Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism.

The intestinal microbiota has been associated with host immunity as well as psoriasis; however, the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically. Here, we sought to examine its role and mechanism of action in the pathogenesis of psoriasis. We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota.

Multifunctional gold nanorods in low-temperature photothermal interactions for combined tumor starvation and RNA interference therapy.

Collateral damage to healthy tissue, uneven heat distribution, inflammatory diseases, and tumor metastasis induction hinder the translation of high-temperature photothermal therapy (PTT) from bench to practical clinical applications. In this report, a multifunctional gold nanorod (GNR)-based nanosystem was designed by attaching siRNA against B7-H3 (B7-H3si), glucose oxidase (GOx), and hyaluronic acid (HA) for efficient low-temperature PTT. Herein, GOx can not only exhaust glucose to induce starvation therapy but also reduce the heat shock protein (HSP), realizing the ablation of tumors without damage to healthy tissues.

Protein degradation: expanding the toolbox to restrain cancer drug resistance.

Despite significant progress in clinical management, drug resistance remains a major obstacle. Recent research based on protein degradation to restrain drug resistance has attracted wide attention, and several therapeutic strategies such as inhibition of proteasome with bortezomib and proteolysis-targeting chimeric have been developed. Compared with intervention at the transcriptional level, targeting the degradation process seems to be a more rapid and direct strategy.

Effect of intestinal microbiota on liver disease and its related future prospection: From the perspective of intestinal barrier damage and microbial metabolites.

Liver diseases contribute notably to the global concern of mortality and disease. Emerging evidence has demonstrated that intestinal microbiota can regulate intestinal barrier function and produce bioactive metabolites. Failure of any aspect of this barrier can result in the translocation of microbes into the blood and a sustained inflammatory response that promotes liver injury, fibrosis, and cirrhosis.

Using a zebrafish xenograft tumor model to compare the efficacy and safety of VEGFR-TKIs.

Purpose: We constructed a zebrafish xenograft tumor model to compare and quantify the antiangiogenic efficacy and safety of nine vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), axitinib, lenvatinib, pazopanib, apatinib, cabozantinib, sunitinib, semaxanib, sorafenib, and regorafenib, in parallel.

Methods: CT26 and GL261 tumor cells were implanted into the perivitelline space of Tg (flk1: eGFP) zebrafish to construct a xenograft tumor model. VEGFR-TKIs' antiangiogenic efficacy was quantified using AngioTool software, and the median effective dose (ED50) was calculated.

Neoantigens: promising targets for cancer therapy.

Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance.

Circulating monocytes in acute pancreatitis.

Acute pancreatitis is a common gastrointestinal disease characterized by inflammation of the exocrine pancreas and manifesting itself through acute onset of abdominal pain. It is frequently associated with organ failure, pancreatic necrosis, and death. Mounting evidence describes monocytes - phagocytic, antigen presenting, and regulatory cells of the innate immune system - as key contributors and regulators of the inflammatory response and subsequent organ failure in acute pancreatitis.

CCT251545 enhances drug delivery and potentiates chemotherapy in multidrug-resistant cancers by Rac1-mediated macropinocytosis.

It was well known that P-glycoprotein (P-gp/ABCB1) is a master regulator of multidrug resistance (MDR) in cancers. However, the clinical benefit from blocking this pathway remains inconclusive, which motivates a paradigm shift towards alternative strategies for enhancing drug influx. Using a patient-derived organoid (PDO)-based drug screening platform, we report that the combined use of chemotherapy and CCT251545 (CCT) displays robust synergistic effect against PDOs and reduces proliferation of MDR cancer cells in vitro, and results in regression of xenograft tumors, reductions in metastatic dissemination and recurrence rate in vivo.

Brd4 proteolysis-targeting chimera nanoparticles sensitized colorectal cancer chemotherapy.

Bromodomain-Containing Protein 4 (BRD4) is a member of the BET family of bromodomains, which participates in gene transcription process and is closely related to tumor progression. We observed the up-regulated expression of BRD4 in colorectal cancer (CRC) after doxorubicin (DOX) treatment, which might be a potential mechanism for DOX resistance. This study constructed the tumor-targeting (cyclo (Arg-Gly-Asp-D-Phe-Lys)-poly(ethylene glycol)-poly(ε-caprolactone)) (cRGD-PEG-PCL) copolymer for co-delivery of DOX and BRD4 PROTAC degrader ARV-825 (ARV-DOX/cRGD-P) for CRC treatment.

Carrier-Free Nanoplatform via Evoking Pyroptosis and Immune Response against Breast Cancer.

Pyroptosis, as a novel mode of cell death, has been proven to have impressive antitumor effects. Dying cells undergoing pyroptosis can elicit antitumor immunity by the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Accordingly, developing an effective, stable, and controllable nanoplatform that can promote these two side effects is a promising option for cancer therapy.

Single-cell transcriptomics reveals distinct cell response between acute and chronic pulmonary infection of .

Knowledge of the changes in the immune microenvironment during pulmonary bacterial acute and chronic infections is limited. The dissection of immune system may provide a basis for effective therapeutic strategies against bacterial infection. Here, we describe a single immune cell atlas of mouse lungs after acute and chronic infection using single-cell transcriptomics, multiplex immunohistochemistry, and flow cytometry.

Hepatitis B Virus Reactivation in Cancer Patients Undergoing Immune Checkpoint Inhibitors Therapy: A Systematic Review.

Immune checkpoint inhibitor (ICI) therapy is now administered to patients with advanced cancers. However, the safety and efficacy of ICIs in cancer patients with hepatitis B virus (HBV) infection is unknown. Therefore, we performed this systematic review to examine the safety and efficacy of ICIs in patients with HBV infection, with particular focus on HBV reactivation.

Regenerative failure of intrahepatic biliary cells in Alagille syndrome rescued by elevated Jagged/Notch/Sox9 signaling.

Despite the robust healing capacity of the liver, regenerative failure underlies numerous hepatic diseases, including the haploinsufficient disorder, Alagille syndrome (ALGS). Cholestasis due to intrahepatic duct (IHD) paucity resolves in certain ALGS cases but fails in most with no clear mechanisms or therapeutic interventions. We find that modulating and allele dosage is sufficient to stratify these distinct outcomes, which can be either exacerbated or rescued with genetic manipulation of Notch signaling, demonstrating that perturbations of Jag/Notch signaling may be causal for the spectrum of ALGS liver severities.

Determining the safety and effectiveness of percutaneous nephrolithotomy and retrograde intrarenal surgery in treating nephrolithiasis in patients with solitary kidneys.

We performed a meta-analysis to compare the safety and effectiveness of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) in treating nephrolithiasis ≥ 2 cm in patients with solitary kidneys. This systematic review was registered on PROSPERO (registration ID: CRD42021270519). The search time was set from the establishment of the databases until April 30, 2021.

New Insights into the Gut Microbiota in Neurodegenerative Diseases from the Perspective of Redox Homeostasis.

An imbalance between oxidants and antioxidants in the body can lead to oxidative stress, which is one of the major causes of neurodegenerative diseases. The gut microbiota contains trillions of beneficial bacteria that play an important role in maintaining redox homeostasis. In the last decade, the microbiota-gut-brain axis has emerged as a new field that has revolutionized the study of the pathology, diagnosis, and treatment of neurodegenerative diseases.

Biomimetic photosensitizer nanocrystals trigger enhanced ferroptosis for improving cancer treatment.

As a novel non-apoptotic cell death pathway, ferroptosis can effectively enhance the antitumor effects of photodynamic therapy (PDT) by disrupting intracellular redox homeostasis. However, the reported nanocomposites that combined the PDT and ferroptosis are cumbersome to prepare, and the unfavorable tumor microenvironment also severely interferes with their tumor suppressive effects. To address this inherent barrier, this study attempted to explore photosensitizers that could activate ferroptosis pathway and found that the photosensitizer aloe-emodin (AE) could induce cellular ferroptosis based on its specific inhibiting activity to Glutathione S-transferase P1(GSTP1), a key protein for ferroptosis.

Brain-Targeted HFn-Cu-REGO Nanoplatform for Site-Specific Delivery and Manipulation of Autophagy and Cuproptosis in Glioblastoma.

Durable glioblastoma multiforme (GBM) management requires long-term chemotherapy after surgery to eliminate remaining cancerous tissues. Among chemotherapeutics, temozolomide is considered as the first-line drug for GBM therapy, but the treatment outcome is not satisfactory. Notably, regorafenib, an oral multi-kinase inhibitor, has been reported to exert a markedly superior effect on GBM suppression compared with temozolomide.

A simple self-assembly nanomicelle based on brain tumor-targeting peptide-mediated siRNA delivery for glioma immunotherapy via intranasal administration.

The blood-brain barrier (BBB) has a key role in preventing drugs from entering the brain. Non-invasive intranasal drug delivery routes that bypass the BBB are increasing in popularity because of their ability to shorten the journey and reduce the loss of genetic drugs such as siRNA in transit. However, the complex synthesis and quality control process of most nose-to-brain delivery carriers and the limited mass production are the main obstacles to their clinical application.

Risk factors of early death in pediatric hemophagocytic lymphohistocytosis: Retrospective cohort study.

Background: Hemophagocytic lymphocytosis (HLH) is a rare life-threatening hyperinflammatory syndrome in which early mortality remains high in patients with HLH.

Methods: We retrospectively collected the medical records of all pediatric patients diagnosed with HLH at the West China Second Hospital of Sichuan University between January 2014 and December 2020. Collect demographic, laboratory, clinical, genetic profiles, treatment information and perform statistical analysis from records.

Exosomes as Anticancer Drug Delivery Vehicles: Prospects and Challenges.

Exosomes, a subset of extracellular vesicles, are widely present in various body fluids and are involved in mediating intercellular communication. They have received extensive attention as diagnostic markers. The excellent physicochemical and biological properties of exosomes make them great potential drug delivery vehicles for the treatment of cancer and other diseases.

Overcoming therapeutic resistance to platinum-based drugs by targeting Epithelial-Mesenchymal transition.

Platinum-based drugs (PBDs), including cisplatin, carboplatin, and oxaliplatin, have been widely used in clinical practice as mainstay treatments for various types of cancer. Although there is firm evidence of notable achievements with PBDs in the management of cancers, the acquisition of resistance to these agents is still a major challenge to efforts at cure. The introduction of the epithelial-mesenchymal transition (EMT) concept, a critical process during embryonic morphogenesis and carcinoma progression, has offered a mechanistic explanation for the phenotypic switch of cancer cells upon PBD exposure.

HDAC/JAK dual target inhibitors of cancer-related targets: The success of nonclearable linked pharmacophore mode.

In recent years, the development of dual target drugs has become a research hotspot in cancer treatment and the reasonable design of the drugs is critical. The nonclearable linked pharmacophore mode is one of the commonly used strategies for designing dual target drugs, it can connect the pharmacophores of two synergistic target inhibitors into one molecule through the linker, which greatly improves the utilization of drugs. Epigenetic modifications as a potential treatment for multiple diseases have always been a subject of great concern, and Histone deacetylases (HDAC) plays an important role.

Nanoparticle-Based Drug Delivery Systems Targeting Tumor Microenvironment for Cancer Immunotherapy Resistance: Current Advances and Applications.

Cancer immunotherapy has shown impressive anti-tumor activity in patients with advanced and early-stage malignant tumors, thus improving long-term survival. However, current cancer immunotherapy is limited by barriers such as low tumor specificity, poor response rate, and systemic toxicities, which result in the development of primary, adaptive, or acquired resistance. Immunotherapy resistance has complex mechanisms that depend on the interaction between tumor cells and the tumor microenvironment (TME).