Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000 promotes colorectal cancer growth.

BACKGROUND: Dopamine and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain. However, recent studies have shown that DARPP-32 is also expressed in other tissues, including colorectal cancer (CRC), where its function is not well understood. AIM: To explore the effect of DARPP-32 on CRC progression. METHODS: The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays. The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, while apoptosis was measured by flow cytometry. The migratory and invasive potential of CRC cell lines were determined using wound healing and transwell chamber assays. In vivo studies involved monitoring the growth rate of xenograft tumors. Finally, the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses. RESULTS: DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC. Overexpression of DARPP-32 was shown to promote cancer cell proliferation, migration, and invasion and reduce apoptosis. DARPP-32 knockdown resulted in the opposite functional effects. Mechanistically, DARPP-32 may regulate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in order to carry out its biological function. CONCLUSION: DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.

A retrospective study analyzing if lymph node ratio carbon nanoparticles predict stage III rectal cancer recurrence.

Background: Lymph node ratio has garnered increasing attention as a prognostic marker for rectal cancer; however, few studies have investigated the relationship between lymph node ratio and rectal cancer recurrence. Additionally, Carbon Nanoparticle tracking is a safe and effective strategy for locating tumors and tracking lymph nodes. However, no studies have reported the relationship between Carbon Nanoparticles and rectal cancer recurrence. Methods: Patients with stage III rectal cancer who underwent radical resection between January 2016 and 2020 were analyzed. The primary outcome was tumor recurrence. 269 patients with stage III rectal cancer were included in this study. The effects of lymph node ratio, Carbon Nanoparticles, and other clinicopathological factors on rectal cancer recurrence were assessed using univariate, multivariate analyses and the t-test. Results: Univariate analysis determined tumor recurrence using cytokeratin 19 fragment, CA-199, CEA, N-stage, positive lymph nodes, total lymph nodes, and lymph node ratio(positive/total); with the lymph node ratio being the most relevant. Receiver operating characteristic (ROC) analysis determined lymph node ratio =0.38 as the optimal cutoff value. The analysis of lymph node ratio ≥0.38 and <0.38 showed statistical differences in three indicators: tumor recurrence, CEA, and use of Carbon Nanoparticles. Conclusion: Lymph node ratio is a strong predictor of stage III rectal cancer recurrence and may be considered for inclusion in future tumor-node-metastasis staging and stage III rectal cancer stratification. In addition, we found that Carbon Nanoparticles use significantly increased total lymph nodes and decreased lymph node ratio.

Pathologic complete response to TNT + camrelizumab for rectal cancer with surgical anus-preservation: case report and literature review.

Background: This case report demonstrates the efficacy of total neoadjuvant therapy (TNT) based on pathological complete response (PCR). We also discuss the surgical approach to preserving the anus and its perioperative management. Case presentaion: The patient was a 26-year-old woman, with blood in the stool and stool thinning for over two months. Preoperative examination revealed locally advanced rectal cancer invading the left anal raphe and enlarged lymph nodes adjacent to the left internal iliac vessels. The lesion was preoperatively classified as T4bN1bM0 IIIC. Considering the size and depth of the tumor, it was difficult to have sufficient margins for radical resection, and the tumor was too close to the anal orifice. Considering the patient's youth and strong desire to preserve the anus, it was decided to use TNT combined with a camrelizumab regimen. After the entire course of neoadjuvant radiotherapy, the tumor size significantly reduced in fibrotic manifestations, and no enlargement of the lymph nodes adjacent to the left internal iliac vessels was observed. She underwent robotic laparoscopic ultra-low anterior rectal resection, left lateral lymph node dissection, and temporary ileostomy, and no significant residue was observed after all bowel tubes were taken for examination, nor was there cancerous involvement at the distal or radial cut edges, or metastasis. The patient was discharged nine days postoperatively, and no major complications were detected. Follow-up was performed without adjuvant chemotherapy. Conclusions: TNT may be a better surgical option for preserving the anus and for complete radical resection in patients with LARC for whom Miles' resection is indicated.

SAR1A regulates the RhoA/YAP and autophagy signaling pathways to influence osteosarcoma invasion and metastasis.

Osteosarcoma is the most prevalent form of primary bone malignancy affecting adolescents. Secretion-associated Ras-related GTPase 1A (SAR1A) is a key regulator of endoplasmic reticulum (ER) homeostasis, but its role as a regulator of osteosarcoma metastasis has yet to be clarified. Bioinformatics analyses revealed SAR1A and RHOA to be upregulated in osteosarcoma patients, with the upregulation of these genes being associated with poor 5-year metastasis-free survival rates. In addition, the upregulation of SAR1A and RHOA in osteosarcoma was highly positively correlated. Immunohistochemical analyses additionally revealed that SAR1A levels were increased in osteosarcoma pulmonary metastases. In vitro wound healing and Transwell assays indicated that knocking down SAR1A or RHOA impaired the invasive and migratory activity of osteosarcoma cells, whereas RHOA overexpression had the opposite effect. Western blotting and immunofluorescent staining revealed the inhibition of osteosarcoma cell epithelial-mesenchymal transition following SAR1A or RHOA knockdown; RHOA overexpression had the opposite effect. Following SAR1A knockdown, phalloidin staining indicated that osteosarcoma cells showed reduced lamellipodia formation. Endoplasmic reticulum stress levels and reactive oxygen species production were enhanced following the knockdown of SAR1A, as was autophagic activity, with lung metastases being reduced in vivo after such knockdown. Knocking down SAR1A suppresses osteosarcoma cell metastasis through the RhoA/YAP, ER stress, and autophagic pathways, offering new insights into the regulation of autophagic activity in the context of osteosarcoma cell metastasis and suggesting that these pathways could be amenable to therapeutic intervention.

CRISPR-based knockout screening identifies the loss of MIEF2 to enhance oxaliplatin resistance in colorectal cancer through inhibiting the mitochondrial apoptosis pathway.

The first-line anticancer agent oxaliplatin (OXL) is the preferred drug for treating colorectal cancer (CRC); however, the development of drug resistance is common in patients treated with OXL, which considerably reduces the efficacy of OXL-based regimens. By performing genome-wide CRISPR/Cas9 library knockdown screening, we found that mitochondrial elongation factor 2 (MIEF2) was among the top candidate genes. The OXL-resistant cell lines and organoids developed in the present study showed stable but low expression of MIEF2. Reduced MIEF2 expression may enhance CRC resistance to OXL by reducing mitochondrial stability and inhibiting apoptosis by decreasing cytochrome C release. In conclusion, among the different biomarkers of OXL resistance in CRC, MIEF2 may serve as a specific biomarker of OXL responsiveness and a potential target for the development of therapies to improve chemotherapeutic effectiveness.

Identification of MEDAG and SERPINE1 Related to Hypoxia in Abdominal Aortic Aneurysm Based on Weighted Gene Coexpression Network Analysis.

Purpose: Abdominal aortic aneurysm (AAA) is a severe cardiovascular disease that often results in high mortality due to sudden rupture. This paper aims to explore potential molecular mechanisms and effective targeted therapies to prevent and delay AAA rupture. Methods: We downloaded two microarray datasets (GSE98278 and GSE17901) from the Gene Expression Omnibus (GEO) database. Differential analysis and single-sample gene set enrichment analysis (ssGSEA) of hypoxia scores were performed on 48 AAA patients in GSE98278. We identified hypoxia- and ruptured AAA-related gene modules using weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the R package clusterProfiler. For candidate genes, validation was conducted on the mouse dataset GSE17901. Finally, we predicted drug candidates associated with the hub genes using the HERB Chinese medicine database. Results: Eighty-two differentially expressed genes were screened in the ruptured and stable groups; 103 differentially expressed genes were identified between the high- and low-hypoxia groups; and WGCNA identified 58 differentially expressed genes. Finally, nine candidate genes were screened, including two hub genes (MEDAG and SERPINE1). We identified pathways such as cytokine-cytokine receptor interaction and T-helper 1-type immune response involved in AAA hypoxia and rupture. We predicted 93 traditional Chinese medicines (TCMs) associated with MEDAG and SERPINE1. Conclusion: We identified the hypoxic molecules MEDAG and SERPINE1 associated with AAA rupture. Our study provides an additional direction for the association between hypoxia and AAA rupture.

YAP knockdown in combination with ferroptosis induction increases the sensitivity of HOS human osteosarcoma cells to pyropheophorbide-α methyl ester-mediated photodynamic therapy.

BACKGROUND AND AIMS: This study was designed to explore the effects of Yes-associated protein (YAP) knockdown on human osteosarcoma (HOS) cell sensitivity to Pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT), and to assess how YAP silencing in combination with treatment with the ferroptosis inducer Erastin improves HOS cell sensitivity to MPPa-PDT in an effort to better clarify the molecular mechanisms underlying these phenotypes. METHODS: At 12 h post-MPPa-PDT, Hoechst staining and flow cytometry were conducted to evaluate the apoptotic death of HOS cells. The expression of YAP in these cells at 12 h post-MPPa-PDT treatment was assessed via Western blotting and immunofluorescent staining. BODIPY581/591-C11 was used to evaluate lipid peroxidation. Following shYAP lentiviral transduction, Western blotting was conducted to assess the expression of proteins associated with proliferation, apoptosis, and ferroptosis. EdU assays and clonogenic assays were performed to analyze cellular proliferation. Erastin-treated HOS cells were used to establish a ferroptosis model. Western blotting was used to measure ferroptosis-associated protein levels following shYAP and erastin treatment, while changes in proliferation and MDA levels in each group were examined using an MDA kit. RESULTS: At 12 h post-MPPa-PDT, HOS cells exhibited apoptotic characteristics including nuclear fragmentation and pyknosis, with concomitant increases in apoptosis-associated proteins as detected via Western blotting and apoptotic induction as measured via flow cytometry. Phosphorylated YAP levels fell and non-phosphorylated YAP levels rose following such treatment. Transfection with shYAP was successful as a means of generating stable HOS cell lines, and Western blotting analyses of these cells revealed reductions in proteins associated with cellular proliferation together with the upregulation of apoptosis-related proteins.  MDA assays indicated that erastin combined with YAP knockdown enhanced the sensitivity of HOS cells to MPPa-PDT treatment. CONCLUSIONS: These data indicate that ferroptosis and YAP knockdown can enhance osteosarcoma cell sensitivity to MPPa-PDT therapy.

Studies Related to Ruptured Abdominal Aortic Aneurysms in the Past 10 Years (2011-2020): A Bibliometric Analysis.

BACKGROUND Ruptured abdominal aortic aneurysms have been a topic of common global interest for the past 20 years, with a steadily increasing number of publications. The purpose of this study was to explore the research themes and the current status of the last 10 years through a bibliometric analysis of the publications in this field. MATERIAL AND METHODS We performed a literature search for ruptured abdominal aortic aneurysms using the Web of Science Core Collection on November 14, 2021 and performed a bibliometric analysis and visualization of the results of the publications using the R-Bibliometrix package and VOSviewer software. RESULTS From 2011 to 2020, 2381 publications were retrieved, including 2073 articles and 308 reviews. The United States had the highest number of publications and has made a large contribution to the field. Jonathan Golledge is an important researcher with the highest number of publications. Journal of Vascular Surgery is ranked first in terms of the number of publications and local citations. Mortality and outcomes, repair treatment, and risk factors are the 3 main focuses in the field, followed by intraluminal thrombus and molecular expression. CONCLUSIONS Our bibliometric analysis suggests mainstream research is focused on clinical studies related to the surgical approach and its prognosis and on pathological mechanisms and hemodynamic studies related to risk factors for abdominal aortic aneurysms rupture. There are many other opportunities for future research in the clinical joint basis of abdominal aortic aneurysms rupture.

A new approach: Laparoscopic right hemicolectomy with priority access to small bowel mesentery.

Background: For laparoscopic right hemicolectomy, the intermediate approach is commonly employed. However, this approach possesses several disadvantages. In this study, we compare priority access to the small bowel mesentery and the intermediate approach. Methods: The clinical data of 196 patients admitted to the First Hospital of Chongqing Medical University for laparoscopic right hemicolectomy from January 2019 to January 2022 were retrospectively collected and divided into the small bowel mesenteric priority access and traditional intermediate access groups. The operative time, intraoperative bleeding, number of lymph node dissection, postoperative anal venting time, toleration of solid and liquid intake, and postoperative hospital stay and complications were compared between the two different approaches. Results: In total, 81 cases of small bowel mesenteric priority access and 115 cases of intermediate approach for right hemi-colonic radical resection were compared. The operative time was 191.98 ± 46.05 and 209.48 ± 46.08 min in the small bowel mesenteric priority access and intermediate access groups, respectively; the difference was statistically significant. There were no significant differences in the intraoperative bleeding and lymph node clearance. However, the scatter plot analysis showed that severe intraoperative bleeding was relatively less frequent in the small mesenteric priority access group, compared with that in the intermediate approach group. Additionally, there were no statistically significant differences in the first exhaust and defecation times, hospital stay after operation, toleration of solid and liquid intake, and postoperative complication between the two groups. Conclusion: In laparoscopic right hemicolectomy, the small bowel mesenteric priority approach can significantly shorten the operation time compared with the intermediate approach. It can reduce intraoperative bleeding and the operation is simple and safe to perform, making it suitable for less experienced surgeons. Therefore, the small bowel mesenteric priority approach has the potential to be a suitable alternative and deserves further clinical promotion and application.