Trimethyl chitosan–cysteine-based nanoparticles as an effective delivery system for portulacerebroside A in the management of hepatocellular carcinoma cells <i>in vitro</i> and <i>in vivo</i>

Portulacerebroside A (PCA), a cerebroside compound extracted from Portulaca oleracea L., has been shown to suppress hepatocellular carcinoma (HCC) cells. This study aims to investigate the effectiveness of trimethyl chitosan–cysteine (TMC-Cys) nanocarrier in delivering PCA for HCC management and to elucidate the molecular mechanisms behind PCA’s function. TMC-Cys nanocarriers notably augmented PCA’s function, diminishing the proliferation, migration, and invasiveness of HCC cells in vitro, reducing hepatocellular tumorigenesis in immunocompetent mice, and impeding metastasis of xenograft tumours in nude mice. Comprehensive bioinformatics analyses, incorporating Super-PRED systems alongside pathway enrichment analysis, pinpointed toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EGFR) as two promising targets of PCA, enriched in immune checkpoint pathway. PCA/nanocarrier (PCA) reduced levels of TLR4 and EGFR and their downstream proteins, including programmed cell death ligand 1, thereby increasing populations and activity of T cells co-cultured with HCC cells in vitro or in primary HCC tumours in mice. However, these effects were counteracted by additional artificial activation of TLR4 and EGFR. In conclusion, this study provides novel evidence of PCA’s function in immunomodulation in addition to its direct tumour suppressive effect. TMC-Cys nanocarriers significantly enhance PCA efficacy, indicating promising application as a drug delivery system.</p

Additional file 1 of A novel multifunctional microneedle patch for synergistic photothermal- gas therapy against maxillofacial malignant melanoma and associated skin defects

Additional file 1: Figure S1. (a) Photographs of SNP-Fe mixtures before (left) and after (right) UV irradiation. (b) FTIR spectrum of SNP-Fe mixtures before and after UV irradiation. (c) XRD of SNP-Fe mixtures before and after UV irradiation. (d) The absorption spectrum of SNP-Fe2+ solution before and after UV irradiation. (e) The concentration of NO in groups before and after the irradiation of NIR. Figure S2. Images of skin after pressing with MNs for 1 min. Figure S3. Images indicating migration of B16 cells (stained with crystal violet, rightmost row) after coculturing with SNP-Fe@MNs-NIR(−)-NO(+), SNP-Fe@MNs-NIR(+)-NO(−) and SNP-Fe@MNs-NIR(+)-NO(+). Figure S4. Proposed mechanisms of SNP-Fe@MNs dominated apoptosis via caspase 3-dependent HSP-70/HSP-90/AKT mediated signaling pathways. HSP-70, that abundant in cancers, proved to inhibit apoptosis through caspase-dependent mechanism by suppressing c-Jun N-terminal kinase (JNK), caspase-independent mechanism by suppressing apoptosis-inducing factor (AIF) and via the interaction with death receptors. In consequence, the upregulated of caspase 3 and down-regulated HSP-70/HSP-90/AKT and Ki67 induced the inhibition of tumor growth [1–3]. Figure S5. The weight-curve of dissected tumor in groups of Control, SNP-Fe@MNs-NIR(−)-NO(+), SNP-Fe@MNs-NIR(+)-NO(−) and SNP-Fe@MNs-NIR(+)-NO(+), respectively (n = 5. * P 0.05). Figure S7. H&E staining of skin and major organs of mice. Table S1. Primer - sequence used in this experiment

Diagram of steam chamber with sample and water steam.

<p>(a) top view (b) side view. Note that the specimen was machined from a human 3rd molar sliced in the buccal direction and with the in-plane tubules perpendicular to heat flow direction.</p

SEM image of human dentine microstructures showing solid dentine material and tubules.

<p>The heat flow is perpendicular to the DEJ interface.</p

TEM image of human enamel, dentin-enamel junction and dentine.

<p>The heat flow is from enamel(E) to dentine(D), (b) is the DEJ image after demineralization. (a):enamel, (b):dentin-enamel junction, (c):dentine</p

Images acquired 1, 2, 10, 20, 100 and 200 second from the beginning of testing of a tooth section surface acquired to determine spatial and temporal surface temperature variations.

<p>Each image in two directions corresponds to an area of 32mm (x) by 24mm (y).</p

DataSheet_2_Association between periodontitis and endometriosis: a bidirectional Mendelian randomization study.docx

IntroductionA potential association between periodontitis and endometriosis has been indicated in previous observational studies. Nevertheless, the causal link between these two disorders has not been clarified.MethodsBased on publicly available genome-wide association study (GWAS) summary datasets, we conducted a bidirectional Mendelian randomization (MR) study to investigate the relationship between periodontitis and endometriosis and its subtypes. Single nucleotide polymorphisms (SNPs) strongly associated with candidate exposures at the genome-wide significance level (P −8) were selected as instrumental variables (IVs). The inverse variance-weighted regression (IVW) was performed to estimate the causal effect of periodontitis on endometriosis. We further conducted two sensitivity analyses, MR-Egger and weighted median, to test the validity of our findings. The main results were replicated via data from the UK Biobank. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causality.ResultsThe IVW method suggested that periodontitis was positively associated with endometriosis of the pelvic peritoneum (OR = 1.079, 95% CI = 1.016 to 1.146, P = 0.014). No causal association was indicated between periodontitis and other subtypes of endometriosis. In reversed analyses, no causal association between endometriosis or its subtypes and periodontitis was found.ConclusionsOur study provided genetic evidence on the causal relationship between periodontitis and endometriosis of the pelvic peritoneum. More studies are necessary to explore the underlying mechanisms.</p

Table_1_A cross-sectional mental-health survey of Chinese postgraduate students majoring in stomatology post COVID-19 restrictions.docx

BackgroundThe psychological status of Chinese postgraduate students majoring in stomatology after the COVID-19 restrictions still remains unclear. The objective of this study is to evaluate the mental status through a cross-sectional survey and gather related theoretical evidence for psychological intervention on postgraduate students majoring in stomatology.MethodsAn online survey was administered, and subjective well-being, anxiety, stress and depression symptoms were assessed using the 5-item World Health Organization Well-Being Index (WHO-5), item Generalized Anxiety Disorder Scale (GAD-7), 10-item Perceived Stress Scale (PSS-10), and Patient Health Questionnaire-9 (PHQ-9), respectively, wherein suicidal ideation and sleep-related problems were measured with PHQ-9 and Insomnia Severity Index (ISI).ResultsA total of 208 participants who completed one questionnaire were considered as valid. It was found that female respondents generally exhibited significantly higher levels of PSS-10, PHQ-9, and GAD-7 scores and shorter physical activity hours than male students. Students from rural areas demonstrated significantly higher levels of PHQ-9, suicidal ideation, and less portion of good or fair family economic support. Additionally, individuals from only-child families reported increased levels of activity hours (1.78 ± 2.07, p = 0.045) and a higher portion (55.10%, p = 0.007) of having clear future plan as compared with multiple-child families. The risk factors for anxiety symptoms (GAD-7 score) were higher scores of PSS-10 (OR = 1.15, 95% CI = 1.09–1.22), PHQ-9 (OR = 1.35, 95% CI = 1.22–1.49), and ISI-7 (OR = 1.14, 95% CI = 1.06–1.23), while owning a clear graduation plan was the protective factor (OR = 0.55, 95% CI = 0.31–0.98). Moreover, the risk factors for depressive symptoms (PHQ-9) included PSS-10 (OR = 1.10, 95% CI = 1.04–1.16), GAD-7 (OR = 1.38, 95% CI = 1.25–1.52), suicidal ideation (OR = 5.66, 95% CI = 3.37–9.51), and ISI-7 (OR = 1.17, 95% CI = 1.09–1.25). Approximately 98.08% of Chinese postgraduates studying stomatology reported experiencing at least moderate stress after the COVID-19 restrictions.ConclusionWithin the limitations of this study, senior students were more inclined to stress, while anxiety symptoms were related to severer levels of stress, depression, and insomnia. Depressive symptoms were associated with higher levels of stress, anxiety, insomnia, suicidal ideation, and lower levels of self-reported well-being. Thus, psychological interventions for postgraduates should be timely and appropriately implemented by strengthening well-being, reasonably planning for the future, and good physique, thereby mitigating the psychological issues after COVID-19 restrictions.</p