as a therapeutic agent. Serum TGF-ß, TNF-α, MDA and GPx levels were studied. Pancreatic tissues were evaluated histopathologically. The expression levels of αSma,IR1α,Perk,Abcc2,Abcc5, and Abcg2 genes were measured with the qRT-PCR. RESULTS: Biochemical results of the melatonin groups exhibited favorable changes compared to the CP and placebo groups. αSma,IR1α,Perk expression levels were significantly lower in the melatonin groups. The expression levels of Abcc2, Abcc5, and Abcg2 were significantly higher in the CP group compared to the sham group, and these gene levels were significantly lower in the melatonin groups compared to the CP group (p < 0.01, p < 0.05, p < 0.05, respectively). DISCUSSION: In light of these favorable positive results, melatonin may be a useful preventive agent in the course of CP.

Polymorphisms in Toll-like receptors 1, 2, 5, and 10 are associated with predisposition to Helicobacter pylori infection.

OBJECTIVE: Toll-like receptors (TLRs) are significant receptors to the innate immune system which symbolizes a family of pattern recognition receptors. We aimed to investigate associations between rs4833095 polymorphism of TLR1, rs3804099 polymorphism of TLR2, rs5744174 polymorphism of TLR5, and rs10004195 polymorphism of TLR10 in dyspeptic individuals with Helicobacter pylori infection. METHODS: Genomic DNA was isolated and genotyping of rs4833095 polymorphism in TLR1, rs3804099 polymorphism in TLR2, rs5744174 polymorphism in TLR5, and rs10004195 polymorphism in TLR10 were investigated in 400 individuals (205 in dyspeptic individuals with H. pylori-positive subjects and 195 dyspeptic individuals with H. pylori-negative subjects) by real-time PCR. Statistical analysis was performed by Pearson's Chi-square test. RESULTS: According to our study; rs4833095 polymorphism in TLR1 C allele, rs3804099 polymorphism in TLR2 C allele, rs5744174 polymorphism in TLR5 C allele, and rs10004195 polymorphism in TLR10 A allele increased the risk of H. pylori infection [odds ratio (OR), 2.01; 95% confidence interval (CI), 1.39-3.16; OR, 1.78; 95% CI, 1.19-2.6; OR, 1.87; 95% CI, 1.25-2.78; OR, 2.66; 95% CI, 1.72-4.099, respectively]. CONCLUSION: This is the first study that investigates TLRs in H. pylori infection in Turkey. Our findings may support the hypothesis that polymorphisms in certain TLRs may cause a genetic predisposition to H. pylori-related gastric problems.