Recent patents on anti-cancer drug discovery最新文献

{"title":"Construction and Identification of a Human Colorectal Adenoma Epithelial Cell Line by SV40 Large T-Antigen Transfection.","authors":"Xiangxue Meng, Xinyue Han, Xiangying Lin, Guanhong Li, Jingnan Wang, Ao Sun, Xiaochen Fu, Bowen Xu, Donghua Yang, Yanping Wu, Min Zhang, Xiaoling Fu","doi":"10.2174/0115748928297500240522080820","DOIUrl":"https://doi.org/10.2174/0115748928297500240522080820","url":null,"abstract":"<p><strong>Background: </strong>Colorectal adenoma represents the critical step in the development of colorectal cancer. The establishment of an immortalized epithelial cell line of colorectal adenoma of human origin would provide a tool for studying the mechanism of precancerous lesions, screening the efficacy of novel drugs, and constructing in vivo disease models. Currently, there is no commercially available stable supply of epithelial cells from precancerous lesions.</p><p><strong>Aims: </strong>This study aimed to establish a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection.</p><p><strong>Methods: </strong>Simian vacuolating virus 40(SV40), SV40-LT overexpressed lentivirus vector, was transfected into primary human colorectal adenomatous polyp epithelial cells. The transfected cells were screened, and the screened cells were amplified to obtain the epithelial cell line: IHCRA- CELL. The cells were identified by morphological observation, cell proliferation, Quantitative real-time PCR (qPCR), and Short Tandem Repeats (STR) experiments. Morphologically, the cells showed epithelial-like characteristics, such as polygon shape, desmosomes mitochondria, and strong positive keratin staining. There was no significant difference between the transfected cells and the primary cells. Through the STR identification experiment, no matching cell lines were found in the cell lines retrieval.</p><p><strong>Conclusion: </strong>We successfully established a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection, which has been patented and is now preserved in the Chinese Typical Culture Preservation Center. It was verified that the transformed cells maintained the phenotype and biological characteristics of epithelial cells. This cell line can be used to study the mechanism of precancerous lesions, screen the efficacy of novel drugs, and construct in vivo disease models.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NIFK, a Potential Prognostic and Immunological Biomarker in Pan-- Cancer Analysis, Significantly Regulates Proliferation and Metastasis of Colorectal Cancer.","authors":"Zhuoyuan Li, Shangbo Zhou, Ting Bin, Yuntao Shi, Leli Zeng, Bo Li, Jia Li, Yulong He, Changhua Zhang","doi":"10.2174/0115748928295346240406185103","DOIUrl":"https://doi.org/10.2174/0115748928295346240406185103","url":null,"abstract":"BACKGROUND\u0000As a binding protein of Ki67, NIFK plays an important role in the mitosis of cells and is closely related to the progression of specific types of tumors. However, there is still a lack of systematic analysis of NIFK in pan-cancer and insufficient research to explore its role in human tumors.\u0000\u0000\u0000METHODS\u0000We systematically evaluated the pan-cancer expression and mutation of NIFK in human cancers using data from The Cancer Genome Atlas (TCGA) through large-scale bioinformatics analysis. In addition, we explored the pan-cancer immunological characteristics of NIFK, especially in colorectal adenocarcinoma (COAD). Furthermore, we used single-cell sequencing to analyze the expression of NIFK in different cells of COAD tissues and performed GO, KEGG, and gene set enrichment analysis of NIFK in COAD. Lastly, we evaluated the effects of NIFK knockdown on the colorectal cancer cell lines in in vitro experiment.\u0000\u0000\u0000RESULTS\u0000We found that NIFK was overexpressed in almost all types of tumors and showed significant prognostic efficacy. Additionally, correlations between NIFK and specific immune features, such as immune cell infiltration, immune checkpoint genes, TMB, and MSI, suggest that NIFK may be used to guide immunotherapy. Subsequently, it was found that the expression of NIFK was significantly upregulated in tumor cells through single-cell sequencing analysis, and the NIFK gene was closely associated with tumor progression and immune therapy response. Finally, we further elucidated the role of NIFK in colorectal cancer and found that downregulation of NIFK expression could inhibit the proliferation, migration, and invasion ability of colorectal cancer cells.\u0000\u0000\u0000CONCLUSION\u0000The results of this study demonstrated that NIFK, as a member of the pan-cancer genes, will serve as a biomarker and a potential therapeutic target for a range of cancer types, providing new insight into precision medicine.","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"20 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140660410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival Benefits of Ganoderma Lucidum in Early-stage Triple-negative Breast Cancer: A Real World Study.","authors":"Baohong Jiang, Na Li, Wei Du, Lijun Zeng, Yuanbin Tang, Lunqi Luo, Hongbo Zhu, Feng Ye","doi":"10.2174/0115748928282946240111114448","DOIUrl":"https://doi.org/10.2174/0115748928282946240111114448","url":null,"abstract":"<p><strong>Background: </strong>Ganoderma lucidum extracts are widely used as adjuvants in the treatment of triple-negative breast cancers (TNBC) in China. However, its clinical value in TNBC remains unclear. Therefore, we investigated the clinical effect of Ganoderma lucidum spore powder (GLSP) on prognosis in patients with early-stage TNBC in this study.</p><p><strong>Methods: </strong>A total of 388 patients who were diagnosed with TNBC at the Sun Yat-sen University Cancer Center from February 2012 to December 2017 were retrospectively reviewed. The propensity score matching (PSM) method was applied to balance baseline data. Kaplan-Meier method and Cox proportional hazards model were used to evaluate the relationship between GLSP and prognosis.</p><p><strong>Results: </strong>Of the 388 patients, 72 (18.6%) patients took GLSP. After PSM, 208 patients were selected for analysis, including 71 (34.1%) patients who took the powder. The median followup period was 51 months. The patients who took GLSP (the treatment group) and those who did not take GLSP (the control group) were similar in most clinico-pathological features before being matched. However, the proportion of patients who received breast-conserving surgery in the treatment group was higher (27.8% vs. 16.1%; p =0.021) than in the control group. No significant difference was found in the baseline data between the two groups for the matched cohort (all p >0.05). Univariate analysis and multivariate analysis showed that patients taking GLSP benefited from improved overall survival (OS) (HR=0.159, p = 0.002) and disease-free survival (DFS) (HR=0.232, p = 0.005) before being matched. The main result of the survival analysis after matching was similar to that described above. Patients in the treatment group achieved both greater OS and DFS benefits than patients in the control group (all p < 0.05). In stratified analysis according to TNM stages, after adjusting for the significant prognostic factors, multivariate analysis revealed that the treatment group had better OS than the control group for patients in stages II and III (HR=0.172, p =0.004).</p><p><strong>Conclusions: </strong>The results of this real-world propensity-score-matched study suggest that GLSP can improve OS and DFS in early-stage TNBC patients. A higher OS was observed for patients taking GLSP, particularly in stage II and stage III.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of Candidate Inflammatory Markers of Epithelial Cells in Hepatocellular Carcinoma Based on Integration Analysis of TCGA/ICGC Databases and Single-cell Sequencing.","authors":"Zupin Huang, Zhuokai Li, Xinliang Lv, Wei Tan","doi":"10.2174/0115748928256530240124093759","DOIUrl":"https://doi.org/10.2174/0115748928256530240124093759","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular Carcinoma (HCC) is closely linked to inflammatory reactions, with chronic liver diseases acting as major risk factors. In the inflammatory microenvironment, repeated damage and repair of liver cells lead to genetic mutations, abnormal proliferation, and tumorigenesis.</p><p><strong>Objective: </strong>This study aimed to investigate the expression profile of specific cell clusters under inflammatory stimulation in HCC and identify potential therapeutic drugs.</p><p><strong>Methods: </strong>Comprehensive analysis of HCC transcriptome data and single-cell sequencing data from TCGA, ICGC, and GEO databases was conducted to explore the specific molecular mechanisms of epithelial cells. Virtual screening of natural compounds in the ZINC database and in vitro cell experiments were performed to identify drugs that regulate the expression of inflammatory factors in epithelial cells.</p><p><strong>Results: </strong>Analysis of the single-cell dataset revealed cell clusters closely associated with HCC, notably Epithelial cells, Hepatocytes, MSC, and iPS cells, with Epithelial cells playing a pivotal role in HCC development. Further investigation of TCGA data unveiled 83 differentially expressed genes (DEGs) related to inflammatory responses in HCC. Intersection analysis of DEGs in epithelial cells and HCC DEGs identified 12 common DEGs, including ADRM1, ATP2B1, FZD5, GPC3, KIF1B, KLF6, LY6E, MET, NAMPT, SERPINE1, SPHK1, and SRI. Prognostic analysis revealed that CCL7, GPR132, ITGB8, PTAFR, SELL, and VIP were influential in the survival prognosis of HCC. A prognostic model based on the expression levels of these genes demonstrated an increased risk of HCC associated with higher differential expression of inflammatory response genes. Additionally, molecular dynamics simulations indicated that compounds NADH and Deferoxamine formed stable docking models with the inflammatory protein VIP, suggesting their potential as candidates for targeted therapy.</p><p><strong>Conclusion: </strong>Inflammatory factors CCL7, GPR132, ITGB8, PTAFR, SELL, and VIP influence the inflammatory cascade response in HCC epithelial cells, and their expression correlates with the survival prognosis of HCC patients. Interfering with VIP expression effectively suppresses proliferation, migration, and invasion of HCC cells, as well as inhibiting the occurrence of inflammatory cascade reactions, thus slowing down the progression of hepatocellular carcinoma. Furthermore, compounds NADH and Deferoxamine have the potential to target and bind to the inflammatory protein VIP, highlighting their relevance in potential HCC treatment.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139652484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin Use and Hepatocellular Carcinoma Risk: A Comprehensive Meta- Analysis and Systematic Review.","authors":"Mahmood Reza Hashemi Rafsanjani, Rasoul Rahimi, Saeid Heidari-Soureshjani, Mohammad Darvishi, Omid-Ali Adeli, Saber Abbaszadeh","doi":"10.2174/0115748928282686231221070441","DOIUrl":"https://doi.org/10.2174/0115748928282686231221070441","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular Carcinoma (HCC) is a public health problem around the world. Several studies have investigated the association between statin use and the risk of HCC, however, more studies are needed in this field.</p><p><strong>Objectives: </strong>This systematic review and meta-analysis aimed to investigate the relationship between statin use and HCC risk.</p><p><strong>Methods: </strong>Systematic searches of Web of Science, Scopus, PubMed, Cochrane, Science Direct, and Embase were conducted for studies published between 1980 and September 2023. Metaanalyses were performed using Stata 15 with a significance level of 0.05.</p><p><strong>Results: </strong>The search retrieved 8,125 articles, of which 40 were included in the meta-analysis after applying eligibility criteria. The total sample was 5,732,948 participants, including 68,698 HCC cases. Statin use was associated with a 44% lower risk of HCC compared to non-use (RR 0.56, 95% CI 0.50-0.63, p < 0.001). The RR was 0.54 (0.42-0.69) in American countries, 0.52 (0.44-0.62) in Asian countries, and 0.63 (0.48-0.84) in European countries. The RR was 0.50 (0.42-0.60) in studies with a mean age <50 years and 0.61 (0.53-0.70) in studies with a mean age ≥50 years. No evidence of publication bias was found (Begg's test p = 0.718).</p><p><strong>Conclusion: </strong>This meta-analysis found statin use is associated with a significantly lower HCC risk. Statins may be a promising preventive intervention against HCC.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Refractory p53 Mutation Large B-cell Lymphoma with Daratumumab and Venetoclax Followed by CAR-T Cell Therapy: Case Report and Animal Study.","authors":"Duanhao Gong, Jia Gu, Kuangguo Zhou, Wei Huang","doi":"10.2174/0115748928273058231128073414","DOIUrl":"https://doi.org/10.2174/0115748928273058231128073414","url":null,"abstract":"<p><strong>Background: </strong>The tumor burden before chimeric antigen receptor T (CAR-T) cell therapy was one of the critical factors affecting the prognosis of lymphoma. It was a challenge to effectively reduce the tumor burden of relapsed/refractory large B-cell lymphoma with p53 mutation.</p><p><strong>Objective: </strong>Here, we have presented a case of relapsed/refractory large B-cell lymphoma with p53 mutation being controlled by the treatment with daratumumab and venetoclax, followed by CAR-T cell therapy.</p><p><strong>Case presentation: </strong>The patient was a 56-year-old female who was diagnosed with relapsed/ refractory diffuse large B cell lymphoma (DLBCL) transformed from follicular lymphoma. The patient was treated with daratumumab, venetoclax, and GEMOX (gemcitabine and oxaliplatin) under the guidance of high-throughput drug sensitivity analysis. We used a CD38 positive lymphoma cell line with p53 mutation to construct tumor models for validating the anti- lymphoma effect of the combination therapy of daratumumab and venetoclax.</p><p><strong>Results: </strong>The patient achieved a complete metabolic response after treatment with daratumumab, venetoclax, and GEMOX. Then, she further achieved a complete molecular response after she subsequently received CAR-T cell therapy, and she has been living without a lymphoma recurrence. The results from the animal study showed that the combination of daratumumab and venetoclax could significantly enhance the antitumor effect on CD38-positive lymphoma with p53 mutation.</p><p><strong>Conclusion: </strong>The results from our successful case and animal experiments provide new avenues for the treatment of relapsed/refractory large B-cell lymphoma with p53 mutation. Further clinical trials are reuqired to treat CD38-positive lymphoma with the combination of daratumumab and venetoclax.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updated Progress on Mass Spectrometry Imaging and its Application in Cancer Treatment and Drug Discovery.","authors":"Mingyue Li, Jingna Zhou, Tingting Zhang, Jingyang Lu, Yajie Wang, Junyu Liu, Xiaoyu Zhang, Haixia Chen","doi":"10.2174/0115748928269691231203164021","DOIUrl":"https://doi.org/10.2174/0115748928269691231203164021","url":null,"abstract":"<p><strong>Background: </strong>Mass spectrometry imaging (MSI) is an imaging method based on mass spectrometry technology that can simultaneously visualize the spatial distribution of various biological molecules. The use of MSI in cancer detection and drug discovery has been extensively investigated in recent years.</p><p><strong>Objective: </strong>This review aims to summarize the latest advances of MSI and its specific applications in cancer detection and drug discovery, providing a basic understanding of the development and application of MSI in the past five years and offering references for the further application of MSI in cancer detection and drug discovery.</p><p><strong>Methods: </strong>In the database, \"mass spectrometry imaging\", \"cancer treatment\", and \"drug discovery\" were used as keywords for literature retrieval, and the time range was limited to \"2018- 2023\". After organizing and analyzing the literature and patents, a review was conducted.</p><p><strong>Results: </strong>Based on the literature, it was found that the updated progress of MSI in the past five years mostly focused on concrete methods, operation procedures, facilities, and composite applications. The patents of MSI were mainly correlated with the mass spectrometry imaging system and its application in cancer treatment. MSI is conducive to investigating the therapeutic schedule of cancer and searching for new drugs.</p><p><strong>Conclusion: </strong>MSI is a convenient, fast and powerful technology that has made great progress in sample preparation, instrumentation, quantitation, and multimodal imaging. MSI has emerged as a powerful technique in various biomedical applications, which has strong potential in cancer detection, treatment, formation mechanism research, discovery of biomarkers, and drug discovery process.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139565416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Key Signaling Pathways in Breast Cancer: From Molecular Mechanism to Therapeutic Interventions.","authors":"Deepika Singh, Ankit Sahoo","doi":"10.2174/0115748928267931231120065335","DOIUrl":"https://doi.org/10.2174/0115748928267931231120065335","url":null,"abstract":"<p><p>Breast cancer is a public health issue in developing and developed countries. Nowadays, the concept of BCSC (breast cancer stem cell) is gaining popularity among oncology researchers. The breast cancer stem cell is a tiny cell fraction inside the tumor mass that shows features that look like stem cells that are implicated in the genesis, recurrence, and metastasis of breast cancer tumors. Extracellular cues, mutations, and epigenetic control all contribute to the intricacy of gene expression control in Breast cancer stem cells. Thus, signaling pathways identified in breast cancer are Hedgehog and NOTCH, signal transducer and transcription 3, wingless-type MMTV integration site family (Wnt)/-catenin, and nuclear factor-kappa B, particularly connected with a phenotype of stem cell. Furthermore, the tumor microenvironment, such as hypoxic regions, can impact these BCSCs. Various approved signaling pathway targeted molecules have been patented, which show protective effects against breast cancer and have been used in clinical uses. PARP inhibitors are found to be very useful in the treatment of breast cancer. Promoting studies on the molecular pathways underlying the development of cancer in breast cancer patients was one of the main objectives of this study topic. The objective of this review Topic was to discover new intrinsic and extrinsic molecular pathways. Research focusing on novel signaling pathways that may lead to novel treatments or identifying patients at-risk of not responding to standard therapy approaches were the areas of focus we highlighted. The paper covers the linkage between breast cancer stem cells and cellular signaling, the tumor microenvironment in BC, and the relevance of signaling pathways and their therapeutic interventions. The review also covered patent applications associated with these signaling pathways and their prospects.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Assessment of Novel (Bncs Formulation) against Brain Tumor.","authors":"Anuradha Mishra, Afza Ahmad, Irfan Ahmad Ansari, Rohit Kumar Tiwari","doi":"10.2174/0115748928272753231212043701","DOIUrl":"10.2174/0115748928272753231212043701","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress refers to non-homeostatic elevation within intracellular reactive oxygen species (ROS) levels and is associated with several neuro-related pathological conditions. Diclofenac is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) for treating aches and pain by reducing inflammation. Diclofenac is also associated with the induction of apoptotic cell death by altering the homeostatic balance within mitochondria. In the present report, the neuroprotective effects of BNC formulation constituted by Bacopa monnieri leaves, Nigella sativa and Curcuma longa rhizome seeds were investigated.</p><p><strong>Methods: </strong>The synthesized formulation was characterized using FT-IR and LC-MS along with organoleptic evaluation. Thereafter neuroprotective efficacy of BNC formulation was subsequently investigated against Diclofenac-induced oxidative stress in SH-SY5Y cells. The cells were pretreated with synthesized formulation and subsequently evaluated for amelioration in Diclofenac-induced cytotoxicity, and ROS augmentation. The neuroprotective effect of synthesized formulation was further explored by evaluating the changes in nuclear morphology, and apoptosis alleviation with concomitant regulatory effects on caspase-3 and -9 activation.</p><p><strong>Results: </strong>Diclofenac was found to be considerably cytotoxic against human neuroblastoma SHSY5Y cells. Intriguingly, Diclofenac-mediated toxicity was reduced significantly in SH-SY5Y cells pretreated with BNC formulation. Augmented ROS levels within Diclofenac-treated SHSY5Y cells were also reduced in the BNC formulation pretreated SH-SY5Y cells. Furthermore, BNC formulation pretreated SH-SY5Y cells also exhibited reduced dissipation of mitochondrial membrane potential, caspase-3 and -9, along with apoptosis after Diclofenac treatment.</p><p><strong>Conclusion: </strong>These findings indicated that, indeed, Diclofenac induces considerable ROSmediated apoptosis in SH-SY5Y cells, which further intriguingly ameliorated Diclofenacmediated cytotoxic effects on SH-SY5Y cells. This manuscript further collected information about available National and International patents published or granted in preparation of and thereof applications against motor and non-motor brain dysfunctions.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Relationships of Chronic Constipation and Irritable Bowel Syndrome with Digestive Tract Cancers: A Mendelian Randomization Study.","authors":"Rencai Fan, Jiaqi Zhang, Jiaofeng Shen, Chenkai Mao, Shicheng Li, Zhixiang Zhuang","doi":"10.2174/0115748928283326231229061358","DOIUrl":"https://doi.org/10.2174/0115748928283326231229061358","url":null,"abstract":"<p><strong>Background: </strong>Chronic constipation and irritable bowel syndrome (IBS) manifest as prevalent gastrointestinal disorders, while digestive tract cancers (DTCs) present formidable challenges to global well-being. However, extant observational studies proffer uncertain insights into potential causal relationships of constipation and IBS with susceptibility to DTCs.</p><p><strong>Methods: </strong>We executed Mendelian randomization (MR) analysis to establish causal connections between these conditions and seven distinct categories of DTCs, including colorectal carcinoma (CRC), hepatocellular cancer (HCC), esophageal malignancy (ESCA), pancreatic adenocarcinoma (PAAD), biliary tract carcinoma (BTCs), gastric carcinoma (GC), and small intestine neoplasm (SIC). Leveraging instrumental variables (IVs) obtained from GWAS data of the FinnGen database, we employed a range of analytical methodologies, including inverse-variance weighting multiplicative random effects (IVW_MRE), inverse-variance weighting fixed effects (IVW_FE), maximum likelihood (ML), weighted median (WM), MR‒Egger regression, and the MR-PRESSO test.</p><p><strong>Results: </strong>We observed a substantial linkage between genetically predicted constipation and increased vulnerability to PAAD (OR = 2.29, 95% CI: 1.422-3.69, P = 0.001) via the IVW method. Following the removal of outlier SNPs through MR-PRESSO, genetically predicted IBS was affiliated with an increased risk of CRC (OR = 1.17, 95% CI: 1-1.37, P = 0.05). Nonetheless, decisive causal correlations of constipation or IBS with other DTCs remain elusive.</p><p><strong>Conclusion: </strong>In summary, genetically predicted constipation was associated with an augmented PAAD risk, and IBS was associated with an increased CRC susceptibility within European cohorts, in agreement with some observational studies. Nevertheless, the causal associations of constipation and IBS with other DTCs remain inconclusive.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}