Design of smart chemotherapy of doxorubicin hydrochloride using nanostructured lipid carriers and solid lipid nanoparticles for improved anticancer efficacy.

Doxorubicin hydrochloride (DOX) is an anticancer agent used in cancer chemotherapy. The purpose of this study was to design nanostructured lipid carriers (NLCs) of DOX as smart chemotherapy to improve its photostability and anticancer efficacy. The characteristics of DOX and DOX-loaded NLCs were investigated using UV-Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, particle size, and zeta potential study. The cytotoxicity of DOX was evaluated against three cancer cell lines (HeLa, A549, and CT-26). The particle size and zeta potential were in the range 58.45-94.08 nm and -5.80 mV - -18.27 mV, respectively. The chemical interactions, particularly hydrogen bonding and van der Waals forces, between DOX and the main components of NLCs was confirmed by FTIR. NLCs showed the sustained release profile of DOX. The photostability results revealed that the NLC system improved the photostability of DOX. Cytotoxicity results using the three cell lines showed that all formulations improved the anticancer efficacy of free DOX, and the efficacy was dependent on cell type and particle size. These results suggest that DOX-loaded NLCs are promising chemotherapeutic agents for cancer treatment.

Long-Wavelength Absorbing Benzimidazolo-Chlorin for Enhanced Photodynamic Therapy.

In this study, we condensed methyl pyropheophorbide-a (2) with 1,2-phenylenediamine to synthesize benzimidazolo-chlorin (3a) as an effective near-infrared photosensitizer (PS) with an absorption maximum of 730 nm. The ability of 3a to generate singlet oxygen, as well as its photodynamic effect on A549 and HeLa cells, was investigated. PS exhibited strong phototoxicity and negligible dark toxicity. Its structure was examined by UV-visible spectroscopy, nuclear magnetic resonance, and high-resolution fast atom bombardment mass spectrometry.

Atomic Substitution to Tune ScO6 Distortion in Ba2MSc2(BO3)4 (M = Na, K, Ba) to Acquire a Large Birefringence.

Replacing alkali metals (K, Na atoms) by an alkaline-earth metal (Ba atom), α-Ba3Sc2(BO3)4 (high-temperature phase) is successfully obtained by a molten salt method, taking Ba2K1.6Na0.4Sc2(BO3)4 as the parent template. Although both of them exhibit similar layered structures composed of ScO6 and BO3 units, α-Ba3Sc2(BO3)4 shows largely distorted ScO6 octahedra (Δd = 0.56) forced by the uniform tension of a larger space effect from BaO12 polyhedrons, rather than regular ScO6 octahedra like in Ba2K1.6Na0.4Sc2(BO3)4. Experimental measurements and calculated analyses elucidate that distorted ScO6 octahedra in α-Ba3Sc2(BO3)4, displaying a second-order Jahn-Teller (SOJT) effect, enlarge the experimental birefringence up to 0.14@550 nm, while Ba2K1.6Na0.4Sc2(BO3)4 with regular ScO6 octahedra only shows Δn = 0.11 under the same condition. In addition, other optical and thermal properties of the two title compounds were characterized. The experimental results indicate that Ba2K1.6Na0.4Sc2(BO3)4 and α-Ba3Sc2(BO3)4 are promising birefringent materials.

Association between Genetic Polymorphisms of MIR3142HG and the Risk of Steroid-Induced Osteonecrosis of the Femoral Head in the Population of Northern China.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (ONFH) is aseptic necrosis of the femoral head caused by glucocorticoid use. Once necrotic femoral head necrosis occurs, it irreversibly affects the quality of life seriously. Studies have shown that the susceptibility to steroid-induced ONFH is likely to be related to the variation of miRNA-coding genes. Therefore, this study aimed was to investigate the effect of MIR3142HG on steroid-induced ONFH. METHODS: Agena MassARRAY was used to genotype MIR3142HG gene rs1582417, rs2431689, rs7727155, and rs17057846 in 199 patients and 725 healthy people. A genetic model and haplotype analysis were used to evaluate the relationship between the MIR3142HG polymorphism and the risk of steroid-induced ONFH. The odds ratio and 95% confidence intervals were obtained through logistic regression to assess the influence of gene polymorphisms on the occurrence of steroid-induced ONFH. RESULTS: The consequences show that rs7727115 is a protective factor, it could reduce the risk of steroid-induced ONFH, and rs1582417 could increase the risk of steroid-induced ONFH. In the genetic model, rs1582417 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. rs7727115 showed a decreased risk in codominant model, dominant model, and log-additive model. In addition, rs2431689 is related to HDL-C (p = 0.012) and ApoA1 (p = 0.010) levels, and rs17057846 (p = 0.024) is related to ApoB levels. Thelinkage analysis indicated 3 single-nucleotide polymorphisms (rs2431689, rs7727115, and rs17057846) in MIR3142HG with significant chain imbalance. In addition, haplotype "GGG" of MIR3142HG was found out and is harmful for steroid-induced ONFH. CONCLUSION: Our results first confirm that the genetic polymorphism of MIR3142HG is associated with steroid-induced ONFH susceptibility in Chinese Han population.

Association between LINC-PINT and LINC00599 gene polymorphism and the risk of steroid-induced osteonecrosis of the femoral head in the population of northern China.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (ONFH) is a complex disease affected by genetics. LncRNA LINC-PINT and LINC00599 have been proved to be associated with susceptibility to a variety of diseases, however it is not clear whether they are related to steroid-induced ONFH. Therefore, this study was aimed at investigating the correlation between the polymorphisms of LINC-PINT and LINC00599 genes and steroid-induced ONFH in the population of northern China. METHODS: A case-control study including 199 patients and 725 controls was designed. The Agena MassARRAY platform was used for the detection of single nucleotide polymorphisms (SNPs) in LINC-PINT and LINC00599 genes. Chi-square test and logistic regression were used to evaluate the association between the above SNPs and steroid-induced ONFH in allelic and genetic models. Besides, one-way ANOVA was used to study the relationship between these SNPs and partial lipid levels. RESULTS: In the LINC00599 gene, two sites are related to steroid-induced ONFH. Among them, rs2272026 increased the risk of the disease in co-dominant (heterozygous) and dominant models. And rs1962430 is a risk factor for this disease in the allelic, co-dominance (heterozygous), dominant and additive model. whereas in women with steroid-induced ONFH, three sites in the LINC-PINT gene are related to the disease. Thereinto, rs157916 reduces the risk of the disease in allelic, co-dominant (homozygous), recessive and additive models. Rs16873842 is related to the reduced risk of the disease in allele, dominant and additive models. And rs7781295 is a protective factor for steroid-induced ONFH in the allelic and additive model. CONCLUSION: Our study suggests that the polymorphisms of LINC-PINT and LINC00599 genes are related to the susceptibility of steroid-induced ONFH in Chinese Han population.

DNA methylation in the OPG/RANK/RANKL pathway is associated with steroid-induced osteonecrosis of the femoral head.

BACKGROUND: Dysregulation of the OPG/RANK/RANKL signalling pathway is a key step in the occurrence of steroid-induced osteonecrosis of the femoral head (ONFH). This study aims to understand the degree of methylation of the OPG, RANK, and RANKL genes in steroid-related ONFH. METHODS: A case-control study was designed, including 50 patients (25 males and 25 females) and 50 matched controls. The European Molecular Biology Open Software Suite (EMBOSS) was used to predict the existence and location of CpG islands in the OPG, RANK, and RANKL genes. The Agena MassARRAY platform was used to detect the methylation status of the above genes in the blood of subjects. The relationship between the methylation level of CpG sites in each gene and steroid-related ONFH was analysed by the chi-square test, logistic regression analysis, and other statistical methods. RESULTS: In the CpG islands of the OPG, RANK, and RANKL genes in patients with steroid-related ONFH, several CpG sites with high methylation rates and high methylation levels were found. Some hypermethylated CpG sites increase the risk of steroid-related ONFH. In addition, a few hypermethylated CpG sites have predictive value for the early diagnosis of steroid-related ONFH. CONCLUSION: Methylation of certain sites in the OPG/RANK/RANKL signalling pathway increases the risk of steroid-related ONFH. Some hypermethylated CpG sites may be used as early prediction and diagnostic targets for steroid-related ONFH.

Rhodojaponin II inhibits TNF-α-induced inflammatory cytokine secretion in MH7A human rheumatoid arthritis fibroblast-like synoviocytes.

Rhodojaponin II (R-II) has been shown to possess anti-inflammatory activity. Herein, we aimed to explore the effect of R-II on tumor necrosis factor-α (TNF-α)-induced inflammation in MH7A rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs). We found that R-II treatment at high concentration suppressed the viability of MH7A cells. R-II suppressed the levels of nitric oxide and prostaglandin E2, and inhibited messenger RNA expression and concentrations of interleukin-1ß (IL-1ß), IL-6 and matrix metalloproteinase-1 in TNF-α-stimulated RA-FLSs. Additionally, R-II repressed TNF-α-induced activation of the Akt, nuclear factor-κB (NF-κB), and toll-like receptor 4 (TLR4)/MyD88 pathways in MH7A cells. Inhibition of the Akt, NF-κB, and TLR4/MyD88 pathways by the corresponding inhibitors reinforced the inhibitory effect of R-II on TNF-α-induced inflammatory cytokine secretion in MH7A cells. R-II ameliorated the severity of collagen-induced arthritis in mice by inhibiting inflammation. In conclusion, R-II repressed TNF-α-induced inflammatory response in MH7A cells by inactivating the Akt, NF-κB, and TLR4/MyD88 pathways.

Exosomes derived from synovial fibroblasts under hypoxia aggravate rheumatoid arthritis by regulating Treg/Th17 balance.

IMPACT STATEMENT: A comparative study of osteoarthritis (OA) and RA mice was implemented to suggest that miR-424 expression was increased in RA, and exosome-miR-424 derived from synovial fibroblasts (SFs-exo) could significantly induce T cells differentiation in which Th17 cells increased and Treg cells decreased via targeting FOXP3. And thus, miR-424 may be a potential therapeutic target for RA.

Protocatechuic acid inhibits proliferation, migration and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is a chronic joint inflammatory disease that is closely associated with dysregulation of fibroblast-like synoviocytes (FLSs). Protocatechuic acid (PCA), a phenolic compound of anthocyanins, has been proven to possess anti-inflammatory activity. However, the role of PCA in RA has not been investigated. In the present study, we aimed to explore the effects of PCA on the RA-FLSs. The results showed that PCA suppressed the proliferation, invasion, and migration of RA-FLSs in a dose-dependent manner. PCA treatment also inhibited the expressions of matrix metalloproteinase (MMP)-3 and MMP-13, as well as the secretion of inflammatory cytokines including TNF-α, IL-1ß, IL-6 in RA-FLSs. Moreover, cell apoptosis of RA-FLSs was significantly induced by PCA treatment. PCA was found to repress the activation of NF-κB signalling, which was evidenced by the decreased expression of p-p65 and increased expression of IκBα. Furthermore, PCA significantly decreased the phosphorylation levels of Akt and mTOR in RA-FLSs. In conclusion, the results indicated that PCA exhibited an inhibitory effect on RA-FLSs via inhibiting the NF-κB and Akt/mTOR signalling pathways. These findings supported the concept that PCA might be a therapeutic agent for RA treatment.

MMP2 and MMP10 Polymorphisms Are Related to Steroid-Induced Osteonecrosis of the Femoral Head among Chinese Han Population.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head is a relatively serious condition which seriously reduces patient quality of life. However, the pathogenesis of steroid-induced ONFH is still unclear. In recent years, more scholars have found that the pathogenesis of steroid-induced ONFH is related to susceptibility factors such as MMPs/TIMPs system. The main purpose of this study is to investigate the correlation between MMP2 and MMP10 gene polymorphisms and steroid-induced ONFH in Chinese Han population. METHODS: Six SNPs in MMP2 and two SNPs in MMP10 were genotyped using Agena MassARRAY RS1000 system from 286 patients of steroid-induced ONFH and in 309 healthy controls. The association between MMP2 and MMP10 polymorphisms and steroid-induced ONFH risk were estimated by the Chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. The relative risk was estimated by odd ratios (ORs) and 95% confidence intervals (CIs). RESULT: We found that the minor TG allele of rs470154 in MMP10 was associated with an increased risk of steroid-induced ONFH (OR = 1.45, 95% CI, 1.03 - 2.05, p = 0.032). In the genetic model analysis, we found that rs2241146 in MMP2 gene and rs470154 in MMP10 gene showed a statistically significant association with increased risk of steroid-induced ONFH. The six SNPs (rs470154, rs243866, rs243864, rs865094, rs11646643, and rs2241146) showed a statistically significant association with different clinical phenotypes. CONCLUSION: Our results verify that genetic polymorphisms of MMP2 and MMP10 contribute to steroid-induced ONFH susceptibility in the population of Chinese Han population, and our study provides new insights into the role that MMP2 and MMP10 plays in the mechanism of ONFH.

Significant association between RETN genetic polymorphisms and alcohol-induced osteonecrosis of femoral head.

BACKGROUND: Alcohol-induced osteonecrosis of femoral head (ONFH) is a complex disease and genetic factors are one of the causes. The purpose of this study is to investigate the effects of RETN (resistin; OMIM: 605565) and LDLR (low density lipoprotein receptor; OMIM: 606945) polymorphisms on the risk of alcohol-induced ONFH in Chinese Han population. METHODS: A case-control study including 201 patients and 201 controls was designed. Seven single nucleotide polymorphisms (SNPs) in RETN gene and four SNPs in LDLR gene were genotyped using Agena MassARRAY platform. In allele model and genetic model, chi-square test and logistic regression were used to study the associations between these SNPs and ONFH susceptibility. In addition, the relationships between these SNPs, clinical phenotypes, and blood lipid level with one-way analysis of variance were analyzed. RESULTS: In the allele model, rs7408174 and rs3745369 in RETN were associated with increased risk of alcohol-induced ONFH, whereas rs34861192 and rs3219175 in RETN showed reduced risk of alcohol-induced ONFH. In the genetic model, rs7408174 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. Rs3745369 showed an increased risk in codominant model, recessive model, and log-additive model. Rs34861192 showed a decreased risk in codominant model, dominant model, and log-additive model, and rs3219175 showed a decreased risk in dominant model and log-additive model. The rs3745368 in RETN was associated with the clinical stage of the disease. CONCLUSION: These results suggest that RETN genetic polymorphisms are associated with the susceptibility of alcohol-induced ONFH in Chinese Han population.

Association between MMP-3 polymorphisms among Chinese patients with osteonecrosis of the femoral head.

Many potential causative factors are related to the initiation and progression of osteonecrosis of the femoral head (ONFH). The matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMPs/TIMPs) system was found to play a significant role in the development of ONFH. The aim of this study is to investigate the association between polymorphisms of MMP-3 and ONFH in the Chinese population. We selected 8 single-nucleotide polymorphisms (SNPs) in 2 genes selected from the MMPs/TIMPs system in a case-control study with 585 cases of ONFH and 507 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. We found that the minor allele of rs650108 and rs522616 (p<0.05) was assumed a risk allele compared to the wild-type allele. In the genetic model analysis, We observed two susceptibility SNPs additionally: rs650108, dominant model analyses (with adjustment: OR=0.73; 95%CI 0.56-0.95; p=0.017) and additive model analyses (with adjustment: OR=0.83; 95%CI 0.70-0.99; p=0.044); and rs522616 recessive model analyses (with adjustment: OR=1.52; 95%CI 1.07-2.14; p=0.018) and additive model analyses (with adjustment: OR=1.21; 95% CI 1.02-1.44; p=0.033). Our results verify that genetic variants of MMP3 contribute to ONFH susceptibility in the population of northern China. In addition, we found that gender differences might interact with MMP3 polymorphisms to contribute to the overall susceptibility to ONFH.