Global, regional, and national analyses of the burden of colorectal cancer attributable to diet low in milk from 1990 to 2019: longitudinal observational study.

Background: Globally, diet low in milk is the third greatest risk factor for colorectal cancer (CRC). However, there has been a lack of detailed worldwide analysis of the burden and trends of CRC attributable to diet low in milk. Objective: We aim to assess the spatiotemporal trends of CRC-related mortality and disability-adjusted life-years (DALYs) attributable to diet low in milk at the global, regional, and national levels from 1990 to 2019. Methods: Data of mortality, DALYs, age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR) of CRC attributable to diet low in milk were extracted from the Global Burden of Disease (GBD) 2019 study. The burden of CRC attributable to diet low in milk was estimated using the ASMR and ASDR, while accounting for sex, age, country, and socio-demographic index (SDI). From 1990 to 2019, the estimated annual percentage change (EAPC) was calculated to clarify the temporal trends in the ASMR and ASDR attributable to diet low in milk. Results: In 2019, there were 166,456 (95% UI = 107,221-226,027) deaths and 3,799,297 (95% UI = 2,457,768-5,124,453) DALYs attributable to diet low in milk, accounting for 15.3 and 15.6% of CRC-related deaths and DALYs in 2019. CRC-related deaths and DALYs attributed to diet low in milk increased by 130.5 and 115.4%, from 1990 to 2019. The burden of CRC attributable to diet low in milk varied notably among regions and nations. High-middle SDI regions had the highest ASDR and ASMR of CRC linked to diet low in milk, while there was a slight downward trend high SDI regions. Among geographical regions, East Asia had the highest number of CRC-related deaths and DALYs attributable to diet low in milk. Notably, the burden of CRC was highest in males and the elderly. With coefficients of -0.36 and -0.36, the EAPC in ASMR and ASDR was significantly inversely correlated with the Human Development Index in 2019. Conclusion: Globally, the number of CRC deaths attributable to diet low in milk has continued to increase over the last 30 years. Therefore, government and authorities should conduct education campaigns to encourage individuals to increase daily milk intake.

Design and synthesis of 7-azaindole derivatives as potent CDK8 inhibitors for the treatment of acute myeloid leukemia.

It is of great significance to design and synthesize novel structural inhibitors with good antitumor activity. In this study, based on rational design, a total of 42 7-azaindole derivatives as novel CDK8 inhibitors were designed and synthesized. All compounds were screened with antitumor activity and compound 6 (1-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)phenyl)-3-(m-tolyl)urea) exhibited the best activity, especially in acute myeloid leukemia (GI50 MV4-11 = 1.97 ± 1.24 µM). This compound also exhibited excellent inhibitory activity against CDK8 (IC50 = 51.3 ± 4.6 nM). Further mechanism studies shown that it could inhibit STAT5 phosphorylation and induce cell cycle arrest in the G1 phase, leading to apoptosis in acute myeloid leukemia cells. In addition, acute toxicity at a dose of 1000 mg kg-1 indicated the low toxicity of this compound.

Epidemiological trends and burden analysis of cervical cancer attributable to unsafe sex: A population-based study from 1990 to 2019.

BACKGROUND: Unsafe sex is recognized as an important risk factor for cervical cancer (CC). Understanding the global disease burden of CC attributable to unsafe sex can assist policymakers in allocating healthcare resources. METHODS: Data were obtained from the 2019 global burden of disease database (GBD). We examined global, regional, and national levels of CC mortality, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) caused by unsafe sex. ASRs were evaluated using estimated annual percentage changes (EAPCs). RESULTS: Attributable to unsafe sex, there were 280,479 CC-related deaths in 2019 and 8,955,013 CC-related DALYs. In the period 1990-2019, the global ASRs of CC due to unsafe sex decreased around the world; for age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR), the EAPCs were -0.93 and -0.95. The highest ASMRs and ASDRs were found in central sub-Saharan Africa and the lowest in Australasia. CONCLUSION: In the past few decades, the ASMR and ASDR of CC caused by unsafe sexual practices have decreased over time, with significant variations observed among different countries and regions. Increased focus is needed on spreading awareness about sexual health and promoting CC prevention and screening, particularly in low- and middle-income nations.

Comparison of high-flow nasal cannula with conventional oxygen therapy for preventing postoperative hypoxemia in patients with lung resection surgery: a systematic review and meta-analysis.

Background: The efficacy of high-flow nasal cannula (HFNC) in patients extubated after lung resection surgery remains inconclusive. Our objective was to execute a meticulous systematic meta-analysis to accurately assess the advantages of HFNC compared to conventional oxygen therapy (COT) for patients extubated after lung resection surgery, by examining postoperative hypoxemia and other patient-focused outcomes. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science and Scopus to identify randomized controlled trials (RCTs) from inception to July 2023. We employed the revised Cochrane risk of bias (RoB) tool (2.0) to evaluate the RoB of the included studies, and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method to ascertain the certainty of the pooled effect estimates. The primary outcome was the incidence of postoperative hypoxemia. Results: Five RCTs (n=564) were included in the ultimate analysis. Utilizing HFNC rather than COT did not reduce the risk of postoperative hypoxemia [relative risk (RR), 0.67; 95% confidence interval (CI): 0.30-1.49; low certainty]. Compared to COT, HFNC may significantly enhance oxygenation index within first 12 hours after extubation in patients with lung resection. There were no significant differences in reintubation rate (RR, 0.25; 95% CI: 0.04-1.54; high certainty), escalation of respiratory support (RR, 0.35; 95% CI: 0.11-1.08; high certainty), change in partial pressure of carbon dioxide (PaCO2) within first 24 hours after extubation, hospital length of stay [mean difference (MD), -0.19; 95% CI: -0.44 to 0.06; moderate certainty], and intensive care unit (ICU) length of stay (MD, 0.02; 95% CI: -0.16 to 0.19; high certainty). Conclusions: Our meta-analysis suggests that preemptive use of HFNC, instead of COT, in extubated patients following lung resection surgery may not significantly impact postoperative hypoxemia incidence, reintubation rate, escalation of respiratory support, postoperative PaCO2 difference, hospital and ICU length of stay. However, HFNC may significantly enhance the oxygenation index within the first 12 hours post-extubation following lung resection surgery. To verify the effect of HFNC on this population, additional large-scale, multicenter studies are essential.

Ferrate (IV) synthesis using derived persulfate during treatment of oil recovery wastewater.

Using oil recovery wastewater as the target material, the degradation of organic matter in oilfield wastewater was studied in an anodic oxidation system using Ti/Ru-Ir oxide-coated anode and 0.7mMNa2SO4 as the electrolyte. The TOC of the wastewater was 210 mg/L at the beginning of the electrolysis in the electrolysis system, and it decreased from 210 to 93.6 mg/L after 50 min of electrolysis. Under the action of this system, sulfate was oxidized to persulfate, and the apparent concentration of persulfate was 15.02 mM, oxidation and degradation of organic matter in wastewater by the action of newly generated persulfate.. Afterwards, NaOH and Fe2(SO4)3 were added to the electrolyzed wastewater, and the TOC in the wastewater was further reduced to 25.1 mg/L due to the coagulation effect of the newly generated Fe(OH)3 precipitate. The TOC removal rate of the wastewater treated by this process reached 88.0%, which meets the discharge requirements. At the same time, the derived persulfate oxidized Fe(OH)3 to generate a green substance, which was identified as Na2FeO3 by IR, UV, and XRD analyses. Na2FeO3 served as a highly effective water-purifying agent, demonstrating superior performance when compared to FeO42-. The method reported in this study not only provides a strategy for waste resource recycling but also offers the potential for mass production of ferrate (IV).

Distribution of HPV types among women with HPV-related diseases and exploration of lineages and variants of HPV 52 and 58 among HPV-infected patients in China: A systematic literature review.

To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.

Cetuximab inhibits colorectal cancer development through inactivating the Wnt/ß-catenin pathway and modulating PLCB3 expression.

Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigated the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment. We extracted differentially expressed genes from the GSE140973, the overlapping genes combined with 151 Wnt/ß-Catenin signaling pathway-related genes were identified. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene, through cell experimental, scrutinized the impact of cetuximab and PLCB3 on CRC cellular progression. The study identified 26 overlapping genes. High expression of PLCB3, correlated with poorer prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both ß-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings revealed PLCB3 promoted cetuximab inhibition on Wnt/ß-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion. The study emphasized the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppressed Wnt/ß-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offered fresh perspectives on cetuximab mechanism in CRC.

Pan-Cancer Analysis Shows that KIFC2 is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Bladder Cancer.

KIFC2 plays an important role in prostate cancer progression and chemotherapy resistance, but the mechanism of its involvement in other malignancies remains unclear. Therefore, this study aimed to analyze and validate the mechanism of effect of KIFC2 in multiple tumors. Bioinformatic analysis was performed in conjunction with multiple databases (The Cancer Genome Atlas, Genotype-Tissue Expression Project, Human Protein Atlas, etc.) to fully explore the potential role of KIFC2 within individual tumors and to analyze the correlation with major research components such as prognosis, mutations, and the tumor microenvironment. The expression of KIFC2 demonstrates a significant correlation with the prognosis, clinical phenotype, tumor mutational burden, microsatellite instability, and tumor microenvironment across various malignancies and is associated with the modulation of diverse functional and signaling pathways. The differences in the expression of KIFC2 in the bladder cancer tissues (14 pairs) were statistically significant. The pan-cancer analysis in this study revealed the multifunctionality of KIFC2 in a variety of tumors, indicating a possible prognostic predictor and potential therapeutic target for tumors.

Gut microbiota-dependent modulation of pre-metastatic niches by Jianpi Yangzheng decoction in the prevention of lung metastasis of gastric cancer.

AIM OF THE STUDY: To evaluate the in vitro and in vivo anti-metastasis efficacy of Jianpi Yangzheng (JPYZ) decoction against gastric cancer (GC) and its potential mechanisms. MATERIALS AND METHODS: The distant metastasis of GC cells administered via tail vein injection was assessed using the pre-metastatic niche (PMN) model. 16S rRNA sequencing and GC-MS/MS were applied to determine the component of the gut microbiota and content of short-chain fatty acids (SCFAs) in feces of mice, respectively. The proportion of myeloid-derived suppressor cells (MDSCs) in the lung was evaluated by flow cytometry and immunofluorescence. Serum or tissue levels of inflammation factors including IL-6, IL-10 and TGF-ß were determined by ELISA or Western blot respectively. RESULTS: Injecting GC cells into the tail vein of mice led to the development of lung metastases and also resulted in alterations in the composition of gut microbiota and the levels of SCFAs produced. Nevertheless, JPYZ treatment robustly impeded the effect of GC cells administration. Mechanically, JPYZ treatment not only prevented the alteration in gut microbiota structure, but also restored the SCFAs content induced by GC cells administration. Specifically, JPYZ treatment recovered the relative abundance of genera Moryella, Helicobacter, Lachnoclostridium, Streptococcus, Tuzzerella, GCA-900066575, uncultured_Lachnospiraceae, Rikenellaceae_RC9_gut_group and uncultured_bacterium_Muribaculaceae to near the normal control levels. In addition, JPYZ abrogated MDSCs accumulation in the lung tissue and blocked inflammation factors overproduction in the serum and lung tissues, which subsequently impede the formation of the immunosuppressive microenvironment. Correlation analysis revealed that the prevalence of Rikenellaceae in the model group exhibited a positive correlation with MDSCs proportion and inflammation factor levels. Conversely, the scarcity of Muribaculaceae in the model group showed a negative correlation with these parameters. This suggests that JPYZ might exert an influence on the gut microbiota and their metabolites, such as SCFAs, potentially regulating the formation of the PMN and consequently impacting the outcome of GC metastasis. CONCLUSION: These findings suggest that GC cells facilitate metastasis by altering the gut microbiota composition, affecting the production of SCFAs, and recruiting MDSCs to create a pro-inflammatory pre-metastatic niche. JPYZ decoction counteracts this process by reshaping the gut microbiota structure, enhancing SCFA production, and inhibiting the formation of the pre-metastatic microenvironment, thereby exerting an anti-metastatic effect.

Nuclear receptor NURR1 functions to promote stemness and epithelial-mesenchymal transition in prostate cancer via its targeting of Wnt/ß-catenin signaling pathway.

Dysregulated activation of Wnt/ß-catenin signaling pathway is a frequent or common event during advanced progression of multiple cancers. With this signaling activation, it enhances their tumorigenic growth and facilitates metastasis and therapy resistance. Advances show that this signaling pathway can play dual regulatory roles in the control of cellular processes epithelial-mesenchymal transition (EMT) and cancer stemness in cancer progression. Aberrant activation of Wnt/ß-catenin signaling pathway is shown to be common in prostate cancer and also castration-resistant prostate cancer (CRPC). However, the transcriptional regulators of this pathway in prostate cancer are still not well characterized. NURR1 (NR4A2) is an orphan nuclear receptor and plays an important role in the development of dopaminergic neurons. Previously, we have shown that NURR1 exhibits an upregulation in isolated prostate cancer stem-like cells (PCSCs) and a xenograft model of CRPC. In this study, we further confirmed that NURR1 exhibited an upregulation in prostate cancer and also enhanced expression in prostate cancer cell lines. Functional and molecular analyses showed that NURR1 could act to promote both in vitro (cancer stemness and EMT) and also in vivo oncogenic growth of prostate cancer cells (metastasis and castration resistance) via its direct transactivation of CTNNB1 (ß-catenin) and activation of ß-catenin to mediate the activation of Wnt/ß-catenin signaling pathway. Moreover, we also demonstrated that NURR1 activity in prostate cancer cells could be modulated by small molecules, implicating that NURR1 could be a potential therapeutic target for advanced prostate cancer management.

Corrigendum to "Emulsifying Lipiodol with pH-Sensitive DOX@HmA nanoparticles for hepatocellular carcinoma TACE treatment eliminate metastasis" Mater. Today Bio, 23, 2023, 100873, ISSN 2590-0064.

[This corrects the article DOI: 10.1016/j.mtbio.2023.100873.].

Global burden of esophageal cancer attributable to high BMI in 204 countries and territories: 1990-2019.

BACKGROUND: Esophageal cancer (EC), a common and fatal disease, includes two histological subtypes; esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (ECA). To aid policymakers in the allocation of resources for the prevention and treatment of EC, updated data on EC deaths and disability-adjusted life years (DALYs) attributable to high body mass index (BMI) are necessary. The objective of this study was to identify trends in EC associated with high BMI between 1990 and 2019 using 2019 Global Burden of Disease data. METHODS: In this observational population-based study, epidemiological data on the association between high BMI and EC were obtained from GBD 2019. The age-standardized mortality rate (ASMRs) and disability-adjusted life year rate (ASDRs) attributable to high BMI-related EC were stratified by year, age, country, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of the ASMRs and ASDRs between 1990 and 2019. RESULTS: In 2019, the proportion of EC deaths and DALYs attributed to high BMI was 18.1% and 18.9%, respectively, resulting in 89 904 (95% confidence interval [CI]: 27 879-171 255) deaths and 2 202 314 (95% CI: 681 901-4 173 080) DALYs. High BMI-related deaths and DALYs showed a strong upward trend, increasing by more than two-fold since 1990. East Asia and Western Europe showed the highest risk of EC mortality and DALYs attributable to high BMI; China and the USA bear the greatest burden. The ASMR and ASDR increased in five SDI regions. CONCLUSIONS: The incidence of EC is increasing, particularly in developing nations, which may be attributed to the prevalence of high BMI. To mitigate the impact of high BMI on the incidence of EC, it is important to increase awareness of its deleterious effects, which may alleviate the burden of this disease.

Downregulation of S100A11 promotes T cell infiltration by regulating cancer-associated fibroblasts in prostate cancer.

OBJECTIVE: This study aims at revealing the relationship between S100A11 and cancer-associated fibroblasts (CAFs) in prostate cancer and improving T cell infiltration into solid tumors. METHODS: H&E, IHC and Sirius red staining were used to detect the stroma content in prostate cancer tissues. Stable S100A11 knockdown cell lines DU 145, 22Rv1, RM-1 and NOR-10 were established by lentivirus transfection. Co-culture system of RM-1 and CAFs was established. CCK-8, wound healing and transwell were proceeded to determine proliferation, migration and invasion of prostate cancer cells. Stably knocked-down RM-1 and CAFs were co-injected into C57BL/6 mice to detect the role of S100A11 in vivo. CAFs, CD4+ T cell and CD8+ T cell in these tumors were assessed by IF. T cell profile was analyzed by flow cytometry. RESULTS: A significant amount of stroma exists in prostate cancer tissues. Downregulation of S100A11 inhibits proliferation, migration and invasion of human prostate cancer cells in vitro, and suppresses the expression of cancer-associated fibroblasts (CAFs) in vivo. Knockdown of S100A11 enhances the inhibitory effect of Erdafitinib on CAFs in both the co-culture system and in vivo. The combined knockdown of S100A11 in tumor cells and CAFs shows a superior therapeutic effect compared to the individual knockdown in tumor cells alone. Knockdown of S100A11, both in RM-1 and CAFs, combined with Erdafitinib treatment reduces tumorigenicity by suppressing the content of CAFs and increasing the infiltration of CD4+ T cell and effective CD8+ T cell in tumor. CONCLUSION: Downregulation of S100A11 plays a crucial role in enhancing the therapeutic response to Erdafitinib and reversing immunosuppressive tumor microenvironment.

Risk factors for perioperative blood transfusion in patients undergoing total laparoscopic hysterectomy.

PURPOSE: The goal is to identify risk factors associated with receiving a blood transfusion during the perioperative period in patients who undergo total laparoscopic hysterectomy (TLH) using a large-scale national database. METHODS: In this retrospective analysis, data from the Nationwide Inpatient Sample (NIS) was utilized to review the medical records of all patients who underwent TLH from 2010 to 2019. The researchers identified patients who had received a blood transfusion during the perioperative period and compared with those who had not. The subsequent factors associated with blood transfusion were examined: hospital characteristics (type of admission and payer, patient demographics (age and race), bed size, teaching status, location, and region of hospital), length of stay (LOS), total charges during hospitalization, in-hospital mortality, comorbidities, and perioperative complications. The data was analyzed using descriptive statistics. The independent risk factors of perioperative blood transfusion after TLH was identified by performing multivariate logistic regression. RESULTS: A total of 79,933 TLH were captured from the NIS database, among which 3433 (4.40%) patients received a perioperative blood transfusion. TLH patients affected by blood transfusion were 2 days longer hospital stays (P < 0.001), higher overall costs (P < 0.001), the patients who received a transfusion after a long-term hospitalization had a significantly higher rate of mortality (0.5% vs. 0.1%; P < 0.001). Perioperative blood transfusion after TLH was associated with chronic blood loss anemia, deficiency anemia, coagulopathy, congestive heart failure, fluid and electrolyte disorders, renal failure, metastatic cancer, sepsis, weight loss, deep vein thrombosis, gastrointestinal hemorrhage, shock, acute myocardial infarction, and pneumonia, stroke, hemorrhage, pulmonary embolism, and disease of the genitourinary system. CONCLUSION: Studying the risk factors of perioperative blood transfusion after TLH is advantageous in order to ensure proper management and optimize outcomes.

Doping proanthocyanidins into gel/zirconium hybrid hydrogel to reshape the microenvironment of diabetic wounds for healing acceleration.

Infection and chronic inflammation caused by oxidative stress are major challenges in chronic wound healing. Preparing a simple, efficient hydrogel with reactive oxygen-scavenging properties for chronic wound repair is a promising strategy. Herein, we report an injectable, self-repairing hydrogel with antioxidant and antibacterial properties that can be used to regenerate diabetic wounds. Hydrogels are prepared by coordination crosslinking of gelatin (Gel), a natural biopolymer derived from collagen, with Zr4+. Because of the dynamic properties of metal ion coordination bonds and the bactericidal effect of Zr4+, the obtained coordination hydrogels exhibit self-healing, injectable, and antibacterial properties. The plant polyphenol "proanthocyanidins," which has reactive oxygen-scavenging and anti-inflammatory effects, was simultaneously loaded into the coordination hydrogel during cross-linking. We obtained a versatile hydrogel that is easy to prepare, resistant to mechanical irritation, and antioxidant, and antibacterial in vitro. We further demonstrated that the injectable self-healing hydrogels could effectively repair diabetic skin wounds and accelerate collagen deposition and wound healing. This study shows that the multifunctional antioxidant hydrogel has great potential in developing multifunctional biomaterials for chronic wound healing.

A new perspective on the current and future development potential of ABCG1.

ABCG1 is an essential protein involved in the efflux of intracellular cholesterol to the extracellular space, thus playing a critical role in reducing cholesterol accumulation in neighboring tissues. Bibliometric analysis pertains to the interdisciplinary field of quantitative examination of diverse documents using mathematical and statistical techniques. It integrates the investigation of structural and temporal patterns in academic publications with an exploration of subject focus and forms of uncertainty. This research paper examines the historical evolution, current areas of interest, and future development trends of ABCG1 through bibliometric analysis. This study aims to offer readers insights into the research status and emerging trends of ABCG1, thereby assisting researchers in the exciting field to explore novel research avenues. Following rigorous selection, research on ABCG1 has remained highly active over the past two decades. ABCG1 has even started to emerge in previously unrelated fields, such as the field of cancer research. According to the analysis conducted by Citespace, a lot of keywords and influential citations were identified. ABCG1 has been found to establish a connection between cancer and cardiovascular disease, highlighting their interrelationship. This review aims to assist readers who have limited familiarity with ABCG1 research in gaining a rapid understanding of its developmental trajectory. Additionally, it aims to offer researchers potential areas of focus for future studies related to ABCG1.

Emulsifying Lipiodol with pH-sensitive DOX@HmA nanoparticles for hepatocellular carcinoma TACE treatment eliminate metastasis.

Lipiodol-based transcatheter arterial chemoembolization (TACE) is currently the predominant and first-line treatment option recommended by the global standard for unresectable hepatocellular carcinoma (HCC). However, the unstable emulsion of Lipiodol causes a substantial proportion of chemotherapy drugs to enter the circulation system, leading to poor accumulation in cancer tissues and unexpected side effects of chemotherapy drugs. Herein, we emulsified Lipiodol with a pH-sensitive drug delivery system assembled from hexahistidine and zinc ions (HmA) with a super-high loading capacity of doxorubicin (DOX) and a promising ability to penetrate bio-barriers for the effective treatment of HCC by TACE. In vitro tests showed that DOX@HmA was comparable to free DOX in killing HCC cells. Impressively, during the in vivo TACE treatment, the anti-tumor efficacy of DOX@HmA was significantly greater than that of free DOX, indicating that DOX@HmA increased the accumulation of DOX in tumor. Emulsifying Lipiodol with pH-sensitive DOX@HmA significantly inhibited cell regeneration and tumor angiogenesis and decreased the systemic side effects of chemotherapy, especially by suppressing pulmonary metastasis in liver VX2 tumors in rabbits by inhibiting epithelial-mesenchymal transition (EMT). Emulsifying tumor microenvironment-responsive drug delivery systems (DDSs) with Lipiodol could be a new strategy for clinical TACE chemotherapy with potentially enhanced HCC treatment.

HELLS modulates the stemness of intrahepatic cholangiocarcinoma through promoting senescence-associated secretory phenotype.

The senescence-associated secretory phenotype (SASP) is closely associated with the tumorigenesis and progression of intrahepatic cholangiocarcinoma (ICC). However, it remains unclear its relation to stemness of ICC. In the study, the stemness indices of ICC were calculated using one-class linear regression (OCLR) and single-sample gene set enrichment analysis (ssGSEA) algorithms. A total of 14 senescence-related stemness genes (SRSGs) were identified using Pearson correlation analysis in ICC. Subsequently, a SRSGs-related classification was established using a consensus clustering for ICC. Different types of ICC exhibit distinct prognosis, immunity, metabolisms, and oncogenic signatures. Additionally, we constructed a risk score model for ICC using principal component analysis (PCA). The risk score was positively correlated with stemness, immune infiltration, metabolisms and oncogenic signatures, but negatively with prognosis in ICC. Patients with a high risk score may respond well to immunotherapy. Furthermore, we employed 3D fibrin gels to select tumor-repopulating cells (TRC) with stemness features. We found that HELLS, belonging to the 14 SRSGs, was up-regulated in ICC-TRC. And silencing HELLS significantly reduced the colony size, inhibited migration and invasion, and attenuated SASP in ICC-TRC. In summary, we provided a novel classification and risk score for ICC and uncovered a molecular mechanism via which CSLCs could obtain an active SASP.