Clinical Application of Tonsillectomy with Preservation of Capsule and Support Tissue.

Objective: The clinical effect of tonsillectomy with the preservation of tonsillar capsule and stent tissue and punctuated suture of tonsillar capsule and stent tissue was analyzed retrospectively. Methods: From January 2013 to January 2022, a total of 960 patients underwent tonsillectomy, consisting of 530 males and 430 females with ages ranging from 4 to 60 years (median age: 11 years). The capsule and scaffold tissues were preserved in all patients during the operation, and the surrounding mucosa, capsule, and scaffold tissues were sutured without tension. Indexes such as operation time, intraoperative blood loss, tonsillar white membrane, incidence of postoperative bleeding, postoperative pain score, and incidence of tonsillar remnant were recorded, and the school attendance of children (≤12 years old) was recorded. Results: The mucosal covering of tonsillar fossa healed well in all patients, and the sutures were completely removed at 4 weeks after reexamination. All patients were followed up for 1-8 years, and there was no residual hyperplasia or residual inflammation. Children under 12 years old could return to school 4 days after surgery without any postoperative complications. Conclusion: Tonsillectomy, preserving the tonsillar capsule and scaffold tissue followed by punctate suturing, offered several advantages: it resulted in less intraoperative blood loss and postoperative pain. Patients could resume a normal diet 6 hours after the surgery without an increased risk of complications. Moreover, it significantly reduced the risk of postoperative bleeding.

Comparative pharmacokinetics of 11 major bioactive components between two dosage forms of Qixue Shuangbu Prescription in rats by ultra-high-performance liquid chromatography-tandem mass spectrometry.

Although Qixue Shuangbu Prescription (QSP) is a classic Chinese medicine prescription for treating chronic heart failure. Low bioavailability due to the insolubility and poor biofilm permeability of the main bioactive ingredients of QSP is still a key factor limiting its efficacy. In this study, a novel self-microemulsifying drug delivery system was proposed to effectively improve the bioavailability of QSP. The qualified ultra-high-performance liquid chromatography-tandem mass spectrometry methodology was established to investigate the pharmacokinetics characteristics of the QSP self-microemulsifying drug delivery system. Our results showed that 11 components in the self-microemulsifying drug delivery system group had prolonged T1/2 and MRT0-t values compared with QSP extract. The Cmax of calycosin-7-glucoside (CG), vanillic acid and paeoniflorin increased 2.5 times, 2.4 times and 2.3 times, respectively. The relative bioavailability values of CG, paeoniflorin and ononin were most significantly affected, increasing by 383.2%, 336.5% and 307.1%, respectively. This study promoted the development of new dosage forms of QSP and provided a useful reference for improving dosage forms to solve the problem of low bioavailability of traditional Chinese medicine.

Identification and quality evaluation of different processed products of Aconitum carmichaelii by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and ultra-high-performance liquid chromatography-tandem mass spectrometry.

Aconitum carmichaelii is widely used to treat chronic and intractable diseases due to its remarkable curative effect, but it is also a highly toxic herb with severe cardiac and neurotoxicity. It has been combined with honey for thousands of years to reduce toxicity and enhance efficacy, but there has been no study on the chemical constituent changes in the honey-processing so far. In this study, the chemical constituents of A. carmichaelii before and after honey-processing were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The results showed that a total of 118 compounds were identified, of which six compounds disappeared and five compounds were newly produced after honey-processing, and the cleavage pathway of main components was elucidated. At the same time, 25 compounds were found to have significant effects on different products, among which four compounds with the biggest difference were selected for quantitative analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. This study not only explained the chemical differences between the different products, but also helped to control the quality of the honey-processed products more effectively, and laid a foundation for further elucidating the mechanism of chemical constituent change during the honey-processing of A. carmichaelii.

Antioxidative effect of Periplaneta americana extract on dextran sulfate sodium-induced ulcerative colitis through activation of the Nrf2 signal.

CONTEXT: Periplaneta americana L. (Blattariae) is used as a treatment for ulcerative colitis (UC) in Chinese traditional medicine. OBJECTIVE: To evaluate the antioxidative activity of P. americana whole body ethanol extract (PAE) on UC mice and whether glycine and proline could be used for quality control and identification of active PAE components. MATERIALS AND METHODS: NCM460 cells were pre-incubated in PAE, AA-L, AA-M, and AA-H (low, high and medium doses of proline and glycine), then treated with recombinant human TNF-α. The glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen (ROS) levels were determined. UC mice were fed with water containing 2.5% dextran sulfate sodium (w/v) after pre-treatment with different doses of PAE once a day for 7 days. ELISA was used to detect the concentrations of inflammation-related factors. Colon tissues of mice were used to detect the activity of myeloperoxidase (MPO), GSH, MDA, and SOD. Histological changes were observed using H&E staining. The expression of target proteins was determined by western blotting. RESULTS: In vivo, PAE treatment reduced the DAI score more than in the model group, restoring the weight and colonic length. It also reduced the severity of colitis, and inflammatory and oxidative stress intensity. Additionally, western blotting showed that the Nrf2 pathway was activated by PAE. In vitro PAE significantly alleviated TNF-α-induced cell damage and oxidative stress, which is relevant to the activation of the Nrf2 pathway. CONCLUSIONS: PAE may relieve oxidative stress through the Nrf2 signaling pathway, and proline and glycine may be used as active components of its antioxidative stress activity.

Dahuang Zhechong pill attenuates hepatic sinusoidal capillarization in liver cirrhosis and hepatocellular carcinoma rat model via the MK/integrin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dahuang Zhechong pill (DHZCP), a traditional Chinese medicine, was derived from the famous book Unk "Synopsis of Prescriptions of the Golden Chamber" during the Han dynasty. Owing to its ability to invigorate the circulation of blood in Chinese medicine, DHZCP is usually used for treating liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Clinical application have shown that DHZCP exhibits satisfactory therapeutic effects in HCC adjuvant therapy; however, little is known about its underlying mechanisms. AIM OF THE STUDY: We aimed to clarify the mechanism of DHZCP against hepatic sinusoidal capillarization in rats with LC and HCC by inhibiting the MK/integrin signaling pathway of liver sinusoidal endothelial cells (LSECs). MATERIALS AND METHODS: The contents of 29 characteristic components in DHZCP were determined by ultraperformance liquid chromatography-tandem mass spectrometry. DEN (Diethylnitrosamine)-induced LC and HCC rat models were constructed, and DHZCP was administered when the disease entered the LC stage. After 4 or 12 weeks of administration, hematoxylin and eosin staining, Masson staining, Metavir score, and SSCP (Single strand conformation polymorphism) gene mutation detection were used to confirm tissue fibrosis and cancer. The levels of NO, ET-1 and TXA2, which can regulate vasomotor functions and activate the MK/Itgα6/Src signaling pathway were evaluated by using immunohistochemistry, chemiluminescence, immunofluorescence, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Similar methods were also used to evaluate the levels of VEGF, VEGFR, Ang-2 and Tie, which can promote pathological angiogenesis and activate the MK/Itgα4/NF-κB signaling pathway. In vitro cell experiments were performed using potential pharmacodynamic molecules targeting integrins in DHZCP were selected by molecular docking, and the effects of these molecules on the function of LSECs were studied by Itgα4+ and Itgα6+ cell models. RESULTS: At the stage of LC, the animal experiments demonstrated that DHZCP mainly inhibited the MK/Itgα6 signaling pathway to increase the number and size of hepatic sinus fenestration, reversed the ET-1/NO and TXA2/NO ratios, regulated hepatic sinus relaxation and contraction balance, reduced the portal vein pressure, and inhibited cirrhotic carcinogenesis. At the HCC stage, DHZCP could also significantly inhibit the MK/Itgα4 signaling pathway, reduce pathological angiogenesis, and alleviate disease progression. The results of the cell experiments showed that Rhein, Naringenin, Liquiritin and Emodin-8-O-ß-D-glucoside (PMEG) were involved in vascular regulation by affecting the MK/integrin signaling pathway. Liquiritin and PMEG mainly blocked the MK/α6 signal, which is important in regulating the vasomotor function of the liver sinus. Naringenin and Rhein mainly acted by blocked the signaling of MK/α4 action signal, which are potent molecules that inhibit pathological angiogenesis. CONCLUSIONS: DHZCP could improve the hepatic sinusoidal capillarization of LC and HCC by inhibiting the MK/Itgα signaling pathway and inhibited disease progression. Rhein, Naringenin, Liquiritin and PMEG were the main active molecules that affected the MK/Itgα signaling pathway.

Photoselective sharp enucleation of the prostate with a front-firing 532-nm laser versus photoselective vaporization of the prostate in the treatment of benign prostatic hyperplasia: a randomised controlled trial with 1-year followup results.

BACKGROUND: We designed a new surgical procedure to treat benign prostatic hyperplasia(BPH). In order to verify its effectiveness and safety, we constructed this randomized controlled trial to compare the efficacy of our innovative enucleation technique- photoselective sharp enucleation of the prostate (PSEP), with a front-firing 532-nm laser and the traditional technique-photoselective vaporization of the prostate (PVP) in the treatment of BPH. METHODS: A total of 154 consecutive patients diagnosed with bladder outlet obstruction secondary to BPH in our center from June 2018 to April 2019 were randomly divided into the PSEP group (n = 77) and the PVP group (n = 77) and were treated surgically with either PSEP or PVP. All patients were assessed preoperatively and followed up at 1, 6, and 12 months postoperatively. The international prostate symptom score,quality-of-life score, postvoid residual urine volume, maximum urine flow rate, prostate volume, prostate-specific antigen, and adverse events were compared. RESULTS: The lower urinary tract symptoms in both groups were significantly improved compared with the baseline at 1, 6, and 12 months postoperatively. The PSEP and PVP groups had an equivalent International Prostate Symptom Score, quality-of-life score, postvoid residual urine volume, maximum urine flow rate, prostate-specific antigen at each follow-up (P > 0.05). The median operative time in the PSEP group was significantly shorter than that in the PVP group (35 min vs. 47 min, P < 0.001). At 6 and 12 months after surgery, the median PV in the PSEP group was smaller than that in the PVP group (P < 0.05). Complication rates were comparable between the groups. CONCLUSION: Both PSEP and PVP can achieve good efficacy and safety in the treatment of BPH. PSEP can remove more tissue than PVP and is associated with higher efficiency. In addition, PSEP eliminates the problem of lack of tissue samples associated with PVP. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifie:ChiCTR1800015867, date:25/04/2018.

[Pharmacokinetic study of Polydopamine Guttate Pills loaded with active components of Sarcandrae Herba in rats].

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established for the determination of active components of Sarcandrae Herba, and applied to the pharmacokinetics study of multiple dosage forms. After SD rats were administered by gavage with three dosage forms [Sarcandrae Herba extract, commercial Sarcandrae Herba Guttate Pills, and polydopamine guttate pills loaded with active components of Sarcandrae Herba(PDA-Sg Guttate Pills)], blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC C_(18) column(2.1 mm×100 mm, 1.7 µm). The mobile phase consisted of water containing 0.2% formic acid and acetonitrile in gradient elution. The negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 2.0. All four components could be detected in the plasma of rats in each group at each time point except the neochlorogenic acid and cryptochlorogenic acid in the Sarcandrae Herba extract group. The guttate pills group showed a significant increase in drug content at each time point. The exposure of the main components of Sarcandrae Herba in blood was effectively increased by PDA-drug loading effect in PDA-Sg Guttate Pills(The AUC_(0-24 h) of neochlorogenic acid, cryptochlorogenic acid, isaziridin and rosmarinic acid reached 2.45, 32.90, 1.54, 4.81 times that of the commercial guttate pills). This study proves the measurability of the above-mentioned multi-component in vitro-in vivo delivery process. The pharmacokinetic study has shown that PDA-Sg Guttate Pills can effectively delay the elimination time and improve the bioavailability of the four components, which can provide theoretical data for the production of the drug.

Gut microbiota and metabonomics used to explore the mechanism of Qing'e Pills in alleviating osteoporosis.

CONTEXT: The traditional Chinese medicine Qing'e Pills (QEP) has been used to treat postmenopausal osteoporosis (PMO). OBJECTIVE: We evaluated the regulatory effects of QEP on gut microbiota in osteoporosis. MATERIALS AND METHODS: Eighteen female SD rats were divided into three groups: sham surgery (SHAM), ovariectomized (OVX) and ovariectomized treated with QEP (OVX + QEP). Six weeks after ovariectomy, QEP was administered to OVX + QEP rats for eight weeks (4.5 g/kg/day, i.g.). After 14 weeks, the bone microstructure was evaluated. Differences in gut microbiota were analysed via 16S rRNA gene sequencing. Changes in endogenous metabolites were studied using UHPLC-Q-TOF/MS technology. GC-MS was used to detect short-chain fatty acids. Furthermore, we measured serum inflammatory factors, such as IL-6, TNF-α and IFN-γ, which may be related to gut microbiota. RESULTS: OVX + QEP exhibited increased bone mineral density (0.11 ± 0.03 vs. 0.21 ± 0.02, p< 0.001) compared to that of OVX. QEP altered the composition of gut microbiota. We identified 19 potential biomarkers related to osteoporosis. QEP inhibited the elevation of TNF-α (38.86 ± 3.19 vs. 29.43 ± 3.65, p< 0.05) and IL-6 (83.38 ± 16.92 vs. 45.26 ± 3.94, p< 0.05) levels, while it increased the concentrations of acetic acid (271.95 ± 52.41 vs. 447.73 ± 46.54, p< 0.001), propionic acid (28.96 ± 5.73 vs. 53.41 ± 14.26, p< 0.01) and butyric acid (24.92 ± 18.97 vs. 67.78 ± 35.68, p< 0.05). CONCLUSIONS: These results indicate that QEP has potential of regulating intestinal flora and improving osteoporosis. The combination of anti-osteoporosis drugs and intestinal flora could become a new treatment for osteoporosis.

Granular indigenous microalgal-bacterial consortium for wastewater treatment: Establishment strategy, functional microorganism, nutrient removal, and influencing factor.

Granular indigenous microalgal-bacterial consortium (G-IMBC) system integrates the advantages of the MBC and granular activated sludge technologies, also with superior microalgal wastewater adaptation capacity. In this review, the concept of IMBC was firstly described, followed by its establishment and acclimation strategies. Characteristics and advantages of G-IMBC system compared to other IMBC systems (i.e., attached and floc IMBC systems) were then introduced. Moreover, the involved functional microorganisms and their interactions, as well as nutrient removal mechanisms were systematically and critically reviewed. Finally, the influencing factors including wastewater characteristics and operation factors were discussed. This study aims to provide a comprehensive up-to-date summary of the G-IMBC system for sustainable wastewater treatment.

Oridonin attenuates hind limb ischemia-reperfusion injury by modulating Nrf2-mediated oxidative stress and NLRP3-mediated inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Oridonin (Ori), extracted from Isodon rubescens (Hemsl.) H.Hara, is a well-known traditional Chinese herbal medicinal product that possesses antioxidant and anti-inflammatory activities. Oxidative stress and inflammation are the main pathophysiological mechanisms in hindlimb IR injury. However, whether Ori has a protective effect on hind limb IR injury is unknown. AIM OF THE STUDY: The present study was designed to determine the effect of Ori on hindlimb IR injury and its relationship with oxidative stress and inflammation. MATERIALS AND METHODS: The hind limb IR injury model in mice was used to evaluate the protective effect and related mechanisms of Ori. Forty-eight C57BL/6 mice (n = 12 per group) were randomly divided into four groups: Sham group; IR group; IR + Ori (10 mg/kg) group and IR + Ori (20 mg/kg) group. Mice in the IR and IR + Ori groups were subjected to hindlimb IR injury, while mice in the Sham group were subjected to no hindlimb IR injury. HE staining, Masson's staining, TTC staining, DHE staining, TUNEL staining, western blotting analysis and quantitative real-time PCR were employed to explore the mechanisms by which Ori exerts a protective effect on a classical hindlimb IR model in mice. RESULTS: We found that Ori pretreatment prevented muscle damage and decreased cell apoptosis levels compared with the vehicle control. Moreover, the SOD2, CAT, MDA and ROS levels in muscle showed that Ori could significantly reduce oxidative stress in hindlimb IR mice, while the IL-1ß and TNF-α levels in muscle showed that Ori could significantly attenuate IR-induced inflammation. We also found that Ori could increase the expression of Nrf2 and its downstream protein HO-1 and inhibit the expression levels of NLRP3-related proteins (NLRP3, ASC and Caspase-1) in vivo. CONCLUSIONS: Our study suggested that Ori has a protective effect on hindlimb IR injury, which may be related to Nrf2-mediated oxidative stress and NLRP3-mediated inflammasome activation.

Preparation of a Self-Assembled Rhein-Doxorubicin Nanogel Targeting Mitochondria and Investigation on Its Antihepatoma Activity.

Mitochondria are involved in the regulation of apoptosis, making them a promising target for the development of new anticancer drugs. Doxorubicin (DOX), a chemotherapeutic drug, can induce reactive oxygen species (ROS)-mediated apoptosis, improving its anticancer effects. Herein, Rhein, an active ingredient in rhubarb, with the capability of self-assembly and mitochondrial targeting, was used in conjunction with DOX to form efficient nanomaterials (Rhein-DOX nanogel) capable of sustained drug release. It was self-assembled with a hydrogen bond, π-π stacking interactions, and hydrophobic interactions as the main driving force, and its loading efficiency was up to 100%. Based on its self-assembly characteristics, we evaluated the mechanism of this material to target mitochondria, induce ROS production, and promote apoptosis. The IC50 of the Rhein-DOX nanogel (3.74 µM) was only 46.3% of that of DOX (11.89 µM), and the tumor inhibition rate of the Rhein-DOX nanogel was 79.4% in vivo, 2.3 times that of DOX. This study not only addresses the disadvantages of high toxicity of DOX and low bioavailability of Rhein, when DOX and Rhein are combined for the treatment of hepatoma, but it also significantly improved the synergistic antihepatoma efficacy of Rhein and DOX, which provides a new idea for the development of long-term antihepatoma agents with low toxicity.

Study on the material basis of Dahuang Zhechong pill of anti-hepatoma effect by promoting vascular normalization.

Dahuang Zhechong Pill (DHZCP) is a traditional Chinese medicine prescription used to treat many diseases especially chronic liver disease accompanied by promotion of vascular normalization. In this work, UPLC-Q-TOF-MS/MS analysis was applied to identify the chemical components absorbed in the blood. HIF-1α, VEGF, Ang2 and Tie2 related to vascular normalization were detected to determine the dynamic changes of pharmacodynamic indicators. Then, the spectrum-effect relationship between the UHPLC fingerprint and pharmacodynamic indicators was evaluated dynamically using partial least squares (PLS). As a result, 103 components were identified from rat serum samples, including 56 original compounds and 47 metabolites. According to the PLS, active constituents of DHZCP acting on HIF-1α, VEGF, Ang2 and Tie2 (8, 15, 17 and 20) were found. In subsequent experiments on cells, 7/11 components of HIF-1α/VEGF were found in HepG2 and HUVEC cells, and 11/14/2 components of HIF-1α/VEGF/Tie2. The main pharmacodynamic components of DHZCP in promoting vascular normalization were successfully identified by the spectrum-effect relationship analysis.

Acupoint nanocomposite hydrogel for simulation of acupuncture and targeted delivery of triptolide against rheumatoid arthritis.

BACKGROUND: Attenuating inflammatory response and relieving pain are two therapeutic therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with practical targeting ability and other complementary strategies urgently need to be explored. To achieve this goal, an acupoint drug delivery system that can target deliver anti-inflammatory drugs and simulate acupuncture in relieving pain was constructed, which can co-deliver triptolide (TP) and 2-chloro-N (6)-cyclopentyl adenosine (CCPA). RESULTS: We have successfully demonstrated that acupoint nanocomposite hydrogel composed of TP-Human serum album nanoparticles (TP@HSA NPs) and CCPA could effectively treat RA. The result shows that CCPA-Gel can enhance analgesic effects specifically at the acupoint, while the mechanical and thermal pain threshold was 4.9 and 1.6 times compared with non-acupoint, respectively, and the nanocomposite gel further enhanced. Otherwise, the combination of acupoint and nanocomposite hydrogel exerted synergetic improvement of inflammation, bone erosion, and reduction of systemic toxicity. Furthermore, it could regulate inflammatory factors and restore the balance of Th17/Treg cells, which provided a novel and effective treatment strategy for RA. Interestingly, acupoint administration could improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48 h), which may explain the better therapeutic efficiency and low toxicity. CONCLUSION: This novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine.

Multi-element processed pyritum mixed to ß-tricalcium phosphate to obtain a 3D-printed porous scaffold: An option for treatment of bone defects.

Bone defects remain a challenging problem for doctors and patients in clinical practice. Processed pyritum is a traditional Chinese medicine that is often used to clinically treat bone fractures. It contains mainly Fe, Zn, Cu, Mn, and other elements. In this study, we added the extract of processed pyritum to ß-tricalcium phosphate and produced a porous composite TPP (TCP/processed pyritum) scaffold using digital light processing (DLP) 3D printing technology. Scanning electron microscopy (SEM) analysis revealed that TPP scaffolds contained interconnected pore structures. When compared with TCP scaffolds (1.35 ± 0.15 MPa), TPP scaffolds (5.50 ± 0.24 MPa) have stronger mechanical strength and can effectively induce osteoblast proliferation, differentiation, and mineralization in vitro. Meanwhile, the in vivo study showed that the TPP scaffold had better osteogenic capacity than the TCP scaffold. Furthermore, the TPP scaffold had good biosafety after implantation. In summary, the TPP scaffold is a promising biomaterial for the clinical treatment of bone defects.

Effect of Teriparatide on pain relief, and quality of life in postmenopausal females with osteoporotic vertebral compression fractures, a retrospective cohort study.

BACKGROUND: Osteoporotic vertebral compression fracture (OVCF) is a common disease in elderly population, which could cause serious back pain and has a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to identify the effect of Teriparatide as a conservative treatment on reducing back pain, and improving quality of life for postmenopausal women with osteoporotic vertebral fractures. METHODS: In a 12-month, retrospective study, 112 postmenopausal women with OVCFs were assigned to Teriparatide group (20 µg Teriparatide, subcutaneous, once daily, n=38) or control group (500 mg calcium and 400-800 IU Vitamin D per day, oral administration, n=74) according to patients' choices between January 2016 and October 2018. Patient-reported outcomes scores including the visual analogue score (VAS), Oswestry disability index (ODI), and short form 36 questionnaire (SF-36) were assessed at baseline, the 3rd months, the 6th months and 1 year after treatment. RESULTS: Treatments with Teriparatide or calcium plus vitamin D supplements had significant effect on improvement of patients' back pain as well as HRQoL, with significantly reduced VAS and ODI and increased SF-36 physical component summary (PCS) and mental component summary (MCS) scores. At the endpoint, Teriparatide showed better therapeutic effect, with greater reductions in VAS and ODI and more increases in SF-36 PCS and MCS scores. However, more adverse events (AEs) were found in Teriparatide group, but symptoms were relatively mild and of short duration. CONCLUSIONS: In postmenopausal women with OVCFs, the consequent persistent back pain and impaired HRQoL, treatment with Teriparatide was associated with more profound therapeutic effects and more AEs compared with calcium plus vitamin D supplements.

Iron accumulation in macrophages promotes the formation of foam cells and development of atherosclerosis.

BACKGROUND: Macrophages that accumulate in atherosclerotic plaques contribute to progression of the lesions to more advanced and complex plaques. Although iron deposition was found in human atherosclerotic plaques, clinical and pre-clinical studies showed controversial results. Several epidemiological studies did not show the positive correlation between a systemic iron status and an incidence of cardiovascular diseases, suggesting that the iron involvement occurs locally, rather than systemically. RESULTS: To determine the direct in vivo effect of iron accumulation in macrophages on the progression of atherosclerosis, we generated Apoe-/- mice with a macrophage-specific ferroportin (Fpn1) deficiency (Apoe-/-Fpn1LysM/LysM). Fpn1 deficiency in macrophages dramatically accelerated the progression of atherosclerosis in mice. Pathophysiological evidence showed elevated levels of reactive oxygen species, aggravated systemic inflammation, and altered plaque-lipid composition. Moreover, Fpn1 deficiency in macrophages significantly inhibited the expression of ABC transporters (ABCA1 and ABCG1) by decreasing the expression of the transcription factor LXRα, which reduced cholesterol efflux and therefore promoted foam cell formation and enhanced plaque formation. Iron chelation relieved the symptoms moderately in vivo, but drastically ex vivo. CONCLUSIONS: Macrophage iron content in plaques is a critical factor in progression of atherosclerosis. The interaction of iron and lipid metabolism takes place in macrophage-rich atherosclerotic plaques. And we also suggest that altering intracellular iron levels in macrophages by systemic iron chelation or dietary iron restriction may be a potential supplementary strategy to limit or even regress the progression of atherosclerosis.

Simultaneous determination of nineteen compounds of Dahuang zhechong pill in rat plasma by UHPLC-MS/MS and its application in a pharmacokinetic study.

Dahuang zhechong pill (DHZCP) is a famous traditional Chinese medicine prescription, which is widely used in the treatment of liver diseases. However, due to the lack of a dynamic DHZCP profile, the in vivo pharmacokinetics of active ingredients within this medicine remains unknown. In this paper, a rapid, sensitive and reliable UHPLC-MS/MS method was used to determine the content of 19 characteristic constituents of DHZCP in rat plasma, including rhein, emodin, chrysophanol, physcion, aloeemodin, p-methoxyphenylacetic acid, hypoxanthine nucleoside, wogonin, wogonoside, baicalin, norwogonin, naringenin, nutmeg acid, paeoniflorin, verbascoside, rhodiola glucoside, forsythoside A, formononetin, and glycyrrhizic acid. An Agilent Extend-C18 column (2.1 mm × 100 mm, 1.8 µm) was used to separate the 19 characteristic constituents, with a mobile phrase of (A) 0.1% formic acid and (B) acetonitrile. The constituents were detected in negative ion mode with multiple reactions monitoring (MRM). The established UHPLC-MS/MS method had good linearity, with a coefficient of determination (r2) of >0.99. The daytime and intra-day precision were less than 12%, and the accuracy ranged from -9.56% to 7.82%. The stability, extraction recovery, and matrix effect met the requirements. The method was successfully applied to the pharmacokinetic study of these nineteen characteristic constituents after oral administration of DHZCP. UHPLC-MS/MS was used for the first time to study the pharmacokinetics of the characteristic chemical constituents in DHZCP, which provided reference and theoretical guidance for further clarification of its pharmacodynamic basis.

Simultaneous improvements on nutrient and Mg recoveries of microalgal bioremediation for municipal wastewater and nickel laterite ore wastewater.

Effects of different mixing ratios between synthetic municipal wastewater (MW) and magnesium (Mg2+)-enriched nickel laterite ore wastewater (NLOWW) on growth of Chlorella sorokiniana (C. sorokiniana), photosynthetic activities, cellular biocomposition, nutrient and Mg2+ removal were investigated in photobioreactors. In the culture without NLOWW, wrinkled cells were observed with low biomass production. The culture mixed with 0.13% NLOWW obtained 1.89-fold higher biomass yield, 3.77-fold enhanced photosynthetic activity (Fv/Fm value), and improved nutrient removal (nitrogen by 102.2%, phosphorus by 39.3%). However, excessive Mg2+ at 100% NLOWW produced highest reactive oxygen species suppressing microalgal growth. The Mg2+ removal capacity increased with NLOWW loading. Moreover, microalgal assimilation primarily contributed to nutrient removal while absorption was the dominant Mg2+ removal pathway. Carbohydrate content in biomass increased with Mg2+ loading. Finally, the approach for MW/NLOWW treatment was demonstrated as economically feasible with revenue of $75.6 per kilogram biomass through a comprehensive economic model.

[Comparative study on differences of Paeonia lactiflora from different habitats based on fingerprint and chemometrics].

This study aims to compare the differences of Paeonia lactiflora from different habitats by establishing fingerprint. The fingerprint of P. lactiflora was established by UPLC. The samples collected from Sichuan,Hebei,Henan,Shanxi and Anhui were analyzed. The common peaks were identified by UPLC-Q-TOF/MS. The relative peak area of the common peaks was analyzed through similarity evaluation system( 2012 edition) for chromatographic fingerprint of traditional Chinese medicine developed by the National Pharmacopoeia Commission. Twelve common peaks were obtained and ten components were identified by reference substance and literature comparison. The similarity of each sample to the reference fingerprint is greater than 0. 900. However,all samples were clearly divided into 5 groups according to habitats after PLS-DA analysis. The peaks 2,6( ethyl gallate),10( galloypaeoniflorin) and 12( benzoyl paeoniflorin) were found to be the main difference components between the samples from five different habitats through the VIP value map. The study found that the variety of ingredients in the different areas are basically similar. But there are some differences in the content of the four components. The results of this study can provide reference at choosing and utilizing P. lactiflora from different places comprehensively.

Rhein reverses doxorubicin resistance in SMMC-7721 liver cancer cells by inhibiting energy metabolism and inducing mitochondrial permeability transition pore opening.

Rhein, a monomeric anthraquinone obtained from the plant herb species Polygonum multiflorum and P. cuspidatum, has been proposed to have anticancer activity. This activity has been suggested to be associated with mitochondrial injury due to the induction of mitochondrial permeability transition pore (mPTP) opening. In this study, the effects of 5-80 µM rhein on cell viability, half-maximal inhibitory concentration (IC50 value), resistance index, and apoptosis were assessed in the liver cancer cell lines SMMC-7721 and SMMC-7721/DOX (doxorubicin-resistant cells). Rhein (10-80 µM) significantly reduced the viability of both cell lines; 20 µM rhein significantly increased sensitivity to DOX and increased apoptosis in SMMC-7721 cells, but reversed resistance to DOX by 7.24-fold in SMMC-7721/DOX cells. Treatment with rhein increased accumulation of DOX in SMMC-7721/DOX cells, inhibited mitochondrial energy metabolism, decreased cellular ATP, and ADP levels, and altered the ratio of ATP to ADP. These effects may result from the binding of rhein with voltage-dependent ion channels (VDACs), adenine nucleotide translocase (ANT), and cyclophilin D, affecting their function and leading to the inhibition of ATP transport by VDACs and ANT. ATP synthesis was greatly reduced and mitochondrial inner membrane potential decreased. Together, these results indicate that rhein could reverse drug resistance in SMMC-7721/DOX cells by inhibiting energy metabolism and inducing mPTP opening. © 2018 BioFactors, 45(1):85-96, 2019.