Strategy to prevent calcification by restricting surface adhesion of Ca2+: Reduced affinity of extracellular polymeric substances for Ca2+ by mild acidic conditions.

Controlling CaCO3 precipitation within anaerobic granular sludge (AnGS) is crucial for the anaerobic treatment of paper recycling wastewater. A viable strategy was proposed to control calcification by adjusting a mild acidic condition in an anaerobic reactor without hindering organic degradation. The results indicated that lowering the bulk pH (6.5 to 6.8) reduced calcium precipitation by 60.1 % in calcium-rich influent (Ca2+ 1200 mg/L) and eradicated CaCO3 deposition on AnGS. Extracellular polymeric substances (EPS) have proven to be crucial participants in Ca2+ migration. The acidic solution weakens the interactions between EPS and Ca2+ and then diminishes the EPS adsorption capacity and affinity for Ca2+. The mild acidic environment goes beyond reducing CaCO3 formation in wastewater. EPS protonation reduced the probability of Ca2+ adhering to the AnGS surface, which halted calcium transportation from bulk liquid to granule. This work offers a feasible strategy to prevent AnGS calcification in high-calcium wastewater.

A disulfide molecule-vancomycin nanodrug delivery system efficiently eradicates intracellular bacteria.

Intracellular bacteria often lead to chronic and recurrent infections; however, most of the known antibiotics have poor efficacy against intracellular bacteria due to their poor cell membrane penetration efficiency into the cytosol. Here, a thiol-mediated nanodrug delivery system, named Van-DM NPs, was developed to improve vancomycin's penetration efficiency and intracellular antibacterial activities. Van-DM NPs were prepared through self-assembly of vancomycin (Van) and the disulfide molecule (DM) in NaOH buffer solution. On the one hand, the disulfide exchange reaction between Van-DM NPs and the bacterial surface enhances vancomycin accumulation in bacteria, increasing the local concentration of vancomycin. On the other hand, the disulfide exchange reaction between Van-DM NPs and the mammalian cell membrane triggered the translocation of Van-DM NPs across the mammalian cell membrane into the cell cytosol. These dual mechanisms promote antibacterial activities of vancomycin against both extracellular and intracellular bacteria S. aureus. Furthermore, in an intravenous S. aureus infection mouse model, Van-DM NPs exhibited high antibacterial capability and efficiently reduced the bacterial load in liver and spleen, where intracellular bacteria tend to reside. Altogether, the reported Van-DM NPs would be highly promising against intracellular pathogenic infections.

Triple strategy-enhanced immunochromatographic assay based on APCB and AIEFM for the ultrasensitive detection of AFM1.

Aflatoxin M1 (AFM1) is highly toxic, widely distributed, and difficult to monitor, posing a serious threat to human health. Therefore, a highly sensitive, rapid, convenient, and low-cost detection method must be urgently established. In this study, a triple strategy-enhanced immunochromatographic assay (ICA) was developed to satisfy these detection requirements. First, a turn-on signal output mode of the fluorescence quenching ICA substituted the turn-off mode of the traditional ICA for sensitive response to trace AFM1, with the limit of detection (LOD) reduced by approximately 4.9-fold. Then, a novel Au and polydopamine (PDA) cogrowth chrysanthemum-like blackbody was prepared as the quenching probe to reduce the background signal. This probe combined the excellent properties of Au nanoparticles with PDA. Thus, its fluorescence quenching constant was higher than that of single Au and PDA nanoparticles by 25.8- and 4.9-fold, respectively. Furthermore, an aggregation-induced emission fluorescence microsphere with a 5.7-fold higher relative quantum yield than a commercial fluorescence microsphere was selected as the signal output carrier to improve the signal-to-noise ratio. The integration of the above triple strategies established a 53.4-fold sensitivity-enhanced fluorescence quenching ICA (LOD = 0.9 pg/mL) for detecting AFM1 in milk, providing a strong technical guarantee for the safety monitoring of milk products.

Finite element analysis of minimally invasive nail placement and traditional nail placement in the treatment of lumbar 1 vertebral compression fracture.

Using the finite element analysis method to help us better understand the biomechanical changes of the spine after surgery and the changes in the stress distribution around the screw implantation area. The finite element model of L1 vertebral compression fracture was constructed by using a large number of finite element programs. On the fracture model, 2 kinds of internal fixation devices are set up, namely: the first type of 4 screws across the injured vertebra through the adjacent upper and lower vertebrae + transverse connector; the second type of 4 screws crosses the injured vertebra through the adjacent upper and lower vertebrae + non-transverse connector. To study the distribution of the maximum displacement and von Mises stress of the intramedullary pedicle screws and rods of the 2 types of internal fixation devices after implantation in the spine under certain loading conditions. In traditional open pedicle screw fixation, the maximum stress in the pedicle screw fixation system in the direction of 3D movement is higher than in percutaneous pedicle screw fixation. There is no significant difference in the Von Mises stress of the pedicle screw between the 2 procedures when the spine performs flexion-extension and lateral flexion activities. When the spine is rotating axially, the Von Mises stress of the pedicle screw in conventional open surgery is significantly less than that of the screw in percutaneous pedicle screw fixation. Traditional open internal fixation produces stress peaks of 891.7 MPa and 886.34 MPa at the transverse joint during axial rotation. Only when the spine is rotating in the axial direction, the maximum displacement of traditional open pedicle screw fixation is smaller than that of percutaneous pedicle screw fixation. There is no significant difference in the maximum displacement between the 2 procedures when the spine is moving in other directions. Traditional open pedicle screw fixation can strengthen the stability of the spine in the direction of axial rotation, and can also be greater to reduce the maximum stress of the pedicle screw axial rotation, so the clinical treatment of unstable fractures of the thoracolumbar spine instability is of great significance.

High-flux smartphone-integrated lateral flow assay based on chrysanthemum-like Au@polydopamine for sensitive detection of enrofloxacin in milk.

Lateral flow assays (LFAs) are widely used in screening analysis. However, the detection flux and sensitivity of LFAs are unsatisfactory because of the 'one-to-one' read mode and the ordinary performance conventional probe. In this work, a high-flux smartphone-integrated LFA (sLFA) based on chrysanthemum-like Au@polydopamine (AuNC@PDA) for the detection of enrofloxacin (ENR) in milk was established. The smartphone-integrated device was developed and applied in the LFA, giving rise to a reading maximum of 64 samples with only two photos in less than 2 min compared to a 'one-to-one' read mode of a conventional LFA in more than 14 min with a 36.4% deviation. For ENR detection, the limits of detection of sLFA based on AuNC@PDA (33.78 pg mL-1) had 5.0-fold and 6.4-fold reduction compared with those based on AuNP (169.99 pg mL-1, conventional probe) and vvAuNP (216.47 pg mL-1, commercial probe), respectively. This study provides an effective technical means for screening ENR in large quantities of milk samples.

Polyethyleneimine-induced fluorescence enhancement strategy for AIEgen: the mechanism and application.

Aggregation-induced emission luminogens (AIEgens) are attracting extensive research attention in the biosensor fields. Herein, we report a new polyethyleneimine (PEI)-induced strategy for enhancing luminescence of TCBPE (an AIEgen) to promote its development in biosensor. The copolymer dots (TCBPE-PEI) with high quantum yield (39.7%) and outstanding stability were synthesized via a one-pot method. The fluorescence enhancement mechanism based on the PEI strategy originated from the restriction of intramolecular motions of TCBPEs and the form of donor-acceptor structures to decrease the inherent energy bandgap. Benefiting from chelating property of TCBPE-PEI by Cu2+, a fluorescence-quenching sensor for Cu2+ detection was developed based on the fluorescence quenching of the electron transfer effect. Especially, a good linear range of 10-250 nM with a low limit of detection 1.1 nM was achieved, and it was further applied in samples successfully. The current work provides a novel approach to fabricate AIEgen biosensors and shows great potential in Cu2+ detection.

Mechanism of Pingxiao capsule promoting breast cancer apoptosis through AKT1/β-catenin signal based on network pharmacology / 中国临床药理学与治疗学

AIM: To explore the potential mechanism of action of Pingxiao capsule in the treatment of breast cancer. METHODS: TCMSP, TCM-ID, GeneCards and other databases were used to screen the related targets of Pingxiao capsule and breast can-

Comparison of the application methods and effects of skin flaps in the repair of defects in different parts of the nose according to the concept of aesthetic nosesubunits / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the difference of application methods and effects of local flap in small and medium-sized defects of different aesthetic subunits of nose, in order to provide reference for clinical work. Methods: A retrospective analysis was made on 59 patients with external nasal masses and scars who underwent surgical treatment in the Department of Aesthetic Plastic Surgery of the Affiliated Hospital of Qingdao University from July 1, 2021 to January 30, 2022, including 27 females and 32 males, aged 15 to 69 years. Using Likert scale, the repair methods and effects of local flap for nasal soft tissue defects were evaluated and summarized from three aspects of texture, flatness and scar concealment. GraphPad Prism 5.0 software was used for data statistics and analysis. Results: The use of skin flaps to repair small and medium-sized areas of the nose could achieve satisfactory results. For patients with different subunits, in terms of skin flatness and scar concealment degree in the operation area, patients' satisfaction with the dorsal and lateral nasal areas was higher than that of the alar and tip areas, respectively (F=6.40, P=0.001; F=10.57, P<0.001). For patients with different skin flap repair methods, the satisfaction of patients with Z-plasty and Dufourmentel skin flap was higher than that of other skin flap repair methods (F=4.38, P=0.002), and the satisfaction of patients with Dufourmentel skin flap was the highest in the degree of scar concealment (F=2.57, P=0.038). Conclusions: In the small and medium-sized defects of the nose, the use of multiple local flaps can achieve good cosmetic effects and functional recovery. The operator should select the appropriate flap repair method according to the characteristics of different aesthetic subunits of the nose.

A positive feedback loop of heparanase/ syndecan1erve growth factor regulates cancer pain progression

Background@#The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)erve growth factor (NGF) on cancer pain from melanoma. @*Methods@#The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. @*Results@#HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. @*Conclusions@#The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

Effect of external diaphragm pacing therapy combined with abdominal functional electrical stimulation on respiratory function for stroke patients / 中国康复理论与实践

ObjectiveTo explore the effect of external diaphragm pacing therapy combined with abdominal functional electrical stimulation on respiratory function for stroke patients. MethodsFrom October, 2020 to September, 2022, 54 stroke patients were randomly divided into control group (n = 18), external diaphragm pacing group (n = 18) and combined treatment group (n = 18). All the groups received breathing training, while the external diaphragm pacing group received external diaphragm pacing therapy, and the combined treatment group received external diaphragm pacing and abdominal functional electrical stimulation therapy, for two weeks. They were measured forced vital capacity (FVC), forced expiratory volume in first second (FEV1), ratio of forced expiratory volume in first second in forced vital capacity (FEV1/FVC), peak expiratory flow (PEF), maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) with pulmonary function instrument; measured diaphragmatic excursion (DE) and diaphragmatic thickness (DT) with ultrasound, before and after treatment. ResultsThree cases in the control group, two cases in the external diaphragm pacing group and one case in the combined treatment group dropped off. The FVC, FEV1, PEF, MIP, MEP and DE improved in all the groups (|t| > 3.366, P < 0.01) after treatment; and the FVC, FEV1, MIP and DE increased more in the combined treatment group and the external diaphragm pacing group than in the control group (P < 0.05); the FVC and FEV1 increased more in the combined treatment group than in the external diaphragm pacing group (P < 0.05). ConclusionExternal diaphragm pacing therapy may improve ventilation and inspiratory muscle strength, and increase diaphragm movement for stroke patients; while the ventilation improved more after combining with abdominal functional electrical stimulation.

Influence of exophthalmos on design of double eyelid incision / 中华医学美学美容杂志

Objective:To compare the postoperative effects of double eyelid surgery with different exophthalmos to find its influence on the surgery and necessary changes in preoperative design and during operation.Methods:A total of 50 female patients with single eyelid seeking beauty from June 2021 to March 2022 were selected from the Department of Plastic Surgery, Affiliated Hospital of Qingdao University. The ocular protrusion was measured by HETEL ophthalmostatometer before surgery. Both eyes at 12-15 mm were taken as normal group ( n=26), both eyes at 16-18 mm as mild protrusion group ( n=14) and both eyes at 19-22 mm as severe protrusion group ( n=10). All the patients were treated with double-eyelid surgery by orbital septum and unified postoperative nursing. Results:After six months of follow-up, there was no difference in eyelid width with closed eyes (all P>0.05). The width of double eyelid with open eyes in normal group was smaller than that in mild protrusion group ( F=23.23, all P<0.05), and the width of double eyelid with open eyes in mild protrusion group was smaller than that in severe protrusion group ( F=47.70, all P<0.05). There was no difference in the improvement rate of facial aesthetics among the three groups ( P>0.05). The " feeling of meet" and scar formation in the normal group were less than those in the mild protrusion group ( F=16.92, F=33.45, all P<0.05), and the " feeling of meet" and scar formation in the mild protrusion group were less than those in the severe protrusion group ( F=27.93, F=28.53, all P<0.05). The improvement rate of normal group was higher than that of mild and severe protrusion group (χ 2=7.25, 7.89, all P<0.05). There was no difference in the improvement rate between the mild and severe protrusion groups ( P>0.05). Conclusions:In clinical practice, it is necessary to make corresponding changes in the preoperative design and operation of double eyelid surgery for patients with high eyeball protrusion.

Effect of individualized blood pressure management on postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor / 中华麻醉学杂志

Objective:To evaluate the effect of individualized blood pressure management on postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor.Methods:One hundred and sixty elderly hypertensive patients of both sexes, aged 60-80 yr, with body mass index of 19-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective radical resection for gastrointestinal tumor under general anesthesia, were divided into 2 groups ( n=80 each) using a random number table method: standardized blood pressure management group (group S) and individualized blood pressure management group (group I). Combined intravenous-inhalational anesthesia was performed, and BIS values were maintained at 40-60 and heart rate at 50-100 times/min during surgery in both groups. In group S, intraoperative systolic blood pressure was maintained above 90 mmHg with a decrease of less than 30% of the baseline value, while intraoperative fluctuation of systolic blood pressure was maintained less than 10% of the baseline value in group I. The use of vasoactive agents, numerical rating scale scores within 3 days after operation, and length of hospital stay were recorded. Postoperative delirium was evaluated by Confusion Assessment Method within 5 days after surgery. Results:Compared with group S, the intraoperative usage rate of norepinephrine was significantly increased, the incidence of postoperative delirium was reduced( P<0.05), and no significant change was found in the numerical rating scale scores and length of hospital stay in group I ( P>0.05). Conclusions:Individualized blood pressure management can reduce the development of postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor.

Analysis of major adverse cardiac events and risk factors during perioperative period of cervical spine surgery / 中国综合临床

Objective:To understand the occurrence of major adverse cardiac events (MACE) during the perioperative period of cervical spine surgery and analyze its risk factors.Methods:A retrospective analysis of 426 cervical spine surgery patients admitted to the from March 2017 to March 2021. The basic information of the patients, including gender, age, body mass index (BMI), underlying diseases, and the Charlson comorbidity index (CCI) was calculated based on the underlying diseases.The preoperative serum cardiac troponin I(cTnI) level and the operation-related indicators were collected,including the type of cervical spine surgery, surgical procedure, approach, duration of surgery, duration of anesthesia, intraoperative bleeding, postoperative pain visual analogue scale (VAS), and electrolyte disturbances. Count data were expressed as cases (%), and comparisons between groups were made using the χ 2 test; logistic regression models were applied to perform a multifactorial analysis of the factors influencing the perioperative occurrence of MACE in patients undergoing cervical spine surgery. Results:Among the 426 patients, 54 (12.68%) experienced MACE during the perioperative period, including 4 cases of unstable angina (7.41%), 4 cases of acute myocardial infarction (7.41%), 33 cases of severe arrhythmia (61.11%), and 13 cases of acute heart failure (24.07%). The results of multivariate logistic regression analysis showed that the older the age group (50-59 years old: odds ratio=1.34, 95% confidence interval: 1.14-1.78; 60-69 years old: odds ratio=1.48, 95% confidence interval: 1.20-1.86; 70-79 years old: odds ratio=1.71, 95% confidence interval: 1.34-2.57; 80-89 years old: odds ratio=1.95, 95% confidence interval: 1.46-2.85), as well as females, CCI scores>3, and preoperative cTnI>0.04 μg/L, postoperative VAS score>5, and electrolyte disorders are all influencing factors for the occurrence of MACE in cervical spine surgery patients during the perioperative period (odds ratios of 1.84, 2.12, 2.34, 2.57, 2.20, 95% confidence intervals of 1.34-2.68, 1.50-3.41, 1.63-3.72, 1.53-4.01, 1.43-3.69, all P<0.05). Conclusions:The incidence of MACE in the perioperative period of cervical spine surgery is relatively high. Elderly age, female, high CCI score, high preoperative serum cTnI, postoperative pain and electrolyte disturbance are independent risk factors for the perioperative period of cervical spine surgery.

Lateral flow immunoassay based on polydopamine-coated metal-organic framework for the visual detection of enrofloxacin in milk.

Herein, we report a new polydopamine (PDA)-coated metal-organic framework (MOF) as a label to improve the sensitivity of lateral flow immunoassay (LFIA). The MOF, UiO-66-NH2, was synthesized via the hydrothermal method, and it exhibited the advantageous features of ordered pore structure, strong absorbance, and high specific surface area. Subsequently, UiO-66-NH2 was coated with PDA to improve the antibody coupling effectivity and light absorption ability. The optical intensity and antibody coupling efficiency of UiO-66@PDA were superior to those of gold nanoparticles (AuNPs). Under the optimum condition, the limit of detection and cutoff value of UiO-66@PDA-LFIA in detecting enrofloxacin were 0.045 and 1.0 ng/mL, respectively, which were lower than those of AuNPs-LFIA (0.095 and 5 ng/mL). The recoveries of UiO-66@PDA-LFIA in low-fat milk and whole milk were 85.6-107.4% and 79.3-115.5%, respectively, with coefficients of variation of 2.91-9.59% and 3.91-11.8%, respectively, as further confirmed by liquid chromatography-tandem mass spectrometry. These results indicate that UiO-66@PDA can be used as a novel probe for LFIA development and applications. Graphical abstract.

Influence of characteristics and incentive types of webcast on users' attitudes.

The novel coronavirus pneumonia brings new opportunities for the webcast. The characteristics of webcast and incentive types are two important potential variables that may affect user attitudes. Therefore, from this perspective, we test the mechanism of the two potential variables on the attitude of webcast users under the framework of ECM-ISC. Structural equation model analysis shows that: the interest of webcast has a significant positive impact on the cognitive attitude and emotional attitude of users; the explicit stimulation of webcast has a significant positive impact on the cognitive attitude and emotional attitude of users; the implicit incentive of webcast has a significant positive impact. The results show significant positive effects on users' cognitive attitude, emotional attitude, and behavior attitude; the interaction of live network characteristics and incentive types has a significant positive impact on users' cognitive attitude and emotional attitude.

Dual role of O2 concentration on the reducing gases produced and NO reduction during sewage sludge combustion in pilot scale cement precalciner.

The reducing gases produced and NO reduction by sewage sludge combustion were investigated in a self-made cement precalciner. The dual role of O2 concentration (0-5 vol%) in the production characteristics of reducing gases and the reduction efficiency of NO were evaluated experimentally. TG-FTIR analysis demonstrated that the key reducing gaseous species produced by sewage sludge combustion were HCN, NH3, CO, and CH4. And experiments demonstrated that O2 concentration had pronounced effects on NH3 distribution, the maximum production rate was obtained at an O2 concentration of 3 vol%. Meanwhile, the reducing gases NH3 and CO were the key species for NO reduction in the cement precalciner, and the reduction efficiency of NO, when reduced by NH3, increased with an increase in O2 concentration, while the reduction performance of NO by CO was limited by O2 concentration. Therefore, O2 concentration greatly influences NO reduction efficiency by sewage sludge combustion; the maximum NO reduction efficiency was 61.67% at an O2 concentration of 3 vol%. The difference in NO reduction by sewage sludge combustion under different O2 concentrations was primarily attributed to NH3 production rate and NO reduction by NH3 and CO, which is greatly affected by O2 concentration. Sewage sludge combustion can result in NO reduction in the cement kiln flue gas and resource utilisation of sewage sludge.

Epidemiology and risk factors associated with avascular necrosis in patients with autoimmune diseases: a nationwide study

Background/Aims@#Avascular necrosis (AVN) is a clinical condition characterized by the death of bone components due to interruption in the blood supply. This study aimed to investigate the epidemiology and determine the risk factors for AVN in patients with autoimmune diseases. @*Methods@#We conducted a population-based retrospective cohort analysis using claims data from the Taiwan National Health Insurance Research Database. A total of 49,636 patients with autoimmune diseases between January 1, 2005 and December 31, 2013 were included. Cox regression analysis was used to identify associated risk factors for the development of AVN. @*Results@#A total of 490/49,636 patients (1.0%) developed symptomatic AVN. The systemic lupus erythematosus patients had a higher risk of AVN compared to other autoimmune diseases. AVN was positively correlated with male sex (p 30 mg (p 0.6 years (p 7.5 mg and a total cumulative dose of corticosteroid 0 to 5 g were independently associated with the development of AVN in autoimmune patients. While hydroxychloroquine use > 0.6 years conferred significant protection against the development of AVN. Clinicians should regularly assess patients with risk factors to enable the early diagnosis of AVN.

Antifungal Activity and Potential Mechanism of 6,7, 4'-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans.

The increased resistance of Candida albicans to conventional antifungal drugs poses a huge challenge to the clinical treatment of this infection. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. This study assessed the effect of 6,7,4'-O-triacetylscutellarein (TA) combined with fluconazole (FLC) on C. albicans in vitro and in vivo. TA combined with FLC showed good synergistic antifungal activity against drug-resistant C. albicans in vitro, with a partial inhibitory concentration index (FICI) of 0.0188-0.1800. In addition, the time-kill curve confirmed the synergistic effect of TA and FLC. TA combined with FLC showed a strong synergistic inhibitory effect on the biofilm formation of resistant C. albicans. The combined antifungal efficacy of TA and FLC was evaluated in vivo in a mouse systemic fungal infection model. TA combined with FLC prolonged the survival rate of mice infected with drug-resistant C. albicans and reduced tissue invasion. TA combined with FLC also significantly inhibited the yeast-hypha conversion of C. albicans and significantly reduced the expression of RAS-cAMP-PKA signaling pathway-related genes (RAS1 and EFG1) and hyphal-related genes (HWP1 and ECE1). Furthermore, the mycelium growth on TA combined with the FLC group recovered after adding exogenous db-cAMP. Collectively, these results show that TA combined with FLC inhibits the formation of hyphae and biofilms through the RAS-cAMP-PKA signaling pathway, resulting in reduced infectivity and resistance of C. albicans. Therefore, this study provides a basis for the treatment of drug-resistant C. albicans infections.

Activity of Compound Agrimony Enteritis Capsules against invasive candidiasis: Exploring the differences between traditional Chinese medicine prescriptions and its main components in the treatment of diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Agrimony Enteritis Capsules (FFXHC) is an ethnomedicine derived from Yi Nationality Herbal Medicine for the treatment of enteritis. We found that compared to berberine hydrochloride (BBR), a component of this medicine, FFXHC was more efficacious in the mouse model of IC mice in significantly alleviating lung and intestinal lesions. " Our study provides a novel perspective into the pharmacological mechanism of action of the ethnic compound FFXHC. AIM OF THE STUDY: To determine the underlying mechanism of the superiority of FFXHC over BBR in IC. MATERIALS AND METHODS: The susceptibility of Candida albicans to FFXHC was evaluated in vitro. The mouse model of IC was established and the survival rate, weight change, the number of organ colonies, and immune organ coefficient of the mice were determined, the effect of FFXHC on the immune function of mice, including changes in the number of immune cells, levels of the related inflammatory cytokines (INF-γ, TNF-α, MCP-1, IL-6, and IL-17A), and the antimicrobial peptide, LL-37 (CRAMP in mice), were determined. Mice feces were collected and changes in the intestinal microecology were studied. RESULTS: Our findings indicated that FFXHC was not active against Candida albicans and did not restore the sensitivity of the resistant strain in vitro; however, it had a therapeutic effect that improve survival rate on mice with IC. The number of lymphocytes and neutrophils of mice with IC treated with FFXHC increased significantly. The intestinal microecology of mice was restored and the abundance of the probiotic Bacteroides was increased, which further stimulated the production of the antimicrobial peptide, LL-37, which is required for acquired immunity. Furthermore, the levels of Th cell-related cytokines, including INF-γ, TNF-α, and IL-17A were significantly increased, whereas those of the proinflammatory cytokines, IL-6 and MCP-1, decreased. With the activation of acquired immunity, the immune function of mice was restored, the body weight and survival rate of mice improved considerably, the coefficients of the thymus and spleen increased, and the number of fungal colonies in the lung and kidney decreased. CONCLUSIONS: FFXHC could eliminate fungi by increasing the relative abundance of probiotics in Bacteroides and the number of neutrophils, thereby promoting the production of CRAMP and resulting in a fungicidal effect, leading to acquired immunity. Although BBR has an antifungal effect, we found that it was not as effective as FFXHC.

Quercetin reverses adriamycin resistance by activating GSK-3β/β-catenin pathways through GAS5 in breast cancer cells / 中国临床药理学与治疗学

AIM: To investigate the ability of quercetin to reverse acquire adriamycin (ADR) resistance and explored its probably mechanism. METHODS: The CCK-8 assay was used to detect the cytotoxicity of quercetin in MCF-7/ADR cells and the reversal effect of ADR. The colony formation assay and Hoechst 332582 staining were used to detect the cell proliferation, cell apoptosis and the accumulation of rhodamine 123 (Rh123) respectively. The RNA expression levels of GAS5 and ABCB1 were detected by qRT-PCR. The protein expression levels of GSK-3β, β-catenin, c-MYC, cyclin D1, and ABCB1 were detected by Western blot. RESULTS: Quercetin (10, 20, 40 μmol/L) significantly enhanced the sensitivity of MCF-7/ADR to ADR, inhibitd cell proliferation, and increased the intracellular accumulation of Rh123. Treatment with quercetin in MCF-7/ADR cells, the expression levels of GAS5 and GSK-3β were increased, whereas the expression levels of β-catenin, c-myc, cyclin D1 and ABCB1 were decreased. Further research revealed that reduction of GAS5 by RNA interference (si-GAS5) induced inhibitory effects on the expressions of GAS5 and GSK-3β, and enhanced the expressions of β-catenin, c-myc, cyclin D1, and ABCB1. Furthermore, treatment by quercetin combined with si-GAS5 in MCF-7/ADR cells, the expressions of these proteins were effectively reversed in comparison to quercetin combined with siRNA negative control (sncRNA). CONCLUSION: Quercetin increases the expression of GAS5by GSK-3β/β-catenin signaling pathway, which inhibits the expression of ABCB1, ultimately reversing ADR resistance in the MCF-7/ADR cells.