Search

Melanoma, the most aggressive skin cancer type, is challenging to treat due to its high metastatic potential and low response to conventional therapies. Innovative approaches, including combination therapies, are crucial for enhancing treatment efficacy while minimizing side effects. It is developed boronophenylalanine‐containing polydopaine (B‐PDA) nanoparticles by encapsulating boronophenylalanine in polydopamine through nitrogen‐boronate coordination, targeting both boron neutron capture therapy (BNCT) and photothermal therapy (PTT). With stability and biocompatibility under physiological conditions, these nanoparticles utilize the phenylalanine residues in BPA to target the overexpressed neutral amino acid transporter 1 (LAT1) in melanoma cells, resulting in enhanced cell‐specific targeting. B‐PDA nanoparticles demonstrated significant photothermal effects under external stimulation, inducing localized heating and triggering heterogeneous tumor cell death, thereby enhancing sensitivity to BNCT. Combining BNCT and PTT, the B‐PDA nanoparticles offer a promising strategy for melanoma treatment. [ABSTRACT FROM AUTHOR]

Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans-cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo, with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC. [ABSTRACT FROM AUTHOR]

Here we describe a cost-effective and simplified cell sorting method using tetrazine bioorthogonal chemistry. We successfully isolated SKOV3 cells from complex mixtures, demonstrating efficacy in separating mouse lymphocytes expressing interferon and HeLa cells expressing virally transduced green fluorescent protein post-infection. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a promising therapy for refractory cancer based on the cytotoxic reaction of 10B (n, α) 7Li. Although two BNCT agents are clinically available, they are quickly metabolized and show modest enrichment in tumor sites, partially limiting BNCT widespread application. Consequently, novel agents that perform active targeting and show good biocompatibility have to be developed. Herein, boronophenylalanine‐containing polydopamine (B‐PDA) nanoparticles are easily fabricated by encapsulating boronophenylalanine (BPA) in polydopamine via nitrogen‐boronate coordination. In this study, B‐PDA achieves increased tumor accumulation and prolonged retention effects in the tumor site and superior antitumor activity post neutron irradiation in the orthotopic xenograft glioma model. In brief, this study offers a novel strategy for BPA delivery and may broaden the perspective on nanomedicine design for BNCT. [ABSTRACT FROM AUTHOR]

Synergistic photothermal immunotherapy has emerged as a favorable therapeutic approach to fight cancer. However, design of an effective photothermal immunotherapy system to suppress tumor growth and simultaneously inhibit tumor metastases continues to be a challenge. Here a dual toll‐like receptor agonists delivery system CPG@Au NRs/m‐R848 for combined photothermal immunotherapy of melanoma is developed. CPG@Au NRs/m‐R848 displays strong antitumor effects by promoting maturation of dendritic cells (DCs) and reprogramming of M2 macrophages into M1 phenotype. Moreover, immunogenic cell death (ICD) induced by photothermal ablation of Au NRs could synergistically produce in situ vaccination effect with CPG ODN and R848, generating systemic and lasting antitumor immunity. It is further proved that CPG@Au NRs/m‐R848 treatment inhibits tumor growth in bilateral B16F10 tumors model by eliciting CD8+ T cell response. Overall, this work suggests that this strategy hold great potential in tumor immunotherapy by regulating tumor‐associated macrophage polarization, triggering DCs maturation and inducing ICD. [ABSTRACT FROM AUTHOR]

Macrophages have been reported to exert a crucial role in hepatocellular carcinoma (HCC). This study aimed to explore the macrophage-related genes and establish a macrophage-related signature (MRS) model to predict the overall survival (OS) of patients with HCC based on these genes' expression. We screened the macrophage-related gene module by weighted gene coexpression network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO) Cox regression analysis was utilized for further selection, and the selected genes were entered into stepwise regression to develop the MRS model, which was further validated in the Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) datasets. We analyzed the biological phenotypes associated with macrophages in terms of functional enrichment, tumor immune signature, and tumor mutational signature. The patient's response to immunotherapy was inferred by the tumor immune dysfunction and exclusion (TIDE) score, the immunophenotype score (IPS), and the IMvigor210 dataset. A novel MRS model was established based on the LASSO regression coefficients of the genes PON1 , IL15RA , NEIL3 , HILPDA , PFN2 , HAVCR1 , ANXA10 , CDCA8 , EPO , S100A9 , TTK , KLRB1 , SPP1 , STC2 , CYP26B1 , GPC1 , G6PD , and CBX2. In either dataset, MRS was identified as an independent risk factor for OS in HCC patients. Additionally, our research indicated that a high-risk score in the MRS model was significantly correlated with tumor staging, pathological grade, tumor–node–metastasis (TNM) stage, and survival. Several genes of the human leukocyte antigen (HLA) family and immune checkpoints were highly expressed in the high-risk group. In addition, the frequency of tumor mutations was also higher in the high-risk group. According to our analyses, a higher risk score in the MRS model may predict a better response to immunotherapy. [ABSTRACT FROM AUTHOR]

Objective. To study the effect of preoperative rehabilitation training on the rehabilitation of patients after total knee arthroplasty. Methods. A total of 120 patients diagnosed with knee osteoarthritis and undergoing total knee arthroplasty were selected and divided into experimental group and control group according to a random number table, with 60 cases in each group. The control group only carried out routine clinical nursing before the operation, and the experimental group used the formulated preoperative rehabilitation training method based on the control group for training. By comparing the visual analogue score (VAS), keen society score (KSS), postoperative time to get out of bed for the first time, patient satisfaction, and other related indicators between the two groups of patients, the recovery of keen joint function of patients after surgery was evaluated. Results. The visual analogue scale (VAS) of the experimental group was significantly lower than that of the experimental group at three days after operation. The keen society score (KSS) of the experimental group was significantly better than that of the control group at three days after surgery and one month after surgery. The time to get out of bed for the first time after operation in the experimental group (44.93 ± 13.63) was significantly less than that in the control group (78.33 ± 13.52). The patient satisfaction of the experimental group was significantly higher than that of the control group (88.30 ± 3.61). The above statistical results were all p < 0.05 of the two groups, and the differences were statistically significant. Conclusion. Preoperative rehabilitation training can significantly reduce the pain of patients after knee replacement, improve the functional state of knee joints, shorten the time to get out of bed for the first time after surgery, and win the best recovery opportunity, which can better improve patient satisfaction in hospitalization and improve medical care services level. [ABSTRACT FROM AUTHOR]

Highly fluorogenic tetrazine bioorthogonal probes emitting at near‐infrared wavelengths are in strong demand for biomedical imaging applications. Herein, we have developed a strategy for forming a palette of novel Huaxi‐Fluor probes in situ, whose fluorescence increases hundreds of times upon forming the bioorthogonal reaction product, pyridazine. The resulting probes show large Stokes shifts and high quantum yields. Manipulating the conjugate length and pull–push strength in the fluorophore skeleton allows the emission wavelength to be fine‐tuned from 556 to 728 nm. The highly photo‐stable and biocompatible probes are suitable for visualizing organelles in live cells without a washing step and for imaging of tumors in live small animals to depths of 500 μm by two‐photon excitation. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) is highly expressed on the surface of most prostate tumor cells and is considered a promising target for prostate cancer imaging and treatment. It is possible to establish a PSMA-targeted theranostic probe to achieve early diagnosis and treatment of this cancer type. In this contribution, we prepared a multifunctional melanin-like polydopamine (PDA) nanocarrier decorated with a small-molecule PSMA inhibitor, N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-l-lysine (DCL). PDA-DCL was then functionalized with perfluoropentane (PFP) and loaded with the photosensitizer chlorin e6 (Ce6) to give Ce6@PDA-DCL-PFP, which was successfully used for ultrasound-guided combined photodynamic/photothermal therapy (PDT/PTT) of prostate cancer. Compared with the corresponding non-targeted probe (Ce6@PDA-PEG-PFP), our targeted probe induced higher cellular uptake in vitro (6.5-fold) and more tumor accumulation in vivo (4.6-fold), suggesting strong active targeting capacity. Meanwhile, this new nanoplatform significantly enhanced the ultrasound contrast signal at the tumor site in vivo, thus facilitating precise and real-time detection of the tumor. In addition, this Ce6-loaded PDA nanoplatform produced a synergistic effect of PDT and PTT under 660 nm and 808 nm irradiation, inducing a more efficient killing effect compared with the individual therapy in vitro and in vivo. Furthermore, the tumor in the targeted group was more effectively suppressed than that in the non-targeted group under the same irradiation condition. This multifunctional probe may hold great potential for precise and early theranostics of prostate cancer. [ABSTRACT FROM AUTHOR]

The article discusses the construction and transliteration of Chinese personal names. Unlike in English speaking countries, Chinese surnames precede the given name; this is an important distinction to bear in mind when alphabetizing personal names as in an index. The author notes that there is a limited number of Chinese surnames, and that eighty-seven percent of the population shares the top one-hundred-twenty-nine surnames. The logographic Chinese writing system can be transliterated into Latin characters using either the Wade-Giles or the Pinyin transcription systems.

Tetramethylpyrazine (TMP), one of the active ingredients of the Chinese herb Lingusticum Wallichii (Chuan Xiong) has been proved to protect the medulla oblongata from chronic hypoxia injury. However, the underlying mechanism remains unclear. The purpose of this study was to determine whether the protective effects of TMP are associated with the heme oxygenase-1 (HO-1) dependant pathway in adult rats. The morphological changes of neurons in the hypoglossal nucleus (12N), the nucleus ambiguus (Amb), the nucleus tractus solitarius (NTS), and the pre-Bötzinger complex (pre-BötC) were investigated by Nissl staining; the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured to evaluate the anti-oxidant effect; some apoptosis parameters, Bax mRNA and Bcl-2 mRNA, were tested; and the double immunochemistry staining of active caspase-3/NeuN was performed. Meanwhile, the HO-1 protein expression and heme oxygenase (HO) activity were examined. Tin-protoporphyrin (SnPP), a potent inhibitor of HO, was used to further confirm the effect of HO-1. We found that TMP ameliorated the neuron loss in 12N, Amb and NTS, the decrease in SOD activity and the increase in MDA content, the decrease in Bcl-2 mRNA of medulla oblongata ( P < 0.05), and the increase in percentage of apoptotic neurons in Amb ( P < 0.05) induced by chronic hypoxia. Co-administration with SnPP abolished the beneficial effects above of TMP to some extent ( P < 0.05). Moreover, TMP significantly increased HO activity and HO-1 protein expression, which was most likely enhanced in the neurons ( P < 0.05), and co-administration of SnPP reduced these up-regulated effects ( P < 0.05). This study demonstrated that HO-1 dependant pathway may be involved in the protective action of TMP against chronic hypoxic damage on medulla oblongata in the rats. [ABSTRACT FROM AUTHOR]

The treatment of colorectal cancer is always a major challenge in the field of cancer research. The number of estimated new cases of colorectal cancer worldwide in 2020 is 1 148 515, and the estimated number of deaths is 576 858, revealing that mortality accounted for approximately half of the disease incidence. The development of new drugs and strategies for colorectal cancer treatment is urgently needed. Thermosensitive injectable hydrogel PDLLA-PEG-PDLLA (PLEL) loaded with cabazitaxel (CTX) is used to explore its anti-tumor effect on mice with orthotopic colorectal cancer. CTX/PLEL is characterized by a solution state at room temperature and a hydrogel state at physiologic temperature. The excipients MPEG-PCL and PDLLA-PEG-PDLLA have good biocompatibility and biodegradability. The simple material synthesis and preparation process renders this system cost-effective and more conducive to clinical transformation. An orthotopic colorectal cancer model is established by transplantation subcutaneous tumors onto the cecum of mice. According to the results of experiments in vivo, CTX/PLEL significantly inhibits orthotopic colorectal cancer and liver metastasis in mice. The results indicate that CTX/PLEL nanoparticle preparations have high security and excellent anti-tumor effects, and have great application potential in colorectal cancer therapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)