Butein, a potential drug for the treatment of bone cancer pain through bioinformatic and network pharmacology.

Bone cancer pain is a difficult-to-treat pathologic condition that impairs the patient's quality of life. The effective therapy options for BCP are restricted due to the unknown pathophysiology. Transcriptome data were obtained from the Gene Expression Omnibus database and differentially expressed gene extraction was performed. DEGs integrated with pathological targets found 68 genes in the study. Butein was discovered as a possible medication for BCP after the 68 genes were submitted to the Connectivity Map 2.0 database for drug prediction. Moreover, butein has good drug-likeness properties. To collect the butein targets, we used the CTD, SEA, TargetNet, and Super-PRED databases. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed butein's pharmacological effects, indicating that butein may aid in treating BCP by altering the hypoxia-inducible factor, NF-kappa B, angiogenesis, and sphingolipid signaling pathways. Moreover, the pathological targets integrated with drug targets were obtained as the shared gene set A, which was analyzed by ClueGO and MCODE. Biological process analysis and MCODE algorithm further analyzed that BCP related targets were mainly involved in signal transduction process and ion channel-related pathways. Next, we integrated targets related to network topology parameters and targets of core pathways, identified PTGS2, EGFR, JUN, ESR1, TRPV1, AKT1 and VEGFA as butein regulated hub genes by molecular docking, which play a critical role in its analgesic effect. This study lays the scientific groundwork for elucidating the mechanism underlying butein's success in the treatment of BCP.

Research focus and thematic trends of transient receptor potential vanilloid member 1 research: a bibliometric analysis of the global publications (1990-2023).

Recently, various studies have been devoted to the study of transient receptor potential vanilloid member 1 (TRPV1)-related diseases, potential drugs, and related mechanisms. The objective of this investigation was to examine the significant areas and cutting-edge developments in TRPV1 study within recent decades. Articles or reviews were obtained from the Web of Science Core Collection. VOSviewer 1.6.18 and CiteSpace 6.1 R2 software were utilized to examine publication growth, distribution by country/region, institution, journal, authorship, references, and keywords. The software identified keywords with a high citation burstiness to determine emerging topics. From 1990 to 2023, the annual global publications increased by 62,000%, from 1 to 621. Journal of neuroscience published the most manuscripts and Nature produced the highest citations. The USA, Seoul National University and Di marzo V were the most productive and impactful institution, country, and author, respectively. "TRPV1," "Capsaicin receptor," "Activation," and "Pain" are the most important keywords. The burst keywords "TRPV1 channel," "Oxidative stress," "TRPV1 structure," and "Cancer" are supposed to be the research frontiers. The present study offers valuable insights into the understanding of TRPV1 and pain-related conditions. The research on TRPV1 has demonstrated a steady increase in studies related to pain-related diseases in the past few decades. The significance of TRPV1 in cancer pathogenesis and the resolution of its structure will emerge as a new academic trend in this field, providing direction for more widespread and comprehensive studies in the future.

Analysis of CFTR gene expression as an immunological and prognostic biomarker in pan-cancers.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel that regulates fluid homeostasis via ATP binding and uses energy to transport relevant substrates across cytomembranes. It has been reported that CFTR plays a crucial role in the incidence and development of various types of cancers by regulating proliferation, metastasis, invasion and apoptosis. However, aberrant CFTR gene expression across different cancers makes it difficult to propose CFTR as a possible pan-cancer biomarker. Here, multiple databases (ONCOMINE, PrognoScan, Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA)), were accessed to investigate the relationship between CFTR gene expression with the immunological and prognostic roles in pan-cancers. The results showed higher CFTR gene expression in tumor tissues compared to normal tissues for most cancers except for CHOL, ESCA, KICH, LAML, SKCM and STAD. Higher expression of the CFTR gene directly correlated with better prognosis for BRCA, GBM, COAD, KIRP, LAML, LUAD, PRAD, SARC and STAD, and CFTR gene expression was higher in stage Ⅰ_Ⅱ compared to stage Ⅲ_ Ⅳ. Furthermore, CFTR gene expression levels were significantly associated with immune infiltrates and immunocytes, in particular, immune checkpoints, in COAD, LIHC, LUAD and LUSC. In conclusion, CFTR can be used as a prognostic marker for nine types of cancers examined in this study where CFTR expression levels play a vital role in forecasting the clinical efficacy of immune checkpoint suppression therapy.

Adaptive carbon ion radiotherapy for locally advanced non-small cell lung cancer: Organ-sparing potential and target coverage.

BACKGROUND: The dose distribution of carbon ion radiotherapy (CIRT) for locally advanced non-small cell lung cancer (LANSCLC) is highly sensitive to anatomical changes. PURPOSE: To demonstrate the dosimetric benefits of adaptive CIRT for LANSCLC and compare the differences between patients with and without adaptive plans based on dosimetry and clinical effect factors. MATERIALS AND METHODS: Of the 98 patients with LANSCLC receiving CIRT, 31 patients underwent replanning following re-evaluations that revealed changes that would have compromised the dose coverage of the target volume or violated dose constraints. Dosimetric parameters and clinical factors were compared between patients with and without adaptive plans. Multivariate analysis identified factors influencing the adaptive planning. RESULTS: The median number of fractions delivered using adaptive plans was eight (range: 2-18). Adaptive plans ensured target coverage, and the maximum spinal cord dose was significantly decreased (p = 0.02). The median reduction in the maximum spinal cord dose was 10.4 Gy (relative biological effectiveness). Patients with adaptive plans had larger tumor volumes (p < 0.001); the median initial internal gross tumor volumes (iGTVs) of patients with adaptive and nonadaptive plans were 125.9 and 49.79 cm3 , respectively. Tumor volumes of patients with adaptive plans were altered to a greater extent (p < 0.001); the median absolute percentage of volume changes in patients in the adaptive and in nonadaptive groups were 20.76% and 3.63%, respectively, while the median movements of iGTV centers were 5.75 and 2.44 mm, respectively. Binary logistic regression analysis revealed that the iGTV volume change and iGTV center movements were significantly different between the groups. CONCLUSIONS: An adaptive plan can effectively ensure target area coverage and protect normal tissues, especially in patients with large tumor volumes and substantial changes. iGTV volume changes and iGTV center movements are the main factors influencing adaptive planning. Weekly simulation computed tomography scans are necessary for treatment evaluation in patients with LANSCLC treated with CIRT.

An optimized herbal combination for the treatment of liver fibrosis: Hub genes, bioactive ingredients, and molecular mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is a chronic liver disease that can lead to cirrhosis, liver failure, and hepatocellular carcinoma, and it is associated with long-term adverse outcomes and mortality. As a primary resource for complementary and alternative medicine, traditional Chinese medicine (TCM) has accumulated a large number of effective formulas for the treatment of liver fibrosis in clinical practice. However, studies on how to systematically optimize TCM formulas are still lacking. AIM OF THE REVIEW: To provide a methodological reference for the systematic optimization of TCM formulae against liver fibrosis and explored the underlying molecular mechanisms; To provide an efficient method for searching for lead compounds from natural sources and developing from herbal medicines; To enable clinicians and patients to make more reasonable choices and promote the effective treatment toward those patients with liver fibrosis. MATERIALS AND METHODS: TCM formulas related to treating liver fibrosis were collected from the Web of Science, PubMed, the China National Knowledge Infrastructure (CNKI), Wan Fang, and the Chinese Scientific Journals Database (VIP). Furthermore, the TCM compatibility patterns were mined using association analysis. The core TCM combinations were found by designing an optimized formulas algorithm. Finally, the hub target proteins, potential molecular mechanisms, and active compounds were explored through integrative pharmacology and docking-based inverse virtual screening (IVS) approaches. RESULTS: We found that the herbs for reinforcing deficiency, activating blood, removing blood stasis, and clearing heat were the basis of TCM formulae patterns. Furthermore, the combination of Salviae Miltiorrhizae (Salvia miltiorrhiza Bunge; Chinese salvia/Danshen), Astragali Radix (Astragalus membranaceus (Fisch.) Bunge; Astragalus/Huangqi), and Radix Bupleuri (Bupleurum chinense DC.; Bupleurum/Chaihu) was identified as core groups. A total of six targets (TNF, STAT3, EGFR, IL2, ICAM1, PTGS2) play a pivotal role in TCM-mediated liver fibrosis inhibition. (-)-Cryptotanshinone, Tanshinaldehyde, Ononin, Thymol, Daidzein, and Formononetin were identified as active compounds in TCM. And mechanistically, TCM could affect the development of liver fibrosis by regulating inflammation, immunity, angiogenesis, antioxidants, and involvement in TNF, MicroRNAs, Jak-STAT, NF-kappa B, and C-type lectin receptors (CLRs) signaling pathways. Molecular docking results showed that key components had good potential to bind to the target genes. CONCLUSION: In summary, this study provides a methodological reference for the systematic optimization of TCM formulae and exploration of underlying molecular mechanisms.

Incretin mimetics and sodium-glucose co-transporter 2 inhibitors as monotherapy or add-on to metformin for treatment of type 2 diabetes: a systematic review and network meta-analysis.

PURPOSE: Although there are many different methods of treating type 2 diabetes (T2D), it is still difficult to draw coincident conclusions concerning the efficacy and safety of different classes of new drugs, and the recommendation level of them has still kept uncertain as second anti-diabetic agents. Therefore, the aim of this study was to summarize evidence on the efficacy and safety of DPP-4is, GLP-1RAs and SGLT-2is as monotherapy or add-on to metformin (Met) for treatment of T2D. MATERIALS AND METHODS: We searched PubMed, Embase, Cochrane library and ClinicalTrials.gov for relevant articles in keeping with established methods using terms associated with anti-diabetic agents up to February, 2020, with no start date restriction. Weighted mean difference and risk ratios with 95% confidence intervals were calculated within traditional and network meta-analysis. Primary outcomes were the mean change in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) change and the frequency of hypoglycemic events from baseline after 12 weeks of treatment. RESULTS: In total, 64 eligible studies comprising 37,780 patients and 7 treatment strategies were included. The results of primary outcomes showed that GLP-1RAs were significantly more effective than DPP-4is or SGLT-2is in reducing HbA1c when add-on to Met. For FPG, both GLP-1RAs and SGLT-2is significantly reduced FPG compared with DPP-4is whether add-on to Met or not. For hypoglycemia, monotherapy has a lower risk than combination therapy except for SGLT-2is. Ranking probability analysis indicated that GLP-1RAs and SGLT-2is, respectively, reduced HbA1c and FPG most when add-on to Met. Meanwhile, GLP-1RAs took the lowest risk to induce the hypoglycemia, whereas GLP-1RAs plus Met the highest. CONCLUSIONS: Both GLP-1RAs and SGLT-2is have their own advantages in efficacy and safety. Monotherapy is beneficial for reducing the risk of hypoglycemia. The recommendation should be a patient-centered approach when selecting treatment choices.