[Optimization of prediction model for personalized water pills based on semantic analysis of traditional Chinese medicine materials].

This study aims to optimize the prediction model of personalized water pills that has been established by our research group. Dioscoreae Rhizoma, Leonuri Herba, Codonopsis Radix, Armeniacae Semen Amarum, and calcined Oyster were selected as model medicines of powdery, fibrous, sugary, oily, and brittle materials, respectively. The model prescriptions were obtained by uniform mixing design. With hydroxypropyl methylcellulose E5(HPMC-E5) aqueous solution as the adhesive, personalized water pills were prepared by extrusion and spheronizaition. The evaluation indexes in the pill preparation process and the multi-model statistical analysis were employed to optimize and evaluate the prediction model of personalized water pills. The prediction equation of the adhesive concentration was obtained as follows: Y_1=-4.172+3.63X_A+15.057X_B+1.838X_C-0.997X_D(adhesive concentration of 10% when Y_1<0, and 20% when Y_1>0). The overall accuracy of the prediction model for adhesive concentration was 96.0%. The prediction equation of adhesive dosage was Y_2=6.051+94.944X_A~(1.5)+161.977X_B+70.078X_C~2+12.016X_D~(0.3)+27.493X_E~(0.3)-2.168X_F~(-1)(R~2=0.954, P<0.001). Furthermore, the semantic prediction model for material classification of traditional Chinese medicines was used to classify the materials contained in the prescription, and thus the prediction model of personalized water pills was evaluated. The results showed that the prescriptions for model evaluation can be prepared with one-time molding, and the forming quality was better than that established by the research group earlier. This study has achieved the optimization of the prediction model of personalized water pills.

A novel therapy for fracture healing by increasing lymphatic drainage.

Background: The musculoskeletal system contains an extensive network of lymphatic vessels. Decreased lymph flow of the draining collecting lymphatics usually occurs in clinic after traumatic fractures. However, whether defects in lymphatic drainage can affect fracture healing is unclear. Methods: To investigate the effect of lymphatic dysfunction on fracture healing, we used a selective VEGFR3 tyrosine kinase inhibitor to treat tibial fractured mice for 5 weeks versus a vehicle-treated control. To ensure successfully establishing deceased lymphatic drainage model for fractured mice, we measured lymphatic clearance by near infrared indocyanine green lymphatic imaging (NIR-ICG) and the volume of the draining popliteal lymph nodes (PLNs) by ultrasound at the whole phases of fracture healing. In addition, hindlimb edema from day 0 to day 7 post-fracture, pain sensation by Hargreaves test at day 1 post-fracture, bone histomorphometry by micro-CT and callus composition by Alcian Blue-Hematoxylin/Orange G staining at day 14 post-fracture, and bone quality by biomechanical testing at day 35 post-fracture were applied to evaluate fracture healing. To promote fracture healing via increasing lymphatic drainage, we then treated fractured mice with anti-mouse podoplanin (PDPN) neutralizing antibody or isotype IgG antibody for 1 week to observe lymphatic drainage function and assess bone repair as methods described above. Results: Compared to vehicle-treated group, SAR-treatment group significantly decreased lymphatic clearance and the volume of draining PLNs. SAR-treatment group significantly increased soft tissue swelling, and reduced bone volume (BV)/tissue volume (TV), trabecular number (Tb.N), woven bone and biomechanical properties of fracture callus. In addition, anti-PDPN treated group significantly reduced the number of CD41+ platelets in PLNs and increased the number of pulsatile lymphatic vessels, lymphatic clearance and the volume of PLNs. Moreover, anti-PDPN treated group significantly reduced hindlimb edema and pain sensation and increased BV/TV, trabecular number (Tb.Th), woven bone and biomechanical properties of fracture callus. Conclusions: Inhibition of proper lymphatic drainage function delayed fracture healing. Use of a anti-PDPN neutralizing antibody reduced lymphatic platelet thrombosis (LPT), increased lymphatic drainage and improved fracture healing. The translational potential of this article: (1) We demonstrated lymphatic drainage function is crucial for fracture healing. (2) To unblock the lymphatic drainage and prevent the risk of bleeding and mortality by blood thinner, we demonstrated PDPN neutralizing antibody is a novel and safe way forward in the treatment of bone fracture healing by eliminating LPT and increasing lymphatic drainage.

Uncovering the Mechanisms of Cinnamic Acid Treating Diabetic Nephropathy Based on Network Pharmacology, Molecular Docking, and Experimental Validation.

BACKGROUND: Cinnamic acid (Cinn) is a phenolic acid of Cinnamomum cassia (L.) J. Presl. that can ameliorate diabetic nephropathy (DN). However, comprehensive therapeutic targets and underlying mechanisms for Cinn against DN are limited. OBJECTIVE: In this study, a network pharmacology approach and in vivo experiments were adopted to predict the pharmacological effects and mechanisms of Cinn in DN therapy. METHODS: The nephroprotective effect of Cinn on DN was investigated by a streptozotocininduced diabetes mellitus (DM) mouse model. The protein-protein interaction network of Cinn against DN was established by a network pharmacology approach. The core targets were then identified and subjected to molecular docking with Cinn. RESULTS: Cinn treatment effectively restored body weight, ameliorated hyperglycemia, and reduced kidney dysfunction markers in DM mice, also demonstrating a reduction in tissue injury. Network pharmacology analysis identified 298 DN-Cinn co-target genes involved in various biological processes and pathways. Seventeen core targets were identified, eight of which showed significant differential expression in the DN and healthy control groups. Molecular docking analysis revealed a strong interaction between Cinn and PTEN. Cinn treatment downregulated the PTEN protein expression in DM mice. CONCLUSION: This study revealed the multi-target and multi-pathway characteristics of Cinn against DN. Cinn improved renal pathological damage of DN, which was related to the downregulation of PTEN.

Berberine Metabolites Stimulate GLP-1 Secretion by Alleviating Oxidative Stress and Mitochondrial Dysfunction.

Berberine (BBR) is a principal component of Rhizoma coptidis known for its therapeutic potential in treating diseases such as type 2 diabetes mellitus (T2DM) and obesity. Despite the trace levels of BBR in plasma, it's believed that its metabolites play a pivotal role in its biological activities. While BBR is recognized to promote GLP-1 production in intestinal L cells, the cytoprotective effects of its metabolites on these cells are yet to be explored. The present study investigates the effects of BBR metabolites on GLP-1 secretion and the underlying mechanisms. Our results revealed that, out of six BBR metabolites, berberrubine (BBB) and palmatine (PMT) significantly increased the production and glucose-stimulated secretion of GLP-1 in GLUTag cells. Notably, both BBB and PMT could facilitate GLP-1 and insulin secretion and enhance glucose tolerance in standard mice. Moreover, a single dose of PMT could markedly increase plasma GLP-1 and improve glucose tolerance in mice with obesity induced by a high-fat diet. In palmitic acid or TNF[Formula: see text]-treated GLUTag cells, BBB and PMT alleviated cell death, oxidative stress, and mitochondrial dysfunction. Furthermore, they could effectively reverse inflammation-induced inhibition of the Akt signaling pathway. In general, these insights suggest that the beneficial effects of orally administered BBR on GLP-1 secretion are largely attributed to the pharmacological activity of BBB and PMT by their above cytoprotective effects on L cells, which provide important ideas for stimulating GLP-1 secretion and the treatment of T2DM.

A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2-Positive Breast Cancer.

Anti-HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2-positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold-silver hollow nanoshells (AuAg HNSs) with exceptional near-infrared (NIR) absorption capability, the small-molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo-and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT-modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF-κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.

Specific molecular weight of Lycium barbarum polysaccharide for robust breast cancer regression by repolarizing tumor-associated macrophages.

The pro-tumorigenic M2-type tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment (TME) promote the progression, angiogenesis, and metastasis of breast cancer. The repolarization of TAMs from an M2-type toward an M1-type holds great potential for the inhibition of breast cancer. Here, we report that Lycium barbarum polysaccharides (LBPs) can significantly reconstruct the TME by modulating the function of TAMs. Specifically, we separated four distinct molecular weight segments of LBPs and compared their repolarization effects on TAMs in TME. The results showed that LBP segments within 50-100 kDa molecular weight range exhibited the prime effect on the macrophage repolarization, augmented phagocytosis effect of the repolarized macrophages on breast cancer cells, and regression of breast tumor in a tumor-bearing mouse model. In addition, RNA-sequencing confirms that this segment of LBP displays an enhanced anti-breast cancer effect through innate immune responses. This study highlights the therapeutic potential of LBP segments within the 50-100 kDa molecular weight range for macrophage repolarization, paving ways to offer new strategies for the treatment of breast cancer.

Profiling the chemical properties of Foeniculum vulgare Mill. and its flavonoids through comprehensive LC-MS/MS to evaluate their anti-motion sickness effect.

Foeniculum vulgare Mill. is a medicinal and food homologous plant, and it has various biological activities. Yet, no research has explored its anti-motion sickness effects. Chemical properties of fennel extracts (FvE) and flavonoids (Fvf) were analyzed based on UPLC-QTRAP-MS to elucidate its potential anti-motion sickness components in the present study. The mice models of motion sickness were stimulated by biaxial rotational acceleration. Behavioral experiments such as motion sickness index and open field test and the measurement of neurotransmitters were used to evaluate the efficacy of compounds on motion sickness. Results showed that FvE contains terpenes, alkaloids, flavonoids, etc. Eight flavonoids including quercetin-3ß-D-glucoside, rutin, hyperoside, quercetin, miquelianin, trifolin, isorhamnetin and kaempferol were identified in the purified Fvf. FvE and Fvf significantly reduced the motion sickness index of mice by 53.2% and 48.9%, respectively. Fvf also significantly alleviated the anxious behavior of mice after rotational stimulation. Among the eight flavonoids, isorhamnetin had the highest oral bioavailability and moderate drug-likeness index and thus speculated to be the bioactive compound in fennel for its anti-motion sickness effect. It reduced the release of 5-HT and Ach to alleviate the motion sickness response and improve the work completing ability of mice and nervous system dysfunction after rotational stimulation. This study provided in-depth understanding of the anti-motion sickness bioactive chemical properties of fennel and its flavonoids, which will contribute to the new development and utilization of fennel.

Synthesis and application of clinically approved small-molecule drugs targeting androgen receptor.

Androgen receptor (AR) plays a crucial role in various physiological processes. Dysregulation of AR signaling has been implicated in several diseases, such as prostate cancer and androgenetic alopecia. Therefore, the development of drugs that specifically target AR has gained significant attention in the field of drug discovery. This review provides an overview of the synthetic routes of clinically approved small molecule drugs targeting AR and discusses the clinical applications of these drugs in the treatment of AR-related diseases. The review also highlights the challenges and future perspectives in this field, including the need for improved drug design and the exploration of novel therapeutic targets. Through an integrated analysis of the therapeutic applications, synthetic methodologies, and mechanisms of action associated with these approved drugs, this review facilitates a holistic understanding of the versatile roles and therapeutic potential of AR-targeted interventions. Overall, this comprehensive review serves as a valuable resource for medicinal chemists interested in the development of small-molecule drugs targeting AR.

Effect of Meditation on Brain Activity during an Attention Task: A Comparison Study of ASL and BOLD Task fMRI.

Focused attention meditation (FAM) training has been shown to improve attention, but the neural basis of FAM on attention has not been thoroughly understood. Here, we aim to investigate the neural effect of a 2-month FAM training on novice meditators in a visual oddball task (a frequently adopted task to evaluate attention), evaluated with both ASL and BOLD fMRI. Using ASL, activation was increased in the middle cingulate (part of the salience network, SN) and temporoparietal (part of the frontoparietal network, FPN) regions; the FAM practice time was negatively associated with the longitudinal changes in activation in the medial prefrontal (part of the default mode network, DMN) and middle frontal (part of the FPN) regions. Using BOLD, the FAM practice time was positively associated with the longitudinal changes of activation in the inferior parietal (part of the dorsal attention network, DAN), dorsolateral prefrontal (part of the FPN), and precentral (part of the DAN) regions. The effect sizes for the activation changes and their association with practice time using ASL are significantly larger than those using BOLD. Our study suggests that FAM training may improve attention via modulation of the DMN, DAN, SN, and FPN, and ASL may be a sensitive tool to study the FAM effect on attention.

Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: An exploratory randomized controlled trial.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an important occurrence in the natural history of idiopathic pulmonary fibrosis (IPF), associated with high hospitalization rates, high mortality and poor prognosis. At present, there is no effective treatment for AE-IPF. Chinese herbal medicine has some advantages in treating IPF, but its utility in AE-IPF is unclear. OBJECTIVE: The treatment of AE-IPF with Kangxian Huanji Granule (KXHJ), a compound Chinese herbal medicine, lacks an evidence-based justification. This study explores the efficacy and safety of KXHJ in patients with AE-IPF. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a randomized, double-blind, placebo-controlled, exploratory clinical trial. A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo; the treatment included a 10 g dose, administered twice daily for 4 weeks, in addition to conventional treatment. Participants were followed up for 12 weeks after the treatment. MAIN OUTCOME MEASURES: The primary endpoints were treatment failure rate and all-cause mortality. Secondary endpoints included the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, the modified British Medical Research Council (mMRC) score, and the St George's Respiratory Questionnaire for IPF (SGRQ-I) score. RESULTS: The rate of treatment failure at 4 weeks was lower in the intervention group compared to the control group (risk ratio [RR]: 0.22; 95% confidence interval [CI]: 0.051 to 0.965, P = 0.023). There was no significant difference in all-cause mortality at 16 weeks (RR: 0.75; 95% CI: 0.179 to 3.138; P > 0.999) or in the acute exacerbation rate during the 12-week follow-up period (RR: 0.69; 95% CI: 0.334 to 1.434; P = 0.317). The intervention group had a shorter length of hospitalization than the control group (mean difference [MD]: -3.30 days; 95% CI, -6.300 to -0.300; P = 0.032). Significant differences in the mean change from baseline in the mMRC (between-group difference: -0.67; 95% CI: -0.89 to -0.44; P < 0.001) and SGRQ-I score (between-group difference: -10.36; 95% CI: -16.483 to -4.228; P = 0.001) were observed after 4 weeks, and also in the mMRC (between-group difference: -0.67; 95% CI: -0.91 to -0.43; P < 0.001) and SGRQ-I (between-group difference: -10.28; 95% CI, -15.838 to -4.718; P < 0.001) at 16 weeks. The difference in the adverse events was not significant. CONCLUSION: KXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF. As a preliminary exploratory study, our results provide a basis for further clinical research. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900026289). Please cite this article as: Li JS, Zhang HL, Guo W, Wang L, Zhang D, Zhao LM, Zhou M. Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: an exploratory randomized controlled trial. J Integr Med. 2023; 21(6): 543-549.

Herbal combinations against COVID-19: A network pharmacology, molecular docking and dynamics study.

OBJECTIVE: The aim of this study is to identify molecules from traditional Chinese medicine (TCM) with potential activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. METHODS: We applied the Apriori algorithm to identify important combinations of herbs in the TCM prescriptions for the treatment of coronavirus disease 2019 (COVID-19). Then, we explored the active components and core targets using network pharmacology. In addition, the molecular docking approach was performed to investigate the interaction of these components with the main structural and non-structural proteins, as well as the mutants. Furthermore, their stability in the binding pockets was further evaluated with the molecular dynamics approach. RESULTS: A combination of Amygdalus Communis Vas., Ephedra Herba and Scutellaria baicalensis Georgi was selected as the important herbal combination, and 11 main components and 20 core targets against COVID-19 were obtained. These components, including luteolin, naringenin, stigmasterol, baicalein, and so on, were the potentially active compounds against COVID-19. The binding affinity of these compounds with the potential targets was as high as the positive controls. Among them, baicalein could interfere with multiple targets simultaneously, and it also interfered with the interaction between spike protein and angiotensin-converting enzyme 2 receptor. Additionally, almost all the systems reached stability during dynamics simulation. CONCLUSION: The combination of A. communis, Ephedra Herba and S. baicalensis was the most important herbal combination for the treatment of COVID-19. Baicalein may be a potential candidate against SARS-CoV-2 and its variants. Please cite this article as: Song JB, Zhao LQ, Wen HP, Li YP. Herbal combinations against COVID-19: A network pharmacology, molecular docking and dynamics study. J Integr Med. 2023;21(6):593-604.

[Quality of moxa with different leaf-to-moxa ratios based on correlation analysis of thermogravimetric properties, cellulose content, and microscopic characteristics of non-secretory trichomes].

The quality of moxa is a key factor affecting the efficacy of moxibustion. Traditional moxa grades are evaluated by the leaf-to-moxa ratio, but there is a lack of support from scientific data. Scanning electron microscopy(SEM), Image Pro Plus, Van Soest method, and stimultaneous thermal analysis(TGA/DSC) were used to characterize the scientific implication of the combustion differences between moxa with different leaf-to-moxa ratios(processed by crusher). The results showed that the median lengths from non-secretory trichomes(NSTs) of natural NSTs and moxa with leaf-to-moxa ratios of 3∶1, 5∶1, 10∶1, and 15∶1 were 542.46, 303.24, 291.18, 220.69, and 170.61 µm, respectively. The cellulose content of moxa increased significantly(P<0.05) with the increase in leaf-to-moxa ratio and the combustion parameters(T_i, t_i, D_i, C,-R_p,-R_v, S, D_b, and J_(total)) all showed an increasing trend. The correlation results showed that the burning properties of moxa(T_i,-R_v, t_i, and J_2) were significantly and positively correlated with cellulose content. NSTs with a length of 1-200 µm were significantly and positively correlated with J_2. NSTs with a length of 200-600 µm were significantly and positively correlated with J_1, T_(peak2), T_(peak1), and-R_v, and negatively correlated with J_(total), T_b, and t_b. As the leaf-to-moxa ratio increases, the NSTs in the moxa become shorter and the cellulose content increases, which is more conducive to ignition performance, heat release, and a milder, longer-lasting burn. The "NSTs-cellulose-TGA/DSC" quantitative evaluation method scientifically reveals the scientific connotation of the combustion of moxa with different leaf-to-moxa ratios and provides a scientific basis for the establishment of quality evaluation methods for moxa with different leaf-to-moxa ratios.

Zuo Gui Wan Promotes Osteogenesis via PI3K/AKT Signaling Pathway: Network Pharmacology Analysis and Experimental Validation.

OBJECTIVE: Osteogenesis is vitally important for bone defect repair, and Zuo Gui Wan (ZGW) is a classic prescription in traditional Chinese medicine (TCM) for strengthening bones. However, the specific mechanism by which ZGW regulates osteogenesis is still unclear. The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis. METHODS: A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs). RESULTS: In total, 487 no-repeat targets corresponding to the bioactive components of ZGW were screened, and 175 target genes in the intersection of ZGW and osteogenesis were obtained. And 28 core target genes were then obtained from a PPI network analysis. A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress, metal ions, and lipopolysaccharide. Additionally, KEGG pathway enrichment analysis revealed that multiple signaling pathways, including the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway, were associated with ZGW-promoted osteogensis. Further experimental validation showed that ZGW could increase alkaline phosphatase (ALP) activity as well as the mRNA and protein levels of ALP, osteocalcin (OCN), and runt related transcription factor 2 (Runx 2). What's more, Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT, and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002. Finally, the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002. CONCLUSION: ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.

Plasmonic nanobipyramids with photo-enhanced catalytic activity under near-infrared II window for effective treatment of breast cancer.

Nanozyme-based catalytic therapy is an effective method for cancer treatment, but insufficient catalytic activity presents a challenge in achieving optimal therapeutic outcomes. External light can provide an innovative approach to modulate nanozyme catalytic activity. Herein, we report on plasmonic gold nanobipyramid@cuprous oxide (Au NBP@Cu2O) nanozyme for the effective phototherapy of breast cancer. In the tumor microenvironment, Cu+-mediated Fenton-like reaction catalyzes the generation of toxic hydroxyl radicals (•OH) from endogenous hydrogen peroxide to induce apoptosis. Additionally, the Au NBP@Cu2O nanostructure improves the absorption performance of Au NBPs in the near-infrared II region through near-field enhancement of equipartite exciters and achieves a high photothermal conversion efficiency value of 58%. Remarkably, the Au NBP@Cu2O nanoheterostructure can capture hot electrons induced by equipartition excitations and promote electron-hole separation under 1064 nm laser irradiation, facilitating the production of more reactive oxygen species (ROS). The mechanism behind this enhanced catalytic activity was unraveled using femtosecond transient absorption spectroscopy. Both in vitro and in vivo investigations have demonstrated the efficacious tumor therapeutic potential of Au NBP@Cu2O nanozyme, particularly under 1064 nm laser irradiation. Furthermore, the proposed therapeutic approach has been proved to effectively block tumor metastasis, providing a promising strategy for the development of multifunctional nanotherapeutics to tackle metastatic tumors. STATEMENT OF SIGNIFICANCE: A highly effective plasmonic nanozyme has been developed to improve catalytic therapy for breast cancer. When exposed to 1064 nm laser irradiation, Au NBP@Cu2O nanozyme can promote the separation of hot electrons and holes thereby facilitating the production of reactive oxygen species. Hot electrons transfer behavior is unveiled by femtosecond transient absorption spectroscopy technique. This enhanced catalytic activity, along with the intrinsic photothermal effect, effectively kills tumor cells.

An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer's Disease with Berberine and Palmatine.

Introduction: Neuroinflammation is one of the major pathogeneses in Alzheimer's disease (AD) and mainly involves abnormal inflammatory activation of microglia by multiple pathological stimuli. The treatment of AD remains a major challenge due to the multifactorial characterization of AD and the inefficient ability of therapeutic drugs to permeate through the blood‒brain barrier (BBB). Accordingly, drug combination treatment and drug carrier delivery have become important therapeutic tools for the treatment of multifactorial diseases, especially AD. Methods: Inflammatory cytokine levels in microglia, including NO, TNF-α, IL-1ß, IL-4, and IL-10, were detected. The Morris water maze and object location task were used to investigate the learning and memory functions of APP/PS1 mice in different treatment groups. The number of neurons and plasticity of synapses were evaluated by immunofluorescence double labelling. Additionally, the ratio of ß-amyloid plaques and the number of activated microglia were evaluated by immunofluorescence staining. The concentrations of ß-amyloid plaques and inflammatory factors in the hippocampus were determined by ELISA. Microglia-derived exosomes (Exos) were extracted and purified by size exclusion chromatography. The distribution of exosomes and drugs was investigated in vitro and in vivo. Results: Compared to single drug interventions, the combination of Ber and Pal (Ber/Pal) modulated microglial inflammatory cytokine levels. Ber/Pal promoted the recovery of learning and memory impairment in APP/PS1 mice. Immunofluorescence staining indicated that Ber/Pal restored neurons, inhibited Aß plaque formation and microglial activation, and regulated the secretion of inflammatory factors. Exos promoted the accumulation of drugs in cells and tissues and improved the targeting of drugs across the BBB. Conclusion: Ber/Pal could offer a synergistic and more comprehensive therapeutic effect in AD. Additionally, the microglia-derived Exos-Ber/Pal delivery system promoted the targeting and permeation of drugs into the brain, suggesting a creative strategy for targeting AD therapy by regulating neuroinflammation in microglial cells.

Fabricating pectin and chitosan double layer coated liposomes to improve physicochemical stability of beta-carotene and alter its gastrointestinal fate.

To improve storage stability and gastrointestinal (GI) stability of liposomes, pectin and chitosan double layer coated liposome (P-C-L) was proposed and optimized using electrostatic deposition technique. The physical-chemical properties and GI fate of the carrier were then investigated in comparison to that of chitosan coated liposomes (C-L) and un-coated liposomes (L). The results showed P-C-L was successfully prepared at 0.2 % chitosan and 0.06 % pectin. It was hydrogen bonds between the amino groups in chitosan and liposomal interfacial region, and the interaction between the carboxyl groups in pectin layer and amino groups in chitosan layer maintained the structure of P-C-L after absorption by electrostatic interaction. The double layer coatings could improve chemical stability of the encapsulated ß-carotene (ßC), as well as the thermal stability of liposomes. What's more, the permeability of liposomal bilayers and ßC release mechanism in simulated GI fluids was changed by the polymer coating. P-C-L exhibited better controlled release for ßC than C-L and L, and displayer beneficial effect on delivering bioactive agents passing through intensity tract. This may assistant developing more efficient delivery system for bioactive agent.

[Quality of moxa from Artemisia argyi and A. stolonifera in different storage years based on simultaneous thermal analysis].

The quality of moxa is an important factor affecting moxibustion therapy, and traditionally, 3-year moxa is considered optimal, although scientific data are lacking. This study focused on 1-year and 3-year moxa from Artemisia stolonifera and A. argyi(leaf-to-moxa ratio of 10∶1) as research objects. Scanning electron microscopy(SEM), Van Soest method, and simultaneous thermal analysis were used to investigate the differences in the combustion heat quality of 1-year and 3-year moxa and their influencing factors. The results showed that the combustion of A. stolonifera moxa exhibited a balanced heat release pattern. The 3-year moxa released a concentrated heat of 9 998.84 mJ·mg~(-1)(accounting for 54% of the total heat release) in the temperature range of 140-302 ℃, with a heat production efficiency of 122 mW·mg~(-1). It further released 7 512.51 mJ·mg~(-1)(accounting for 41% of the total heat release) in the temperature range of 302-519 ℃. The combustion of A. argyi moxa showed a rapid heat release pattern. The 3-year moxa released a heat of 16 695.28 mJ·mg~(-1)(accounting for 70% of the total heat release) in the temperature range of 140-311 ℃, with an instantaneous power output of 218 mW·mg~(-1). It further released 5 996.95 mJ·mg~(-1)(accounting for 25% of the total heat release) in the temperature range of 311-483 ℃. Combustion parameters such as-R_p,-R_v, D_i, C, and D_b indicated that the combustion heat quality of 3-year moxa was superior to that of 1-year moxa. It exhibited greater combustion heat, heat production efficiency, flammability, mild and sustained burning, and higher instantaneous combustion efficiency. This study utilized scientific data to demonstrate that A. stolonifera could be used as excellent moxa, and the quality of 3-year moxa surpassed that of 1-year moxa. The research results provide a scientific basis for the in-depth development of A. stolonifera moxa and the improvement of moxa quality standards.

[Classification optimization of traditional Chinese medicine materials based on additive physical properties of powder].

According to the method of predicting the physical properties of oily powder based on the additive physical properties of Chinese medicinal powder, Dioscoreae Rhizoma and calcined Ostreae Concha with high sieve rate and good fluidity were mixed and crushed with Persicae Semen, Platycladi Semen, Raphani Semen, Ziziphi Spinosae Semen, and other typical oily materials with high fatty oil content in proportion to obtain 23 mixed powders. Fifteen physical properties such as bulk density, water absorption, and maximum torque force were measured, and the physical properties of typical oily powders were predicted. When the mixing and grinding ratio was in the range of 5∶1-1∶1, the r value in the correlation equation between the weighted average score of the mixed powder and the powder proportion ranged from 0.801 to 0.986, and the linearity was good, indicating that the method of predicting the physical properties of oily powder based on the additive physical properties of traditional Chinese medicine(TCM)powder was feasible. The results of cluster analysis showed that the classification boundaries of the five kinds of TCM materials were clear, and the similarity of the physical fingerprints of powdery and oily materials decreased from 80.6% to 37.2%, which solved the problem of fuzzy classification boundaries of powdery and oily materials due to the lack of representativeness of oily material model drugs. The classification of TCM materials was optimized, laying a foundation for optimizing the prediction model of the prescription of personalized water-paste pills.

Lecithin/chitosan nanoparticle drug carrier improves anti-tumor efficacy of Monascus pigment rubropunctatin.

Rubropunctatin, a metabolite isolated from the fungi of the genus Monascus, is a natural lead compound applied for the suppression of tumors with good anti-cancer activity. However, its poor aqueous solubility has limited its further clinical development and utilization. Lecithin and chitosan are excellently biocompatible and biodegradable natural materials, which have been approved by the FDA as drug carrier. Here, we report for the first time the construction of a lecithin/chitosan nanoparticle drug carrier of the Monascus pigment rubropunctatin by electrostatic self-assembly between lecithin and chitosan. The nanoparticles are near-spherical with a size 110-120 nm. They are soluble in water and possess excellent homogenization capacity and dispersibility. Our in vitro drug release assay showed a sustained release of rubropunctatin. CCK-8 assays revealed that lecithin/chitosan nanoparticles loaded with rubropunctatin (RCP-NPs) had significantly enhanced cytotoxicity against mouse mammary cancer 4T1 cells. The flow cytometry results revealed that RCP-NPs significantly boosted cellular uptake and apoptosis. The tumor-bearing mice models we developed indicated that RCP-NPs effectively inhibited tumor growth. Our present findings suggest that lecithin/chitosan nanoparticle drug carriers improve the anti-tumor effect of the Monascus pigment rubropunctatin.

The potential of the gut microbiome for identifying Alzheimer's disease diagnostic biomarkers and future therapies.

Being isolated from the peripheral system by the blood-brain barrier, the brain has long been considered a completely impervious tissue. However, recent findings show that the gut microbiome (GM) influences gastrointestinal and brain disorders such as Alzheimer's disease (AD). Despite several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid plaques, neurofibrillary tangles, and oxidative stress, being proposed to explain the origin and progression of AD, the pathogenesis remains incompletely understood. Epigenetic, molecular, and pathological studies suggest that GM influences AD development and have endeavored to find predictive, sensitive, non-invasive, and accurate biomarkers for early disease diagnosis and monitoring of progression. Given the growing interest in the involvement of GM in AD, current research endeavors to identify prospective gut biomarkers for both preclinical and clinical diagnoses, as well as targeted therapy techniques. Here, we discuss the most recent findings on gut changes in AD, microbiome-based biomarkers, prospective clinical diagnostic uses, and targeted therapy approaches. Furthermore, we addressed herbal components, which could provide a new venue for AD diagnostic and therapy research.