Multimodal phototherapy agents target lipid droplets for near-infrared imaging-guided type I photodynamic/photothermal therapy.

The construction and optimization of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) functions remain challenging. In this study, we aimed to design and synthesize four donor-acceptor (D-A) type aggregation-induced emission molecules: PSI, TPSI, PSSI, and TPSSI. We employed phenothiazine as an electron donor and 1,3-bis(dicyanomethylidene)indan as a strong electron acceptor in the synthesis process. Among them, TPSSI exhibited efficient type I reactive oxygen species generation, high photothermal conversion efficiency (45.44 %), and near-infrared emission. These observations can be attributed to the introduction of a triphenylamine electron donor group and a thiophene unit, which resulted in increased D-A strengths, a reduced singlet-triplet energy gap, and increased free intramolecular motion. TPSSI was loaded into bovine serum albumin to prepare biocompatible TPSSI nanoparticles (NPs). Our results have indicated that TPSSI NPs can target lipid droplets with negligible dark toxicity and can efficiently generate O2•- in hypoxic tumor environments. Moreover, TPSSI NPs selectively targeted 4T1 tumor tissues and exhibited a good PDT-PTT synergistic effect in vitro and in vivo. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technologies. STATEMENT OF SIGNIFICANCE: The construction of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy, and photothermal therapy functions, and its optimization remain challenging. In this study, we construct four donor-acceptor aggregation-induced emission molecules using phenothiazine as an electron donor and 1,3-Bis(dicyanomethylidene)indan as a strong electron acceptor. By optimizing the molecular structure, an integrated phototherapy agent with fluorescence imaging ability and high photodynamic / photothermal therapy performance was prepared. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technology.

Effect of acupuncture therapy for postoperative gastrointestinal dysfunction in gastric and colorectal cancers: an umbrella review.

Background: Gastrointestinal dysfunction is a prevalent postoperative complication in patients undergoing surgery for gastric cancer and colorectal cancer. Acupuncture holds promise as a great potential therapeutic intervention. The efficacy of acupuncture therapy for postoperative gastrointestinal dysfunction has been assessed in some studies, however, the variability in results and study quality influences practical clinical application. Therefore, it is necessary to summarize and analyze the published clinical research data in this field. Objective: This study aimed to synthesize evidence from systematic reviews and meta-analyses in order to assess the efficacy of acupuncture therapy for postoperative gastrointestinal dysfunction in patients with gastric and colorectal cancer. Design: Umbrella review of systematic reviews and meta-analyses. Methods: We searched China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), China Science and Technology Journal Database (VIP), Chinese biomedical literature service system (SinoMed), PubMed, Embase, Cochrane Library, and Web of Science for all systematic review/meta-analysis of acupuncture for postoperative gastrointestinal dysfunction in gastric and colorectal cancers. From the establishment of the database to July 8, 2023. Two independent reviewers conducted literature extraction and evaluation. The quality of included studies was assessed using The preferred reporting items for systematic reviews and meta-analysis statements 2020 (PRISMA2020), the quality of the methods was assessed using a measuring tool to assess systematic reviews 2 (AMSTAR 2), and the level of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE). The statistical analysis was conducted using RevMan 5.4, and the effect size was expressed as Odds Ratio (OR), Mean Difference (MD), and 95% confidence interval (CI) based on the extracted data type (test level α= 0.05). The heterogeneity was assessed using the I 2 statistic and Q-test (χ2). The outcome indicators such as time to first defecation and time to first flatus were utilized as endpoints to assess the efficacy of different acupuncture therapies. Results: A total of six systematic reviews/meta-analyses were included in this study, involving 12 different acupuncture therapies. PRISMA 2020 indicated that the studies all scored between 13-20.5. There were deficiencies in protocol and registration, assessment of the quality of evidence for outcome indicators, risk of bias, and declaration of conflict of interest. The AMSTAR 2 evaluations showed that five studies were very low quality and one was low quality. The level of evidence for various acupuncture interventions varied from very low to moderate.For patients with gastrointestinal dysfunction after gastric cancer surgery, ear acupressure [MD=-11.92, 95% (-14.39,-9.44), P<0.00001], moxibustion [MD=-19.16, 95% (-23.00,-16.22), P<0.00001], warm needling [MD=-12.81, 95% (-17.61,-8.01), P<0.00001], acupoint application [MD=-6.40, 95% (-10.26,-2.54), P=0.001], manual acupuncture [MD=-18.32, 95% (-26.31,-10.39), P<0.00001] and transcutaneous electrical acupoint stimulation (TEAS) [MD=-5.17, 95% (-9.59,-0.74), P=0.02] could promote the recovery of gastrointestinal function after surgery.For postoperative colorectal cancer patients, electroacupuncture [MD=-15.17, 95% (-28.81,-1.54), P<0.05], manual acupuncture [MD=-20.51, 95% (-39.19,-1.84), P<0.05], warm needling [MD=-18.55, 95% (-23.86,-13.24), P<0.05], ear acupressure [MD=-5.38, 95% (-9.80,-0.97), P<0.05], acupoint application [MD=-26.30, 95% (-32.81,-19.79), P<0.05], ear acupressure+acupressure [MD=-9.67, 95% (-13.58,-5.76), P<0.05], ear acupressure+manual acupuncture [MD=-18.70, 95% (-21.01,-16.39), P<0.05], ear acupressure+moxibustion [MD=-22.90, 95% (-30.10,-15.70), P<0.05], moxibustion+acupressure [MD=-14.77, 95% (-20.59,-8.95), P<0.05] improved postoperative gastrointestinal function. In addition, the efficacy of acupressure [MD=-12.00, 95% (-31.60,7.60), P>0.05] needed to be further demonstrated. Conclusion: Acupuncture therapy has a positive therapeutic impact on postoperative gastrointestinal dysfunction in gastric and colorectal cancers, but this finding should still be taken with caution.

Molecular Mechanism of the Asarum-Angelica Drug Pair in the Treatment of Periodontitis Based on Network Pharmacology and Experimental Verification.

(1) To examine the potential mechanism of the Asarum-Angelica drug pair against periodontitis and provide an experimental basis for the treatment of periodontitis with herbal medicine. (2) The core components and core targets of the Asarum-Angelica drug pair in the treatment of periodontitis were detected according to network pharmacology methods. Finally, the effect of the Asarum-Angelica drug pair on osteogenic differentiation was observed in mouse embryonic osteoblast precursor cells. (3) According to the results of network pharmacology, there are 10 potential active ingredients in the Asarum-Angelica drug pair, and 44 potential targets were obtained by mapping the targets with periodontitis treatment. Ten potential active ingredients, such as kaempferol and ß-sitosterol, may play a role in treating periodontitis. Cell experiments showed that the Asarum-Angelica drug pair can effectively promote the expression of osteoblast markers alkaline phosphatase (ALP), Runt-related Transcription Factor 2 (RUNX2), and BCL2 mRNA and protein in an inflammatory environment (p < 0.05). (4) Network pharmacology effectively analyzed the molecular mechanism of Asarum-Angelica in the treatment of periodontitis, and the Asarum-Angelica drug pair can promote the differentiation of osteoblasts.

Target-Guided Isolation and Purification of Antioxidants from Urtica laetevirens Maxim. by HSCCC Combined with Online DPPH-HPLC Analysis.

Urtica laetevirens Maxim. is used extensively in traditional Chinese medicine (TCM) for its potent antioxidative properties. In this study, three antioxidants were purified from U. laetevirens. using HSCCC guided by online DPPH-HPLC analysis. Firstly, the online DPPH-HPLC analysis was performed to profile out the antioxidant active molecules in U. laetevirens. The ultrasonic-assisted extraction conditions were optimized by response surface methodology and the results showed the targeted antioxidant active molecules could be well enriched under the optimized extraction conditions. Then, the antioxidant active molecules were separated by high-speed countercurrent chromatography ethyl acetate/n-butanol/water (2:3:5, v/v/v) as the solvent system. Finally, the three targets including 16.8 mg of Isovitexin, 9.8 mg of Isoorientin, and 26.7 mg of Apigenin-6,8-di-C-ß-d-glucopyranoside were obtained from 100 mg of sample. Their structures were identified by 1H NMR spectroscopy.

Yiqi Yangjing recipe stimulates apoptosis while suppressing the energy metabolism via under-expression of PFKFB3 in A549 cells.

Background: Lung cancer is a malignant tumor associated with high morbidity and mortality. Yiqi Yangjing recipe (YYR) is a formula of traditional Chinese medicine (TCM) that is commonly used for the treatment of lung cancer with good clinical efficacy. The specific anti-cancer mechanism of YYR is still unknown. We need to embark on a more in-depth pharmacological study of YYR to determine the complex compound ingredients, which could be promoted in clinical practice to achieve efficacy in prolonging recurrent metastasis of lung cancer. Methods: The cytotoxic effects of YYR on A549 cells were evaluated by Cell Counting Kit-8 (CCK-8) assay. The PFKFB3-under-expressed and overexpressed A549 cell lines were constructed via PFK15 treatment and transfection, respectively. The effects of YYR on PFKFB3 messenger RNA (mRNA) and protein expression were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. The pro-apoptotic and anti-glycolytic abilities of YYR were measured using flow cytometry assay and hippocampal XF96 extracellular flux analyzer. An in vivo tumorigenicity assay was performed on nude mice to confirm the anti-cancer effects of YYR. Results: YYR has a noticeable cytotoxic activity on A549 cells, with the treatment with both YYR and PFK15 significantly inducing apoptosis. YYR and PFK15 treatment reduced the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in A549 cells. Similar to PFK15, YYR can down-regulate PFKFB3 expression, and PFKFB3 overexpression suppressed the apoptosis, which was reversed by YYR. Animal experiments confirmed that YYR was able to inhibit tumor growth, induce tumor cell apoptosis, and down-regulate PFKFB3 in tumor tissues. Conclusions: This study demonstrated that YYR promoted lung cancer cell apoptosis and inhibited energy metabolism by targeting PFKFB3. Furthermore, we believe that YYR may be a suitable supplement or alternative drug for lung cancer treatment.

Integrating Chinese Herbal Medicine into Conventional Care Was Related to Lower Risk of Sarcopenia Among Rheumatid Arthritis Patients: A Retrospective, Population-Based Study.

Objective: Sarcopenia is a frequently observed comorbidity of rheumatoid arthritis (RA) due to the chronic activation of the innate immune system. Accumulating evidence has indicated that Chinese herbal medicine (CHM) safely suppresses proinflammatory pathways and controls inflammation-associated disease, but its effect in reducing the risk of developing sarcopenia among RA subjects has not been established. We conducted a population-level cohort study to compare the sarcopenia risk in patients with RA who use or do not use CHM. Methods: Using claims from a nationwide insurance database, we recruited patients with newly diagnosed RA and without sarcopenia between 2002 and 2010. Propensity score matching was applied to randomly select sets of CHM users and non-CHM users to compare the sarcopenia risk until the end of 2013. The risk of new-onset sarcopenia was assessed using the Cox proportional hazards model. Results: As compared to non-CHM users, those receiving CHM treatment had a lower incidence of sarcopenia (7.69 vs 9.83 per 1000 person-years). CHM was correlated with a decreased chance of sarcopenia after controlling for potential covariates. Notably, use of CHM for more than two years may diminish the risk of getting sarcopenia by about 47% when taken as prescribed. Prescriptions of several herbal formulae may benefit the reduction of sarcopenia risk, such as Yan-Hu-Suo, Bei-Mu, Da-Huang, Huang Qin, Ping-Wei-San (PWS), Shu-Jing-Huo-Xue-Tang (SJHXT) and Chuan-Xiong-Cha-Tiao-San (CXCTS). Conclusion: This study produced new evidence as it is the first to show that the longer duration of CHM use was correlated to reduced risk of sarcopenia in a dose-dependent manner, implying that CHM treatment could be embraced as a routine care strategy for preventing sarcopenia.

Use of Chinese Herbal Medicine Was Related to Lower Risk of Osteoporotic Fracture in Sarcopenia Patients: Evidence from Population-Based Health Claims.

Introduction: With population aging, sarcopenia and its accompanying risk of osteoporotic fracture has drawn increased attention. Nowadays, while Chinese herbal medicine (CHM) is often used as complementary therapy for many medical conditions, its effect against likelihood of osteoporotic fracture among sarcopenia subjects was not fully elucidated yet. We therefore conducted a population-level study to compare osteoporotic fracture risk for sarcopenia persons with or without CHM use. Methods: Using the patient record from a nationwide insurance database, we recruited persons with newly diagnosed sarcopenia and simultaneously free of osteoporotic fracture between 2000 and 2010. Propensity score matching was then applied to randomly select sets of CHM users and non-CHM users. All of them were tracked until end of 2013 to measure the incidence and adjusted hazard ratios (HRs) for new new-onset fracture in multivariable Cox proportional hazards model. Results: Compared to non-CHM users, the CHM users indeed had a lower incidence of osteoporotic fracture (121.22 vs 156.61 per 1000 person-years). Use of CHM correlated significantly with a lower fracture likelihood after adjusting for potential covariates, and those receiving CHM treatment for more than two years experienced a remarkably lower risk by 73%. Uses of several herbal formulae were correlated to reduced risk of osteoporotic fracture, such as Caulis Spatholobi, Xuduan, Duzhong, Danshen, Shu-Jing-Huo-Xue-Tang, Du-Huo-Ji-Sheng-Tang, Shao-Yao-Gan-Cao-Tang, and Shen-Tong-Zhu-Yu -Tang. Conclusion: Our study depicted that cumulative CHM exposure was inversely associated with osteoporotic fracture risk in a duration-dependent manner, implying that CHM treatment may be embraced as routine care in preventing incident osteoporotic fracture.

Effects of Mindfulness-Based Elder Care (MBEC) on symptoms of depression and anxiety and spiritual well-being of institutionalized seniors with disabilities: a randomized controlled trial.

BACKGROUND: Despite the need to incorporate seniors from various settings into mindfulness-based empirical research, issues of geriatric frailties and non-compliance remain. This study aimed to evaluate the effects of a mindfulness-based elder care (MBEC) program on mental health and spiritual well-being among seniors with disabilities in long-term care residential settings. METHODS: This single-blind, randomized controlled trial (RCT) randomly assigned seventy-seven participants into an MBEC group or control group of an eight-week MBEC program. Participants were assessed every four weeks at baseline (T0), mid-intervention (T1), post-intervention (T2) and follow-up (T3) using the Geriatric Depression Scale Short Form (GDS-SF), the State-Trait Anxiety Inventory (STAI) and the Spiritual Well-Being Scale (SWBS), respectively. RESULTS: Linear mixed model (LMM) showed that MBEC participants' mental health improved significantly after completing the intervention; compared with controls, the MBEC group exhibited significantly lower anxiety (state-anxiety at T2; trait-anxiety at T2 and T3) and fewer depressive symptoms. Spiritual well-being was also significantly enhanced compared to that in the control group. CONCLUSIONS: MBEC has positive effects on both mental health and spiritual well-being outcomes among seniors with disabilities. In long-term care facilities, seniors with abilities have the potential to adhere to and engage in activities of a mindfulness-based intervention. This low risk, easily accessible, and effective 8-week program is recommended to be integrated into regular long-term care institutional routines. TRIAL REGISTRATION: This study was registered with Clinical Trial Registry (ClinicalTrials.gov - U.S. National Library of Medicine #NCT05123261. Retrospectively registered on 07/04/2021.). The CONSORT 2010 guidelines were used in this study for properly reporting how the randomized trial was conducted.

Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet.

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS: YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.

Relationship between high dose intake of vitamin B12 and glaucoma: Evidence from NHANES 2005-2008 among United States adults.

Objective: Glaucoma has currently become the second leading cause of blindness in the world. Serum vitamin B12 level has been found to be involved in the development and progression of glaucoma. We performed the present study to confirm this association. Methods: This cross-sectional study included 594 participants aged 40 years and older in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. Retinal imaging was performed using the Ophthalmic Digital Imaging system (Retinography) to assess the retina for the presence of features of glaucomatous lesions. Logistic regression models were used to assess the association between dietary vitamin intake and glaucoma. Results: After screening, 594 subjects were finally included. Among all vitamin intakes, we observed significant differences between the two groups for vitamin B12 intake (5.93 vs. 4.77 mg, p = 0.033). According to the logistic regression results, the intake of vitamin B12 was significantly positively associated with glaucoma (model 1: OR = 1.078, 95% CI = 1.019-1.141; model 2: OR = 1.092, 95% CI = 1.031-1.158; model 3: OR = 1.092, 95% CI = 1.029-1.158). After performing a quantile regression, we observed a significant positive association between vitamin B12 intake and incident glaucoma in the fourth quartile (model 1: OR = 1.133, 95% CI = 1.060-1.210; model 2: OR = 1.141, 95% CI = 1.072-1.215; model 3: OR = 1.146, 95% CI = 1.071-1.226). Conclusions: Therefore, the above results, high-dose intake of vitamin B12 may promote the development of glaucoma.

Renal-clearable porous hollow copper iron oxide nanoparticles for trimodal chemodynamic-photothermal-chemo anti-tumor therapy.

Multifunctional nanoplatforms with the synergistic effects of multiple therapeutic modalities have become a research focus due to their superior anti-tumor properties over single therapeutic modalities. Herein, we developed around 14 nm porous hollow copper iron oxide nanoparticles (PHCuFeNPs) with pore sizes of around 2-3 nm as a cisplatin carrier and photothermal therapeutic agent. The PHCuFeNPs were synthesized via a galvanic reaction between Cu2S nanoparticles and iron pentacarbonyl (Fe(CO)5) followed by etching in the organic phase to make the pores. They were stable under normal physiological conditions, but the pores were etched in a weak acidic tumor microenvironment, resulting in the controlled release of Cu and Fe ions for enhanced chemodynamic therapy and accelerated cisplatin release for chemotherapy. Under 980 nm laser irradiation, the PHCuFeNPs could effectively heat up to further promote the release process for synergistic therapy. Besides, they were proved to mediate immunogenic cell death to activate the immune system for potential immunotherapy. Together with their ability to degrade into fragments for fast renal metabolism, we believe that these PHCuFeNPs could provide a biocompatible and efficient multi-antitumor therapeutic approach.

Mn3O4@polyaniline nanocomposite with multiple active sites to capture uranium(VI) and iodide: synthesis, performance, and mechanism.

A major challenge for radioactive wastewater treatment and associated environmental remediation is how to simultaneously remove cationic and anionic radionuclides. Herein, a series of Mn3O4@polyaniline (Mn3O4@PANI) nanocomposites were successfully prepared and used to remove U(VI) and I- from aqueous solution, two highly concomitant species in nuclear pollution settings. Batch adsorption experiments reveal that the component Mn3O4 is predominantly responsible for U(VI) removal, but PANI for I-. The nanocomposite with 24.2 wt% Mn3O4 possesses high removal percentages (> 85%) either for U(VI) or I- over a wide pH range, fast removal kinetics, and excellent adsorption selectivity at high concentrations of competing ions. Benefiting from the contributions of the two components and the high adsorption affinities, the nanocomposite achieves the simultaneous removal to coexisting U(VI) and I-, with a maximum adsorption capacity 102.6 mg/g for U(VI) and 126.1 mg/g for I-. X-ray photoelectron spectroscopy (XPS) results reveal that the U(VI) adsorption occurs via coordination bonding with Mn-O, -NH- , and =N- groups in the nanocomposite, whereas I- adsorption proceeds mainly through I anionic species exchange with Cl- and interactions with π-bonds in PANI, as well as the electrostatic attraction onto Mn3O4. Considering the excellent performance and multiple active sites, the Mn3O4@PANI nanocomposite is promising to remove practical radioactive U(VI) and I-.

Exploring the Core Prescription and Underlying Mechanism of Traditional Chinese Medicine in Treating Allergic Rhinitis in Children: A Real- World Study Based on an Illustrious Senior Traditional Chinese Medicine Practitioner.

BACKGROUND: Traditional Chinese medicine (TCM) is widely used to treat allergic rhinitis (AR) in China, especially in children. However, due to the complicated composition rules and unclear underlying mechanisms, effective herbal prescriptions' popularization and application are limited. PURPOSE: This study tried to detect the core prescription of herbs in treating AR in children, reveal its mechanism based on the ingredients' network, and explore the main signaling pathways. METHODS: We screened medical records of children patients with AR who were treated by TCM in DongZhiMen Hospital from Aug 2009 to Jan 2020 and adopted a descriptive analysis method on herbal characteristics. We used association rules to mine core prescriptions and used network pharmacology to establish the ingredient-target-pathway network through online databases and TCMSP, Genecards, KEGG pathway, Excel, R-Studio, and Cytoscape software. RESULTS: The analysis of 1,092 clinical visits highlighted that the principle of formulating prescription was as follows: 'pungent and warm herbs were used more frequently while cold-natured herbs were paid equal attention as warm-natured herbs.' The core prescription was formed by FangFeng, BaiZhi, CangErzi, and ChanTui. These herbs covered 130 underlying targets and 141 signaling pathways of AR, which mainly had an effect on signal transduction and immunoregulation. CONCLUSION: The core prescription based on these real-world clinical records includes FangFeng, BaiZhi, CangErzi, and ChanTui. It principally acts on targets of signal transduction pathways and immune pathways.

Er-Xian decoction attenuates ovariectomy-induced osteoporosis by modulating fatty acid metabolism and IGF1/PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Er-Xian decoction (EXD) is a traditional Chinese medicine (TCM) formula used to treat osteoporosis (OP). However, the anti-OP mechanism of EXD has not yet been fully elucidated. AIM OF THE STUDY: The study aimed to verify the anti-OP effect of EXD and to explore its underlying mechanism. METHODS: The anti-OP targets and mechanisms of EXD were predicted by network pharmacological analysis. Then, an ovariectomized (OVX) rat model was established to validate the key anti-OP mechanism of EXD. Firstly, the therapeutic effect of EXD on OP was confirmed using micro-CT bone analysis, pathological observation, and ELISA detection. Secondly, serum metabolites related to key biological processes were detected using an automatic biochemical analyzer and GC-MS. Finally, ELISA, qRT-PCR, and western blot were utilized to further explore the potential key anti-OP pathway of EXD. RESULTS: A total of 159 anti-OP targets of EXD were identified. Functional annotation revealed that OP treatment using EXD was associated with lipid metabolism, fatty acid (FA) metabolism, and PI3K/AKT signaling pathway. Experimental studies confirmed that EXD ameliorated ovariectomy-induced bone loss and bone microstructure deterioration. EXD treatment also upregulated the level of serum estrogen and downregulated the level of OC, PⅠNP, CTX-1, TC, and LDL-C. Besides, principal component analysis (PCA) and heat map of serum FAs distinguished OVX rats from the SHAM and EXD groups. Serum concentrations of important n-3 FAs, including C20:3N3, C20:5N3, and C22:5N3, were significantly increased in the EXD group. The increased stearoyl-CoA desaturase 1 (SCD1) index 1 and index 2 in the OVX group were reversed by EXD administration. Additionally, EXD reversed the decreased serum IGF1 level and tibia IGF1R, PI3K, and AKT expression in OVX rats. CONCLUSION: EXD ameliorated ovariectomy-induced bone loss by modulating lipid metabolism, FA metabolism, and IGF1/PI3K/AKT pathway.

Dynamic Evolution of Cardiac Function and Glucose and Lipid Metabolism in Ovariectomized Rats and the Intervention Effect of Erxian Decoction.

Aims: Abnormal changes in cardiac function have been reported in menopausal women, but there are few clinical studies on this topic. Erxian decoction (EXD) is a classic prescription that is widely used in the treatment of female menopausal diseases. The purpose of this study was to investigate the dynamic evolution of cardiac function and glucose and lipid metabolism in ovariectomized (OVX) rats and the intervention effect of EXD. Materials and Methods: The OVX climacteric rat model was established by bilateral ovariectomy. After successful modeling, the rats were randomly divided into four groups: the sham operation (SHAM) group (equal volumes of purified water), OVX group (equal volumes of purified water), estradiol (E2) group (1.8 × 10-4 g/kg), and EXD group (9 g/kg). Each group of rats was treated for 16 weeks. At the 4th, 8th, 12th, and 16th weeks after treatment, the cardiac function of the rats in each group was evaluated by ultrasound. The coaxial method was used to measure blood pressure (BP). Serum endothelin-1 (ET-1) and angiotensin-2 (Ang II) levels were determined by the enzyme-linked immunosorbent assay (ELISA). The strip method was used to measure fasting blood glucose (FBG). The serum total cholesterol (TC) and triglyceride (TG) levels of rats were measured with the oxidase method. Direct methods were used to measure serum high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels. At week 16 of dosing, serum E2 levels were determined by E2 radioimmunoassay. The myocardium and uterus of the rats in each group were stained with HE (hematoxylin-eosin). The ultrastructure of the rat myocardium was observed by electron microscopy. Results: After the 16th week of treatment, the serum E2 level decreased (P < 0.05), and the uterus was atrophied in OVX rats. The cardiac ejection fraction (EF%) decreased at 4 weeks after treatment, and systolic and diastolic function decreased after 12 weeks. After the 16th week, the EF%, which reflects the "pump" function of the heart, decreased significantly (P < 0.05 or P < 0.01). At the 4th, 8th, 12th, and 16th weeks of treatment, the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean pressure (MBP) of the rats in the OVX group increased with time (P < 0.05 or P < 0.01). The serum ET-1 and Ang II levels of rats in the OVX group increased (P < 0.05 or P < 0.01). In the OVX group, FBG was increased (P < 0.05 or P < 0.01), and blood lipids, especially LDL-C, were significantly increased (P < 0.05 or P < 0.01). After the 16th week of treatment, the myocardial tissue of OVX rats showed obvious pathological changes. EXD significantly increased serum E2 levels (P < 0.01), decreased ET-1 and Ang II levels (P < 0.01), reduced the cardiac function risk factors BP, FBG, and blood lipids, and significantly improved cardiac function and structural changes in OVX rats (P < 0.05 or P < 0.01). Conclusions: EXD can improve abnormal cardiac structure and function in OVX rats.

Bufadienolides originated from toad source and their anti-inflammatory activity.

Bufadienolide, an essential member of the C-24 steroid family, is characterized by an α-pyrone positioned at C-17. As the predominantly active constituent in traditional Chinese medicine of Chansu, bufadienolide has been prescribed in the treatment of numerous ailments. It is a specifically potent inhibitor of Na+/K+ ATPase with excellent anti-inflammatory activity. However, the severe side effects triggered by unbiased inhibition of the whole-body cells distributed α1-subtype of Na+/K+ ATPase, restrict its future applicability. Thus, researchers have paved the road for the structural alteration of desirable bufadienolide derivatives with minimal adverse effects via biotransformation. In this review, we give priority to the present evidence for structural diversity, MS fragmentation principles, anti-inflammatory efficacy, and structure modification of bufadienolides derived from toads to offer a scientific foundation for future in-depth investigations and views.

The Prescription of Chinese Herbal Medicine and Risk of Endometriosis in Women with Rheumatoid Arthritis: A Population-Based Cohort Study.

Purpose: The systemic inflammation is believed to provide an outline of the association between rheumatoid arthritis (RA) and endometriosis. This retrospective cohort study aimed to explore the association of Chinese herbal medicine (CHM) use with the prevention of endometriosis onset in women diagnosed with RA. Methods: We utilized the claims data from the National Health Insurance of Taiwan from 2000 to 2009 and excluded individuals diagnosed with endometriosis before being diagnosed with RA, using age at clinical diagnosis. After selection and propensity-score matching, a total of 5992 females aged ≧20 years old and with newly diagnosed RA but without endometriosis at baseline were included, which contained 2996 CHM users and 2996 non-CHM users. All of them were followed until the end of 2013 to measure the incidence of endometriosis. Results: During the study period, we noticed that CHM users had a substantially lower incidence of endometriosis compared to non-CHM users (2.54 vs 5.19 per 1000 person-years). Use of CHM correlated significantly with a lower endometriosis likelihood even after adjusting for potential covariates, with the adjusted hazard ratio of 0.47 (95% confidence interval, 0.35-0.65). A longer duration of CHM use was associated with a reduction in endometriosis risk, especially in those using CHM for more than 730 days. Uses of several herbal products may be associated with a lower risk of endometriosis, like Ge-Gen, Da-Huang, Huang-Qin, Ye-Jiao-Teng, Chuan-Niu-Xi, Shu-Jing-Huo-Xue-Tang, Du-Huo-Ji-Sheng-Tang, Ge-Gen-Tang, Shao-Yao-Gan-Cao-Tang, Ping-Wei-San, Gan-Lu-Yin, and Dang-Gui-Nian-Tong-Tang. Conclusion: Taken together, adding CHM to conventional therapy may reduce the incidence of endometriosis in women with RA. The therapeutic mechanisms and safety of these natural products may be a direction for future clinical studies.

On the Core Prescriptions and Their Mechanisms of Traditional Chinese Medicine in Hepatitis B, Liver Cirrhosis, and Liver Cancer Treatment.

Background: As a frequent cause of death in cancer patients, liver cancer usually occurs in hepatitis B and cirrhosis. In China, Chinese people have been using traditional Chinese medicine (TCM) in treating various chronic liver diseases, which could effectively improve the symptoms and slow down the progression of liver diseases. However, due to the complexity rules of TCM prescription, their action mechanisms are still not clearly understood, which may affect the popularization of effective prescriptions. This study aims to identify the core TCM herbs in the treatment of hepatitis B, liver cirrhosis, and liver cancer so as to clarify the mechanism of action of the core herb networks. Methods: There were 1,673 prescriptions for chronic liver diseases collected in this study, of which 854 were hepatic B prescriptions, 530 were for liver cirrhosis, and 289 were for liver cancer. The basic characteristics of herbal medicine were firstly explained via descriptive analysis, then the core prescriptions of herbal medicine were analyzed through association rule, and finally, the mechanism of core prescriptions was explored with the help of systematic network pharmacology and by applying such databases as TCMIP, HERB, OMIM, GeneCards, KEGG, and software like RStudio and Cytoscape. Results: The rule of the core prescriptions in these cases was characterized by the application of herbs with both cold and warm properties, in which bitter herbs with cold property took priority. Tonifying deficiency, clearing heat, and activating blood circulations to remove stasis were common treatment principles for the three liver diseases. Turmeric Root Tuber (YuJin), White Peony Root (BaiShao), Bupleurum (ChaiHu), Salvia miltiorrhiza (DanShen), and Astragali Radix (HuangQi) were prescribed the most in hepatitis B treatment to invigorate the spleen and soothe the liver. Astragali Radix (HuangQi), Tuckahoe (FuLing), Atractylodis Macrocephalae Rhizoma (BaiZhu), Fructus Polygoni Orientalis (ShuiHongHuaZi), and Curcumae Rhizome (EZhu) were most frequently applied in liver cirrhosis treatment to replenish qi and activate blood. Oldenlandia (BaiHuaSheSheCao), Bearded Scutellaria (BanZhiLian), Curcumae Rhizome (EZhu), and Cardamom (DouKou) were most frequently prescribed to eliminate cancer toxin, invigorate the spleen, and activate blood. These core herbs mainly act through signal transduction and immune system pathways, in which the PI3K-Akt pathway plays a key role. The core prescription for liver cirrhosis regulated more endocrine system pathways than the hepatitis B prescription, and liver cancer prescription regulated more nervous system-related pathways. Conclusion: Three core prescriptions for hepatitis B, liver cirrhosis, and liver cancer treatment were identified, which acted mainly through signal transduction and immune system pathways to regulate immunity and cell growth and participate in inflammation inhibition, in which liver cancer prescription regulated more pathways, especially more nervous system-related pathways than the other two.

Adding Chinese Herbal Medicine to Routine Care is Associated With a Lower Risk of Rheumatoid Arthritis Among Patients With Asthma: A Population-Based Retrospective Cohort Study.

Objective: Due to the shared pathogenesis of asthma and rheumatoid arthritis (RA), patients with asthma were found to have a higher risk of RA. While the benefits and safety of Chinese herbal medicine (CHM) for asthma have been reported, the scientific evidence regarding its effect on RA is limited. This longitudinal cohort study aimed to determine the relation between CHM use and RA risk in patients with asthma. Methods: Using the nationwide claims data, we enrolled 33,963 patients 20-80 years of age who were newly diagnosed with asthma and simultaneously free of RA between 2000 and 2007. From this sample, we utilized propensity score matching to create sets of participants as treatment and control groups, which comprised 13,440 CHM users and 13,440 non-CHM users. The incidence rate and hazard ratio (HR) for RA between the two groups were estimated at the end of 2013. A Cox proportional hazards model was constructed to examine the impact of the CHM use on the risk of RA. Results: The cumulative incidence of RA was substantially lower in the CHM user group. In the follow-up period, 214 patients in the CHM user group (1.92 per 1,000 person-years) and 359 patients in the non-CHM user group (2.92 per 1,000 person-years) developed RA (adjusted HR = 0.63, 95% confidence interval: 0.54-0.75). Of the commonly-prescribed formulae, nine CHM products were associated with a lower RA risk: Xiao-Qing-Long-Tang, Ma-Xing-Gan-Shi-Tang, Ding-Chuan-Tang, Xin-Yi-Qing-Fei-Tang, Bei Mu, Jie Geng, Xing Ren, Da Huang, and San Chi. Conclusion: This study found that patients with asthma who received CHM treatment, in addition to the conventional therapy, had a lower risk of RA. Use of CHM treatment may be integrated into conventional therapy to reduce subsequent RA risk among asthma patients.

Environmentally benign cinchonain IIa from Uncaria laevigata for corrosion inhibition of Q235 steel in HCl corrosive medium: Experimental and theoretical investigation.

Traditional corrosion inhibitors make great contribution to metal protection, but also cause environmental pollution. To solve the problem, plant extracts as green corrosion inhibitors have attracted much attention in recent years. Plants are good raw materials for corrosion inhibitors and also meet the requirements of industry. However, they have not been successfully applied in industry due to the unknown composition of the effective corrosion inhibitors and large dosage thereof. Therefore, cinchonain IIa was separated from Uncaria laevigata with abundant sources and low cost from nature in this work. Here we hypothesized that cinchonain IIa could show good corrosion inhibition performance for Q235 steel in the acidic medium. Through experiments and theoretical calculation, we studied the corrosion inhibition effect of cinchonain IIa on Q235 in 1 M HCl solution at 298 K for 48 h. Electrochemical experiments revealed that the inhibition efficiency of 200 mg/L cinchonain IIa in 1 M HCl for Q235 steel was 94.08% for 48 h. It even showed over 93% corrosion inhibition efficiency and durable protection performance to 28 d. Surface observations indicated that cinchonain IIa were firmly attached to the steel surface by forming a protective film. Moreover, quantum chemical calculation and molecular dynamics simulation revealed the inhibition mechanism at molecular and atomic level. Compared with some plant extracts, here we demonstrate that the outstanding advantages of cinchonain IIa include sustained protective effect, small dosage, and low toxicity. Accordingly, it may be used as a green industrial corrosion inhibitor with great potential in oilfield acidification and acid pickling.