Erratum: Author correction to 'Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy' [Acta Pharm Sin B 13 (2023) 1303-1317].

[This corrects the article DOI: 10.1016/j.apsb.2022.08.024.].

Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy.

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe3O4@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe3O4@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe3O4@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T2 magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe3O4@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.

Supplementation with α-ketoglutarate improved the efficacy of anti-PD1 melanoma treatment through epigenetic modulation of PD-L1.

Patients with advanced melanoma have shown an improved outlook after anti-PD1 therapy, but the low response rate restricts clinical benefit; therefore, enhancing anti-PD1 therapeutic efficacy remains a major challenge. Here, our findings showed a significantly increased abundance of α-KG in healthy controls, anti-PD1-sensitive melanoma-bearing mice, and anti-PD1-sensitive melanoma patients; moreover, supplementation with α-KG enhanced the efficacy of anti-PD1 immunotherapy and increased PD-L1 expression in melanoma tumors via STAT1/3. We also found that supplementation with α-KG significantly increased the activity of the methylcytosine dioxygenases TET2/3, which led to an increased 5-hydroxymethylcytosine (5-hmC) level in the PD-L1 promoter. As a consequence, STAT1/3 binding to the PD-L1 promoter was stabilized to upregulate PD-L1 expression. Importantly, single-cell sequencing of preclinical samples and analysis of clinical data revealed that TET2/3-STAT1/3-CD274 signaling was associated with sensitivity to anti-PD1 treatment in melanoma. Taken together, our results provide novel insight into α-KG's function in anti-PD1 treatment of melanoma and suggest supplementation with α-KG as a novel promising strategy to improve the efficacy of anti-PD1 therapy.

C. acnes qPCR-Based Antibiotics Resistance Assay (ACQUIRE) Reveals Widespread Macrolide Resistance in Acne Patients and Can Eliminate Macrolide Misuse in Acne Treatment.

Background: Macrolides have been widely used to treat moderate-to-severe acne for more than 50 years. However, the prevalent antibiotic resistance of Propionibacterium acnes, along with the absence of clinically available resistance tests, has made macrolide misuse a frequent occurrence around the globe, with serious consequences. Objective: We developed Cutibacterium acnes quantitative PCR (qPCR)-based antibiotics resistance assay (ACQUIRE) to enable fast and accurate detection of C. acnes macrolide resistance in clinical settings, representing an opportunity to administer antibiotics more wisely and improve the quality of care. Methods: A cross-sectional observational study (n = 915) was conducted to probe into the macrolide resistance of C. acnes in patients with acne. Results: The high sensitivity of ACQUIRE enabled us to reveal a much higher C. acnes 23S recombinant DNA (rDNA) point mutation rate (52%) and thus a higher macrolide resistance (75.5%) compared to previous reports. Carriage of ermX gene was discovered on 472 (53%) subjects, which concurs with previous studies. Conclusion: The macrolide resistance of C. acnes is much higher than previously reported. Integrating ACQUIRE into acne treatment modalities may eliminate macrolide misuse and achieve better clinical improvements.

Tumor targeting and penetrating biomimetic mesoporous polydopamine nanoparticles facilitate photothermal killing and autophagy blocking for synergistic tumor ablation.

The synergistic manipulation of autophagy blocking with tumor targeting and penetration effects to enhance cancer cell killing during photothermal therapy (PTT) remains a substantial challenge. Herein, we fabricated a biomimetic nanoplatform by precisely coating homologous prostate cancer cell membranes (CMs) onto the surface of mesoporous polydopamine nanoparticles (mPDA NPs) encapsulating the autophagy inhibitor chloroquine (CQ) for synergistically manipulating PTT and autophagy for anticancer treatment. The resulting biomimetic mPDA@CMs NPs-CQ system could escape macrophage phagocytosis, overcome the vascular barrier, and home in the homologous prostate tumor xenograft with high tumor targeting and penetrating efficiency. The mPDA NPs core endowed the mPDA@CMs NPs-CQ with good photothermal capability to mediate PTT killing of prostate cancer cells, while NIR-triggered CQ release from the nanosystem further arrested PTT-induced protective autophagy of cancer cells, thus weakening the resistance of prostate cancer cells to PTT. This combined PTT killing and autophagy blocking anticancer strategy could induce significant autophagosome accumulation, ROS generation, mitochondrial damage, endoplasmic reticulum stress, and apoptotic signal transduction, which finally results in synergistic prostate tumor ablation in vivo. This prostate cancer biomimetic nanosystem with synergistically enhanced anticancer efficiency achieved by manipulating PTT killing and autophagy blocking is expected to serve as a more effective anticancer strategy against prostate cancer. STATEMENT OF SIGNIFICANCE: Autophagy is considered as one of the most efficient rescuer and reinforcement mechanisms of cancer cells against photothermal therapy (PTT)-induced cancer cell eradication. How to synergistically manipulate autophagy blocking with significant tumor targeting and penetration to enhance PTT-mediated cancer cell killing remains a substantial challenge. Herein, we fabricated a biomimetic nanoplatform by precisely coating homologous cancer cell membranes onto the surface of mesoporous polydopamine nanoparticles with encapsulation of the autophagy inhibitor chloroquine for synergistic antitumor treatment with high tumor targeting and penetrating efficiency both in vitro and in vivo. This biomimetic nanosystem with synergistically enhanced anticancer efficiency by manipulating PTT killing and autophagy blocking is expected to serve as a more effective anticancer strategy.

Mechanisms underlying the wound healing potential of propolis based on its in vitro antioxidant activity.

BACKGROUND: Propolis is a resinous substance collected by honeybees, Apis mellifera, from various plant sources. Having various pharmacological and biological activities, it has been used in folk medicine and complementary therapies since ancient times. PURPOSE: To evaluate the effects and underlying mechanism of the protective effects of the ethanol extract of Chinese propolis (EECP) on L929 cells injured by hydrogen peroxide (H2O2). STUDY DESIGN: The wound healing activities of EECP in L929 cells with H2O2-induced damage were investigated. METHODS: The main components of EECP were analyzed by RP-HPLC, and the free radical scavenging capacity and reducing power were also measured. The effects of EECP on the expression of antioxidant-related genes in fibroblast L929 cells were determined using qRT-PCR and western blotting. RESULTS: EECP had significant protective effects against cell death induced by H2O2 and significantly inhibited the decline of collagen mRNA expression caused by H2O2 in L929 cells. CONCLUSION: EECP induced the expression of antioxidant-related genes, such as HO-1, GCLM, and GCLC, which has great implications for the potential of propolis to alleviate oxidative stress in wound tissues. The protective effects of propolis have great implications for using propolis as a wound healing regent.

Comparisons of ethanol extracts of chinese propolis (poplar type) and poplar gums based on the antioxidant activities and molecular mechanism.

The biological activities of propolis are varied from plant sources and the prominent antioxidant effects of Chinese propolis (poplar type) have been extensively reported. Oxidative stress is associated with inflammation and induces many diseases. In the study, to evaluate antioxidant capacities and clarify the underlying molecular mechanisms of ethanol extracts of Chinese propolis (EECP) and ethanol extracts of poplar gums (EEPG), we analyzed their compositions by HPLC, evaluating their free radical scavenging activities and reducing power by chemical analysis methods. Moreover, we studied the roles of EECP and EEPG on the elimination of ROS and expressions of antioxidant genes (HO-1, TrxR1, GCLM, and GCLC) in RAW264.7 cells. We further investigated the effects of MAPKs on the antioxidant genes expression by specific inhibitors. The nucleus translocation effects of Nrf2 were also measured by confocal microscopy analysis. The results indicated that EECP had higher TPC and FDC values but regarding TFC values were not significant. EECP also possessed more contents of 11 compounds than EEPG. Both phytochemical analysis and cell experiment reflected that EECP exerted stronger antioxidant activities than EEPG. EECP and EEPG enhanced endogenous antioxidant defenses by eliminating reactive oxygen species directly and activating Erk-Nrf2-HO1, GCLM, and TrxR1 signal pathways.

Anti-inflammatory effects of ethanol extracts of Chinese propolis and buds from poplar (Populus×canadensis).

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is used widely in a number of cultures as a folk medicine and is gaining wider recognition for its potential therapeutic use, due to its wide range of biological properties and pharmacological activities, especially its anti-inflammatory effects. Despite an increasing number of studies focused on the biological activities of propolis together with its botanical sources, studies on Chinese propolis are insufficient. This study was designed to investigate the anti-inflammatory properties of ethanol extracts from Chinese propolis (EECP) and poplar buds (EEPB) from Populus×canadensis Moench (Salicaceae family). MATERIALS AND METHODS: Phytochemical analysis of EECP and EEPB was performed via total phenolic and flavonoid content measurements followed by high-performance liquid chromatography (HPLC) analysis. DPPH and ABTS free-radical scavenging methods were used to evaluate their anti-oxidant properties. The anti-inflammatory effects of EECP and EEPB were investigated in vitro by evaluating their modulating effects on the key inflammatory cytokines and mediators in LPS/IFN-γ co-stimulated RAW 264.7 cells and by measuring nuclear factor (NF)-κB activation in TNF-α or IL-1ß stimulation HEK 293 cells using reporter gene assays. Their effects on acute inflammatory symptoms (LPS-induced endotoxemia and acute pulmonary damage) were also examined in mice. RESULTS: EECP and EEPB exhibited strong free-radical scavenging activity and significant in vitro anti-inflammatory effects by modulating key inflammatory mediators of mRNA transcription, inhibiting the production of specific inflammatory cytokines, and blocking the activation of nuclear factor (NF)-κB. The administration of EECP and EEPB (25 and 100 mg/kg) provided significant protective effects by attenuating lung histopathological changes and suppressing the secretion of LPS-stimulated inflammatory cytokines, such as interleukin-6 (IL-6), IL-10, MCP-1, TNF-α and IL-12p70 production in endotoxemic mice. CONCLUSIONS: The results presented here reveal the potent anti-inflammatory properties of Chinese propolis and poplar buds, and provide biological information for developing suitable substitute(s) for propolis in the prevention and treatment of inflammatory diseases.

[Advance in studies on antioxidant activity of propolis and its molecular mechanism].

Propolis is an adhesive substance mixed with plant resins collected by honeybees (Apis mellifera) and secretions from their mandibular gland and wax gland, with wide pharmacological activity and healthcare functions. Its antioxidant activity has long been regarded as one of the most important biological activities of propolis. This article summarizes studies on the antioxidant activity of propolis extracts from different geographic origins and with different extraction methods, as well as several important monomer active ingredients in propolis, and concludes the potential molecular mechanism of antioxidant activity of propolis and its monomer ingredients, with the aim of providing ideas for further studies on pharmacological activity of propolis, as well as reference for in-depth development of propolis products.

Report of 12 cases of ankylosing spondylitis patients treated with Tripterygium wilfordii.

OBJECTIVE: Description of the clinical response of 12 consecutive cases of disease-active ankylosing spondylitis (AS) treated with the herbal medicine Tripterygium wilfordii Hook f (TwHf; lei gong teng, thunder god vine), which has been reported in controlled studies to be effective in rheumatoid arthritis (RA). METHODS: The clinical status of 12 patients with active AS who were started on 60 mgday(-1) of a commercial tablet preparation of TwHf extract. were monitored at weeks 1, 3, and 6. RESULTS: Compared to baseline, there was significant improvement in mean values of physician assessment, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and Bath ankylosing spondylitis global score (BAS-G) at weeks 3 and 6, with no changes in liver enzymes or complete blood count (CBC). CONCLUSION: A placebo-controlled double-blind study for Tripterygium is warranted. Until then, this particular report should be considered as case reports and not an endorsement of the use of Tripterygium in clinical practice.