Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells

Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.

An overview of the contemporary diagnosis and management approaches for anaplastic thyroid carcinoma

Thyroid carcinoma is a complex disease with several types,the most common being well-differentiated and undifferentiated.The latter,“undifferentiated carcinoma”,also known as anaplastic thyroid carcinoma(ATC),is a highly aggr-essive malignant tumor accounting for less than 0.2%of all thyroid carcinomas and carries a poor prognosis with a median survival of 5 months.BRAF gene mutations are the most common molecular factor associated with this type of thyroid carcinoma.Recent advances in targeted biological agents,immuno-therapy,stem cell therapy,nanotechnology,the dabrafenib/trametinib com-bination therapy,immune checkpoint inhibitors(ICI)and artificial intelligence offer novel treatment options.The combination therapy of dabrafenib and tra-metinib is the current standard treatment for patients with BRAF-V600E gene mutations.Besides,the dabrafenib/trametinib combination therapy,ICI,used alone or in combination with targeted therapies have raised some hopes for improving the prognosis of this deadly disease.Younger age,earlier tumor stage and radiotherapy are all prognostic factors for improved outcomes.Ultimately,therapeutic regimens should be tailored to the individual patient based on surveillance and epidemiological data,and a multidisciplinary approach is ess-ential.

Six transmembrane epithelial antigens of the prostate to illustrate inflammatory response in gastrointestinal cancers

Gastrointestinal cancer(GIC)is a common and widespread form of tumor,with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions.However,many patients are already in the late stages when first diagnosed with such cancer,resulting in a poor prognosis.Thus,it is necessary to explore new methods and research directions in order to improve the treatment of GIC.Given the specific nature of the gastrointestinal tract,research should focus on the mechanisms of various inflammations and the interactions between food entering and exiting from the gastrointestinal tract and cancer cells.Interestingly,six transmembrane epithelial antigens of the prostates(STEAPs)have been found to be significantly linked to the progression of malignant tumors,associated with intracellular oxidative stress and playing a major role in inflammation with their structure and function.This paper explores the mechanism of STEAPs in the inflammatory response of GIC,providing a theoretical basis for the prevention and early intervention of GIC.The basic properties of the STEAP family as metal reductase are also explained.When it comes to intervention for GIC prevention,STEAPs can affect the activity of Fe^(3+),Cu^(2+) reductase and regulate metal ion uptake in vivo,participating in inflammation-related iron and copper homeostasis.Thus,the mechanism of STEAPs on inflammation is of important value in the prevention of GIC.

Feasibility and limitations of combined treatment for lateral pelvic lymph node metastases in rectal cancer

Colorectal cancer ranks among the most commonly diagnosed cancers globally,and is associated with a high rate of pelvic recurrence after surgery.In efforts to mitigate recurrence,pelvic lymph node dissection(PLND)is commonly advocated as an adjunct to radical surgery.Neoadjuvant chemoradiotherapy(NACRT)is a therapeutic approach employed in managing locally advanced rectal cancer,and has been found to increase the survival rates.Chua et al have proposed a combination of NACRT with selective PLND for addressing lateral pelvic lymph node metastases in rectal cancer patients,with the aim of reducing recurrence and improving survival outcomes.Nevertheless,certain studies have indicated that the addition of PLND to NACRT and total mesorectal excision did not yield a significant reduction in local recurrence rates or improvement in survival.Consequently,meticulous patient selection and perioperative chemotherapy may prove indispensable in ensuring the efficacy of PLND.

New targets for cancer promotion and therapy in gliomas: Scinderin

Glioma is one of the most common primary intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event in tumor cell migration.Scinderin(SCIN),an actin severing and capping protein that regulates the actin cytoskeleton,is involved in the prolif-eration and migration of certain cancer cells.However,its biological role and molecular mechanism in glioma remain unclear.Lin et al explored the role and mechanism of SCIN in gliomas.The results showed that SCIN mechanically affected cytoskeleton remodeling and inhibited the formation of lamellipodia via RhoA/FAK signaling pathway.This study identifies the cancer-promoting role of SCIN and provides a potential therapeutic target for SCIN in glioma treatment.

Mechanisms and potential applications of COPS6 in pan-cancer therapy

The COP9 signalosome subunit 6(COPS6)is abnormally overexpressed in many malignancies,yet its precise role in carcinogenesis is unknown.To gain a better understanding of COPS6's role,the authors conducted a pan-cancer analysis using various bioinformatics techniques such as differential expression patterns,prognostic value,gene mutations,immune infiltration,correlation analysis,and functional enrichment assessment.Results showed that COPS6 was highly correlated with prognosis,immune cell infiltration level,tumor mutation burden,and microsatellite instability in patients with a range of tumor types.This suggests that COPS6 may be a potential target for cancer treatment.Overall,this research provides insight into COPS6's role in cancer development and its potential therapeutic applications.

The pharmacological mechanism and molecular details of Platycodon grandiflorum in the treatment of novel coronavirus Pneumonia(COVID-19)

Background:Novel coronavirus pneumonia(COVID-19)has developed as a pandemic of global concern.There is an urgent need to develop effective and safe therapies.Platycodon grandiflorum(PG),one of the most famous traditional Chinese herbs,may be satisfied.In this study,we explored the pharmacological mechanism of PG in the treatment of COVID-19.Method:The active compounds and potential targets were acquired from public databases.The protein-protein interaction,the Gene Ontology,and the Kyoto Encyclopedia of Genes and Genomes were determined through bioinformatics analysis.Molecular docking and molecular dynamics were performed to further verify the findings.Result:A total of 38 bioactive ingredients and 276 gene targets of PG were identified.There were 78 intersected targets of PG and COVID-19.The network analysis revealed that luteolin,Platycogenic acid A,Platycogenic acid C,Polygalacic acid,and acacetin may be candidate agents.The AKT1,VEGFA,TP53,MAPK3,TNF,IL6,CASP3,EGFR,STAT3,and CCND1 were the important potential drug targets.Gene Ontology terms are involved in biological processes,which are mainly concentrated in inorganic substances and apoptosis,etc.The Kyoto Encyclopedia of Genes and Genomes pathway was involved in several aspects,such as Virus infection and immune regulation-related pathways.Molecular docking results showed that compounds of PG are closely bound to related targets.Molecular dynamics further found that Robin,Flavplatycoside,and dimethyl 3-O-β-D-glucopyranosylplatycogenate A can maintain good stability and flexibility in the composite system.Conclusion:PG has multicomponent,multitarget,and multichannel characteristics,which can provide an important theoretical basis to treat patients with COVID-19.

Network analysis and molecular docking of the mechanism of Shengmai decoction in treating patients with severe novel coronavirus pneumonia

Background:Studies have shown that,Shengmai injection(Shengmai decoction)which has been included in the diagnosis and treatment of coronavirus disease 2019(COVID-19),is effective in the early treatment of patients with severe COVID-19.However,the mechanism of its intervention in severe stage of COVID-19 at molecular level is still unclear.Therefore,it is necessary to further explore the mechanism of Shengmai decoction in the treatment of patients with severe COVID-19 based on network pharmacology.Methods:The Traditional Chinese Medicine Systems Pharmacology,BATMAN,UniProt databases and the published literatures which contain the reported compounds that have therapeutic effects on COVID-19 were used to screen out the active ingredients and targets of Shengmai decoction,and the“drug-active compound-target”network was constructed.The GeneCards database was used to screen out the targets of COVID-19.The protein-protein interaction network map was constructed by mapping two genes,and the network of active ingredients,targets and disease was constructed using Cytoscape software.Thereafter,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the key targets were performed using the Metascape Site Maintenance website and David databases.The Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment of the mapping targets were analyzed.Results:The active component-target network contained 73 main compounds and 457 targets.The first five main active components(hydroquinone,guanosine,ophiopogon C,ophiopogon B,ophiopogon D)were obtained by topological analysis of 33 common targets.Using the Matthews correlation coefficient algorithm,the key targets included albumin,tumor necrosis factor,and cyclic adenosine response element binding.Compounds in Shengmai decoction were found to have good binding effect and strong interaction with caspase-8,caspase-3,apoptosis regulator Bcl-2,tumor necrosis factor,C-C motif chemokine 3,to inhibit the inflammatory response and improve lung injury.Additionally,31 biological processes were obtained by Gene Ontology enrichment,mainly related to lipopolysaccharide response and cytokine-mediated signal pathways,and 71 biological processes were obtained by Kyoto Encyclopedia of Genes and Genomes enrichment,mainly related to pulmonary tuberculosis,hepatitis B,and mitogen-activated protein kinase signal pathways.Conclusion:Shengmai decoction has multicomponent,multitarget and multichannel characteristics,which can provide an important theoretical basis to treat patients with severe COVID-19.

Autophagy-associated long non-coding RNA signature for lung adenocarcinoma

Background:Autophagy-associated long non-coding RNAs(aalncRNAs)take an important position in the tumorigeness of lung cancer,but current researches have not systematically investigated autophagy-associated lncRNAs in lung adenocarcinoma(LUAD).Methods:In this research,RNA-sequences of LUAD patients were downloaded from the TCGA and autophagy-associated genes were obtained from the GSEA website.The Pearson's test was conducted to find the correlation between autophagy-associated lncRNAs and autophagy-associated genes.AalncRNAs with prognostic significance were identified by using Cox and LASSO regression analysis in R,gradually.Risk score model was built to estimate prognosis-associated lncRNAs.Results:A risk score model was established according to the expressions of 7 aalncRNAs(RP11-102K13.5,RP11-1029J19.4,LINC00942,KLHL7-AS1,AC092198.1,C20orf197,LINC01116),and low-risk group was found to have a better prognosis(P<0.001).Next,single gene expression survival analysis show that 4 out of these lncRNAs were significantly associated with the survival of patients.In addition,the AUC value of model reached 0.724,demonstrating the good predictive ability of the model.Conclusion:These aalncRNAs in LUAD might possibly offered biological markers for the diagnosis and therapy of lung adenocarcinoma.