AIF1 Regulates the Progression of Esophageal Squamous Cell Carcinoma Through Negative Regulation of Immune T Cell Efflux Function by TIGIT Signal.

Background: Esophageal cancer stands as one of the most aggressive and lethal malignancies among digestive tract tumors.

Aims: This study aimed to explore whether AIF1 regulated immune infiltration in esophageal cancer and its association with TIGIT.

Methods: AKR cells transfected with an AIF1 overexpression vector were subcutaneously injected into mice.

Oral microbiota-regulating and inflammation-targeted polymersome-hydrogels for RNAi therapy of ulcerative colitis.

The treatment of ulcerative colitis is harassed by its intricate pathogenesis and the harsh gastrointestinal environment. Herein, oral microbiota-regulating and inflammation-targeted polymersome-hydrogels are developed by incorporating gallic acid and tumor necrosis factor α-specific siRNA-encapsulated polymersomes (GA-siTNFα-PS) into self-healable and eatable hydrogels (SHE-Gel) formed from thiolated sodium alginate and dopamine-modified oxidized inulin (DA-OIn) for oral RNAi therapy of ulcerative colitis. SHE-Gel is stable in stomach, resides in the intestine, and degrades in the colon by colon-specific inulinase.

Intranasal and Intravenous Sequential Administration of Survivin Peptide-CpG Nanovaccines Elicits Potent Immunity Toward Glioblastoma.

Peptide vaccines hold great promise for treatment of glioblastoma (GBM), though their efficacy remains suboptimal due to factors such as immunosuppressive tumor microenvironment, poor accessibility to tumor site and inadequate activation of antigen-presenting cells. Here, this work reports on survivin peptide-CpG oligodeoxynucleotide (ODN) nanovaccines (SPOD-NV), which feature antigen peptides strategically displayed on polymersomes with CpG ODN encapsulated as an immunostimulatory adjuvant. Sequential administration via intranasal and intravenous routes elicits robust immune response against murine GBM.

Co-activating STING-TLR9 pathways promotes radiotherapy-induced cancer vaccination.

Vaccination may cure cancer patients by inducing tumor-specific immune responses. Radiotherapy is an appealing strategy to generate cancer vaccines in situ; thus far, however, only modest and short-lived immune responses are achieved. We here show that radiation combined with co-activating STING-TLR9 can generate powerful in situ cancer vaccines.

Muramyl Dipeptide-Presenting Polymersomes as Artificial Nanobacteria to Boost Systemic Antitumor Immunity.

The clinical efficacy of cancer vaccines is closely related to immunoadjuvants that play a crucial role in magnifying and prolonging the immune response. Muramyl dipeptide (MDP), a minimal and conserved peptidoglycan found in almost all bacteria, can trigger robust immune activation by uniquely antagonizing the nucleotide-binding oligomerization domain 2 (NOD2) pathway. However, its effectiveness has been hindered by limited solubility, poor membrane penetration, and rapid clearance from the body.

A Biomimetic Autophagosomes-Based Nanovaccine Boosts Anticancer Immunity.

Personalized cancer vaccines based on tumor cell lysates offer promise for cancer immunotherapy yet fail to elicit a robust therapeutic effect due to the weak immunogenicity of tumor antigens. Autophagosomes, obtained from pleural effusions and ascites of cancer patients, have been identified as abundant reservoirs of tumor neoantigens that exhibit heightened immunogenicity. However, their potential as personalized cancer vaccines have been constrained by suboptimal lymphatic-targeting performances and challenges in antigen-presenting cell endocytosis.

Uplifting Antitumor Immunotherapy with Lymph-Node-Targeted and Ratio-Controlled Codelivery of Tumor Cell Lysate and Adjuvant.

Cancer vaccines provide a potential strategy to cure patients. Their clinical utilization and efficacy is, however, limited by incomplete coverage of tumor neoantigens and unspecific and restricted activation of dendritic cells (DCs). Tumor cell lysates (TCLs) containing a broad spectrum of neoantigens, while are considered ideal in formulating personalized vaccines, induce generally poor antigen presentation and transient antitumor immune response.

Deciphering complex antibiotic resistance patterns in through whole genome sequencing and machine learning.

Introduction: Helicobacter pylori (H.pylori, Hp) affects billions of people worldwide. However, the emerging resistance of Hp to antibiotics challenges the effectiveness of current treatments.

Co-delivery of gemcitabine and paclitaxel plus NanoCpG empowers chemoimmunotherapy of postoperative "cold" triple-negative breast cancer.

Triple-negative breast cancer (TNBC) due to lack of clear target and notorious "cold" tumor microenvironment (TME) is one of the most intractable and lethal malignancies. Tuning "cold" TME into "hot" becomes an emerging therapeutic strategy to TNBC. Herewith, we report that integrin-targeting micellar gemcitabine and paclitaxel (ATN-mG/P, ATN sequence: Ac-PhScNK-NH) cooperating with polymersomal CpG (NanoCpG) effectively "heated up" and treated TNBC.

Lysosomal-mediated drug release and activation for cancer therapy and immunotherapy.

The development of carrier systems that are able to transport and release therapeutics to target cells is an emergent strategy to treat cancer; however, they following endocytosis are usually trapped in the endo/lysosomal compartments. The efficacy of drug conjugates and nanotherapeutics relies critically on their intracellular drug release ability, for which advanced systems responding to the unique lysosomal environment such as acidic pH and abundant enzymes (e.g.

CD44-targeting hydrophobic phosphorylated gemcitabine prodrug nanotherapeutics augment lung cancer therapy.

Gemcitabine (GEM) is among the most used chemotherapies for advanced malignancies including non-small cell lung cancer. The clinical efficacy of GEM is, however, downplayed by its poor bioavailability, short half-life, drug resistance, and dose-limiting toxicities (e.g.

Arsenic sulfide reverses cisplatin resistance in non-small cell lung cancer in vitro and in vivo through targeting PD-L1.

Background: Recent studies have found that programmed death ligand 1 (PD-L1) might be involved in chemotherapy resistance in non-small cell lung cancer (NSCLC). Arsenic sulfide (As S ) has been recognized to have antitumor activities and enhance the cytotoxic effect of chemotherapy drugs. In this study, we aimed to verify the relationship between PD-L1 and cisplatin (DDP) resistance and identify whether As S could reverse DDP resistance through targeting PD-L1 in NSCLC.

Selective transferrin coating as a facile strategy to fabricate BBB-permeable and targeted vesicles for potent RNAi therapy of brain metastatic breast cancer in vivo.

Brain metastases are a most disturbing situation for breast cancer patients as there is basically no adequate treatment available. Any potential drug formulation has to be able to cross the blood-brain barrier (BBB) and specific to metastatic brain tumors without causing unacceptable adverse effects. Here, we developed transferrin-functionalized chimeric polymersomes carrying siRNA against polo-like kinase 1 (Tf@TBP-CPs-siPLK1) for treating brain metastatic MDA-MB 231 triple negative breast cancer (TNBC) xenografts in mice.

Neoadjuvant chemoradiotherapy plus postoperative adjuvant XELOX chemotherapy versus postoperative adjuvant chemotherapy with XELOX regimen for local advanced gastric cancer-A randomized, controlled study.

Objective: The aim of this study was to compare the clinical efficacy of neoadjuvant chemoradiotherapy (NACRT) combined with postoperative adjuvant XELOX (Oxaliplatin +Capecitabine) chemotherapy and postoperative adjuvant chemotherapy (ACT) with XELOX for local advanced gastric cancer (LAGC).

Methods: In this prospectively randomized trial, we investigated the effect of NACRT combined with postoperative ACT for LAGC. 60 patients were randomly divided into NACRT group and ACT group, with 30 patients in each group.

Up-regulation of miR-204 inhibits proliferation, invasion and apoptosis of gallbladder cancer cells by targeting Notch2.

Gallbladder carcinoma (GC) is an extremely malignant gastrointestinal tumor, but relevant mechanisms are still under investigation. MicroRNA (miR) is differentially expressed in a variety of tumors. Here we explored miR-204 in patients with GC and related mechanisms.

αβ Integrin-Targeting Polymersomal Docetaxel as an Advanced Nanotherapeutic for Nonsmall Cell Lung Cancer Treatment.

Docetaxel (DTX) widely used for treating nonsmall cell lung cancer (NSCLC) patients is associated with dose-limiting side effects, especially neurotoxicity and myelosuppression. Here, we have developed cyclic cNGQGEQc peptide-directed polymersomal docetaxel (cNGQ-PS-DTX) as a targeted and multifunctional formulation for NSCLC. cNGQ-PS-DTX carrying 8.

Transferrin-binding peptide functionalized polymersomes mediate targeted doxorubicin delivery to colorectal cancer in vivo.

Transferrin receptor (TfR) is a promising target validated in the clinical trials for managing various malignancies. Transferrin (Tf) and single chain antibody fragment can target TfR and are typically conjugated to nanomedicines via post-modification, which poses significant production challenges. Here, we report that the polymersomes functionalized with a Tf-binding peptide CGGGHKYLRW (TBP-Ps) can selectively and stably bind Tf and subsequently mediate targeted doxorubicin (Dox) delivery to TfR over-expressing HCT-116 colorectal cancer cells in vitro and in vivo.

Cyclic RGD-Functionalized and Disulfide-Crosslinked Iodine-Rich Polymersomes as a Robust and Smart Theranostic Agent for Targeted CT Imaging and Chemotherapy of Tumor.

There is tremendous interest in integrating CT imaging with chemotherapy; however, reported iodine-based nanosystems such as nanogels and nano-emulsions display typically reduced contrast coefficient, low drug loading and stability, and poor targetability. Here, cRGD-functionalized disulfide-crosslinked iodine-rich polymersomes (cRGD-XIPs) were designed as a novel, robust and smart theranostic agent and investigated for targeted CT imaging and chemotherapy of malignant tumors. cRGD-XIPs were prepared from co-self-assembly of poly(ethylene glycol)--poly(dithiolane trimethylene carbonate--iodinated trimethylene carbonate) (PEG-P(DTC-IC)) and cRGD-PEG-P(DTC-IC) block copolymers.

Sema4A Responds to Hypoxia and Is Involved in Breast Cancer Progression.

Semaphorin4A (Sema4A) is a family member of semaphorins expressed in immune cells and is also related with disease progression of tumor disease. In this study, we investigate the expression and pathological role of Sema4A in breast cancer (BCa). Our data showed that the expression of Sema4A increased in the tissues and serum of BCa patients when compared with normal controls.

Small intestinal diverticulum with bleeding: Case report and literature review.

Rationale: Small intestinal diverticulum with bleeding is an important reason for obscure gastrointestinal bleeding (OGB) , in addition to tumor and vascular diseases. Small intestinal diverticulum with bleeding is difficult to detect by barium meal and angiographic methods and has been regarded as an important cause of obscure gastrointestinal tract bleeding in adolescents. Because of its complicated etiology and non-specific clinical manifestations, it is relatively difficult to detect small intestinal diverticulum with bleeding, especially in patients with a large amount of bleeding and hemodynamic instability.

Lipidomic analysis of serum samples from migraine patients.

Background: Migraine is a prevalent, disabling type of primary headache disorder associated with a high socioeconomic burden. The clinical management of migraine is challenging. This study was to identify potential serum lipidomic biomarkers of migraine.

Low levels of serum serotonin and amino acids identified in migraine patients.

Migraine is a highly disabling primary headache associated with a high socioeconomic burden and a generally high prevalence. The clinical management of migraine remains a challenge. This study was undertaken to identify potential serum biomarkers of migraine.

WDR26 promotes mitophagy of cardiomyocytes induced by hypoxia through Parkin translocation.

Myocardial ischemia is a heart condition caused by reduction of blood flow to the heart, preventing heart from receiving enough oxygen. Myocardial ischemia is the most common cause of death globally. Heart ischemic preconditioning (IPC) has a protective effect against myocardial cell death induced by ischemia and ischemia-reperfusion injury.

miRNA-148b regulates radioresistance in non-small lung cancer cells via regulation of MutL homologue 1.

Radioresistance represents a major obstacle in cancer treatment, the underlying mechanism of which is complex and not well understood. miR-148b has been reported to be implicated regulating radioresistance in lymphoma cells. However, this function has not been investigated in lung cancer cells.