Anoikis-related genes in breast cancer patients: reliable biomarker of prognosis.

BACKGROUND: Breast cancer (BC) is the most common cancer in women, and its progression is closely related to the phenomenon of anoikis. Anoikis, the specific programmed death resulting from a lack of contact between cells and the extracellular matrix, has recently been recognized as playing a critical role in tumor initiation, maintenance, and treatment. The ability of cancer cells to resist anoikis leads to cancer progression and metastatic colonization. However, the impact of anoikis on the prognosis of BC patients remains unclear. METHOD: This study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect transcriptome and clinical data of BC patients. Anoikis-related genes (ARGs) were classified into subtypes A and B through consensus clustering. Subsequently, survival prognosis analysis, immune cell infiltration analysis, and functional enrichment analysis were performed for both subtypes. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a set of 10 ARGs related to prognosis was identified. Immune cell infiltration and tumor microenvironment analyses were conducted on these 10 ARGs to develop a prognostic model. Furthermore, single-cell data analysis and real-time polymerase chain reaction (RT-PCR) analysis were employed to study the expression of the 10 identified prognostic ARGs in BC cells. RESULTS: One hundred thirty-five ARGs were identified as differentially expressed genes in the TCGA and GEO databases, with 42 of them associated with the survival prognosis of BC patients. Analyses involving Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Uniform Manifold Approximation and Projection (UMAP) revealed distinct expression patterns of ARGs between types A and B. Patients in type A exhibited worse survival prognosis and lower immune cell infiltration compared to type B. Subsequent analyses identified 10 key ARGs (YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, LAMB3, CD24, SLC2A1, CDC25C, and SLC39A6) relevant to BC prognosis. Kaplan-Meier analysis indicated that high-risk patients based on these ARGs had a poorer BC prognosis. Additionally, Cox regression analysis established gender, age, T (tumor), N (nodes), and risk score as predictive factors in a nomogram model for BC. The model demonstrated diagnostic value for BC patients at 1, 3, and 5 years. Decision curve analysis (DCA) verified the risk score as a reliable predictor of BC patient survival rates. Moreover, RT-PCR results confirmed differential expressions of YAP1, PIK3R1, BAK1, PHLDA2, CD24, SLC2A1, and CDC25C in BC cells, with SLC39A6, EDA2R, and LAMB3 showing low expression levels. CONCLUSION: ARGs markers can be used as BC biomarkers for risk stratification and survival prediction in BC patients. Besides, ARGs can be used as stratification factors for individualized and precise treatment of BC patients.

Sodium hyaluronate and pranoprofen improve visual function and reduce inflammation in patients with dry eye.

OBJECTIVE: The aim of this study was to investigate the clinical use of sodium hyaluronate (SH) combined with pranoprofen in treating patients with dry eye. METHODS: A total of 117 patients with dry eye who were treated in the Traditional Chinese Medicine Hospital of Kunshan from March 2020 and May 2022 were included. According to the therapy approaches, they were treated with SH (SH group), pranoprofen (pranoprofen group), and SH combined with pranoprofen (joint group) (n = 39). RESULTS: The effective rates of dry eye were 79.49%, 74.36% and 94.87% in the SH group, the pranoprofen group and the joint group, respectively (p < 0.05). After treatment, the tear BUT and SIT in the joint group were all prominently increased than those in the other two groups (p < 0.05). The corneal fluorescein staining and dry eye symptom scores in the joint group after treatment were dramatically lower than those in the other two groups (p < 0.001). After treatment, the visual contrast sensitivity (12 c/d, 18 c/d and 24 c/d) in the joint group was markedly higher than those in the other two groups (p < 0.001). The CPR, TNF-α, IFN-γ and IL-1ß levels in the joint group were notably decreased than those in other two groups (p < 0.001). After treatment, the VRQOL quality-of-life scores in the joint group were significantly higher than those in the other two groups (p < 0.05). CONCLUSION: SH combined with pranoprofen showed clear therapeutic benefit in treating dry eye, and the curative effect was more favorable than with either medication alone.

Chemical Constituents from the Heartwood of Solanum Verbascifolium L. And Their Anti-Inflammatory Activities Combined Network Pharmacology.

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 µM (P<0.01) and 40 µM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 µM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications.

Dendrocandin U from Dendrobium officinale Kimura et Migo Inhibits M1 Polarization in Alveolar Macrophage by Suppressing NF-κB Signaling Pathway.

Dendrobium officinale Kimura et Migo is a valuable and homologous medicine and food traditional Chinese medicine. Currently there are few studies on the anti-inflammatory activity of lipophilic components. The aim of this study was to explore the anti-inflammatory effect and mechanism of the lipophilic compounds in Dendrobium officinale. Six compounds were isolated and identified, including three bibenzyl compounds, dendrocandin U, dendronbibisline B, erianin, and three lignans, (-)-syringaresinol, (+)-syringaresinol-O-ß-D-glucopyranoside, 5-methoxy-(+)-isolariciresinol. Among them, dendronbibisline B and 5-methoxy-(+)-isolariciresinol were isolated from Dendrobium officinale for the first time. Besides, we found dendrocandin U, dendronbibisline B and (-)-syringaresinol exhibited the anti-inflammation to inhibit nitric oxide secretion induced by lipopolysaccharide (LPS)/interferon (IFN-γ) in MH-S cells. Furthermore, dendrocandin U could inhibit the expression of tumor necrosis factor-α (TNF-α), Cluster of Differentiation 86 (CD86), and reduce inflammatory morphological changes of macrophages. Meanwhile, we confirmed that the anti-inflammation mechanism of dendrocandin U was to inhibit M1 polarization by suppressing toll-like receptor 4 (TLR4)/recombinant myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. In this paper, dendrocandin U with significant anti-inflammatory activity was found from Dendrobium officinale, which could provide a basis for the study of its anti-inflammatory drugs.

Recent progress in advanced biomaterials for long-acting reversible contraception.

Unintended pregnancy is a global issue with serious ramifications for women, their families, and society, including abortion, infertility, and maternal death. Although existing contraceptive strategies have been widely used in people's lives, there have not been satisfactory feedbacks due to low contraceptive efficacy and related side effects (e.g., decreased sexuality, menstrual cycle disorder, and even lifelong infertility). In recent years, biomaterials-based long-acting reversible contraception has received increasing attention from the viewpoint of fundamental research and practical applications mainly owing to improved delivery routes and controlled drug delivery. This review summarizes recent progress in advanced biomaterials for long-acting reversible contraception via various delivery routes, including subcutaneous implant, transdermal patch, oral administration, vaginal ring, intrauterine device, fallopian tube occlusion, vas deferens contraception, and Intravenous administration. In addition, biomaterials, especially nanomaterials, still need to be improved and prospects for the future in contraception are mentioned.

Accuracy improvement of laser tracker registration based on enhanced reference system points weighting self-calibration and thermal compensation.

Improving the accuracy of large measurement systems consisting of multiple laser trackers and Enhanced Reference System (ERS) points is technically challenging. In practice, standard devices with precise distance limits are often used to improve the registration accuracy of laser trackers. However, these standard devices are expensive and need to be calibrated by the Coordinate Measuring Machine (CMM). In addition, the stability of ERS points can significantly affect registration errors. Therefore, this paper proposes a laser tracker registration method based on ERS point-weighted self-calibration and thermal deformation compensation. First, a self-calibration method for simple standard devices based on multilateration measurements is presented, which only utilizes large measurement systems without additional high-precision measurement instruments. Based on this, a weighted registration optimization algorithm for the registration process of a relocation laser tracker is proposed. Then, the position errors of ERS points caused by temperature changes are calculated and compensated based on the thermal deformation coefficient of large structural components. The compensated ERS points are used for the registration of the laser trackers. Finally, the effectiveness of the proposed method is demonstrated by a field measurement experiment on a large spherical shell. Compared with the most widely used benchmark method, the proposed method reduces the average registration error of all ERS points from 0.103 to 0.02 mm.

Potential role of lncRNA LOXL1-AS1 in human cancer development: a narrative review.

Background and Objective: Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs consisting of more than 200 nucleotides that are widely involved in various physiological and pathobiological processes in the body. LncRNA plays a crucial role in tumorigenesis and development with its unique functions, such as playing a role in a variety of biological processes of malignant tumors as a cancer-promoting factor or a cancer-suppressor factor. Lysyl oxidase-like protein 1-antisense RNA1 (LOXL1-AS1) is a novel functional lncRNA recently reported. This article reviews the current findings on the role of LOXL1-AS1 in cancer, and discusses the potential clinical significance and application prospects, in order to provide a theoretical basis and reference for the clinical diagnosis, treatment and screening of prognostic markers for malignant tumors. Methods: The PubMed and Embase databases were searched using the keywords "cancer" or "tumor" or "neoplasm" and "LOXL1-AS1" for publications from 2018 to the present. The English literature was searched, with a focus on relevant articles. These articles validated the role and mechanism of LOXL1-AS1 in different cancers. Key Content and Findings: LOXL1-AS1 is a recently reported novel lncRNA, which is abnormally expressed and upregulated in more than ten cancers, and is positively correlated with adverse clinical features and poor prognosis in cancer patients. LOXL1-AS1 competently binds to a variety of microRNAs to regulate the expression of downstream target genes and regulate related signaling pathways, including proliferation, migration, invasion and inhibition of malignant biological behaviors such as apoptosis. Conclusions: LOXL1-AS1 is expected to become a novel biomarker for cancer diagnosis and treatment, with great potential as an independent prognostic indicator.

Analysis of the potential biological value of pyruvate dehydrogenase E1 subunit ß in human cancer.

BACKGROUND: The pyruvate dehydrogenase E1 subunit ß (PDHB) gene which regulates energy metabolism is located in mitochondria. However, few studies have elucidated the role and mechanism of PDHB in different cancers. AIM: To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer. In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer. METHODS: Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas (TCGA) database. Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases. Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients. The correlation between PDHB and receiver operating characteristic diagnostic curve, clinicopathological staging, somatic mutation, tumor mutation burden (TMB), microsatellite instability (MSI), DNA methylation, and drug susceptibility in pan-cancer was also analyzed. Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment, as well as the co-expression analysis of PDHB and immune checkpoint (ICP) genes. The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing, and the functional enrichment analysis of PDHB-related genes was performed. The study also validated the level of mRNA or protein expression of PDHB in several cancers. Finally, in vitro experiments verified the regulatory effect of PDHB on the proliferation, migration, and invasion of liver cancer. RESULTS: PDHB was significantly and differently expressed in most cancers. PDHB was significantly associated with prognosis in patients with a wide range of cancers, including kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, breast invasive carcinoma, and brain lower grade glioma. In some cancers, PDHB expression was clearly associated with gene mutations, clinicopathological stages, and expression of TMB, MSI, and ICP genes. The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment. In addition, single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells. This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation, migration, and invasion functions of hepatoma cells. CONCLUSION: As a member of pan-cancer, PDHB may be a novel cancer marker with potential value in diagnosing cancer, predicting prognosis, and in targeted therapy.

Effect evaluation of different preventive measures for ileus after abdominal operation: A systematic review and network meta-analysis.

Background: Different approaches to the prevention of postoperative ileus have been evaluated in numerous randomized controlled trials. This network meta-analysis aimed to investigate the relative effectiveness of different interventions in preventing postoperative ileus. Methods: Randomized controlled trials (RCTS) on the prevention of postoperative ileus were screened from Chinese and foreign medical databases and compared. STATA software was used for network meta-analysis using the frequency method. Random-effects network meta-analysis was also used to compare all schemes directly and indirectly. Results: A total of 105 randomized controlled trials with 18,840 participants were included in this report. The results of the network meta-analysis showed that intravenous analgesia was most effective in preventing the incidence of postoperative ileus, the surface under the cumulative ranking curve (SUCRA) is 90.5. The most effective intervention for reducing the first postoperative exhaust time was postoperative abdominal mechanical massage (SUCRA: 97.3), and the most effective intervention for reducing the first postoperative defecation time was high-dose opioid antagonists (SUCRA: 84.3). Additionally, the most effective intervention for reducing the time to initiate a normal diet after surgery was accelerated rehabilitation (SUCRA: 85.4). A comprehensive analysis demonstrated the effectiveness and prominence of oral opioid antagonists and electroacupuncture (EA) combined with gum. Conclusion: This network meta-analysis determined that oral opioid antagonists and EA combined with chewing gum are the most effective treatments and optimal interventions for reducing the incidence of postoperative ileus. However, methods such as abdominal mechanical massage and coffee require further high-quality research.

Evaluation of the Effect and Mechanism of Sanhuang Ointment on MRSA Infection in the Skin and Soft Tissue via Network Pharmacology.

Introduction: Skin and soft tissue infection (SSTI) is a frequently encountered clinical disease, and Sanhuang ointment, a traditional Chinese medicine, is used to treat it. However, the pharmacological effect of Sanhuang ointment on SSTI and its underlying mechanism remains unclear. Here, we investigate the protective effect of Sanhuang ointment on Methicillin-resistant Staphylococcus aureus (MRSA) infection in the skin and soft tissues and the underlying mechanism by network pharmacological analysis, followed by in vivo experimental validation. Methods: Via network pharmacology, the active components and disease targets of Sanhuang ointment were screened and intersected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A rat model of skin and soft tissue infection was established, and pathological features were observed. Large, medium, and small-dose groups (1 g, 0.5 g, and 0.25 g/animal, with the total amount of Vaseline, dispensed 1 g/animal) of Sanhuang ointment were prepared and Mupirocin ointment was used as a positive control (0.5 g/animal, with the total amount of Vaseline, dispensed 1 g/animal). The expressions of key proteins of the IL-17/NF-κB signaling pathway and downstream inflammatory factors were analyzed by histomorphological analysis, enzyme-linked immunosorbent assay, polymerase chain reaction, and Western blotting. Results: In all, 119 active components and 275 target genes of Sanhuang ointment were identified and intersected with MRSA infection-related genes via network pharmacology analysis, and 34 target genes of Sanhuang ointment were found to be involved in skin and soft tissue infections with MRSA. Sanhuang ointment (1 g/mouse) could effectively ameliorate histopathological changes and significantly inhibit the expression of key proteins involved in the IL-17/NF-κB signaling pathway and downstream inflammatory factors (p < 0.05). Conclusion: Sanhuang ointment has a protective effect on MRSA infection and inhibits inflammation by inhibiting the IL-17/NF-κB signaling pathway. Our findings are important for the secondary development and new drug development of Sanhuang ointment.

Chitosan-CaP microflowers and metronidazole loaded calcium alginate sponges with enhanced antibacterial, hemostatic and osteogenic properties for the prevention of dry socket after tooth removal.

Tooth removal, particularly for patients with severe periodontitis, can frequently cause massive bleeding, postoperative infection, and bone resorption, resulting in a dry socket. Thus, developing bio-multifunctional materials with excellent antibacterial, hemostatic, and osteogenic characteristics for the prevention of dry sockets after tooth removal is highly desirable in clinical applications. Herein, chitosan-CaP microflowers (CM) and metronidazole (MD) loaded calcium alginate (CA) sponges (CA@CM/MD) with enhanced antibacterial, hemostatic, and osteogenic properties were developed via Ca2+ crosslinking, lyophilization, and electrostatic interaction for the prevention of dry socket after tooth removal. The fabricated CM particles display 3-dimensional, relatively homogeneous, and flower-shaped architectures. The CA@CM/MD composite sponges were facilely shaped into the tooth root as well as exhibit interconnected porous and lamellar structures with remarkable porosity, suitable maximum swelling ratio, as well as excellent compressive and hemostatic performance. Besides, the in vitro cellular assessment demonstrates that the prepared CA@CM/MD composite sponges possess satisfactory cytocompatibility. Importantly, the designed sponges significantly suppress the growth of S. aureus and E. coli, as well as promote cellular osteogenic differentiation by upregulating the formation of alkaline phosphatase. Our findings indicate that the tooth root-shaped composite sponges hold great promise for wound management after tooth removal.