JARID2, a novel regulatory factor, promotes cell proliferation, migration, and invasion in oral squamous cell carcinoma.

BACKGROUND: Accurate regulation of gene expression is crucial for normal development and function of cells. The prognostic significance and potential carcinogenic mechanisms of the related gene JARID2 in OSCC are not yet clear, but existing research has indicated a significant association between the two. METHODS AND MATERIALS: The relationship between the expression of the JARID2 gene in tumor samples of OSCC patients and clinical pathological factors was analyzed using immunohistochemistry experiments and RT-qPCR analysis. Based on the clinical pathological data of patients, bioinformatics analysis was conducted using public databases to determine the function of JARID2 in OSCC. Knockdown OSCC cell lines were constructed, and the impact of JARID2 on the biological behavior of OSCC cell lines was assessed through CCK-8, wound healing assay, and transwell analysis. RESULTS: Immunohistochemistry experiments confirmed the correlation between JARID2 and the prognosis of OSCC patients, while RT-qPCR experiments demonstrated its expression levels in tissue and cells. CKK-8 experiments, wound healing assays, and Transwell experiments indicated that knocking down JARID2 had a negative impact on the proliferation, invasion, and migration of OSCC cells. Bioinformatics analysis results showed that the expression of JARID2 in OSCC is closely associated with patient gene co-expression, gene function enrichment, immune infiltration, and drug sensitivity. CONCLUSION: Our study indicates that JARID2 is a novel prognostic biomarker and potential therapeutic target for OSCC.

Unraveling the gut microbiota and short-chain fatty acids characteristics and associations in a cancer cachexia mouse model.

OBJECTIVE: Cachexia is a common pathological condition in cancer patients, affecting prognosis and treatment outcomes. The relationship between cachexia and gut microbiota and short-chain fatty acids (SCFAs) remains understudied. This research aimed to establish a cachexia mouse model and explore the gut microbiota-SCFAs connection. The study provides fundamental insights into the regulatory mechanisms of cancer cachexia and potential therapeutic strategies. METHODS: A cachexia mouse model was created using C26 cells, with relevant indicators measured. Histological and immunohistochemical analyses assessed muscle structure and protein expression. ELISA was performed to detect the levels of IL-1ß, IL-6, TNF-α, and LPS in serum to evaluate inflammation.16S rDNA sequencing and GC-MS quantified gut microbiota and SCFAs. Bioinformatics analysis identified indicator species and explored microbiota-SCFAs correlations.ROC analysis was performed to assess the potential of gut microbiota and SCFAs in identifying cachexia. RESULTS: The cachexia mouse model exhibited weight loss, muscle atrophy, and elevated inflammatory factors. Gut microbiota in cachexia mice showed decreased diversity and imbalance. Fourteen bacterial genera were identified as potential cachexia indicators. Functional prediction indicated alterations in the functional composition of gut microbial communities in cachexia mice, particularly in carbohydrate and lipid metabolism pathways. Four SCFAs showed significant changes, potentially serving as diagnostic factors. Specific microbial taxa were positively or negatively correlated with changes in SCFAs, and these microbial taxa and differential SCFAs were also correlated with inflammatory cytokines. CONCLUSION: Our study uncovers the gut microbiota and SCFAs features in a cachexia mouse model, revealing novel correlations between them. These newfound insights into the interplay between cachexia, gut microbiota, and SCFAs provide a crucial foundation for understanding the mechanisms behind cancer cachexia development and potential therapeutic approaches.

The Effect of Metabolic Syndrome on Colorectal Cancer Prognosis after Primary Surgery.

PURPOSE: The purpose of this study was to explore whether metabolic syndrome (MetS) affects the prognosis of colorectal cancer (CRC) patients after primary surgery and to analyze the effect of the specific components of MetS on CRC prognosis. METHODS: The PubMed, Embase and Cochrane Library databases were searched from inception to July 29, 2021. Overall survival (OS) and disease-free survival (DFS) were compared between the MetS group and the non-MetS group. RESULTS: The studies included in the meta-analysis included 4773 patients. All seven studies compared OS between the two groups, and after pooling all hazard ratios (HRs), no significant difference was found between the MetS group and the non-MetS group (HR = 1.17, 95% CI = 0.91 to 1.49, P = 0.21). Four studies compared DFS between the MetS group and the non-MetS group after pooling all the HRs, and there was no difference between the MetS group and the non-MetS group (HR = 1.05, 95% CI = 0.74 to 1.49, P = 0.21). Among the specific components of MetS, high fasting plasma glucose levels (HR = 1.25, 95% CI = 1.00 to 1.58, P = 0.05) had a marginally significant association with poor OS. CONCLUSION: MetS may not affect the prognosis of CRC after primary surgery. However, high fasting plasma glucose levels might contribute to poor OS.

Comparison of Postoperative Outcome and Prognosis Among Laparoscopic Left Colectomy and Laparoscopic Sigmoidectomy in Sigmoid Colon Cancer Patients: A Propensity Score Matching Study.

PURPOSE: The purpose of this study was to investigate the effect of laparoscopic left colectomy (LLC) and laparoscopic sigmoidectomy (LSD) on short-term outcomes and prognosis of sigmoid colon cancer (SCC) patients using propensity score matching (PSM). METHODS: In this retrospective study, the SCC patients who underwent LLC or LSD surgery were collected from a single clinical center from Jan 2011 to Dec 2019. Short-term outcomes and prognosis were compared between patients who received LSD surgery and LLC surgery. RESULTS: A total of 356 patients were included in this study. After 1:1 PSM analysis, there were 50 patients who underwent LLC surgery and 50 patients who underwent LSD surgery left in this study. No significant difference was found in baseline characteristics after PSM (P > .05). In comparison with the LLC surgery group, the LSD surgery group had shorter operation time (P = .003) after PSM. Moreover, the surgical procedure was not an independent predictor for overall survival (OS) (P = .918, 95% CI = .333-2.688) and disease-free survival DFS (P = .730, 95% CI = .335-2.150), but age (OS: P = .009, 95% CI = 1.010-1.075; DFS: P = .014, 95% CI = 1.007-1.061) and tumor stage (OS: P = .004, 95% CI = 1.302-3.844; DFS: P < .01, 95% CI = 1.572-4.171) were the independent risk factors for OS and DFS in SCC patients. CONCLUSION: There was no significant difference between the two surgical procedures for prognosis of SCC patients. However, the possible reasons for changing the surgical procedures should be cautious by surgeons.

Mitophagy-mediated inflammation and oxidative stress contribute to muscle wasting in cancer cachexia.

Cancer cachexia is commonly seen in patients with malignant tumors, which usually leads to poor life quality and negatively affects long-term prognosis and survival. Mitochondria dysfunction and enhanced autophagy are well-established to play an important role in skeletal muscle wasting. However, whether mitophagy is engaged in the pathogenesis of cancer cachexia requires further investigation. This study comprised a clinical study and animal experimentation. Clinical data such as CT images and laboratory results were obtained and analyzed. Then mice model of cancer cachexia and mitophagy inhibition were established. Data including skeletal muscle mass and function, mitochondria structure and function, inflammatory factors as well as ROS concentration. Mitophagy was enhanced in cancer cachexia patients with increased inflammatory factors. Greater disruption of skeletal muscle fiber and mitochondria structure were seen in cancer cachexia, with a higher level of inflammatory factors and ROS expression in skeletal muscle. Meanwhile, ATP production was undermined, indicating a close relationship with mitophagy, inflammation, and oxidative stress in the skeletal muscle of cancer cachexia mice models. In conclusion, mitophagy is activated in cancer cachexia and may play a role in skeletal muscle atrophy, and inflammation and oxidative stress might participate in mitophagy-related skeletal muscle injury.

Higher body mass index was associated with better prognosis in diabetic patients with stage II colorectal cancer.

PURPOSE: The purpose of this study is to analyze the effect of body mass index (BMI) on patients with concurrent colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM). METHODS: Patients who underwent primary radical CRC surgery from Jan 2011 to Jan 2020 were retrospectively collected. The perioperative information, overall survival (OS) and disease-free survival (DFS) were compared between the higher BMI group and the lower BMI group. RESULTS: A total of 574 patients with concurrent CRC and T2DM were included in this study. The higher BMI group had higher portion of hypertension (p < 0.01) and coronary heart disease (CHD) (p < 0.01). Furthermore, the higher BMI group had better OS (p = 0.016) and DFS (p = 0.040) than the lower BMI group in stage II CRC. In multivariate analysis, age (OS: p = 0.002, HR = 2.016, 95% CI = 1.307-3.109/ DFS: p = 0.003, HR = 1.847, 95% CI = 1.230-2.772), TNM stage (OS: p < 0.01, HR = 1.667, 95% CI = 1.281-2.169/ DFS: p = 0.001, HR = 1.545, 95% CI = 1.207-1.977), overall complications (OS: p = 0.004, HR = 1.837, 95% CI = 1.218-2.880/ DFS: p = 0.006, HR = 1.783, 95% CI = 1.184-2.686) and major complications (OS: p = 0.005, HR = 2.819, 95% CI = 1.376-5.774/ DFS: p = 0.014, HR = 2.414, 95% CI = 1.196-4.870) were independent factors of OS and DFS. Moreover, BMI (p = 0.019, HR = 0.413, 95% CI = 0.197-0.864) was an independent factor of OS in stage II CRC. CONCLUSION: Higher BMI was associated with better OS in diabetic patients with stage II CRC.

The short-term and oncologic outcomes of younger VS older colorectal cancer patients undergoing primary surgery: a propensity score matching analysis.

PURPOSE: The purpose of the current study is to analyze the difference of short-term and oncologic outcomes between younger and older colorectal cancer (CRC) patients who underwent primary CRC surgery using a propensity score matching (PSM) analysis. METHODS: We retrospectively collected CRC patients who underwent primary surgery in a single clinical database from Jan 2011 to Jan 2020. The short-term and oncologic outcomes were compared between younger aged group and older aged group. RESULTS: A total of 4599 patients were included in this study, and there were 4196 patients in older aged group and 403 patients in younger aged group. After 1:1 ratio PSM, there were 401 patients in each group. No significant difference was found in terms of baseline information after PSM (p>0.05). Younger aged group had larger retrieved lymph nodes before (p<0.001) and after PSM (p=0.001) than older aged group. In multivariate analysis, younger age was an independent predictor of better overall survival (OS) (p<0.001, HR=2.303, 95% CI=1.658-3.199) and disease-free survival (DFS) (p=0.008, HR=1.425, 95% CI=1.098-1.850). In terms of different tumor stage after PSM, younger aged group had better OS than older group in stage II (p<0.001) and stage IV (p=0.028) CRC, and younger aged group had better DFS than older group in stage II (p=0.016) CRC. CONCLUSION: Younger CRC patients had larger retrieved lymph nodes and better prognosis than older CRC patients after primary CRC surgery.

Hypertension Remission after Colorectal Cancer Surgery: A Single-Center Retrospective Study.

The purpose of this study was to evaluate the effect of colorectal cancer surgery on hypertension. Patients who underwent colorectal cancer surgery were retrospectively enrolled. Hypertension before and 1 year after colorectal cancer surgery was recorded. As a result, eighty patients had remission of hypertension, 307 patients had no remission 1 year after colorectal cancer surgery, and the remission rate was 20.7%. In conclusion, patients with concurrent colorectal cancer and hypertension had a 20.7% remission rate 1 year after colorectal cancer surgery. Age, but not the type of surgery, was a predictive factor for the remission of hypertension.

Does Chronic Kidney Disease Affect the Surgical Outcome and Prognosis of Patients with Gastric Cancer? A Meta-Analysis.

The purpose of this meta-analysis was to evaluate the impact of chronic kidney disease on short-term complications and long-term survival in patients with gastric cancer.The PubMed, Embase, and Cochrane Library databases were searched from inception to May 18, 2021. The search strategy focused on two keywords: chronic kidney disease and gastric cancer. Pooled odds ratios, mean differences, and hazard ratios were analyzed. RevMan 5.3 was used for data analysis in this meta-analysis.A total of seven studies including 3,346 patients were included in this meta-analysis. The chronic kidney disease group had a higher proportion of males and older patients, lower albumin levels, higher comorbidity rates, and higher N staging. The chronic kidney disease group had higher rates of overall postoperative complications (OR = 2.05, 95% CI = 1.38 to 3.05, P = 0.0004), more severe postoperative complications (OR = 2.06, 95% CI = 1.59 to 2.66, P < 0.00001), and higher rates of cardiovascular-related complications, anastomotic leakage, pneumonia, wound infections, pancreatic-related diseases and short-term death. Furthermore, the chronic kidney disease group had poorer overall survival than the nonchronic kidney disease group (HR = 2.89, 95% CI = 2.20 to 3.80, P < 0.00001).Preexisting chronic kidney disease was associated with higher complications and poorer overall survival following gastrectomy in patients with gastric cancer.

Comparison of surgical and oncologic outcomes in very elderly patients (≥ 80 years old) and elderly (65-79 years old) colorectal cancer patients: a propensity score matching.

PURPOSE: The purpose of this study was to investigate the short-term outcomes and prognosis of elderly and very elderly colorectal cancer (CRC) patients after primary CRC surgery using propensity score matching (PSM). METHODS: This study retrospectively collected the medical records of CRC patients ≥ 65 years old undergoing primary CRC surgery from Jan 2011 to Jan 2020. Short-term outcomes, overall survival (OS) and disease-free survival (DFS) were compared between very elderly CRC patients (≥ 80 years old) and elderly CRC patients (65-79 years old). RESULTS: A total of 2084 patients were enrolled for analysis. After PSM, 331 very elderly patients were matched to 331 elderly patients. In terms of short-term outcomes, the very elderly patients had longer postoperative hospital stays (p = 0.007) after PSM. In terms of OS, it was found that age (p < 0.01, HR = 1.878, 95% CI 1.488-2.371), tumor stage (p < 0.01, HR = 1.865, 95% CI 1.603-2.170), overall complications (p < 0.01, HR = 1.514, 95% CI 1.224-1.872) and major complications (p = 0.001, HR = 2.012, 95% CI 1.319-3.069) were independent prognostic factors. For DFS, age (p < 0.01, HR = 1.816, 95% CI 1.579-2.088), tumor stage (p < 0.01, HR = 1.816, 95% CI 1.579-2.088), overall complications (p = 0.002, HR = 1.379, 95% CI 1.128-1.685) and major complications (p = 0.002, HR = 1.902, 95% CI 1.259-2.874) were found to be independent prognostic factors. Moreover, elderly patients had a better OS and DFS than very elderly patients. CONCLUSION: Very elderly patients had a poorer prognosis than elderly patients after primary CRC surgery. Surgeons should be cautious when treating very elderly CRC patients.

Predictors associated with planned and unplanned admission to intensive care units after colorectal cancer surgery: a retrospective study.

PURPOSE: The purpose of the current study is to identify the predictors of planned and unplanned admission to intensive care units (ICU) after colorectal cancer (CRC) surgery. METHODS: We retrospectively collected CRC patients' information from January 2016 to June 2021 in a single clinical center. The predictors of planned and unplanned admission to ICU after CRC surgery were analyzed. RESULTS: A total of 4263 patients were included in this study and there were 349 (8.2%) CRC patients who were admitted to ICU. There were 34 (9.7%) CRC patients in unplanned ICU admission group and 315 (90.3%) CRC patients in planned ICU admission group. Older age (p < 0.01, OR = 1.093, 95% CI = 1.079-1.108), male (p = 0.013, OR = 0.721, 95% CI = 0.557-0.933), lower body mass index (BMI) (p = 0.001, OR = 0.932, 95% CI = 0.896-0.971), type 2 diabetes mellitus (T2DM) (p = 0.035, OR = 1.422, 95% CI = 1.024-1.975), coronary heart disease (CHD) (p = 0.036, OR = 1.579, 95% CI = 1.031-2.420), colon cancer (p = 0.002, OR = 1.475, 95% CI = 1.149-1.894), advanced tumor stage (p = 0.003, OR = 1.265, 95% CI = 1.082-1.478), longer operation time (p = 0.005, OR = 1.002, 95% CI = 1.001-1.003), and larger blood loss (p < 0.01, OR = 1.002, 95% CI = 1.001-1.002) were independent predictors of planned ICU admission. Older age (p < 0.01, OR = 1.062, 95% CI = 1.029-1.097) and longer operation time (p = 0.003, OR = 1.004, 95% CI = 1.001-1.007) were independent predictors of unplanned ICU admission. CONCLUSION: Cautions should be paid for CRC patients with predictive factors to avoid unnecessary ICU admission.

Effect of endoscopic resection on short-term surgical outcomes of subsequent laparoscopic gastrectomy: a meta-analysis.

BACKGROUND: Endoscopic resection (ER) might affect subsequent laparoscopic gastrectomy (LG) because of the electrical coagulation, but the effect remains controversial. The purpose of this meta-analysis was to analyze the effect of ER on the short-term surgical outcomes of subsequent LG. MATERIALS AND METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched to find eligible studies published from inception to March 21, 2021. Short-term surgical outcomes were compared between the ER-LG group and the LG-only group. The registration ID of this current meta-analysis on PROSPERO is CRD42021238031. RESULTS: Nine studies involving 3611 patients were included in this meta-analysis. The LG-only group had a higher T stage (T1-T2: OR=2.42, 95% CI=1.09 to 5.34, P=0.03; T3-T4: OR=0.41, 95% CI=0.19 to 0.91, P=0.03) than the ER-LG group. The ER-LG group showed a shorter operation time than the LG-only group (MD=-5.98, 95% CI=-10.99 to -0.97, P=0.02). However, no difference was found in operation time after subgroup analysis of propensity score matching studies. No significant difference was found in intraoperative blood loss, time to first oral feeding, or postoperative hospital stay between the ER-LG group and the LG-only group. And no significance was found in overall complications (OR=1.16, 95% CI=0.89 to 1.50, P=0.27), complications of grade ≥ II (OR=1.11, 95% CI=0.71 to 1.73, P=0.64), complications of grade ≥ III b (OR=1.47, 95% CI=0.49 to 4.43, P=0.49) between the ER-LG group and the LG-only group. CONCLUSIONS: ER did not affect subsequent LG in terms of short-term outcomes, and the ER-LG group might have a shorter operation time than the LG-only group.

Does liver cirrhosis affect the surgical outcome of primary colorectal cancer surgery? A meta-analysis.

PURPOSE: The purpose of this meta-analysis was to evaluate the effect of liver cirrhosis (LC) on the short-term and long-term surgical outcomes of colorectal cancer (CRC). METHODS: The PubMed, Embase, and Cochrane Library databases were searched from inception to March 23, 2021. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of enrolled studies, and RevMan 5.3 was used for data analysis in this meta-analysis. The registration ID of this current meta-analysis on PROSPERO is CRD42021238042. RESULTS: In total, five studies with 2485 patients were included in this meta-analysis. For the baseline information, no significant differences in age, sex, tumor location, or tumor T staging were noted. Regarding short-term outcomes, the cirrhotic group had more major complications (OR=5.15, 95% CI=1.62 to 16.37, p=0.005), a higher re-operation rate (OR=2.04, 95% CI=1.07 to 3.88, p=0.03), and a higher short-term mortality rate (OR=2.85, 95% CI=1.93 to 4.20, p<0.00001) than the non-cirrhotic group. However, no significant differences in minor complications (OR=1.54, 95% CI=0.78 to 3.02, p=0.21) or the rate of intensive care unit (ICU) admission (OR=0.76, 95% CI=0.10 to 5.99, p=0.80) were noted between the two groups. Moreover, the non-cirrhotic group exhibited a longer survival time than the cirrhotic group (HR=2.96, 95% CI=2.28 to 3.85, p<0.00001). CONCLUSION: Preexisting LC was associated with an increased postoperative major complication rate, a higher rate of re-operation, a higher short-term mortality rate, and poor overall survival following CRC surgery.

The outcome of young vs. old gastric cancer patients following gastrectomy: a propensity score matching analysis.

PURPOSE: The purpose of the current study was to compare the postoperative complications, overall survival and disease-free survival in young and old gastric cancer patients after gastrectomy using propensity score matching (PSM). METHODS: Adult patients (aged ≥ 18 years) who underwent gastrectomy for gastric cancer in a single clinical center from January 2013 to December 2017 were enrolled continuously for retrospective analysis. To minimize the selection bias between the young and old groups, the PSM was conducted in this study. RESULTS: A total of 558 patients were included in this study, with 51 patients in the young group (aged ≤ 45 years) and 507 patients in the old group (aged > 45 years). After 1:1 matching according to PSM, 51 patients in the young group were matched to 51 patients in the old group. After PSM, there was no difference in the baseline information. In terms of short-term outcomes, no difference was found in operation time (P = 0.190), intraoperative blood loss (P = 0.336), retrieved lymph nodes (P = 0.948), blood transfusion (P = 0.339), postoperative hospital stay (P = 0.194), or postoperative complications (P = 0.477) between the two groups. For overall survival, no statistically significant difference was found in all stages (P = 0.383), stage I (P = 0.431), stage II (P = 0.875) or stage III (P = 0.446) gastric cancer. Furthermore, regarding disease-free survival, no differences were found between the two groups in all stages (P = 0.378), stage I (P = 0.431), stage II (P = 0.879) or stage III (P = 0.510) gastric cancer. CONCLUSION: Age might not be an independent prognostic factor for short-term outcomes, OS, or DFS in gastric cancer patients who underwent gastrectomy. The pTNM stage of GC might be an independent prognostic factor for OS and DFS.

Polycomb repressive complex 2 and its core component EZH2: potential targeted therapeutic strategies for head and neck squamous cell carcinoma.

The polycomb group (PcG) comprises a set of proteins that exert epigenetic regulatory effects and play crucial roles in diverse biological processes, ranging from pluripotency and development to carcinogenesis. Among these proteins, enhancer of zeste homolog 2 (EZH2) stands out as a catalytic component of polycomb repressive complex 2 (PRC2), which plays a role in regulating the expression of homologous (Hox) genes and initial stages of x chromosome inactivation. In numerous human cancers, including head and neck squamous cell carcinoma (HNSCC), EZH2 is frequently overexpressed or activated and has been identified as a negative prognostic factor. Notably, EZH2 emerges as a significant gene involved in regulating the STAT3/HOTAIR axis, influencing HNSCC proliferation, differentiation, and promoting metastasis by modulating related oncogenes in oral cancer. Currently, various small molecule compounds have been developed as inhibitors specifically targeting EZH2 and have gained approval for treating refractory tumors. In this review, we delve into the epigenetic regulation mediated by EZH2/PRC2 in HNSCC, with a specific focus on exploring the potential roles and mechanisms of EZH2, its crucial contribution to targeted drug therapy, and its association with cancer markers and epithelial-mesenchymal transition. Furthermore, we aim to unravel its potential as a therapeutic strategy for oral squamous cell carcinoma.

Molecular basis, potential biomarkers, and future prospects of OSCC and PD-1/PD-L1 related immunotherapy methods.

Oral squamous cell carcinoma (OSCC) affects a large number of individuals worldwide. Despite advancements in surgery, radiation, and chemotherapy, satisfactory outcomes have not been achieved. In recent years, the success of drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has led to breakthroughs in cancer treatment, but systematic summaries on their effectiveness against OSCC are lacking. This article reviews the latest research on the PD-1/PD-L1 pathway and the potential of combination therapy based on this pathway in OSCC. Further, it explores the mechanisms involved in the interaction of this pathway with exosomes and protein-protein interactions, and concludes with potential future OSCC therapeutic strategies.

A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation.

Cancer vaccine gains great attention with the advances in tumor immunology and nanotechnology, but its long-term efficacy is restricted by the unsustainable immune activity after vaccination. Here, we demonstrate the vaccine efficacy is negatively correlated with the tumor burden. To maximum the vaccine-induced immunity and prolong the time-effectiveness, we design a priming-boosting vaccination strategy by combining with radiofrequency ablation (RFA), and construct a bisphosphonate nanovaccine (BNV) system. BNV system consists of nanoparticulated bisphosphonates with dual electric potentials (BNV(+&-)), where bisphosphonates act as the immune adjuvant by blocking mevalonate metabolism. BNV(+&-) exhibits the spatial and temporal heterogeneity in lymphatic delivery and immune activity. As the independent components of BNV(+&-), BNV(-) is drained to the lymph nodes, and BNV(+) is retained at the injection site. The alternately induced immune responses extend the time-effectiveness of antitumor immunity and suppress the recurrence and metastasis of colorectal cancer liver metastases after RFA. As a result, this trinity system integrated with RFA therapy, bisphosphonate adjuvant, and spatiotemporal immune effect provides an orientation for the sustainable regulation and precise delivery of cancer vaccines.

Remodeling of intestinal epithelium derived extracellular vesicles by nanoparticles and its bioeffect on tumor cell migration.

Extracellular vesicles (EVs) are an effective tool to elucidate the bioeffect of nanomedicines. To clarify the interaction between oral nanomedicines and intestinal epithelial cells, and their bioeffects on downstream cells, polystyrene nanoparticles (PS-NPs) with different sizes were used as the model nanomedicines for EVs induction. Caco-2 monolayers were selected as the model of the intestinal epithelium and DLD-1 cells as the colorectal cancer model proximal to the gastrointestinal tract. It is found that compared with small-sized (25, 50, 100 nm) PS-NPs, the large-sized (200 and 500 nm) exhibited higher co-localization with multivesicular bodies and lysosomes, and more significant reduction of lysosomal acidification in Caco-2 cells. Proteomic and western-blotting analysis showed that the EVs remodeled by large-sized PS-NPs exhibited a higher extent of protein expression changes. The in vitro and in vivo signaling pathway detection in DLD-1 cells and DLD-1 cell xenograft nude mice showed that the remodeled EVs by large-sized PS-NPs inhibited the activation of multiple signaling pathways including Notch3, EGF/EGFR, and PI3K/Akt pathways, which resulted in the inhibition of tumor cell migration. These results primarily clarify the regulation mechanisms of nanomedicines-EVs-receptor cells chain. It provides a new perspective for the rational design and bioeffect evaluation of oral drug nanomaterials and sets up the fundamental knowledge for novel tumor therapeutics in the future.

Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme-Induced Proximity Labeling.

Achieving increasingly finely targeted drug delivery to organs, tissues, cells, and even to intracellular biomacromolecules is one of the core goals of nanomedicines. As the delivery destination is refined to cellular and subcellular targets, it is essential to explore the delivery of nanomedicines at the molecular level. However, due to the lack of technical methods, the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date. Here, we develop an enzyme-induced proximity labeling technology in nanoparticles (nano-EPL) for the real-time monitoring of proteins that interact with intracellular nanomedicines. Poly(lactic-co-glycolic acid) nanoparticles coupled with horseradish peroxidase (HRP) were fabricated as a model (HRP(+)-PNPs) to evaluate the molecular mechanism of nano delivery in macrophages. By adding the labeling probe biotin-phenol and the catalytic substrate H2O2 at different time points in cellular delivery, nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles. Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP (+)-PNPs in macrophages over time. Based on dynamic clustering analysis of these proteins, we further discovered that different organelles, including endosomes, lysosomes, the endoplasmic reticulum, and the Golgi apparatus, are involved in delivery with distinct participation timelines. More importantly, the engagement of these organelles differentially affects the drug delivery efficiency, reflecting the spatial-temporal heterogeneity of nano delivery in cells. In summary, these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

Macrophage polarization in bone implant repair: A review.

Macrophages (MΦ) are highly adaptable and functionally polarized cells that play a crucial role in various physiological and pathological processes. Typically, MΦ differentiate into two distinct subsets: the proinflammatory (M1) and anti-inflammatory (M2) phenotypes. Due to their potent immunomodulatory and anti-inflammatory properties, MΦ have garnered significant attention in recent decades. In the context of bone implant repair, the immunomodulatory function of MΦ is of paramount importance. Depending on their polarization phenotype, MΦ can exert varying effects on osteogenesis, angiogenesis, and the inflammatory response around the implant. This paper provides an overview of the immunomodulatory and inflammatory effects of MΦ polarization in the repair of bone implants.