6-Shogaol Derived from Ginger Inhibits Intestinal Crypt Stem Cell Differentiation and Contributes to Irritable Bowel Syndrome Risk.

Dietary factors play a crucial role in irritable bowel syndrome (IBS) pathogenesis. Therefore, the dietary contraindications for patients with IBS require further supplementation. Recent investigations have revealed that ginger consumption may pose a risk of aggravating the symptoms and incidence of IBS; however, the specific mechanism remains unknown.

KRAS-mutant non-small cell lung cancer (NSCLC) therapy based on tepotinib and omeprazole combination.

Background: KRAS-mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS-G12C selective inhibitors, leading to short median progression-free survival, and overall survival. The MET receptor tyrosine kinase (c-MET), the cognate receptor of hepatocyte growth factor (HGF), was reported to be overexpressed in KRAS-mutant lung cancer cells leading to tumor-growth in anchorage-independent conditions.

Methods: Cell viability assay and synergy analysis were carried out in native, sotorasib and trametinib-resistant KRAS-mutant NSCLC cell lines.

HMGB1 Expression Levels Correlate with Response to Immunotherapy in Non-Small Cell Lung Cancer.

Purpose: High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC).

Patients And Methods: RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI.

IDH2/R140Q mutation confers cytokine-independent proliferation of TF-1 cells by activating constitutive STAT3/5 phosphorylation.

Background: R140Q mutation in isocitrate dehydrogenase 2 (IDH2) promotes leukemogenesis. Targeting IDH2/R140Q yields encouraging therapeutic effects in the clinical setting. However, therapeutic resistance occurs in 12% of IDH2/R140Q inhibitor treated patients.

Study on morphology optimization of open-pit mine slope based on section and spatial morphology effect.

Reasonable design of the slopes of mining field is an important prerequisite for optimizing open-pit mine boundary, ensuring safe production and improving economic benefits of open-pit mines. This study took the open-pit coal mine coal mine in Block I of Thar coal field in Pakistan as the research background, based on the section morphology effect of slope stability and the occurrence characteristics of coal seam and weak layer, the section morphology of slope was optimized step by step from two-dimensional angle by using the rigid body limit equilibrium method. The three-dimensional numerical simulation method is used to analyze the three-dimensional spatial effect of slope stability and reveal the influence of the spatial geometry of the slope stability.

Ginseng-derived nanoparticles reprogram macrophages to regulate arginase-1 release for ameliorating T cell exhaustion in tumor microenvironment.

Background: Lines of evidence indicated that, immune checkpoints (ICs) inhibitors enhanced T cell immune response to exert anti-tumor effects. However, T cell exhaustion has been so far a major obstacle to antitumor immunotherapy in colorectal cancer patients. Our previous studies showed that ginseng-derived nanoparticles (GDNPs) inhibited the growth of various tumors by reprograming tumor-associated macrophages (TAMs) and downregulated the ICs expression on T cells in tumor microenvironment (TME), but the underlying effector mechanisms remained unclear.

Geniposide protects against neurotoxicity in mouse models of rotenone-induced Parkinson's disease involving the mTOR and Nrf2 pathways.

Ethnopharmacological Relevance: Fructus Gardeniae, with the effects of discharging fire, eliminating vexation, reducing fever and causing diuresis, and cooling blood to remove apthogentic heat, could be used to treat Parkinson's disease (PD). Geniposide, as the main active ingredient of Fructus Gardeniae, has been shown to have neuroprotective effects in several rodent models. Rotenone, a commonly used neurotoxin, induced PD model progresses slowly, but simulates the pathological changes of PD's slow progression.

Azeliragon inhibits PAK1 and enhances the therapeutic efficacy of AKT inhibitors in pancreatic cancer.

Pancreatic cancer is a lethal malignancy for which there is currently no effective treatment strategy. We previously reported that p21-activated kinase 1 (PAK1) is aberrantly expressed in pancreatic cancer patients and that targeted inhibition of PAK1 significantly suppressed pancreatic cancer progression in vitro and in vivo. In this study, we identified the drug azeliragon as a novel inhibitor of PAK1.

Biomimetic retractable DNA nanocarrier with sensitive responsivity for efficient drug delivery and enhanced photothermal therapy.

Background: The coalition of DNA nanotechnology with diversiform inorganic nanoparticles offers powerful tools for the design and construction of stimuli-responsive drug delivery systems with spatiotemporal controllability, but it remains challenging to achieve high-density oligonucleotides modification close to inorganic nanocores for their sensitive responsivity to optical or thermal signals.

Results: Inspired by Actinia with retractable tentacles, here we design an artificial nano-Actinia consisted of collapsible DNA architectures attached on gold nanoparticle (AuNP) for efficient drug delivery and enhanced photothermal therapy. The collapsible spheroidal architectures are formed by the hybridization of long DNA strand produced in situ through rolling circle amplification with bundling DNA strands, and contain numerous double-helical segments for the intercalative binding of quercetin as the anti-cancer drug.

Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer.

Clinically, activated EGFR mutation associated chemo-drugs resistance has severely threaten NSCLC patients. Nanoparticle based small interfering RNA (siRNA) therapy representing another promising alternative by silencing specific gene while still suffered from charge associated toxicity, strong immunogenicity and poor targetability. Herein, we reported a novel EGFR-mutant NSCLC therapy relying on edible and cation-free kiwi-derived extracellular vesicles (KEVs), which showed sevenfold enhancement of safe dosage compared with widely used cationic liposomes and could be further loaded with Signal Transducer and Activator of Transcription 3 interfering RNA (siSTAT3).

Noncontact Intraocular Pressure Measurement over Bandage Contact Lens and the Effect of Pentacam and Corvis ST's IOP Correction System.

Purpose: To evaluate the influence of intraocular pressure (IOP) measurement while wearing bandage contact lens (BCL) and the effect of Pentacam and Corvis ST's correction systems.

Methods: It was a prospective comparative study. Forty healthy subjects (40 eyes) were included in this study.

Ginseng-derived nanoparticles potentiate immune checkpoint antibody efficacy by reprogramming the cold tumor microenvironment.

Cold tumor microenvironment (TME) marked with low effector T cell infiltration leads to weak response to immune checkpoint inhibitor (ICI) treatment. Thus, switching cold to hot TME is critical to improve potent ICI therapy. Previously, we reported extracellular vesicle (EV)-like ginseng-derived nanoparticles (GDNPs) that were isolated from Panax ginseng C.

Rational optimization of a human neutralizing antibody of SARS-CoV-2.

SARS-CoV-2 has caused a worldwide epidemic of coronavirus disease 19 (COVID-19). Antibody drugs present an effective weapon for tens of millions of COVID-19 patients. Antibodies disrupting the interactions between the receptor-binding domain (RBD) of SARS-CoV-2 S protein and the angiotensin converting enzyme 2 (ACE2) effectively block SARS-CoV-2 cell entry into host cells.

ZhiJingSan Inhibits Osteoclastogenesis via Regulating RANKL/NF-κB Signaling Pathway and Ameliorates Bone Erosion in Collagen-Induced Mouse Arthritis.

Bone erosion is the most evident pathological condition of rheumatoid arthritis (RA), which is the main cause of joint deformities and disability in RA patients. At present, the conventional RA drugs have not achieved satisfactory effect in improving bone erosion. ZhiJingSan (ZJS), which is a traditional Chinese prescription composed of scolopendra (dried body of , ) and scorpion (dried body of ), exhibits anti-rheumatism, analgesic and joint deformities improvement effects.

Dihydroartemisinin overcomes the resistance to osimertinib in EGFR-mutant non-small-cell lung cancer.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), is commonly used to treat EGFR-mutant non-small-cell lung cancer (NSCLC). However, acquired resistance to mutant EGFR (T790M) can evolve following osimertinib treatment. High reactive oxygen species (ROS) levels in lung cancer cells can influence heme levels and have an impact on osimertinib resistance.

Formononetin ameliorates oxaliplatin-induced peripheral neuropathy via the KEAP1-NRF2-GSTP1 axis.

Management of oxaliplatin-induced peripheral neuropathy (OIPN) has proven challenging owing to the concern that any OIPN-preventing agents may also decrease the efficacy of the chemotherapeutic agent and fail to reverse established neuronal damage. Nevertheless, targeting redox signaling pathways constitutes a promising therapy in OIPN and we have previously demonstrated the protective role of nuclear factor erythroid-2 related factor 2 (NRF2) in this disorder. Here, we investigated the protective properties of formononetin (FN), a clinical preparation extract, in OIPN.

Shi Xiao San ameliorates the development of adenomyosis in an ICR mouse model.

The use of Shi Xiao San (SXS), composed of and , can be traced back to the Song dynasty. Traditionally, SXS has been used to treat irregular menstruation, pelvic pain, progressive dysmenorrhea, and postpartum lochiorrhea. The management of adenomyosis (AM) is challenging and to the best of our knowledge there are currently no effective therapeutic strategies.

Identification of a novel PAK1 inhibitor to treat pancreatic cancer.

Pancreatic cancer is one of the most aggressive cancers with poor prognosis and a low 5-year survival rate. The family of P21-activated kinases (PAKs) appears to modulate many signaling pathways that contribute to pancreatic carcinogenesis. In this work, we demonstrated that PAK1 is a critical regulator in pancreatic cancer cell growth.

Identification of a selective inhibitor of IDH2/R140Q enzyme that induces cellular differentiation in leukemia cells.

Background: IDH2/R140Q mutation is frequently detected in acute myeloid leukemia (AML). It contributes to leukemia via accumulation of oncometabolite D-2-HG. Therefore, mutant IDH2 is a promising target for AML.

Prolonged melittin release from polyelectrolyte-based nanocomplexes decreases acute toxicity and improves blood glycemic control in a mouse model of type II diabetes.

Gating modifier toxins (GMTs) from animal venom have shown great potential in controlling blood glucose levels in type II diabetes (T2D), but their high acute toxicity and quick clearance in the body hamper their potential therapeutic use. Inspired by their highly positive charge, we have developed a nanocomplex system based on polyelectrolytes, in which strong interactions form between positively charged GMTs and negatively charged dextran sulfate (DS). Using melittin as a model GMT and adapting flash nanocomplexation (FNC) technology for complex preparation, uniform nanocomplexes (polydispersity index: ~0.

Osimertinib and dihydroartemisinin: a novel drug combination targeting head and neck squamous cell carcinoma.

Background: Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis with limited progression-free survival and overall survival, even when treated with different combinations of chemotherapy, targeted therapies and immunotherapy. We explored and the effect of the epidermal growth factor receptor (EGFR) inhibitor, osimertinib, alone and in combination with dihydroartemisinin (DHA) in HNSCC.

Methods: The combination of osimertinib with DHA was tested in the FaDu and CAL27 HNSCC cell lines.

Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth.

Background: It is unclear whether plant-derived extracellular vesicles (EVs) can mediate interspecies communication with mammalian cells. Tumor-associated macrophages (TAMs) display a continuum of different polarization states between tumoricidal M1 phenotype and tumor-supportive M2 phenotypes, with a lower M1/M2 ratio correlating with tumor growth, angiogenesis and invasion. We investigated whether EVs from ginseng can alter M2-like polarization both in vitro and in vivo to promote cancer immunotherapy.

Targeting PKCι-PAK1 signaling pathways in EGFR and KRAS mutant adenocarcinoma and lung squamous cell carcinoma.

Introduction: p21-activated kinase 1 (PAK1) stimulates growth and metastasis in non-small cell lung cancer (NSCLC). Protein kinase C iota (PKCι) is an enzyme highly expressed in NSCLC, regulating PAK1 signaling. In the present study we explored whether the PKCι-PAK1 signaling pathway approach can be an efficient target in different types of NSCLC cell and mouse models.