Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.

Attenuating glucose metabolism by Fbxw7 promotes Taxol sensitivity of colon cancer cells through downregulating NADPH oxidase 1 (Nox1).

BACKGROUND: Colorectal cancer (CRC), one of the most common malignancies worldwide, is associated with poor survival and has a high mortality rate. Taxol is a chemotherapeutic agent that has been clinically applied as a first-line drug against diverse cancers. Yet, development of drug resistance has become the major challenge for anti-cancer treatments. F-box and WD40 domain protein 7 (Fbxw7) is a known tumor suppressor which is frequently downregulated in cancers. However, the biological roles and mechanisms of Fbxw7 in Taxol resistance are still under investigation. METHODS: We report that Fbxw7 is significantly inactivated in CRC tumors and cell lines compared with normal tissues and colon cells. Expressions of Fbxw7 and Nox1 were detected from human colon tumors and cells by qRT-PCR and Western blot. Glycolysis rate was assessed by glucose uptake and lactate product assay. Interactions between Fbxw7 and Nox1 were determined by co-immunoprecipitation (Co-IP). Chemosensitivity and resistance of colon cancer cells were determined by MTT assay and Annexin V-FITC assay. RESULTS: Overexpression of Fbxw7 sensitized colon cancer cells to Taxol. Moreover, we observed a negative correlation between Fbxw7 and glucose metabolism. From the established Taxol-resistant (TR) cell line from HCT-116, Fbxw7 was found to be markedly downregulated in HCT-116 TR cells. We detected that NADPH oxidase 1 (Nox1), a superoxide-generating NADPH oxidase, is negatively regulated by Fbxw7. The Co-IP assay showed that Fbxw7 interacted with Nox1, which was observed to be significantly upregulated in CRC tissues. Nox1 therefore promotes the Taxol resistance and glucose metabolism of colon cancer cells. Finally, rescue experiments demonstrated that the Fbxw7-promoted Taxol sensitivity was partially through the Nox1-glycolysis axis. Restoration of Nox1 in Fbxw7-overexpressed TR colon cancer cells significantly recovered the Taxol resistance, which could be further overridden by glycolysis inhibition. CONCLUSIONS: Collectively, this study uncovered that targeting the Fbxw7-Nox1-glucose metabolism axis could be an effective strategy against chemoresistant colon cancer.

Transanal minimally invasive surgery vs endoscopic mucosal resection for rectal benign tumors and rectal carcinoids: A retrospective analysis.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) is a good choice for resection of rectal neoplasms. Endoscopic mucosal resection (EMR) is also widely used in the treatment of benign rectal tumors such as rectal polyps and rectal adenomas. However, no studies have compared the outcome of TAMIS and EMR. AIM: To compare the short-term outcomes after TAMIS and EMR for rectal carcinoid and benign tumors (including rectal polyps and adenomas). METHODS: From January 2014 to January 2019, 44 patients who received TAMIS and 53 patients who received EMR at The Fifth People's Hospital of Shanghai were selected. Primary outcomes (surgical-related) were operating time, blood loss, length of postoperative hospital stay, rate of resection margin involvement and lesion fragmentation rate. The secondary outcomes were complications such as hemorrhage, urinary retention, postoperative infection and reoperation. RESULTS: No significant differences were observed in terms of blood loss (12.48 ± 8.00 mL for TAMIS vs 11.45 ± 7.82 mL for EMR, P = 0.527) and length of postoperative hospital stay (3.50 ± 1.87 d for TAMIS vs 2.72 ± 1.98 d for EMR, P = 0.065) between the two groups. Operating time was significantly shorter for EMR compared with TAMIS (21.19 ± 9.49 min vs 49.95 ± 15.28 min, P = 0.001). The lesion fragmentation rate in the EMR group was 22.6% (12/53) and was significantly higher than that (0%, 0/44) in the TAMIS group (P = 0.001). TAMIS was associated with a higher urinary retention rate (13.6%, 6/44 vs 1.9%, 1/53 P = 0.026) and lower hemorrhage rate (0%, 0/44 vs 18.9%, 10/53 P = 0.002). A significantly higher reoperation rate was observed in the EMR group (9.4%, 5/53 vs 0%, 0/44 P = 0.036). CONCLUSION: Compared with EMR, TAMIS can remove lesions more completely with effective hemostasis and lower postoperative hemorrhage and reoperation rates. TAMIS is a better choice for the treatment of rectal carcinoids.