Reyanning mixture inhibits M1 macrophage polarization through the glycogen synthesis pathway to improve lipopolysaccharide-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Reyanning (RYN) mixture is a traditional Chinese medicine composed of Taraxacum, Polygonum cuspidatum, Scutellariae Barbatae and Patrinia villosa and is used for the treatment of acute respiratory system diseases with significant clinical efficacy. AIM OF THE STUDY: Acute lung injury (ALI) is a common clinical disease characterized by acute respiratory failure. This study was conducted to evaluate the therapeutic effects of RYN on ALI and to explore its mechanism of action. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical components of RYN. 7.5 mg/kg LPS was administered to induce ALI in rats. RYN was administered by gavage at doses of 2 ml/kg, 4 ml/kg or 8 ml/kg every 8 h for a total of 6 doses. Observations included lung histomorphology, lung wet/dry (W/D) weight ratio, lung permeability index (LPI), HE staining, Wright-Giemsa staining. ELISA was performed to detect the levels of TNF-α, IL-6, IL-10, Arg-1,UDPG. Immunohistochemical staining detected IL-6, F4/80 expression. ROS, MDA, SOD, GSH/GSSG were detected in liver tissues. Multiple omics techniques were used to predict the potential mechanism of action of RYN, which was verified by in vivo closure experiments. Immunofluorescence staining detected the co-expression of CD86 and CD206, CD86 and P2Y14, CD86 and UGP2 in liver tissues. qRT-PCR detected the mRNA levels of UGP2, P2Y14 and STAT1, and immunoblotting detected the protein expression of UGP2, P2Y14, STAT1, p-STAT1. RESULTS: RYN was detected to contain 1366 metabolites, some of the metabolites with high levels have anti-inflammatory, antibacterial, antiviral and antioxidant properties. RYN (2, 4, and 8 ml/kg) exerted dose-dependent therapeutic effects on the ALI rats, by reducing inflammatory cell infiltration and oxidative stress damage, inhibiting CD86 expression, decreasing TNF-α and IL-6 levels, and increasing IL-10 and Arg-1 levels. Transcriptomics and proteomics showed that glucose metabolism provided the pathway for the anti-ALI properties of RYN and that RYN inhibited lung glycogen production and distribution. Immunofluorescence co-staining showed that RYN inhibited CD86 and UGP2 expressions. In vivo blocking experiments revealed that blocking glycogen synthesis reduced UDPG content, inhibited P2Y14 and CD86 expressions, decreased P2Y14 and STAT1 mRNA and protein expressions, reduced STAT1 protein phosphorylation expression, and had the same therapeutic effect as RYN. CONCLUSION: RYN inhibits M1 macrophage polarization to alleviate ALI. Blocking glycogen synthesis and inhibiting the UDPG/P2Y14/STAT1 signaling pathway may be its molecular mechanism.

Yinxieling decoction ameliorates psoriasis by regulating the differentiation and functions of Langerhans cells via the TGF-ß1/PU.1/IL-23 signal axis.

Langerhans cells (LCs) play a critical role in skin immune responses and the development of psoriasis. Yinxieling (YXL) is a representative Chinese herbal medicine for the treatment of psoriasis in South China. It was found to improve psoriasis without obvious side effects in the clinic. Here we attempted to clarify whether and how YXL regulates the differentiation and functions of LCs in Imiquimod (IMQ)-induced psoriasis in vivo and induced LCs in vitro. The Psoriasis Area Severity Index (PASI) score was used to evaluate the efficacy of YXL for IMQ-induced psoriasis-like mice. Flow cytometry was utilized to analyze the effects of YXL, to regulate the differentiation, migration, maturation, and antigen presentation of LCs. The results show that YXL significantly alleviated skin inflammation, as reduced in PASI score and classic psoriasis characteristics in pathological sections. Although there was no effect on the proportion of total DCs in the skin-draining lymph nodes, the expression of epidermal LCs and its transcription factor PU.1 were both markedly inhibited. LCs were also prevented from migrating from epidermal to skin-draining lymph nodes and mature. In addition, the number of LCs carrying antigens in the epidermis increased, which suggested that YXL could effectively prevent LCs from presenting antigens. In vitro, YXL had a significant impact on inhibiting the differentiation of LCs. Further data showed that YXL decreased the relative expression of transforming growth factor-ß (TGFß) messenger RNA (mRNA) and interleukin-23 (IL-23) mRNAs. Thus, YXL alleviates psoriasis by regulating differentiation, migration, maturation, and antigen presentation via the TGFß/PU.1/IL-23 signal axis.

Intestinal mucosal barrier: a potential target for traditional Chinese medicine in the treatment of cardiovascular diseases.

Cardiovascular disease (CVD) is a serious public health problem, and among non-communicable diseases, CVD is now the leading cause of mortality and morbidity worldwide. CVD involves multiple organs throughout the body, especially the intestinal tract is the first to be involved. The impairment of the intestinal mucosal barrier is considered a significant pathological alteration in CVD and also contributes to the accelerated progression of the disease, thereby offering novel insights for CVD prevention and treatment. The treatment of Chinese medicine is characterized by multi-metabolites, multi-pathways, and multi-targets. In recent years, the studies of Traditional Chinese Medicine (TCM) in treating CVD by repairing the intestinal mucosal barrier have gradually increased, showing great therapeutic potential. This review summarizes the studies related to the treatment of CVD by TCM (metabolites of Chinese botanical drugs, TCM formulas, and Chinese patent medicine) targeting the repair of the intestinal mucosal barrier, as well as the potential mechanisms. We have observed that TCM exerts regulatory effects on the structure and metabolites of gut microbiota, enhances intestinal tight junctions, improves intestinal dyskinesia, repairs intestinal tissue morphology, and preserves the integrity of the intestinal vascular barrier through its anti-inflammatory, antioxidant, and anti-apoptotic properties. These multifaceted attributes position TCM as a pivotal modulator of inhibiting myocardial fibrosis, and hypertrophy, and promoting vascular repairment. Moreover, there exists a close association between cardiovascular risk factors such as hyperlipidemia, obesity, and diabetes mellitus with CVD. We also explore the mechanisms through which Chinese botanical drugs impact the intestinal mucosal barrier and regulate glucose and lipid metabolism. Consequently, these findings present novel insights and methodologies for treating CVD.

Unlocking the potential of Chinese herbal medicine residue-derived biochar as an efficient adsorbent for high-performance tetracycline removal.

This study employed hydrothermal carbonization (HTC) in conjunction with ZnCl2 activation and pyrolysis to produce biochar from one traditional Chinese medicine astragali radix (AR) residue. The resultant biochar was evaluated as a sustainable adsorbent for tetracycline (TC) elimination from water. The adsorption performance of TC on two micropore-rich AR biochars, AR@ZnCl2 (1370 m2 g-1) and HAR@ZnCl2 (1896 m2 g-1), was comprehensively evaluated using adsorption isotherms, kinetics, and thermodynamics. By virtue of pore diffusion, π-π interaction, electrostatic attraction, and hydrogen bonding, the prepared AR biochar showed exceptional adsorption properties for TC. Notably, the maximum adsorption capacity (930.3 mg g-1) of TC on HAR@ZnCl2 can be achieved when the adsorbent dosage is 0.5 g L-1 and C0 is 500 mg L-1 at 323 K. The TC adsorption on HAR@ZnCl2 took place spontaneously. Furthermore, the impact of competitive ions behavior is insignificant when coexisting ion concentrations fall within the 10-100 mg L-1 range. Additionally, the produced biochar illustrated good economic benefits, with a payback of 701 $ t-1. More importantly, even after ten cycles, HAR@ZnCl2 still presented great TC removal efficiency (above 77%), suggesting a good application prosperity. In summary, the effectiveness and sustainability of AR biochar, a biowaste-derived product, were demonstrated in its ability to remove antibiotics from water, showing great potential in wastewater treatment application.

Vitamin intake and periodontal disease: a meta-analysis of observational studies.

OBJECTIVE: A meta-analysis was performed to assess the epidemiological correlation between dietary intake of various types of vitamin intake and the risk of periodontal disease. METHODS: A comprehensive computerized search was conducted in eight databases, namely PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine Disc, CNKI, VIP, and WanFang Database, and a random effect model was applied to combine pooled odds ratio (ORs) with corresponding 95% confidence intervals (CIs) of the included studies, and the sensitivity analysis was performed to explore the impact of a single study on the comprehensive results. RESULTS: We finally included 45 effect groups from 23 observational studies, with a total number of study participants of 74,488. The results showed that higher levels of vitamin A (OR: 0.788, 95% CI: 0.640-0.971), vitamin B complex (OR: 0.884, 95% CI: 0.824-0.948), vitamin C (OR: 0.875, 95% CI: 0.775-0.988), vitamin D (OR: 0.964, 95% CI: 0.948-0.981), and vitamin E (OR: 0.868, 95% CI: 0.776-0.971) intake all were negatively correlated with periodontal disease. After removing each study, leave-one-out sensitivity analysis indicated no significant change in the overall results of any of the five meta-analyses. CONCLUSIONS: The results from this meta-analysis demonstrated a negative association between high-dose vitamin A, vitamin B complex, vitamin C, vitamin D, and vitamin E consumption and the likelihood of developing periodontal disease, revealing the significant role of vitamins in preventing periodontal disease.

Photoresponsive metal-organic framework with combined photodynamic therapy and hypoxia-activated chemotherapy for the targeted treatment of rheumatoid arthritis.

Activated M1-type macrophages, which produce inflammatory factors that exacerbate rheumatoid arthritis (RA), represent crucial target cells for inhibiting the disease process. In this study, we developed a novel photoresponsive targeted drug delivery system (TPNPs-HA) that can effectively deliver the hypoxia-activated prodrug tirapazamine (TPZ) specifically to activated macrophages. After administration, this metal-organic framework, PCN-224, constructed uing the photosensitizer porphyrin, exhibits the ability to generate excessive toxic reactive oxygen species (ROS) when exposed to near-infrared light. Additionally, the oxygen-consumed hypoxic environment further activates the chemotherapeutic effect of TPZ, thus creating a synergistic combination of photodynamic therapy (PDT) and hypoxia-activated chemotherapy (HaCT) to promote the elimination of activated M1-type macrophages. The results highlight the significantly potential of this photoresponsive nano-delivery system in providing substantial relief for RA. Furthermore, these findings support its effectiveness in inhibiting the disease process of RA, thereby offering new possibilities for the development of precise and accurate strategies for RA.

Preparation of a novel MOF-POPM and its application in online purification and enrichment of oleanolic acid in medicinal plants.

In present work, a method for enrichment, purification, and content determination of oleanolic acid (OA) in medicinal plants was established based on on-line solid phase extraction (SPE). A metal organic frameworks-porous organic polymer monolith (MOF-POPM) was prepared with functionalized UiO-66-(OH)2 as monomer and was used as SPE column for online enrichment and purification of OA. The ratio of adsorbent, enriching and eluting solvent, mobile phase pH, and flow rate had been systematically investigated. Under the optimum conditions, the linear range of OA was 0.59-2500 µg/mL with r = 0.9996. The limit of detection (LOD) was 0.18 µg/mL and the limit of quantification (LOQ) was 0.59 µg/mL. The intra-day relative standard deviations (RSDs) and inter-day RSDs of retention time and peak area were less than 0.3% and 1.3%, respectively. The average recoveries of OA in medicinal plants samples ranged from 87.7 to 104.6%. The results demonstrated that the online system was reliable and accurate for enrichment, purification, and content determination of OA in medicinal plants.

Screening and characterization of biocontrol bacteria isolated from Ageratum conyzoides against Collectotrichum fructicola causing Chinese plum (Prunus salicina Lindl.) anthracnose.

Chinese plum (Prunus salicina Lindl.) is a nutritionally and economically important stone fruit widely grown around the world. Anthracnose, caused by Collectotrichum spp., is one of the primary biotic stress factors limiting plum production. Medicinal plants may harbor rhizospheric or endophytic microorganisms that produce bioactive metabolites that can be used as anthracnose biocontrol agents. Here, 27 bacterial isolates from the medicinal plant A. conyzoides with diverse antagonistic activities against C. fructicola were screened. Based on morphological, physiological, biochemical, and molecular characterization, 25 of these isolates belong to different species of genus Bacillus, one to Pseudomonas monsensis, and one more to Microbacterium phyllosphaerae. Eight representative strains showed high biocontrol efficacy against plum anthracnose in a pot experiment. In addition, several Bacillus isolates showed a broad spectrum of inhibitory activity against a variety of fungal phytopathogens. Analysis of the volatile organic compound profile of these eight representative strains revealed a total of 47 compounds, most of which were ketones, while the others included alkanes, alkenes, alcohols, pyrazines, and phenols. Overall, this study confirmed the potential value of eight bacterial isolates for development as anthracnose biocontrol agents.

Anaerobic selenite-reducing bacteria and their metabolic potentials in Se-rich sediment revealed by the combination of DNA-stable isotope probing, metagenomic binning, and metatranscriptomics.

Microorganisms play a critical role in the biogeochemical cycling of selenium (Se) in aquatic environments, particularly in reducing the toxicity and bioavailability of selenite (Se(IV)). This study aimed to identify putative Se(IV)-reducing bacteria (SeIVRB) and investigate the genetic mechanisms underlying Se(IV) reduction in anoxic Se-rich sediment. Initial microcosm incubation confirmed that Se(IV) reduction was driven by heterotrophic microorganisms. DNA stable-isotope probing (DNA-SIP) analysis identified Pseudomonas, Geobacter, Comamonas, and Anaeromyxobacter as putative SeIVRB. High-quality metagenome-assembled genomes (MAGs) affiliated with these four putative SeIVRB were retrieved. Annotation of functional gene indicated that these MAGs contained putative Se(IV)-reducing genes such as DMSO reductase family, fumarate and sulfite reductases. Metatranscriptomic analysis of active Se(IV)-reducing cultures revealed significantly higher transcriptional levels of genes associated with DMSO reductase (serA/PHGDH), fumarate reductase (sdhCD/frdCD), and sulfite reductase (cysDIH) compared to those in cultures not amended with Se(IV), suggesting that these genes played important roles in Se(IV) reduction. The current study expands our knowledge of the genetic mechanisms involved in less-understood anaerobic Se(IV) bio-reduction. Additinally, the complementary abilities of DNA-SIP, metagenomics, and metatranscriptomics analyses are demonstrated in elucidating the microbial mechanisms of biogeochemical processes in anoxic sediment.

Cryptotanshinone-Doped Photothermal Synergistic MXene@PDA Nanosheets with Antibacterial and Anti-Inflammatory Properties for Wound Healing.

Humans are threatened by bacteria and other microorganisms, resulting in countless pathogen-related infections and illnesses. Accumulation of reactive oxygen species (ROS) in infected wounds activates strong inflammatory responses. The overuse of antibiotics has led to increasing bacterial resistance. Therefore, effective ROS scavenging and bactericidal capacity are essential and the advanced development of collaborative therapeutic techniques to combat bacterial infections is needed. Here, this work developes an MXene@polydopamine-cryptotanshinone (MXene@PDA-CPT) antibacterial nanosystem with excellent reactive oxygen and nitrogen species scavenging ability, which effectively inactivates drug-resistant bacteria and biofilms, thereby promoting wound healing. In this system, the adhesion of polydopamine nanoparticles to MXene produced a photothermal synergistic effect and free radical scavenging activity, presenting a promising antibacterial and anti-inflammatory strategy. This nanosystem causes fatal damage to bacterial membranes. The loading of cryptotanshinone further expanded the advantages of the system, causing a stronger bacterial killing effect and inflammation mitigatory effect with desired biosafety and biocompatibility. In addition, combining nanomaterials and active ingredients of traditional Chinese medicine, this work provides a new rationale for the future development of wound dressings, which contributes to eliminating bacterial resistance, delaying disease deterioration, and alleviating the pain of patients.

Revealing the Effect of Photothermal Therapy on Human Breast Cancer Cells: A Combined Study from Mechanical Properties to Membrane HSP70.

Hyperthermia-induced overexpression of heat shock protein 70 (HSP70) leads to the thermoresistance of cancer cells and reduces the efficiency of photothermal therapy (PTT). In contrast, cancer cell-specific membrane-associated HSP70 has been proven to activate antitumor immune responses. The dual effect of HSP70 on cancer cells inspires us that in-depth research of membrane HSP70 (mHSP70) during PTT treatment is essential. In this work, a PTT treatment platform for human breast cancer cells (MCF-7 cells) based on a mPEG-NH2-modified polydopamine (PDA)-coated gold nanorod core-shell structure (GNR@PDA-PEG) is developed. Using the force-distance curve-based atomic force microscopy (FD-based AFM), we gain insight into the PTT-induced changes in the morphology, mechanical properties, and mHSP70 expression and distribution of individual MCF-7 cells with high-resolution at the single-cell level. PTT treatment causes pseudopod contraction of MCF-7 cells and generates a high level of intracellular reactive oxygen species, which severely disrupt the cytoskeleton, leading to a decrease in cellular mechanical properties. The adhesion maps, which are recorded by aptamer A8 functional probes using FD-based AFM, reveal that PTT treatment causes a significant upregulation of mHSP70 expression and it starts to exhibit a partial aggregation distribution on the MCF-7 cell surface. This work not only exemplifies that AFM can be a powerful tool for detecting changes in cancer cells during PTT treatment but also provides a better view for targeting mHSP70 for cancer therapy.

Bimetallic infinite coordination nanopolymers via phototherapy and STING activation for eliciting robust antitumor immunity.

Phototherapy can trigger immunogenic cell death of tumors in situ, whereas it is virtually impossible to eradicate the tumor due to the intrinsic resistance and inefficient anti-tumor immunity. To overcome these limitations, novel bimetallic infinite coordination nanopolymers (TA-Fe/Mn-OVA@MB NPs) were synthesized using model antigen ovalbumin (OVA) as a template to assemble tannic acid (TA) and bi-metal, supplemented with methylene blue (MB) surface absorption. The formulated TA-Fe/Mn-OVA@MB NPs possess excellent photothermal and photodynamic therapy (PTT/PDT) performance, which is adequate to destroy tumor cells by physical and chemical attack. Especially, these TA-Fe/Mn-OVA@MB NPs are capability of promoting the dendritic cells (DCs) maturation and antigen presentation via manganese-mediated cGAS-STING pathway activation, finally activating cytotoxicity T lymphocyte and promoting memory T lymphocyte differentiation in the peripheral lymphoid organs. In conclusion, this research offers a versatile metal-polyphenol nanoplatform to integrate functional metals and therapeutic molecule for topical phototherapy and robust anti-tumor immune activation.

Molecular/Nanomechanical Insights into Electrostimulation-Inhibited Energy Metabolism Mechanisms and Cytoskeleton Damage of Cancer Cells.

Inhibiting energy metabolism of cancer cells is an effective way to treat cancer but remains a great challenge. Herein, electrostimulation (ES) is applied to effectively suppress energy metabolism of cancer cells to induce rapid cell death, and deeply reveal the underlying mechanisms at the molecular and nanomechanical levels by combined use of fluorescence imaging and atomic force microscopy. Cancer cells are found significantly less tolerant to ES than normal cells; and ES causes "domino effect" to induce mitochondrial dysfunction to impede electron transport chain (ETC) and tricarboxylic acid (TCA) cycle pathways, leading to fatal energy-supply crisis and death of cancer cells. From the perspective of cell mechanics, the Young's modulus decreases and cytoskeleton destruction of MCF-7 cell membranes caused by F-actin depolymerization occurs, along with down-regulation and sporadic distribution of glucose transporter 1 (GLUT1) after ES. Such a double whammy renders ES highly effective and promising for potential clinical cancer treatments.

Immunoinducible Carbon Dot-Incorporated Hydrogels as a Photothermal-Derived Antigen Depot to Trigger a Robust Antitumor Immune Response.

Immunogenic tumor cell death (ICD) induced by photothermal therapy (PTT) fails to elicit a robust antitumor immune response partially due to its inherent immunosuppressive microenvironment and poor antigen presentation. To address these issues, we developed an immunoinducible carbon dot-incorporated hydrogel (iCD@Gel) through a dynamic covalent Schiff base reaction using mannose-modified aluminum-doped carbon dots (M/A-CDs) as a cross-linking agent. The M/A-CDs possessed superior photothermal conversion efficiency and served as nanocarriers to load cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) for inducing the maturation of dendritic cells (DCs) via mannose receptor-mediated targeting delivery. Upon intratumoral injection, the as-prepared iCD@Gel induced ICD, and damage-associated molecular patterns (DAMPs) were released via photothermal ablation under 808 nm NIR irradiation. Subsequently, the iCD@Gel synergized with the DAMPs to significantly promote the maturation and antigen cross-presentation ability of DCs. This work provides a promising strategy to develop carbon dot-based therapeutic hydrogels for photothermal therapy and immune activation.

A Multifunctional Nano-Delivery System Against Rheumatoid Arthritis by Combined Phototherapy, Hypoxia-Activated Chemotherapy, and RNA Interference.

Purpose: Effective therapy for rheumatoid arthritis (RA) keeps a challenge due to the complex pathogenesis of RA. It is not enough to completely inhibit the process of RA with any single therapy method. The purpose of the research is to compensate for the insufficiency of monotherapy using multiple treatment regimens with different mechanisms. Material and Methods: In this study, we developed a new method to synthesize mesoporous silica nanoparticles hybridized with photosensitizer PCPDTBT (HNs). Branched polyethyleneimine-folic acid (PEI-FA) could be coated on the surface of HNs through electrostatic interactions. It simultaneously blocked the hypoxia-activated prodrug tirapazamine loaded into the mesopores and binded with Mcl-1 siRNA (siMcl-1) that interfered with the expression of the anti-apoptotic protein Mcl-1. Released from the co-delivery nanoparticles (PFHNs/TM) Tirapazamine and siMcl-1 upon exposure to acidic conditions of endosomes/lysosomes in activated macrophages. Under NIR irradiation, photothermal therapy and photodynamic therapy derived from PCPDTBT, hypoxia-activated chemotherapy derived from tirapazamine, and RNAi derived from siMcl-1 were used for the combined treatment for RA by killing activated macrophages. PEI-FA-coated PFHNs/TM exhibited activated macrophage-targeting characteristics, thereby enhancing the in vitro and in vivo NIR-induced combined treatment of RA. Results: The prepared PFHNs/TM have high blood compatibility (far below 5% of hemolysis) and ideal in vitro phototherapy effect while controlling the TPZ release and binding siMcl-1. We prove that PEI-FA-coated PFHNs/TM not only protect the bound siRNA but also are selectively uptaked by activated macrophages through FA receptor-ligand-mediated endocytosis, and effectively silence the target anti-apoptotic protein by siMcl-1 transfection. In vivo, PFHNs/TM have also been revealed to be selectively enriched at the inflammatory site of RA, exhibiting NIR-induced anti-RA efficacy. Conclusion: Overall, these FA-functionalized, pH-responsive PFHNs/TM represent a promising platform for the co-delivery of chemical drugs and nucleic acids for the treatment of RA cooperating with NIR-induced phototherapy.

Mangasese doped polypyrole nanoparticels for photothermal/chemodynamic therapy and immune activation.

Photothermal therapy (PTT) is a promising treatment that efficiently suppresses local cancer, but fails to induce a robust antitumor immune response against tumor metastasis and recurrence. In this study, a NIR responsive nano-immunostimulant (Mn/A-HP NI) is fabricated by entrapping manganese and azo-initiator (AIPH) into hyaluronic acid-based polypyrrole nanoparticle. The as-prepared Mn/A-HP NIs with a high photothermal conversion efficiencey of 20.17% dramatically induced the imunogenic cell death of tumor cells and triggered the release ATP and HMGB1. Meanwhile, the hyperthermia induced AIPH decomposition to produce alkyl radicals which further destroyed cancer cells. Furthermore, the Mn/A-HP NIs were capable of promoting the maturation and antigen cross-presentation ability of dendritic cells. Consequently, the multifunctional Mn/A-HP NIs provided a combined treatment via integrating PTT/chemo-dynamic therapy and immune activation for tumor therapy.

Multifunctional light-activatable nanocomplex conducting temperate-heat photothermal therapy to avert excessive inflammation and trigger augmented immunotherapy.

Photothermal therapy (PTT) has been known as an effective weapon against cancer. However, the necrosis induced by hyperthermia post PTT can trigger excessive inflammation response and arouse tumor self-protection resulting in tumor immunosuppression, metastasis and recurrence. To settle this issue, we here reported a multifunctional light-activatable nanocomplex (MILAN) to avoid hyperthermia and achieve temperate-heat PTT for extensive apoptosis, but not necrosis, and further antitumor immune response augmentation to inhibit metastasis and recurrence. Upon NIR irradiation, MILAN would controllably maintain around 43 °C, thus evoking the temperature-triggered phase transformation for the controllable drug release. Then, the released gambogic acid broke the thermoresistance of tumor cells, realizing enhanced apoptosis. Thereafter, the generated tumor-associated antigen accompanied with MILAN could facilitate dendritic cells (DCs) maturation for improved antigen presentation. Furthermore, MILAN promoted the tumor perfusion of DCs and T lymphocytes in triple-negative breast cancer (TNBC) models. Simultaneously, the immunosuppressive microenvironment was relieved and a strong systemic immune response was elicited against tumor progress through MILAN. Consequently, systemic immunity and persistent immune memory effect were fortified for pronounced cancer metastasis and recurrence inhibition. This work tactfully avoids the side effects of hyperthermia and brought a novel insight into cancer immunotherapy against TNBC.

Nano-Based Co-Delivery System for Treatment of Rheumatoid Arthritis.

A systemic autoimmune condition known as rheumatoid arthritis (RA) has a significant impact on patients' quality of life. Given the complexity of RA's biology, no single treatment can totally block the disease's progression. The combined use of co-delivery regimens integrating various diverse mechanisms has been widely acknowledged as a way to make up for the drawbacks of single therapy. These days, co-delivery systems have been frequently utilized for co-treatment, getting over drug limitations, imaging of inflammatory areas, and inducing reactions. Various small molecules, nucleic acid drugs, and enzyme-like agents intended for co-delivery are frequently capable of producing the ability to require positive outcomes. In addition, the excellent response effect of phototherapeutic agents has led to their frequent use for delivery together with chemotherapeutics. In this review, we discuss different types of nano-based co-delivery systems and their advantages, limitations, and future directions. In addition, we review the prospects and predicted challenges for the combining of phototherapeutic agents with conventional drugs, hoping to provide some theoretical support for future in-depth studies of nano-based co-delivery systems and phototherapeutic agents.

Calcium and phosphorus co-doped carbon dots enhance osteogenic differentiation for calvarial defect repairin situ.

Calvarial bone defect remains a clinical challenge due to the lack of efficient osteo-inductive agent. Herein, a novel calcium and phosphorus codoped carbon dot (Ca/P-CD) for bone regeneration was synthesized using phosphoethanolamine and calcium gluconate as precursors. The resultant Ca/P-CDs exhibited ultra-small size, stable excitation dependent emission spectra and favorable dispersibility in water. Moreover, Ca/P-CDs with good biocompatibility rapidly entered the cytoplasm through endocytosis and increased the expression of bone differentiation genes. After mixing with temperature-sensitive hydrogel, Ca/P-CDs were injectedin situinto calvarial defect and promoted the repair of bone injury. These Ca/P-CDs provide a new treatment method for the bone repair and should be expended the application in the biomedical fields.

Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation.

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.