Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia.

There is an urgent need for research into effective interventions for pain management to improve patients' life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs' tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.

Red blood cell membrane-coated functionalized Cu-doped metal organic framework nanoformulations as a biomimetic platform for improved chemo-/chemodynamic/photothermal synergistic therapy.

Nanoformulations for combining chemotherapy, chemodynamic therapy, and photothermal therapy have enormous potential in tumor treatment. Coating nanoformulations with cell membranes endows them with homologous cellular mimicry, enabling nanoformulations to acquire new functions and properties, including homologous targeting and long circulation in vivo, and can enhance internalization by homologous cancer cells. Herein, we fused multifunctional biomimetic nanoformulations based on Cu-doped zeolitic imidazolate framework-8 (ZIF-8). Hydroxycamptothecin (HCPT), a clinical anti-tumor drug, was encapsulated into ZIF-8, which was subsequently coated with polydopamine (PDA) and red blood cell membrane. The as-fabricated biomimetic nanoformulations showed an enhanced cell uptake in vitro and the potential to prolong blood circulation in vivo, producing effective synergistic chemotherapy, chemodynamic therapy, and photothermal therapy under the 808 nm laser irradiation. Together, the biomimetic nanoformulations showed a prolonged blood circulation and evasion of immune recognition in vivo to provide a bio-inspired strategy which may have the potential for the multi-synergistic therapy of breast cancer.

Red Blood Cell Membrane-Camouflaged Polydopamine and Bioactive Glass Composite Nanoformulation for Combined Chemo/Chemodynamic/Photothermal Therapy.

Combinations of different therapeutic strategies, including chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT), are needed to effectively address evolving drug resistance and the adverse effects of traditional cancer treatment. Herein, a camouflage composite nanoformulation (TCBG@PR), an antitumor agent (tubercidin, Tub) loaded into Cu-doped bioactive glasses (CBGs) and subsequently camouflaged by polydopamine (PDA), and red blood cell membranes (RBCm), was successfully constructed for targeted and synergetic antitumor therapies by combining CT of Tub, CDT of doped copper ions, and PTT of PDA. In addition, the TCBG@PRs composite nanoformulation was camouflaged with a red blood cell membrane (RBCm) to improve biocompatibility, longer blood retention times, and excellent cellular uptake properties. It integrated with long circulation and multimodal synergistic treatment (CT, CDT, and PTT) with the benefit of RBCms to avoid immune clearance for efficient targeted delivery to tumor locations, producing an "all-in-one" nanoplatform. In vivo results showed that the TCBG@PRs composite nanoformulation prolonged blood circulation and improved tumor accumulation. The combination of CT, CDT, and PTT therapies enhanced the antitumor therapeutic activity, and light-triggered drug release reduced systematic toxicity and increased synergistic antitumor effects.

Can Cordyceps cicadae be used as an alternative to Cordyceps militaris and Cordyceps sinensis? - A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps cicadae (Mig.) Massee is one of the oldest and well-known traditional Chinese medicine (TCM), with its uses recorded as far back as the 5th century A.D. For centuries, C. cicadae has been used as food, tonic and folk medicine to treat malaria, palpitations, cancer, fever, diabetes, eye diseases, dizziness, and chronic kidney diseases. Although C. cicadae has been used as TCM for over 1600 years, it is not the most popular amongst the Cordyceps family. Cordyceps Sinensis (C. sinensis) and Cordyceps militaris (C. militaris) are the most studied and widely used, with a number of commercially available products derived from these two Cordyceps species. AIM OF THE REVIEW: This review seeks to look at the research that has been conducted on C. cicadae over the past 30 years, reporting on the biological activities, development and utilization. This information was compared to that focused on C. sinensis and C. militaris. MATERIALS AND METHODS: A literature search was conducted on different scientific search engines including, but not limited to "Web of Science", "ScienceDirect" and "Google Scholar" to identify published data on C. cicadae, I. cicadae, P. cicadae, C. sinensis and C. militaris. RESULTS: Research conducted on C. cicadae over the past two decades have shown that it poses similar biological properties and chemical composition as C. sinensis and C. militaris. C. cicadae has been reported to grow in many geographic locations, as compared to C. sinensis, and can be artificially cultivated via different methods. CONCLUSION: There exists sufficient evidence that C. cicadae has medicinal benefits and contain bioactive compounds similar to those found on C. sinensis and C. militaris. However, more research and standardization methods are still needed to directly compare C. cicadae with C. sinensis and C. militaris, in order to ascertain the suitability of C. cicadae as an alternative source of Cordyceps products.

Jatrorrhizine inhibits mammary carcinoma cells by targeting TNIK mediated Wnt/ß-catenin signalling and epithelial-mesenchymal transition (EMT).

BACKGROUND: Traf2 and Nck interacting serine protein kinase (TNIK) is a tumour target protein which its high expression is closely related to the occurrence and development of mammary carcinoma cells. Molecular docking revealed that jatrorrhizine, a protoberberine alkaloid, exhibits good binding affinity and interaction with TNIK. However, the underlying mechanisms of jatrorrhizine targeting TNIK inhibits the proliferation and metastasis of breast cancer cells remain unclear. METHODS: To figure out the mechanisms in vitro and in vivo, the CRISPR/Cas9 technology was used to knockout TNIK gene and detected qualitatively by immunofluorescence and immunoblotting assay. The MTT cell viability assay for cytotoxicity test, the apoptosis were detected by flow cytometry, the migration and invasion were evaluated by colony formation, wound healing assay and cell invasion assay, respectively. Anticancer effects were further corroborated by 4T1/Luc homograft tumour model. RESULTS: The results showed that targeted knockout of TNIK that attenuated Wnt/ß-catenin signalling and epithelial-mesenchymal transition (EMT) expression, the effects were potentiated by the addition of jatrorrhizine. Moreover, jatrorrhizine distinctly inhibited the proliferation of MDA-MB-231, MCF-7 and 4T1 cells with IC50 values of 11.08 ± 1.19 µM, 17.11 ± 4.54 µM and 22.14 ± 2.87 µM, induced mitochondrial dysfunction and early apoptosis involving mitochondrial apoptotic pathway. These results were further corroborated by the 4T1 tumour-bearing mice, which showed that jatrorrhizine significantly suppressed the proliferation and metastasis of mammary carcinoma cells without obvious toxicity. CONCLUSION: These findings provide an overall perspective that jatrorrhizine potentially restrains TNIK regulating Wnt/ß-catenin signalling and EMT expression for mammary cancer targeted therapy.

Comprehensive evaluation of wild Cordyceps cicadae from different geographical origins by TOPSIS method based on the macroscopic infrared spectroscopy (IR) fingerprint.

Cordyceps cicadae is an entomogenous fungus that has been used as a valuable traditional Chinese herbal tonic, however, it can be difficult to discern the false from the genuine. In this study, the macroscopic IR fingerprint methods containing Fourier transform infrared spectroscopy (FT-IR) and second derivative infrared spectroscopy (SD-IR) were used to elucidate wild C. cicadae. The TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) method was used to comprehensively evaluate C. cicadae from different geographical origins based on the macroscopic infrared spectroscopy (IR) fingerprint. The FT-IR spectra of C. cicadae exhibited the major characteristics of the absorptive peaks of carbohydrates, lipids and nucleosides at the position of 3291, 2925, 2845, 1651, 1547, 1455, 1080 and 950 cm-1. The high resolution of SD-IR further amplified the difference and revealed the potentially characteristic IR absorption spectrum. TOPSIS evaluation showed that C. cicadae from Anhui possess the strongest intensity of absorption bands among all the samples. Notably, FT-IR combined with SD-IR can effectively reveal the overall chemical components without damaging medicinal materials, and TOPSIS methods can provide a novel scientific evidence for comprehensively assessing different origins of wild C. cicadae.

Biological characteristics of Edgeworthia tomentosa (Thunb.) Nakai flowers and antimicrobial properties of their essential oils.

Edgeworthia tomentosa (Thunb.) Nakai belongs to Thymelaeaceae family, its alabastrum is used as the traditional Chinese medicine 'Buddleja Officinalis Maxim'. The present study was to elucidate the ultrastructure characteristics of the flower, the phytochemical composition of the aroma essential oils (EOs) and the relevant antimicrobial properties. There were exclusive characters of calyx, ovule, anther and pollen grain of the flowers under scanning electron microscopy. A total of 40 phytochemical components representing 98% of the EOs were successfully identified: monoterpenes and sesquiterpenes were the dominant terpenoids according to Kovats retention index and MS database. EOs exhibited a broad spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria, the best bacteriostatic effect was against Diplococcus pneumonia with MIC and MBC values ranging between 7.8 and 62.5 and 26.0-71.0 µg/mL, respectively. These results demonstrate that the surface microscopic morphological characteristics of Edgeworthia chrysantha Lindl. flowers, are full-scale chemical composition and antimicrobial properties of the EOs.

Biological characteristics, bioactive components and antineoplastic properties of sporoderm-broken spores from wild Cordyceps cicadae.

BACKGROUND: Cordyceps cicadae, an entomogenous fungus has been used as a dietary therapeutic in traditional Chinese medicine for several millennia, in the form of powders and decoction. However, wild C. cicadae is notably scarce. To date, there is still a lack of comprehensive and deep studies on the biological characteristics, chemical profiles and antineoplastic mechanisms of C. cicadae, especially its spores. AIM OF THE STUDY: This study aimed to identify wild C. cicadae using rDNA-ITS sequences. Active constituents and volatile ingredients of C. cicadae sporoderm-broken spore powders (CCBSP) were elucidated using UPLC-ESI-Q-TOF-MS and GC-MS, respectively. The underlying anti-neoplastic mechanisms of CCBSP were further investigated in A549 lung carcinoma cells. RESULTS: Molecular phylogenetic analysis of nuclear rDNA sequences indicated that wild C. cicadae belonged to Paecilomyces cicadae. Eight primary compounds from CCBSP were identified by MS fragmentation ions including nucleosides, cordycepic acid, cordycepin, beauvericin and myriocin. In total, forty-nine volatile components representing 99.56% of CCBSP were clearly identified. CCBSP exhibited antiproliferative effects on A549 cells with IC50 value of 125.54 ± 2.71 µg/ml, blocking the cell cycle in the G2/M phase. The nuclear morphology exhibited typical characteristics of apoptosis by Hoechst fluorescent stain. AnnexinV-FITC/PI staining revealed that the number of apoptotic cells increased after CCBSP treatment. Furthermore, immunofluorescence experiments indicated that CCBSP lowered the expressions of ß-catenin and N-cadherin, which was accompanied by repressed Wnt/ß-catenin signalling and activation of caspase-mediated apoptosis pathways. CONCLUSIONS: rDNA-ITS sequencing enabled molecular identification of wild C. cicadae. Importantly, these findings provide the first evidence regarding the full-scale bioactive components and antineoplastic properties of CCBSP. These data highlight the significance of C. cicadae as a potential antineoplastic agent.

Apoptosis of human breast cancer cells induced by microencapsulated betulinic acid from sour jujube fruits through the mitochondria transduction pathway.

Betulinic acid (BA), a natural pentacyclic triterpenoid, was isolated from sour jujube fruits for the first time. An inclusion complex comprising BA and ß-cyclodextrin (ß-CD) was formed to improve the dissolution of BA, but little is known about its anticancer effect. In this study, the anti-proliferative and apoptosis mechanisms of BA-ß-CD on human breast cancer MCF-7 cells were further investigated. Experimental results confirmed that the complexation model inhibited the growth of MCF-7 cells in a dose-dependent manner, arrested cell cycle in the G2/M phase and induced apoptosis via the mitochondria transduction pathway. Gene and protein analyses showed that the complexation model significantly inhibited Bcl-2 expression and promoted Bax expression, causing caspase-3 and caspase-9 cascade activation. These findings corroborated evidence on microencapsulated BA as an apoptosis inducer in MCF-7 cells. Thus, sour jujube fruits may have potential use as a breast cancer chemotherapeutic agent.