A novel self-assembled nanoplatform based on retrofitting poloxamer 188 for triple-negative breast cancer targeting treatment.

Poloxamer 188 is a widely used pharmaceutical excipient, which can be found in a variety of drug formulations. In this study, a novel self-assembled nanoplatform was developed for active targeting of folate receptor-overexpressing triple-negative breast cancer. This platform, FPP NPs, was prepared by the retrofitted poloxamer 188 derivatives, resulting in nanoparticles with an appropriate size (< 100 nm), good stability, and satisfactory biocompatibility. Cellular uptake and in vivo distribution studies showed that the FPP NPs had strong tumor cell uptake and active targeting capabilities. Furthermore, docetaxel (DTX) was loaded into FPP NPs in this research. The resulting DTX/FPP NPs exhibited high drug encapsulation efficiency and drug loading capacity, and could rapidly release DTX under slightly acidic conditions, significantly increasing the antitumor activity of the encapsulated drug both in vitro and in vivo. In addition, DTX/FPP NPs could significantly decrease the hepatotoxicity and nephrotoxicity of DTX. Therefore, this drug delivery nanoplatform, based on retrofitted poloxamer 188 with self-assembly properties in aqueous solution and active targeting capabilities to tumors, may provide a promising approach for targeted treatment of triple-negative breast cancer.

Image recognition of traditional Chinese medicine based on deep learning.

Chinese herbal medicine is an essential part of traditional Chinese medicine and herbalism, and has important significance in the treatment combined with modern medicine. The correct use of Chinese herbal medicine, including identification and classification, is crucial to the life safety of patients. Recently, deep learning has achieved advanced performance in image classification, and researchers have applied this technology to carry out classification work on traditional Chinese medicine and its products. Therefore, this paper uses the improved ConvNeXt network to extract features and classify traditional Chinese medicine. Its structure is to fuse ConvNeXt with ACMix network to improve the performance of ConvNeXt feature extraction. Through using data processing and data augmentation techniques, the sample size is indirectly expanded, the generalization ability is enhanced, and the feature extraction ability is improved. A traditional Chinese medicine classification model is established, and the good recognition results are achieved. Finally, the effectiveness of traditional Chinese medicine identification is verified through the established classification model, and different depth of network models are compared to improve the efficiency and accuracy of the model.

Characteristic quality analysis for biologically induced agarwood columns in Aquilaria sinensis.

Current artificial agarwood-inducing techniques yield low quality and quantities of agarwood. On account of unclear agarwood formation mechanism there's still no high-efficiency agarwood inducing method globally spread. In this study, a complete agarwood column was taken out of the live tree trunk at 6 months post-treatment by a novel agarwood-inducing method (Agar-Bit) in cultivated Aquilaria sinensis trees, and was first divided into 8 parts (A1-4, B1-4) involving agarwood layer (A part) and brown inner layer (B part) according to its color and length for analysis. These eight parts were analyzed microscope observation, 6 chromones' contents and characteristic chromatograms by HPLC (high performance liquid chromatography), GC-MS (gas chromatography-mass spectrometer) with to determine chemical changes. Other quality characteristics, TLC (thin-layer chromatography) and alcohol soluble extraction content, were also determined. Our results showed that resin changed with A to B part and microstructure changed with length. Six chromones in the eight parts varied with layers. Result of characteristic chromatograms showed that both A and B parts contained six characteristic peaks. Volatile component distributed mainly in A part, but important chromones were also detected in B parts. Results from TLC and alcohol soluble extraction content also showed that B part contained characteristic compounds of agarwood. In addition, some compounds in the essential oil detected by GC-MS in A part produced by Agar-Bit were similar to that found in natural agarwood, compounds in B parts were similar to BC agarwood, as were the results for the TLC and alcohol soluble extraction content. In conclusion, the chemical distribution obtained here from Agar-Bit could provide some clues to optimize high production and high efficiency stimulating method for whole tree full of resin in Aquilaria sinensis and to reveal the subtle agarwood formation mechanism throughout a whole trunk.

Allyl halide induced electrochemical degradation of lignin into double-bonded phenolic monomers.

Lignin is one of the major macromolecule in nature that contains an aromatic ring structure, and also a potential source of high-value products such as biofuels and chemicals. However, Lignin is a kind of complex heterogeneous polymer which can produce many degradation products during processing or treatment. These degradation products are difficult to separate, making it challenging to use lignin directly for high-value applications. This study proposes an electrocatalytic method to degrade lignin by using allyl halides to induce double-bonded phenolic monomers, while avoiding separation. In an alkaline solution, the three basic structural units (G, S, and H) of lignin were transformed into phenolic monomers by introducing allyl halide, which could effectively expand lignin application space. This reaction was achieved using a Pb/PbO2 electrode as the anode and copper as the cathode. It was further confirmed that double-bonded phenolic monomers were obtained by degradation. 3-allylbromide has more active allyl radicals and significantly higher product yields than 3-allylchloride. The yields of 4-allyl-2-methoxyphenol, 4-allyl-2,6-dimethoxyphenol and 2-allylphenol could reach 17.21 g/kg-lignin, 7.75 g/kg-lignin, and 0.67 g/kg-lignin respectively. These mixed double-bond monomers can be used as monomer materials for in-situ polymerization without further separation, which lays the foundation for high value-added applications of lignin.

Puerarin Alleviates Vascular Cognitive Impairment in Vascular Dementia Rats.

Cerebral ischemia triggers vascular dementia (VD), which is characterized by memory loss, cognitive deficits, and vascular injury in the brain. Puerarin (Pur) represents the major isoflavone glycoside of Radix Puerariae, with verified neuroprotective activity and cardiovascular protective effects. However, whether Pur ameliorates cognitive impairment and vascular injury in rats with permanent occlusion of bilateral common carotid arteries (BCCAO) remains unknown. This work aimed to assess Pur's effects on BCCAO-induced VD and to dissect the underlying mechanisms, especially examining the function of transient receptor potential melastatin-related 2 (TRPM2) in alleviating cognitive deficits and vascular injuries. Rats with BCCAO developed VD. Pur (50, 100, and 150 mg/kg) dose-dependently attenuated the pathological changes, increased synaptic structural plasticity in the dorsal CA1 hippocampal region and decreased oxidative stress, which eventually reduced cognitive impairment and vascular injury in BCCAO rats. Notably, Pur-improved neuronal cell loss, synaptic structural plasticity, and endothelial vasorelaxation function might be mediated by the reactive oxygen species (ROS)-dependent TRPM2/NMDAR pathway, evidenced by decreased levels of ROS, malondialdehyde (MDA), Bax, Bax/Bcl2, and TRPM2, and increased levels of superoxide dismutase (SOD), Bcl2, and NR2A. In conclusion, Pur has therapeutic potential for VD, alleviating neuronal cell apoptosis and vascular injury, which may be related to the ROS-dependent TRPM2/NMDAR pathway.

Citronellal ameliorates doxorubicin-induced hepatotoxicity via antioxidative stress, antiapoptosis, and proangiogenesis in rats.

Doxorubicin (DOX) is a very effective broad-spectrum anticancer drug, yet its clinical application is badly restricted due to its serious side effects. Citronellal (CT), a specialized metabolite of plants found in Cymbopogon spp., is proved to exhibit many beneficial properties. In the current study, we intended to investigate the effect of CT on DOX-induced hepatotoxicity in rats. Rats were treated with CT (200 mg/kg b.w./day orally), and given DOX (2.5 mg/kg b.w./week, intraperitoneally) to induce hepatotoxicity for six consecutive weeks. The results showed that CT administration could attenuate the DOX-induced pathological changes of liver tissues and ameliorated the inappropriate alteration of liver function biomarkers (serum glutamic aspartate aminotransferase, glutamic pyruvic transaminase, and albumin) in serum and oxidative stress parameters (malondialdehyde, superoxide dismutase, and reduced glutathione) in the liver. Moreover, CT mitigated the Bax/Bcl-2 ratio and caspase-3 expression to inhibit cell apoptosis. Further study indicated that CT therapy could enhance the protein levels of p-PI3K, p-Akt, and CD31 in the liver. These results demonstrate that CT can ameliorate DOX-induced hepatotoxicity in rats mediated by antioxidative stress, antiapoptosis, and proangiogenesis.

The antihypertension effect of hydrogen sulfide (H2S) is induced by activating VEGFR2 signaling pathway.

AIMS: Previous studies demonstrated that H2S has an antihypertension effect on hypertension, but the mechanism involved is unclear until now. The aim of the study is to elucidate the effect of H2S on PH and the mechanism involved. MAIN METHODS: In this study, GYY4137 (a H2S donor) were administered to spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) by intraperitoneally injection daily for consecutive 14 days. Systolic blood pressure (SBP), endothelial-dependent relaxation (EDR), plasma malondialdehyde (MDA), superoxide dismutase (SOD), and H2S levels were measured. Human umbilical vein endothelial cells (HUVECs) were also used to elucidate the mechanism involved in the protect effect of H2S on the injured vessels. KEY FINDINGS: Our results showed that GYY4137 normalized the SBP (P < 0.0001), increased EDR (P < 0.01), reduced oxidative stress (increased the content of SOD and reduced the content of MDA) of SHR. Meanwhile, GYY4137 could promote the proliferation (P < 0.01) and migration (P < 0.01) of HUVECs, increase the expression of endothelial NO synthase (eNOS) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) both in SHR and HUVECs treated with GYY4137. In addition to the above results, the PIP3/Akt signaling pathway was activated and the expression of caspase 3 was increased by GYY4137. However, all the above effects of GYY4137 were blocked by ZD6474 (a VEGFR2 inhibitor). SIGNIFICANCE: GYY4137 had a hypotensive and vascular protect effect on PH. This effect might be mediated through upregulating the expression of VEGFR2, which subsequently alleviating oxidant-provoked vascular endothelial dysfunction, and promoting the proliferation and migration of endothelial cells in SHR.

Advance of sporadic Alzheimer's disease animal models.

Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disease. In the past decades, numbers of promising drug candidates showed significant anti-AD effects in preclinical studies but failed in clinical trials. One of the major reasons might be the limitation of appropriate animal models for evaluating anti-AD drugs. More than 95% of AD cases are sporadic AD (sAD). However, the anti-AD drug candidates were mainly tested in the familial AD (fAD) animal models. The diversity between the sAD and fAD might lead to a high failure rate during the development of anti-AD drugs. Therefore, an ideal sAD animal model is urgently needed for the development of anti-AD drugs. Here, we summarized the available sAD animal models, including their methodology, pathologic features, and potential underlying mechanisms. The limitations of these sAD animal models and future trends in the field were also discussed.

Effect of bajijiasu isolated from Morinda officinalis F. C. how on sexual function in male mice and its antioxidant protection of human sperm.

ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, the physiological aspects of human fertility have been seriously influenced by the interactions of genetic and environmental factors. Almost one in 20 males has been affected by male infertility, providing a great challenge and an opportunity to use natural compounds as alternatives to chemical drugs with comprehensive adverse effects. However, ample evidences are scanty to support the physiological mechanisms of natural compounds used to treat male infertility. In traditional Chinese medicine, Morinda officinalis F. C. How is widely used as a herb that invigorates the kidneys and supports yang, the original energy in the human body, to resist diseases and in treating male infertility. In this study, we evaluated whether bajijiasu isolated from the roots of M. officinalis F.C. How is a potential agent for the treatment of male infertility. MATERIALS AND METHOD: In this study, both normal and kidney-yang-deficient mice were administered bajijiasu orally at different concentrations. To determine the pharmacological mechanism of bajijiasu, we observed the sexual behavior and genital organ coefficients, determined their serum hormone levels, analyzed their sperm quality parameters, and examined histopathological sections from them. We also used enzymatic assays to determine the effects of bajijiasu on superoxide dismutase, glutathione peroxidase, and malondialdehyde. Confocal micro-Raman spectroscopy was used to investigate the changes in the DNA of H2O2-damaged human sperm after treatment with bajijiasu in vitro. RESULTS: Our results showed that bajijiasu enhanced the sexual behavior of both normal and kidney-yang-deficient mice. It also markedly increased the testosterone concentrations, reduced the levels of cortisol, improved the quality of the sperm, and counteracted the histopathological impairment induced by hydroxyurea in the kidney-yang-deficient mice. The enzymatic assay and Raman spectra showed that bajijiasu protects the DNA of sperm from damage by H2O2. CONCLUSION: Bajijiasu is a potential androgen-like drug that modulates hormone levels to some extent without producing reproductive-organ lesions, enhances the sexual function of male mice, and protects the DNA of human sperm from H2O2 damage. Thus, bajijiasu is an active ingredient of M. officinalis F.C. How that improves the human reproductive capacity.

Quantum molecular dynamics study of expanded beryllium: evolution from warm dense matter to atomic fluid.

By performing quantum molecular dynamics (QMD) simulations, we investigate the equation of states, electrical and optical properties of the expanded beryllium at densities two to one-hundred lower than the normal solid density, and temperatures ranging from 5000 to 30000 K. With decreasing the density of Be, the optical response evolves from the one characteristic of a simple metal to the one of an atomic fluid. By fitting the optical conductivity spectra with the Drude-Smith model, it is found that the conducting electrons become localized at lower densities. In addition, the negative derivative of the electrical resistivity on temperature at density about eight lower than the normal solid density demonstrates that the metal to nonmetal transition takes place in the expanded Be. To interpret this transition, the electronic density of states is analyzed systematically. Furthermore, a direct comparison of the Rosseland opacity obtained by using QMD and the standard opacity code demonstrates that QMD provides a powerful tool to validate plasma models used in atomic physics approaches in the warm dense matter regime.

Protective effects of bajijiasu in a rat model of Aß25₋35-induced neurotoxicity.

ETHNOPHARMACOLOGICAL RELEVENCE: Neurodegenerative diseases (NDs) caused by neurons and/or myelin loss lead to devastating effects on patients׳ lives. Although the causes of such complex diseases have not yet been fully elucidated, oxidative stress, mitochondrial and energy metabolism dysfunction, excitotoxicity, inflammation, and apoptosis have been recognized as influential factors. Current therapies that were designed to address only a single target are unable to mitigate or prevent disease progression, and disease-modifying drugs are desperately needed, and Chinese herbs will be a good choice for screening the potential drugs. Previous studies have shown that bajijiasu, a dimeric fructose isolated from Morinda officinalis radix which was used frequently as a tonifying and replenishing natural herb medicine in traditional Chinese medicine clinic practice, can prevent ischemia-induced neuronal damage or death. MATERIALS AND METHODS: In order to investigate whether bajijiasu protects against beta-amyloid (Aß25₋35)-induced neurotoxicity in rats and explore the underlying mechanisms of bajijiasu in vivo, we prepared an Alzheimer׳s disease (AD) model by injecting Aß25-35 into the bilateral CA1 region of rat hippocampus and treated a subset with oral bajijiasu. We observed the effects on learning and memory, antioxidant levels, energy metabolism, neurotransmitter levels, and neuronal apoptosis. RESULTS: Bajijiasu ameliorated Aß-induced learning and memory dysfunction, enhanced antioxidative activity and energy metabolism, and attenuated cholinergic system damage. Our findings suggest that bajijiasu can enhance antioxidant capacity and prevent free radical damage. It can also enhance energy metabolism and monoamine neurotransmitter levels and inhibit neuronal apoptosis. CONCLUSION: The results provide a scientific foundation for the use of Morinda officinalis and its constituents in the treatment of various AD. Future studies will assess the multi-target activity of the drug for the treatment of AD.

Theoretical investigation of the increase in the Rosseland mean opacity for hot dense mixtures.

Based on a detailed configuration accounting model with the term structures treated by the unresolved transition array model, a large scale calculation has been performed for the opacities of medium- and high-Z materials and mixtures. Agreement between our calculated results and previous theoretical simulations is obtained. By filling in the low-opacity regions of one material with the high-opacity regions of other materials, the Rosseland mean opacity of their combination will be increased. This should be of great interest to hohlraum design in indirect-drive inertial confinement fusion. Based on our studies, many mixtures, such as Au+Nd, or Ho+Sn, can result in a similar (or higher) increase in the Rosseland mean as the previously proposed Au+Gd mixture.