Exosomes Mediate the Production of Oxaliplatin Resistance and Affect Biological Behaviors of Colon Cancer Cell Lines.

BACKGROUND: Colon cancer has high mortality rate which making it one of the leading causes of cancer deaths. Oxaliplatin is a common chemotherapeutic drug, but it has disadvantages such as drug resistance. OBJECTIVE: The purpose of this study is to explore the mechanism of exosomes in the resistance of oxaliplatin and verify whether elemene and STAT3 inhibitors reverse the resistance to oxaliplatin. METHODS: Related cell line models were constructed and the proliferation, migration, invasion, apoptosis and resistance to oxaliplatin were evaluated for all three cells of HCT116/L, sensitive cell HCT116 and HCT116+HCT116/L-exosomes (HCT116-exo). It was to explore probable signaling pathways and mechanisms by Western blotting. RESULTS: HCT116-exo drug-resistant chimeric cells showed greater capacity for proliferation, migration and invasion than HCT116 sensitive cells. After the above cells were treated with oxaliplatin, the apoptosis rate of chimeric drug-resistant cells HCT116-exo and its IC50 increased compared with the sensitive cells HCT116. The proliferation, invasion and migration of cells treated with STAT3 inhibitor or ß-elemene combined with oxaliplatin reduced compared with those treated with oxaliplatin or ß-elemene alone. The STAT3 inhibitor or ß-elemene in combination with oxaliplatin increased the rate of apoptosis relative to oxaliplatin or ß-elemene alone. Drug-resistant cell exosomes could promote the EMT process, related to the participation of FGFR4, SHMT2 and STAT3 inhibitors. CONCLUSION: Drug-resistant cell exosomes could induce resistance, and improve the capacity of colon cancer towards proliferate, invade, migrate and promote the EMT process. The ß-elemene combined with oxaliplatin could reverse the above results which might be related to the STAT3 pathway and EMT pathway in colon cancer.

Efficacy of a smartphone application assisting home-based rehabilitation and symptom management for patients with lung cancer undergoing video-assisted thoracoscopic lobectomy: a prospective, single-blinded, randomised control trial (POPPER study).

BACKGROUND: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and post-discharge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation. METHODS: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. We screened 265 patients and randomly assigned 136 equally to the app group and usual care group. The primary outcome was pulmonary function recovery at 30 days postoperatively. Secondary outcomes included symptom burden and interference with daily living (both rated using the MD Anderson Symptom Inventory for Lung Cancer), aerobic exercise intensity, emergency department visits, app-related safety, and satisfaction with the app. FINDINGS: Of the 136 participants, 56.6% were women and their mean age was 61 years. The pulmonary function recovery ratio 1 month after surgery in the app group was significantly higher than that in the usual care group (79.32% vs. 75.73%; P=0.040). The app group also recorded significantly lower symptom burden and interference with daily living scores and higher aerobic exercise intensity after surgery than the usual care group. Thirty-two alerts were triggered in the app group. The highest pulmonary function recovery ratio and aerobic exercise intensity were recorded in those patients who triggered alerts in both groups. INTERPRETATION: Using a smartphone app is an effective approach to accelerate home-based rehabilitation after VATS lobectomy. The symptom alert mechanism of this app could optimise recovery outcomes, possibly driven by patients' increased self-awareness.

Feasibility and safety of percutaneous intramyocardial septal cryoablation: A canine model with 6-month follow-up.

Echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) is a novel treatment option for hypertrophic obstructive cardiomyopathy (HOCM). The safety and feasibility of using this procedure for cryoablation are unknown. We aimed to investigate the feasibility and safety of echocardiography-guided percutaneous intramyocardial septal cryoablation (PIMSCA) for septal thickness reduction in a canine model. Eight canines underwent PIMSCA, and had electrocardiography, echocardiography(ECG), myocardial contrast echocardiography (MCE), serological and pathological examinations during the preoperative, immediate postoperative, and 6-month follow-up. All eight canines underwent successful cryoablation and continued to be in sinus rhythm during ablation and without malignant arrhythmias. MCE showed that the ablation area had decreased myocardial perfusion after the procedure. Troponin I levels were significantly elevated [0.010 (0.005, 0.297) ng/mL vs. 3.122 (1.152, 7.990) ng/mL, p < 0.05)]. At 6-month follow-up after the procedure, all animals were alive, with thinning of the interventricular septum (7.26 ± 0.52 mm vs. 3.86 ± 0.29 mm, p < 0.05). Echocardiography showed no significant decrease in the left ventricular ejection fractions (LVEF) (54.32 ± 2.93 % vs. 54.70 ± 2.47 %, p > 0.05) or changes by pulse-wave Doppler E/A (1.17 ± 0.43 vs. 1.07 ± 0.43, p > 0.05), E/e' (8.09 ± 1.49 vs. 10.05 ± 2.68, p > 0.05). Pathological findings proved the effectiveness of cryoablation in myocardial tissues. We observed pericardial effusions and premature ventricular complexes (PVCs) associated with the procedure. Our findings provided preliminary evidence of the safety and feasibility of PIMSCA in reducing interventricular septum, which provides a potentially new treatment option for HOCM.

Safety, efficacy, and survival outcomes of immune checkpoint inhibitors rechallenge in patients with cancer: a systematic review and meta-analysis.

BACKGROUNDS: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05). CONCLUSION: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.

Determination of 3-nitropropionic acid in sugarcane using dispersive solid-phase extraction and gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

A method for accurately determining 3-nitropropionic acid in sugarcane was established for the first time using gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (GC - APCI-MS/MS). Under acidic conditions, 3-nitropropionic acid is methylated to obtain methyl 3-nitropropionate. The derivative product was purified using dispersive solid-phase extraction (d-SPE) method and analyzed using GC - APCI-MS/MS. The recovery experiments were conducted at three concentrations: low, medium, and high. The recovery rates ranged from 75.1% to 90.2%, the relative standard deviations were <8.2%, and the limit of quantification was 2.0 µg/kg. The method offers the advantage of being accurate, sensitive, and specific, meeting the requirements of the determination of 3-nitropropionic acid in sugarcane.

The transition of surgical simulation training and its learning curve: a bibliometric analysis from 2000 to 2023.

BACKGROUND: Proficient surgical skills are essential for surgeons, making surgical training an important part of surgical education. The development of technology promotes the diversification of surgical training types. This study analyzes the changes in surgical training patterns from the perspective of bibliometrics, and applies the learning curves as a measure to demonstrate their teaching ability. METHOD: Related papers were searched in the Web of Science database using the following formula: TS=[(training OR simulation) AND (learning curve) AND (surgical)]. Two researchers browsed the papers to ensure that the topics of articles were focused on the impact of surgical simulation training on the learning curve. CiteSpace, VOSviewer, and R packages were applied to analyze the publication trends, countries, authors, keywords, and references of selected articles. RESULT: Ultimately, 2461 documents were screened and analyzed. The USA is the most productive and influential country in this field. Surgical endoscopy and other interventional techniques publish the most articles, while surgical endoscopy and other interventional techniques is the most cited journal. Aggarwal Rajesh is the most productive and influential author. Keyword and reference analyses reveal that laparoscopic surgery, robotic surgery, virtue reality, and artificial intelligence were the hotspots in the field. CONCLUSION: This study provided a global overview of the current state and future trend in the surgical education field. The study surmised the applicability of different surgical simulation types by comparing and analyzing the learning curves, which is helpful for the development of this field.

Finite Element Analysis of Six Internal Fixations in the Treatment of Pauwels Type III Femoral Neck Fracture.

OBJECTIVE: The current investigation sought to utilize finite element analysis to replicate the biomechanical effects of different fixation methods, with the objective of establishing a theoretical framework for the optimal choice of modalities in managing Pauwels type III femoral neck fractures. METHODS: The Pauwels type III fracture configuration, characterized by angles of 70°, was simulated in conjunction with six distinct internal fixation methods, including cannulated compression screw (CCS), dynamic hip screw (DHS), DHS with de-rotational screw (DS), CCS with medial buttress plate (MBP), proximal femoral nail anti-rotation (PFNA), and femoral neck system (FNS). These models were developed and refined using Geomagic and SolidWorks software. Subsequently, finite element analysis was conducted utilizing Ansys software, incorporating axial loading, torsional loading, yield loading and cyclic loading. RESULTS: Under axial loading conditions, the peak stress values for internal fixation and the femur were found to be highest for CCS (454.4; 215.4 MPa) and CCS + MBP (797.2; 284.2 MPa), respectively. The corresponding maximum and minimum displacements for internal fixation were recorded as 6.65 mm for CCS and 6.44 mm for CCS + MBP. When subjected to torsional loading, the peak stress values for internal fixation were highest for CCS + MBP (153.6 MPa) and DHS + DS (72.8 MPa), while for the femur, the maximum and minimum peak stress values were observed for CCS + MBP (119.3 MPa) and FNS (17.6 MPa), respectively. Furthermore, the maximum and minimum displacements for internal fixation were measured as 0.249 mm for CCS + MBP and 0.205 mm for PFNA. Additionally, all six internal fixation models showed excellent performance in terms of yield load and fatigue life. CONCLUSION: CCS + MBP had the best initial mechanical stability in treatment for Pauwels type III fracture. However, the MBP was found to be more susceptible to shear stress, potentially increasing the risk of plate breakage. Furthermore, the DHS + DS exhibited superior biomechanical stability compared to CCS, DHS, and PFNA, thereby offering a more conducive environment for fracture healing. Additionally, it appeared that FNS represented a promising treatment strategy, warranting further validation in future studies.

Exosomes derived from pulmonary metastatic sites enhance osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS.

Osteosarcoma, a prevalent primary malignant bone tumor, often presents with lung metastases, severely impacting patient survival rates. Extracellular vesicles, particularly exosomes, play a pivotal role in the formation and progression of osteosarcoma-related pulmonary lesions. However, the communication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure, with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely unknown. This study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor site. This transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate (MARCKS) expression. Addressing this phenomenon, in this study we employ cationic bovine serum albumin (CBSA) to form nanoparticles (CBSA-anta-194/215) via electrostatic interaction with antagomir-miR-194/215. These nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles (anta-194/215@Exo) targeting osteosarcoma lung metastatic sites. Intervention with bioengineered exosome mimetics (anta-194/215@Exo) not only impedes osteosarcoma progression but also significantly prolongs the lifespan of tumor-bearing mice. These findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS, making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases.

Gasdermin D drives focal crystalline thrombotic microangiopathy by accelerating immunothrombosis and necroinflammation.

ABSTRACT: Thrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein that serves as the final downstream effector of the pyroptosis/interleukin-1ß (IL-1ß) pathway, contributes to TMA and its consequences by amplifying neutrophil maturation and subsequent necrosis. Using a murine model of focal crystalline TMA, we found that Gsdmd deficiency ameliorated immunothrombosis, acute tissue injury, and failure. Gsdmd-/- mice exhibited a decrease in mature IL-1ß, as well as in neutrophil maturation, ß2-integrin activation, and recruitment to TMA lesions, in which they formed reduced neutrophil extracellular traps in both arteries and interstitial tissue. The GSDMD inhibitor disulfiram dose-dependently suppressed human neutrophil pyroptosis in response to cholesterol crystals. Experiments with GSDMD-deficient, human-induced, pluripotent stem cell-derived neutrophils confirmed the involvement of GSDMD in neutrophil ß2-integrin activation, maturation, and pyroptosis. Both prophylactic and therapeutic administration of disulfiram protected the mice from focal TMA, acute tissue injury, and failure. Our data identified GSDMD as a key mediator of focal crystalline TMA and its consequences, including ischemic tissue infarction and organ failure. GSDMD could potentially serve as a therapeutic target for the systemic forms of TMA.

The incorporation of acetylated LAP-TGF-ß1 proteins into exosomes promotes TNBC cell dissemination in lung micro-metastasis.

Triple-negative breast cancer (TNBC) stands as the breast cancer subtype with the highest recurrence and mortality rates, with the lungs being the common site of metastasis. The pulmonary microenvironment plays a pivotal role in the colonization of disseminated tumor cells. Herein, this study highlights the crucial role of exosomal LAP-TGF-ß1, the principal form of exosomal TGF-ß1, in reshaping the pulmonary vascular niche, thereby facilitating TNBC lung metastasis. Although various strategies have been developed to block TGF-ß signaling and have advanced clinically, their significant side effects have limited their therapeutic application. This study demonstrates that in lung metastatic sites, LAP-TGF-ß1 within exosomes can remarkably reconfigure the pulmonary vascular niche at lower doses, bolstering the extravasation and colonization of TNBC cells in the lungs. Mechanistically, under the aegis of the acetyltransferase TIP60, a non-canonical KFERQ-like sequence in LAP-TGF-ß1 undergoes acetylation at the K304 site, promoting its interaction with HSP90A and subsequent transport into exosomes. Concurrent inhibition of both HSP90A and TIP60 significantly diminishes the exosomal burden of LAP-TGF-ß1, presenting a promising therapeutic avenue for TNBC lung metastasis. This study not only offers fresh insights into the molecular underpinnings of TNBC lung metastasis but also lays a foundation for innovative therapeutic strategies.

Occurrence and prevalence of per- and polyfluoroalkyl substances in the sediment pore water of mariculture sites: Novel findings of PFASs from the Bohai and Yellow Seas using a newly established analytical method.

A new method for the determination of 26 legacy and emerging per- and polyfluoroalkyl substances (PFASs) in marine sediment pore water was developed using online solid phase extraction coupled with liquid chromatography-tandem mass spectrometry. The proposed method requires only about 1 mL of pore water samples. Satisfactory recoveries of most target PFASs (83.55-125.30 %) were achieved, with good precision (RSD of 1.09-16.53 %), linearity (R2 ≥ 0.990), and sensitivity (MDLs: 0.05 ng/L-5.00 ng/L for most PFASs). Subsequently, the method was applied to determine PFASs in the sediment pore water of five mariculture bays in the Bohai and Yellow Seas of China for the first time. Fifteen PFASs were detected with total concentrations ranging from 150.23 ng/L to 1838.48 ng/L (mean = 636.80 ng/L). The ∑PFASs and PFOA concentrations in sediment pore water were remarkably higher than those in surface seawater (tens of ng/L), indicating that the potential toxic effect of PFASs on benthic organisms may be underestimated. PFPeA was mainly distributed in pore water, and the partition of PFHpA (50.99 %) and PFOA (49.01 %) was almost equal in the solid and liquid phases. The proportions of all other PFASs partitioned in marine sediments were significantly higher than those in pore water.

Ethylene induced AcNAC3 and AcNAC4 take part in ethylene synthesis through mediating AcACO1 during kiwifruit (Actinidia chinensis) ripening.

BACKGROUND: Ethylene plays a vital role in the ripening process of kiwifruit. A terrific amount of transcription factors (TFs) have been shown to regulate ethylene synthesis in various fruits. RESULTS: In this research, two new NAC TFs, named AcNAC3 and AcNAC4, were isolated from kiwifruit, which belonged to NAM subfamily. Bioinformatics analysis showed that both AcNAC3 and AcNAC4 were hydrophilic proteins with similar three-dimensional structures. The expression levels of AcNAC3, AcNAC4 and AcACO1 increased during kiwifruit ripening, as well as were induced by ethylene and repressed by 1-methylcyclopropene (1-MCP). Correlation analysis exhibited that ethylene production was positively correlated with the expression levels of AcNAC3, AcNAC4 and AcACO1. Moreover, both AcNAC3 and AcNAC4 acted as transcriptional activators and could bind to and activate AcACO1 promoter. CONCLUSION: All results unveiled that the ethylene-induced AcNAC3 and AcNAC4 were transcriptional activators, and might participate in kiwifruit ripening and ethylene biosynthesis through activating AcACO1, providing a new insight of ethylene synthetic regulation during kiwifruit ripening. © 2024 Society of Chemical Industry.

Role of hepatitis B core-related antigen in predicting the occurrence and recurrence of hepatocellular carcinoma in patients with chronic hepatitis B: A systemic review and meta-analysis.

BACKGROUND AND AIM: The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC. RESULTS: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40-4.06, P < 0.001, I2 = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44-5.82, P < 0.001, I2 = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26-2.32, P < 0.001, I2 = 7.89%, P = 0.031). CONCLUSIONS: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions.

S-Adenosylmethionine (SAM) diet promotes innate immunity via histone H3K4me3 complex.

S-adenosylmethionine (SAM) was a methyl donor for modifying histones, which had crucial roles in lipid accumulation, tissue injury, and immune responses. SAM fluctuation might be linked to variations in histone methylation. However, the underlying molecular mechanisms of whether the SAM diet influenced the immune response via histone modification remained obscure. In this study, we utilized the Caenorhabditis elegans as a model to investigate the role of SAM diet in innate immunity. We found that 50 µM SAM increased resistance to Gram-negative pathogen Pseudomonas aeruginosa PA14 by reducing the bacterial burden in the intestine. Furthermore, through the genetic screening in C. elegans, we found that SAM functioned in germline to enhance innate immunity via an H3K4 methyltransferase complex to upregulate the immune response genes, including irg-1 and T24B8.5. Intriguingly, SAM also protected mice from P. aeruginosa PA14 infection by reducing the bacterial burden in lung. These findings provided insight into the mechanisms of molecular connections among SAM diet, histone modifications and innate immunity.

Berberine-based self-assembly agents with enhanced synergistic antitumor efficacy.

Tumors are still a major threat to people worldwide. Nanodrug delivery and targeting systems can significantly improve the therapeutic efficacy of chemotherapeutic drugs for antitumor purposes. However, many nanocarriers are likely to exhibit drawbacks such as a complex preparation process, limited drug-loading capacity, untargeted drug release, and toxicity associated with nanocarriers. Therefore, new therapeutic alternatives are urgently needed to develop antitumor drugs. Natural products with abundant scaffold diversity and structural complexity, which are derived from medicinal plants, are important sources of new antitumor drugs. Here, two carrier-free berberine (BBR)-based nanoparticles (NPs) were established to increase the synergistic efficacy of tumor treatment. BBR can interact with glycyrrhetinic acid (GA) and artesunate (ART) to self-assemble BBR-GA and BBR-ART NPs without any nanocarriers, respectively, the formation of which is dominated by electrostatic and hydrophobic interactions. Moreover, BBR-GA NPs could lead to mitochondria-mediated cell apoptosis by regulating mitochondrial fission and dysfunction, while BBR-ART NPs induced ferroptosis in tumor cells. BBR-based NPs have been demonstrated to possess significant tumor targeting and enhanced antitumor properties compared with those of simple monomer mixes both in vitro and in vivo. These carrier-free self-assemblies based on natural products provide a strategy for synergistic drug delivery and thus offer broad prospects for developing enhanced antitumor drugs.

The role of DGAT1 and DGAT2 in regulating tumor cell growth and their potential clinical implications.

Lipid metabolism is widely reprogrammed in tumor cells. Lipid droplet is a common organelle existing in most mammal cells, and its complex and dynamic functions in maintaining redox and metabolic balance, regulating endoplasmic reticulum stress, modulating chemoresistance, and providing essential biomolecules and ATP have been well established in tumor cells. The balance between lipid droplet formation and catabolism is critical to maintaining energy metabolism in tumor cells, while the process of energy metabolism affects various functions essential for tumor growth. The imbalance of synthesis and catabolism of fatty acids in tumor cells leads to the alteration of lipid droplet content in tumor cells. Diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2, the enzymes that catalyze the final step of triglyceride synthesis, participate in the formation of lipid droplets in tumor cells and in the regulation of cell proliferation, migration and invasion, chemoresistance, and prognosis in tumor. Several diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 inhibitors have been developed over the past decade and have shown anti-tumor effects in preclinical tumor models and improvement of metabolism in clinical trials. In this review, we highlight key features of fatty acid metabolism and different paradigms of diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 activities on cell proliferation, migration, chemoresistance, and prognosis in tumor, with the hope that these scientific findings will have potential clinical implications.

Oncolytic bacteria VNP20009 expressing IFNß inhibits melanoma progression by remodeling the tumor microenvironment.

In the tumor microenvironment (TME), tumor-associated NEs (TANs) have the potential to be protumorigenic or antitumorigenic within the TME in response to environmental cues. The diversity and plasticity of NEs (NEs) underlie the dual potential of TANs in the TME. Here, we utilized the tumor-targeting bacterium VNP20009 (VNP) to carry a plasmid expressed IFNß (VNP-IFNß), which can deliver IFNß and remodel TANs to an antitumorigenic phenotype, and performed preclinical evaluations in the B16F10 lung metastasis model and the B16F10 subcutaneous xenograft model. Compared with VNP, VNP-IFNß recruited more NEs and macrophages (Mφs) with antitumor phenotypes in lung metastases and activated dendritic cells (DCs) differentiation, which activated antitumor immune responses of CD4+ T cells, and ultimately inhibited melanoma progression. This study enriches the bacterial-mediated tumor therapy by using tumor-targeting bacteria to deliver IFNß to the tumor site and inhibit melanoma growth and metastasis by remodeling the tumor immune microenvironment.

Sialic Acid Conjugate-Modified Cationic Liposomal Paclitaxel for Targeted Therapy of Lung Metastasis in Breast Cancer: What a Difference the Cation Content Makes.

Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells in vitro due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis in vivo. By leveraging electrostatic forces and ligand-receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.

Management of chronic pancreatitis: recent advances and future prospects.

As a progressive fibroinflammatory disease, chronic pancreatitis (CP) often manifests as recurrent bouts of abdominal pain with or without complications, causing a heavy burden of health care. In recent years, some meaningful insights into the management of CP have been obtained from randomized controlled trials, systematic reviews, and meta-analyses, which were of great importance. Based on this research, it is shown that there are various treatments for CP. Therefore, it is of great importance to choose a suitable strategy for patients with CP individually. Relevant evidence on the management of CP was summarized in this review, including nutrition supplements, medication, endoscopy, surgery, exploration of novel therapies as well as evaluation and prediction of treatment response.