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Background This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV).Methods We searched five databases for randomized controlled trials (RCTs) evaluating the effects of EVV on healthy adults. The primary outcomes were relative risk (RR) of sero-conversion or sero-response of EVV in healthy adults between the groups that received EVV and the controls.Results Twenty-nine RCTs (n = 23573) were included. There was a significant difference in RR of sero-conversion of EVV (RR 13.18; 95% CI 11.28–15.41; I2 = 33%; P

Abstract Extracellular vesicles (EVs) are phospholipid bilayer-enclosed biological particles that are secreted by almost all living cells including animals, plants, and microorganisms. Chinese herbal medicines (CHM) have a long history of using plant-based remedies to treat and prevent human diseases. Chinese herbal medicine-derived extracellular vesicle (CHMEV) generic term refers to nanoscale membrane structures isolated from medicinal plants such as ginseng, ginger, and Panax notoginseng. In recent years, CHMEVs have garnered substantial attention as a novel class of functional components due to their high bioavailability, safety, easy accessibility, and diverse therapeutic effects, indicating their great potential for development as a new dosage form of CHM. Research on CHMEVs in traditional Chinese medicine (TCM) has become a prominent area of interest, opening new avenues for further exploration into the therapeutic effects and functional mechanisms of CHM. Nonetheless, as an emerging field, there is much unknown about these vesicles, and current research remains inconsistent. The review comprehensively summarizes the biogenesis, isolation methods, and physical, and biochemical characterizations of CHMEVs. Additionally, we highlight their biomedical applications as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, regenerative, and antiaging activities. Finally, we propose current challenges and future perspectives. By summarizing the existing literature, we aim to offer valuable clues and inspiration for future CHMEV research, thereby facilitating research standardization of CHMEVs in the treatment of human diseases and drug discovery.

Abstract Breast cancer remains a malignancy that poses a serious threat to human health worldwide. Chemotherapy is one of the most widely effective cancer treatments in clinical practice, but it has some drawbacks such as poor targeting, high toxicity, numerous side effects, and susceptibility to drug resistance. For auto-amplified tumor therapy, a nanoparticle designated GDTF is prepared by wrapping gambogic acid (GA)-loaded dendritic porous silica nanoparticles (DPSNs) with a tannic acid (TA)-Fe(III) coating layer. GDTF possesses the properties of near-infrared (NIR)-enhanced and pH/glutathione (GSH) dual-responsive drug release, photothermal conversion, GSH depletion and hydroxyl radical (·OH) production. When GDTF is exposed to NIR laser irradiation, it can effectively inhibit cell proliferation and tumor growth both in vitro and in vivo with limited toxicity. This may be due to the synergistic effect of enhanced tumor accumulation, and elevated reactive oxygen species (ROS) production, GSH depletion, and TrxR activity reduction. This study highlights the enormous potential of auto-amplified tumor therapy.

Herein, a sandwich electrochemical sensing strategy for aflatoxin b1 (AFB1) detection based on hybrid-nanoengineering was presented. First, Au nanoparticle was doped into zeolitic imidazolate framework-8 (ZIF-8) to form Au@ZIF-8 by in-situ growth method, followed by multi-walled carbon nanotubes (MWCNTs) addition to synthesize MWCNTs/Au@ZIF-8 via self-assembly. The structural “confinement effect” of ZIF-8 afforded a microenvironment for Au nanoparticles and SMCNTs in a certain spatial region, giving MWCNTs/Au@ZIF-8 excellent electrochemical property as the substrate material. In addition, Au-Pt bimetallic nanoparticle, which exhibited excellent stability and catalytic activity was loaded on the hollow cerium oxide (CeO2) to form AuPt@CeO2 nanoparticle through one-step aqueous phase reduction. Owning to its high surface-to-volume ratio, satisfied electron transfer efficiency and biocompatibility, massive toluidine blue (TB) and AFB1 antibody (Ab) could be modified on the AuPt@CeO2 to form AuPt@CeO2-Ab-TB, which acted as signal tag for the ultrasensitive assay of AFB1. The proposed electrochemical sensing system exhibited wide detection range (2 × 10-5 − 20 ng/mL) and low detection limit (2.13 fg/mL), which has been successfully applied to AFB1 determination in four real samples. The hybrid nanoengineering presented in this work is an active attempt to prepare high-performance substrate material and signal tag, which provides a new insight for the development of highly sensitive and specific electrochemical sensing systems.

Bone metastasis is the prevalent form of metastasis in breast cancer, resulting in severe pain, pathological fractures, nerve compression, hypercalcemia, and other complications that significantly impair patients' quality of life. The infiltration and colonization of breast cancer (BC) cells in bone tissue disrupt the delicate balance between osteoblasts and osteoclasts within the bone microenvironment, initiating a vicious cycle of bone metastasis. Once bone metastasis occurs, conventional medical therapy with bone-modifying agents is commonly used to alleviate bone-related complications and improve patients' quality of life. However, the utilization of bone-modifying agents may cause severe drug-related adverse effects. Plant-derived natural products such as terpenoids, alkaloids, coumarins, and phenols have anti-tumor, anti-inflammatory, and anti-angiogenic pharmacological properties with minimal side effects. Certain natural products that exhibit both anti-breast cancer and anti-bone metastasis effects are potential therapeutic agents for breast cancer bone metastasis (BCBM). This article reviewed the effects of plant-derived natural products against BCBM and their mechanisms to provide a reference for the research and development of drugs related to BCBM.

Herbal medicines (HMs) have long played a pivotal role in preventing and treating various human diseases and have been studied widely. However, the complexities present in HM metabolites and their unclear mechanisms of action have posed significant challenges in the modernization of traditional Chinese medicine (TCM). Over the past two decades, mass spectrometry imaging (MSI) has garnered increasing attention as a robust analytical technique that enables the simultaneous execution of qualitative, quantitative, and localization analyses without complex sample pretreatment. With advances in technical solutions, MSI has been extensively applied in the field of HMs. MSI, a label-free ion imaging technique can comprehensively map the spatial distribution of HM metabolites in plant native tissues, thereby facilitating the effective quality control of HMs. Furthermore, the spatial dimension information of small molecule endogenous metabolites within animal tissues provided by MSI can also serve as a supplement to uncover pharmacological and toxicological mechanisms of HMs. In the review, we provide an overview of the three most common MSI techniques. In addition, representative applications in HM are highlighted. Finally, we discuss the current challenges and propose several potential solutions. We hope that the summary of recent findings will contribute to the application of MSI in exploring metabolites and mechanisms of action of HMs.

Abstract Effective diagnosis and therapy for bacterial infections, especially those caused by multidrug-resistant (MDR) species, greatly challenge current antimicrobial stewardship. Monocytes, which can chemotactically migrate from the blood to infection site and elicit a robust infection infiltration, provide a golden opportunity for bacterial theranostics. Here, a nano-Trojan Horse was facilely engineered using mannose-functionalized manganese-eumelanin coordination nanoparticles (denoted as MP-MENP) for precise two-step localization and potent photothermal-immunotherapy of MDR bacterial infection. Taking advantage of the selective recognition between mannose and inflammation-associated monocytes, the MP-MENP could be passively piggybacked to infection site by circulating monocytes, and also actively target infiltrated monocytes that are already accumulated in infection microenvironment. Such dual-pronged targeting enabled an efficient imaging diagnosis of bacterial infection. Upon laser irradiation, the MP-MENP robustly produced local hyperemia to ablate bacteria, both extracellularly and intracellularly. Further combined with photothermal therapy-induced immunogenic cell death and MP-MENP-mediated macrophage reprogramming, the immunosuppressive infection microenvironment was significantly relieved, allowing an enhanced antibacterial immunity. Collectively, the proposed nanotheranostic Trojan Horse, which integrates dual-pronged targeting, precise imaging diagnosis, and high-performance photothermal immunotherapy, promises a new way for complete eradication of MDR bacterial infection.

Abstract Background Escitalopram is selective serotonin reuptake inhibitors (SSRIs) and one of the most commonly prescribed newer antidepressants (ADs) worldwide. We aimed to explore the efficacy, acceptability and tolerability of escitalopram in comparison with other ADs in the acute-phase treatment of major depressive disorder (MDD). Methods Medline/PubMed, EMBASE, the Cochrane Library, CINAHL, and Clinical Trials.gov were searched from inception to July 10, 2023. Trial databases of drug-approving agencies were hand-searched for published, unpublished and ongoing controlled trials. All randomized controlled trials comparing escitalopram against any other antidepressant for patients with MDD. Responders and remitters to treatment were calculated on an intention-to-treat basis. For dichotomous data, risk ratios (RRs) were calculated with 95% confidence intervals (CI). Continuous data were analyzed using standardized mean differences (with 95% CI) using the random effects model. Results A total of 30 studies were included in this meta‑analysis, among which sixteen trials compared escitalopram with another SSRI and 14 compared escitalopram with a newer AD. Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (RR 0.67, 95% CI 0.50—0.87). Escitalopram was also more effective than citalopram in terms of remission (RR 0.53, 95% CI 0.30—0.93). Conclusions Escitalopram was superior to other ADs for the acute phase treatment of MDD in terms of efficacy, acceptability and tolerability. However, no significant difference was found between escitalopram and other ADs in early response or follow-up response to treatment of MDD.

Abstract Background SHARPIN (SHANK‐associated RH domain interactor) is a component of the linear ubiquitination complex that regulates the NF‐κB signaling pathway. To better understand the function of SHARPIN, we sought to establish a novel genetically engineered Syrian hamster with SHARPIN disruption using the CRISPR/Cas9 system. Methods A single‐guide ribonucleic acid targeting exon 1 of SHARPIN gene was designed and constructed. The zygotes generated by cytoplasmic injection of the Cas9/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatal mutants were identified by genotyping. SHARPIN protein expression was detected using Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymic weights were measured, and organ coefficients were calculated. Histopathological examination of the spleen, liver, lung, small intestine, and esophagus was performed independently by a pathologist. The expression of lymphocytic markers and cytokines was evaluated using reverse transcriptase‐quantitative polymerase chain reaction. Results All the offspring harbored germline‐transmitted SHARPIN mutations. Compared with wild‐type hamsters, SHARPIN protein was undetectable in SHARPIN−/− hamsters. Spleen enlargement and splenic coefficient elevation were spotted in SHARPIN−/− hamsters, with the descent of MLNs and thymuses. Further, eosinophil infiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagi were obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless, the expression of CCR3, CCL11, Il4, and Il13 was upregulated in the esophagi. The expression of NF‐κB and phosphorylation of NF‐κB and IκB protein significantly diminished in SHARPIN−/− animals. Conclusions A novel SHARPIN KO hamster was successfully established using the CRISPR/Cas9 system. Abnormal development of secondary lymphoid organs and eosinophil infiltration in multiple organs reveal its potential in delineating SHARPIN function and chronic inflammation.

Background and aims: Momordica charantia L. (M. charantia) has been traditionally utilized as a medicinal intervention for managing type 2 diabetes mellitus (T2DM). The current study was designed to offer a GRADE-assessed systematic review and meta-analysis of randomized controlled trials (RCTs) examining the impact of M. Charantia intake on glycemic indexes and the lipid profile of patients with T2DM. Methods: A comprehensive search was conducted across several databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, from the inception of each database until April 22, 2023. The Hartung-Knapp adjustment was applied to ensure conservative summary estimates with broad confidence intervals. Results: A total of eight trials involving 423 patients with T2DM were included in this study. Compared to the control group, the intake of M. charantia supplementation resulted in significant reductions in fasting blood glucose (FBG) (WMD: −0.85 mmol/L; 95%CI: −1.44, −0.26; p = 0.005; I2 = 73.4 %), postprandial glucose (PPG) (WMD: −2.28 mmol/L; 95%CI: −3.35, −1.21; p = 0.000; I2 = 66.9 %), glycosylated hemoglobin A1c (HbA1c) (WMD: −0.38 %; 95%CI: −0.53, −0.23; p = 0.000; I2 = 37.6 %), and total cholesterol (TC) (WMD: −0.38 mmol/L; 95%CI: −0.70, −0.07; p = 0.017; I2 = 63.6 %). These results remained statistically significant even after applying the Hartung-Knapp adjustment. However, no significant differences were observed in terms of triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Conclusions: The findings of this study suggest that M. charantia could serve as a potential alternative for individuals with T2DM, particularly those with elevated total cholesterol levels. However, further high-quality studies are necessary to validate these results.

Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.

Objective: To systematically evaluate the efficacy and safety of topical application of botanical (TAB) adjuvants in the treatment of melasma and provide evidence-based medical evidence for their clinical application. Methods: Medline, Web of Science, EMBASE, Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, databases were searched to identify all randomized controlled clinical trials on TAB adjuvant treatment for melasma from inception to May 2023. The primary outcomes included clinical efficacy, adverse effects, recurrence rate, and melanin index. Subgroup analyses were performed using the Melasma Area Severity Index (MASI) scores. Results: This study included 16 randomized trials with 1386 participants. Eligible trials demonstrated that topical phytomedicine adjuvant treatment for melasma increased clinical effectiveness (RR = 1.14, 95% CI (1.10, 1.19), P ＜0.00001), decreased recurrence rate (RR = 0.28, 95% CI (0.13, 0.59), P = 0.0009), and decreased melanin index (MI) (MD = −22.2,95% CI (−31.79, −12.61), P

Perilla frutescens (PF) leaf is a traditional Chinese medicine and food with beneficial effects on allergic asthma. We sought to elucidate the active compounds, the targets, and underlying mechanisms of PF leaf in the treatment of allergic asthma by using experimental pharmacology and network pharmacology. An OVA-allergic asthma murine model was constructed to evaluate the effect of PF leaf on allergic asthma. And the network pharmacology and western blotting were performed to evaluate its underlying mechanisms in allergic asthma. PF leaf treatment significantly improved the lung function of OVA model mice and mitigated lung injury by significantly reducing of OVA-specific immunoglobulin E in serum, and interleukin 4, interleukin 5 and tumor necrosis factor alpha in the bronchoalveolar lavage fluid. 50 core targets were screened based on 8 compounds (determined by high performance liquid chromatography) through compound-target- disease network. Furthermore, MAPK signaling pathway was identified as the pathway mediated by PF leaf with the most potential against allergic asthma. And the WB results showed that PF leaf could down-regulate the expression of p-ERK, p-JNK and p-p38, which was highly consistent with the predicted targets and pathway network. In conclusion, this study provides the evidence to support the molecular mechanisms of PF leaf on the treatment of allergic asthma using network pharmacology and in vivo experiments.

BackgroundGut microbiota influence food allergy. We showed that the natural compound berberine reduces IgE and others reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function.ObjectiveWe sought to evaluate an oral Berberine-containing natural medicine with a boiled peanut oral immunotherapy (BNP) regimen as a treatment for food allergy using a murine model and to explore the correlation of treatment-induced changes in gut microbiota with therapeutic outcomes.MethodsPeanut-allergic (PA) mice, orally sensitized with roasted peanut and cholera toxin, received oral BNP or control treatments. PA mice received periodic post-therapy roasted peanut exposures. Anaphylaxis was assessed by visualization of symptoms and measurement of body temperature. Histamine and serum peanut-specific IgE levels were measured by ELISA. Splenic IgE+B cells were assessed by flow cytometry. Fecal pellets were used for sequencing of bacterial 16S rDNA by Illumina MiSeq. Sequencing data were analyzed using built-in analysis platforms.ResultsBNP treatment regimen induced long-term tolerance to peanut accompanied by profound and sustained reduction of IgE, symptom scores, plasma histamine, body temperature, and number of IgE+ B cells (p

GoalsTo assess the efficacy and safety of Chinese Medicine Prescription “W-LHIT” in subjects with simple obesity, and to explore its potential mechanism of action.MethodsThirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the “W-LHIT” capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding.Results72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment.ConclusionW-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.

IntroductionFood allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential as a food allergy treatment, we further developed a purified version named EBF-2 and identified active compounds. We investigated the mechanisms of EBF-2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production.MethodsIgE plasma cell line U266 cells were cultured with EBF-2 and FAHF-2, and their effects on IgE production were compared. EBF-2 was evaluated in a murine PN allergy model for its effect on PN-specific IgE production, number of IgE+ plasma cells, and PN anaphylaxis. Effects of berberine on IgE production, the expression of transcription factors, and mitochondrial glucose metabolism in U266 cells were evaluated.ResultsEBF-2 dose-dependently suppressed IgE production and was over 16 times more potent than FAHF-2 in IgE suppression in U266 cells. EBF-2 significantly suppressed PN-specific IgE production (70%, p

Objective. Dysregulation of epithelial-mesenchymal transition (EMT) in the airway epithelium is associated with airway remodeling and the progression of pulmonary fibrosis. Many treatments have been shown to inhibit airway remodeling and pulmonary fibrosis progression in asthma and chronic obstructive pulmonary disease (COPD) by regulating EMT and have few side effects. This review aimed to describe the development of airway remodeling through the EMT pathway, as well as the potential therapeutic targets in these pathways. Furthermore, this study aimed to review the current research on drugs to treat airway remodeling and their effects on the EMT pathway. Findings. The dysregulation of EMT was associated with airway remodeling in various respiratory diseases. The cytokines released during inflammation may induce EMT and subsequent airway remodeling. Various drugs, including herbal formulations, specific herbal compounds, cytokines, amino acid or protein inhibitors, microRNAs, and vitamins, may suppress airway remodeling by inhibiting EMT-related pathways.

Liposome is a conventional drug delivery system which has been widely used in the pharmacy field. However, its applications are greatly restricted in clinical practice by the disadvantages of cholesterol and nonselective distribution. Herein, a novel platform for anti-tumor drug delivery was developed by incorporating an amphiphilic stachydrine-octadecane conjugate (SS) as the mitochondria-targeting molecule onto the triptolide-liposome surfaces (SS-TP LPs). The polyethylene glycol (PEG) and the suitable particle size (about 133 nm) of liposomes facilitated their stabilities, the long half-life in blood and the escape from the rapid elimination. The SS-TP LPs were internalized and accumulated into the mitochondria of cancer cells in a time-dependent manner, followed by triggering permeabilization of the mitochondrial outer membrane by inhibiting Bcl-2, and then further caused greater cancer cell death via releasing cytochrome C and initiating a cascade of caspase 3 reactions. In the Pan02 tumor-bearing mice, the SS-TP LPs showed significant efficacy in inhibiting tumor growth and reducing tumor size but synchronously exhibited specific mitochondria-targeting and much lower subacute toxicity compared with the free TP and TP LPs. Our study suggests that SS-TP LPs can be a promising anticancer drug delivery system for mitochondria-targeted therapy in pancreatic cancer.

Objective: To observe the effect of Wuweizi syrup on brain aging mice model induced by d-galactose in mice. Methods: 72 mice were randomly divided into blank group, model group, naokangling group and low, middle and high dose Wuweizi syrup group. After 3 days of adaptive feeding, except for the blank group, the rest mice were subcutaneously (sc) injected with d-galactose 1.25 g/kg at neck back to replicate the aging model. Sc injection was given for 40 consecutive days, and corresponding drugs were given by gavage on the 11th day of modeling. On the 39th day, the dark experiment was carried out to measure the learning ability of mice. After the last administration for 2 h, brain, liver, thymus and spleen were taken and weighed to calculate the organ index. Blood was taken and CAT, GSH and SOD levels in whole blood were determined. Some brain and liver tissues were taken to prepare homogenates, and MDA levels in tissue homogenates and plasma were measured. Brain, liver, thymus and spleen were stained with HE, and pathological sections were made for observation under light microscope. Results: Compared with the blank group, in the model group, the incubation period of mice was significantly reduced and the number of shuttle back and forth was significantly increased (P

The heating area of the material is large and the thermal efficiency is high, but it is necessary to control the suitable drying temperature of different medicinal materials to preserve the effective ingredients. Different kinds of Chinese medicine need different drying conditions to fulfill good drying requirements. Natural drying in the shade is one of the traditional drying methods, which takes a long time and is easily affected by the weather. The water volatilizes slowly. It is prone to mildew and discoloration during the drying process. However, it can better preserve the volatile oil components of Chinese medicine. The hot-air drying machine has lower requirements. The medicinal materials have a large heating area and high thermal efficiency, but it is necessary to control the appropriate drying temperature of different medicinal materials in order to preserve the active ingredients of the medicinal materials; it is not suitable for medicinal materials that stick and bind easily. The microwave drying method possesses superiority in drying some valuable medicinal materials such as Renshen (Radix et Rhizoma Ginseng) and Lurong (Cornu Cervi Pantotrichum), and the effective ingredients are preserved at a high degree; it can also achieve the purpose of killing enzymes and protecting glycosides and have a good bactericidal effect, but it is not suitable for Chinese medicines containing heat-sensitive ingredients, because it will destroy most of the proteins, amino acids, and peptides of Chinese medicine and result in the loss of efficacy. The far-infrared drying method is suitable for drying thin-layer medicinal materials and is friendly to the environment. Freeze-drying can preserve the active ingredients very well and greatly retain the efficacy, but it has obvious limitations in preserving some Chinese medicinal materials that need to kill enzymes and protect glycosides; besides, the cost is relatively high and the drying time is long.

Objectives To find out the association between the sensorineural hearing loss and coronavirus disease 2019 (COVID-19), the expression of ACE2 and TMPRSS2 in hamsters and mice was detected.

Isoliquiritigenin (ILQ) is a natural flavonoid with various pharmacological activities. In this study, we optimized the preparation method of self-nano-emulsion-loaded ILQ to further improve its bioavailability based on our previous study. In addition, its effect on the treatment of eosinophilic esophagitis was also evaluated. Combined surfactants and co-surfactants were screened, and the optimal formulation of ILQ-SNEDDS was determined according to droplet size, droplet dispersity index (DDI), and drug loading. The formulation was composed of ethyl oleate (oil phase), Tween 80 & Cremophor EL (surfactant, 7:3), and PEG 400 & 1,2-propylene glycol (cosurfactant, 1:1), with a mass ratio of 3:6:1. Its physicochemical properties, including drug loading, droplets’ size, Zeta potential, appearance, and Fourier transform infrared (FTIR) spectroscopy, were characterized. In vitro release profile, in situ intestinal absorption, and in vivo pharmacokinetics were applied to confirm the improvement of oral ILQ bioavailability by NEDDS. Finally, the efficacy of ILQ-SNEDDS in the treatment of food allergy-induced eosinophilic esophagitis (EOE) was further evaluated. When the ILQ drug loading was 77.9 mg/g, ILQ-SNEDDS could self-assemble into sub-spherical uniform droplets with an average size of about 33.4 ± 2.46 nm (PDI about 0.10 ± 0.05) and a Zeta potential of approximately −10.05 ± 3.23 mV. In situ intestinal absorption showed that optimized SNEDDS significantly increased the apparent permeability coefficient of ILQ by 1.69 times, and the pharmacokinetic parameters also confirmed that SNEDDS sharply increased the max plasma concentration and bioavailability of ILQ by 3.47 and 2.02 times, respectively. ILQ-SNEDDS also significantly improved the apparent signs, allergic index, hypothermia and body weight of EoE model mice. ILQ-SNEDDS treatment significantly reduced the levels of inflammatory cytokines, such as TNF-α, IL-4, and IL-5, and the level of PPE-s-IgE in serum, and significantly inhibited the expression of TGF-β1 in esophageal tissue. SNEDDS significantly improved the solubility and bioavailability of ILQ. Additionally, ILQ-SNEDDS treatment attenuated symptomatology of EoE model mice, which was associated with inhibiting the production of TH2 inflammatory cytokines and PPE-s-IgE and the expression of TGF-β1. The above results shows that ILQ-SNEDDS has great potential as a good candidate for the treatment of eosinophilic esophagitis.

Airway remodeling is associated with dysregulation of epithelial-mesenchymal transition (EMT) in patients with asthma. Sinomenine (Sin) is an effective, biologically active alkaloid that has been reported to suppress airway remodeling in mice with asthma. However, the molecular mechanisms behind this effect remain unclear. We aimed to explore the potential relationship between Sin and EMT in respiratory epithelial cells in vitro and in vivo. First, 16HBE cells were exposed to 100 μg/mL LPS and treated with 200 μg/mL Sin. Cell proliferation, migration, and wound healing assays were performed to evaluate EMT, and EMT-related markers were detected using Western blotting. Mice with OVA-induced asthma were administered 35 mg/kg or 75 mg/kg Sin. Airway inflammation and remodeling detection experiments were performed, and EMT-related factors and proteins in the TGF-β1 pathway were detected using IHC and Western blotting. We found that Sin suppressed cell migration but not proliferation in LPS-exposed 16HBE cells. Sin also inhibited MMP7, MMP9, and vimentin expression in 16HBE cells and respiratory epithelial cells from mice with asthma. Furthermore, it decreased OVA-specific IgE and IL-4 levels in serum, relieved airway remodeling, attenuated subepithelial collagen deposition, and downregulating TGF-β1and Smad3 expression in mice with asthma. Our results suggest that Sin suppresses EMT by inhibiting IL-4 and downregulating TGF-β1 and Smad3 expression.

Triptolide (TP) is a potential drug candidate for the treatment of cancer, but its use was hampered by its systemic toxicity and poor water solubility. Hence, a TP-CSO prodrug was synthesized by conjugating TP to chitosan oligosaccharide (CSO), and characterized by 1H NMR, FTIR, DSC and XRD analyses. The TP-CSO containing about 4 wt% of TP exhibited excellent water solubility (15 mg/mL) compared to TP (0.017 mg/mL). Compared with TP, the pharmacokinetics of the conjugate after oral administration showed a three-fold increase in the half-life in the blood circulation and a 3.2-fold increase in AUC (0–∞). The orally administered TP-CSO could more effectively inhibit tumor progression but with much lower systemic toxicity compared with TP, indicating significant potential for further clinical trials. In conclusion, CSO-based conjugate systems may be useful as a platform for the oral delivery of other sparingly soluble drugs.

Our purpose is to study the effect of different component ratio of Astragalus Total Saponins (ATS) and Verbena Total Glycosides (VTG) on the cerebral infarction area and the serum biochemical indicators in the focal cerebral ischemia-reperfusion rat model. Compared with the model group, different component ratio of ATS and VTG could significantly improve the neurological deficit scores to the focal cerebral ischemia-reperfusion rat model, and the group of 7:3, 6:4, 5:5 got the best results; it could reduce the mortality of rat model to a certain extent, and the group of 5:5 group got the best results; it can significantly reduce the cerebral infarction area, and the group of 7:3, 5:5, 4:6 got the best results; it could significantly reduce the content of TNF-α, and the group of 8:2, 6:4 got the best results; it could significantly reduce the content of NO, and the group of 7:3, 5:5 got the best results; it could significantly increase the content of SOD, and the group of 6:4, 5:5 got the best results. This indicates that different component ratio of ATS and VTG may protect the damage of focal cerebral ischemia-reperfusion rat model to a certain extent, which are compared using the comprehensive weight method and the ratio of 5:5 was proved to be the optimal active ratio. Keywords: Component ratio, ATS, VTG, Focal cerebral ischemia-reperfusion, The cerebral infarction area, TNF-α, NO, SOD

Objective: The aim of the study was to investigate the protective characteristic of chlorogenic acid, a natural glucosyl xanthone found in Lonicera Japonica on the cerebral ischemia reperfusion injury and the underlying mechanism. Methods: Focal cerebral ischemia reperfusion model was built by blocking the left middle cerebral artery in rats by using the suture-occluded method. Before operation, the corresponding drugs were given for each group once a day for 7 days. After 1 h of final administration, the model was built, after operation, reperfusion was conducted for 22 h, Before the reperfusion 10 min tail vein injection of large, medium and small dose of chlorogenic acid and then mortality was calculated, and Neurological deficit score (NDS) was conducted, and serum was collected to measure the NSE level; a 2 mm thick brain slice located at the intersection of optic nerves was collected for TTC staining, and the percentage of cerebral infarction area was calculated; brain homogenate was collected to measure the ICAM-1, VCAM-1, EPO and HIF-1α levels in brain tissue of cerebral ischemia reperfusion rat models; NGF was detected using immunohistochemical method; the morphological changes in brain tissue was observed with HE staining. Results: All focal cerebral ischemia reperfusion rat models were duplicated successfully. Every chlorogenic acid group with different dosage can significantly reduce the mortality, NDS and cerebral infarction area of rats, and significantly increase the EPO, HIF-1α and NGF levels in brain tissue; significantly improve the pathological lesions of hippocampus and cortex in brain tissue. Conclusion: The results showed that chlorogenic acid could protect the focal cerebral ischemia reperfusion injury rat models by adjusting the inflammatory factor, hypoxia factor and nerve growth factor. Keywords: Chlorogenic acid, Cerebral ischemia reperfusion, Animal model

Aim: The research was to study the effect of Motherwort total alkaloids on the prostate hyperplasia mice model of pathological changes of related tissue morphology. Results: Compared with the model group(MG), Motherwort total alkaloid high, medium dose group(HD, MD) could significantly reduced the pathological changes of the prostate (P

Cistanche is the traditional and precious Chinese herbal, with two thousand years of use history in China. It has the effect on tonifying kidney, strong supplement to the liver and kidney, and replenishing essence and blood, known as the “desert ginseng”. Here, we explored the mechanism of Phenylethanoid Glycosides of Cistanche (PGC) to the model mice of menopausal syndrome, as well as the therapeutic effect and characteristics of PGC to the menopausal syndrome. In this study, KM mice were reproduced by the complete resection of the ovaries on both sides of the back to establish the model mice of menopausal syndrome (MPS), and received distilled water or drugs, respectively. Model mice received distilled water. Mice received 200 mg/(kg day) high doses of Phenylethanoid Glycosides of Cistanche (HPGC), and 100 mg/(kg day) medium doses of Phenylethanoid Glycosides of Cistanche (MPGC), and 50 mg/(kg day) low doses of Phenylethanoid Glycosides of Cistanche (LPGC). After 21 days, it could determine the number of independent activities and the number of standing, the latent period of first entering the dark room, and the electric number. It also calculated the viscera index of uterus, thymus, spleen, measured the levels of estradiol (E2), testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the serum. Furthermore, it observed the pathological changes of uterus, thymus, spleen and pituitary of mice. The results showed that behavioral indicators: Compared with the model group (MG), HPGC, MPGC, LPGC could increase the independent activities (P

The effect of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats was observed. The model group, nimodipine group, cerebral collateral group, and large, medium and small dose group of the Rabdosia rubescens total flavonoids were administered with corresponding drugs but sham operation group and model group were administered the same volume of 0.5%CMC, 1 times a day, continuous administration of 7 d. After 1 h at 7 d to medicine, left incision in the middle of the neck of rats after anesthesia, we can firstly expose and isolate the left common carotid artery (CCA), and then expose external carotid artery (ECA) and internal carotid artery (ICA). The common carotid artery and the external carotid artery are ligated. Then internal carotid artery with arterial clamp is temporarily clipped. Besides, cut the incision of 0.2 mm from 5 cm of the bifurcation of the common carotid artery. A thread Line bolt is inserted with more than 18–20 mm from bifurcation of CCA into the internal carotid artery until there is resistance. Then the entrance of the middle cerebral artery is blocked and internal carotid artery is ligated (the blank group only exposed the left blood vessel without Plugging wire). Finally it is gently pulled out the plug line after 2 h. Results: Compared with the model mice, Rabdosia rubescens total flavonoids can significantly relieve the injury of brain in hippocampus and cortex nerve cells; experimental rat focal cerebral ischemia was to improve again perfusion model of nerve function defect score mortality; significantly reduce brain homogenate NOS activity and no content, MDA, IL-1, TNF-a, ICAM-1 content; increase in brain homogenate SOD and ATPase activity (P

This paper aims to study the effects of different proportion of astragaloside and curcumin on STZ induced Diabetes Mellitus (DM) model of mice, and to select a better proportion of active components. Its ultimate purpose is to lay a basis for the follow-up research on astragaloside-curcumin capsule. Increase-decrease baseline geometric proportion design method and comprehensive performance evaluation utilised to study the effect of different proportion of astragaloside and curcumin on DM mice models, which have an intravenous tail injection of STZ. The proportions of the two components are 10:0, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 0:10 respectively. And we will screen out the optimal composition. Blood glycated serum protein (GSP), hepatic glycogen and insulin tested to observe pathological changes in the pancreas. The mice DM model was copied successfully. Compared with the model group, groups treated with the metformin and with different proportions of astragaloside and curcumin help lower the blood glucose levels and GSP levels, increase glycogen stores of model mice by different degrees, and avoid pathological changes of pancreas in the model mice. The ratio of 3:7 was selected as the optimal one, based on the comprehensive performance evaluation method, followed by the ratio of 4:6. The optimal proportion of DM models is 3:7, followed by 4:6. The ratio of total astragaloside and curcumin can lower blood glucose levels, GSP levels, promote the formation of glycogen, and improve the pathological changes of pancreas in the model mice. Keywords: Astragaloside, Curcumin, Baseline geometric proportion design method, STZ

Through the study of the effect of different ratio of Astragalus Total Saponins (ATS) and curcumin on Diabetes Mellitu (DM) model rats, we want to improve the screening model of the distribution ratio in Chinese Medicine, screening out the optimal proportion of the prevention and control of DM. By injecting streptozotocin (STZ) in the tail vein of rats to induct the DM rats model, we measured the dynamic change, insulin and insulin antibody (IAA) levels, glycosylated serum protein (GSP) content, lipid metabolism and the changes of renal pathology in DM model rats. The different distribution ratio of ATS and Curcumin can significantly reduce GSP, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL); significantly increased serum insulin levels and high density lipoprotein (HDL) content, significantly decreased IAA level on the DM rats model induced by STZ. Different proportions of ATS and Curcumin have a good therapeutic effect on DM model rats, and 6:4 is the optimal proportion for the prevention and treatment of DM. Keywords: Astragalus total saponins (ATS), Curcumin, Different proportion, Rats, Diabetes model

Aim: To establish a Friend murine leukemia virus (FLV)-induced immunodeficient BALB/C mouse model and investigate the effects of Fuzheng Paidu tablets on the body weight, thymus, spleen, and CD4+ and CD8+ T lymphocytes of FLV-infected mice. FLV was passaged twice in BALB/c mice. The infected mice were divided into six groups of ten mice based on their weights. The groups included the normal control group; virus control group; AZT group; high- (2.8 g/kg), medium- (1.4 g/kg), and low-dose (0.7 g/kg) Fuzheng Paidu tablet groups; and Fuzheng Paidu decoction (10 g/kg) group. The mice were administered Fuzheng Paidu tablets via gavage for 21 days. The body weight and changes in the thymus, spleen, and CD4+ and CD8+ T lymphocytes of each mouse were measured. Results: The splenic weight of the virus control group is significantly higher than that of the normal control group, with significant splenomegaly. In addition, the splenic inhibition indices of the AZT group and the high- and medium-dose Fuzheng Paidu tablet groups were approximately 93.80%, 37.80%, and 28.07%, respectively. Furthermore, the high and medium dose Fuzheng Paidu tablets could increase the thymus weights of the infected mice. Conclusion: Fuzheng Paidu tablets could inhibit splenomegaly, lower the splenic indices, and increase the thymic weights and thymic indices of FLV-induced immunodeficient mice. Keywords: Friend murine leukemia virus, BALB/c mice, AZT

Objective: In this report, the effects of cynomorium flavonoids on mouse model of perimenopausal depression were investigated. Method: 60 ovariectomized female mice were randomly divided into 6 groups evenly: high, medium and low doses of cynomorium flavonoids groups (400 mg kg−1, 200 mg kg−1, 100 mg kg−1), Gengnian’an capsule group (675 mg kg−1), soy isoflavones soft capsule group (250 mg kg−1), and model group. Give the corresponding drug five days after surgery once a day, consecutive thirty days. The model group and control group were given the water of same volume. The model related groups were applied with different stress for consecutive eighteen days. Kill the mice and remove the thymus, spleen, uterus and one hand of brain when it is 2 h after the last administration in mice of each group. Observe the histological changes of each group under light microscope. Results: By observing the pathological section, compared with model group, the pathological changes of the uterus and hypothalamus of mice were significantly improved. The thymic cortex markedly thickened, volume of splenic nodule also significantly increased, and the number of lymphocytes significantly increased (p

Three co-formers of 2-chloro-4-nitroaniline (CNA), 2,5-dihydroxybenzoic acid (DHB), and 4,4′-biphenol (DOD) were selected to prepare the co-crystal of progesterone (PROG) based on crystal engineering strategies. These co-crystals were successfully obtained via slow evaporation from different solutions and were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, and differential scanning calorimetry. Different binding networks were observed in the co-crystal structures of PROG. The PROG-CNA co-crystal had the fastest rates and highest concentrations of PROG in PBS solution compared with PROG or other co-crystals in the dissolution experiments. This might be attributable to more stable and abundant interactions between the PROG and CNA molecules. Our investigations provide positive support for the selection of suitable co-formers using crystal engineering strategies.

Ischemic stroke (IS) is the predominant form of stroke pathology, and its clinical management remains constrained by therapeutic time frame. The gut microbiota (GM), comprising a multitude of bacterial and archaeal cells, surpasses the human cell count by approximately tenfold and significantly contributes to the human organism's growth, development, and overall well-being. The microbiota-gut-brain axis (MGBA) in recent years has established a strong association between gut microbes and the brain, demonstrating their intricate involvement in the progression of IS. The regulation of IS by the GM, encompassing changes in composition, abundance, and distribution, is multifaceted, involving neurological, endocrine, immunological, and metabolic mechanisms. This comprehensive understanding offers novel insights into the therapeutic approaches for IS. The objective of this paper is to examine the mechanisms of interaction between the GM and IS in recent years, assess the therapeutic effects of the GM on IS through various interventions, such as dietary modifications, probiotics, fecal microbiota transplantation, and antibiotics, and offer insights into the potential clinical application of the GM in stroke treatment. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota influence food allergy. We showed that the natural compound berberine reduces IgE and others reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function. Objective: We sought to evaluate an oral Berberine-containing natural medicine with a boiled peanut oral immunotherapy (BNP) regimen as a treatment for food allergy using a murine model and to explore the correlation of treatmentinduced changes in gut microbiota with therapeutic outcomes. Methods: Peanut-allergic (PA) mice, orally sensitized with roasted peanut and cholera toxin, received oral BNP or control treatments. PA mice received periodic post-therapy roasted peanut exposures. Anaphylaxis was assessed by visualization of symptoms and measurement of body temperature. Histamine and serum peanut-specific IgE levels were measured by ELISA. Splenic IgE+B cells were assessed by flow cytometry. Fecal pellets were used for sequencing of bacterial 16S rDNA by Illumina MiSeq. Sequencing data were analyzed using built-in analysis platforms. Results: BNP treatment regimen induced long-term tolerance to peanut accompanied by profound and sustained reduction of IgE, symptom scores, plasma histamine, body temperature, and number of IgE+ B cells (p <0.001 vs Sham for all). Significant differences were observed for Firmicutes/ Bacteroidetes ratio across treatment groups. Bacterial genera positively correlated with post-challenge histamine and PN-IgE included Lachnospiraceae, Ruminococcaceae, and Hydrogenanaerobacterium (all Firmicutes) while Verrucromicrobiacea. Caproiciproducens, Enterobacteriaceae, and Bacteroidales were negatively correlated. Conclusions: BNP is a promising regimen for food allergy treatment and its benefits in a murine model are associated with a distinct microbiota signature. [ABSTRACT FROM AUTHOR]