Effectiveness of an ERAS-based exercise-nutrition management model in enhancing postoperative recovery for thoracoscopic radical resection of lung cancer: A randomized controlled trial.

BACKGROUND: To analyze the effect of an exercise-nutrition management model based on the Enhanced Recovery After Surgery (ERAS) concept on patients undergoing thoracoscopic radical surgery for lung cancer. METHODS: From June 2019 to December 2022, 85 lung cancer patients who underwent thoracoscopic radical lung cancer surgery were randomly divided into 2 groups. The control group, consisting of 42 patients, received routine nursing care during the perioperative period. The study group, comprising 43 patients, implemented an exercise-nutrition management model based on the ERAS concept during the perioperative period. We compared general data, perioperative indicators, compliance, and complications between the 2 groups. Additionally, we assessed the nutritional status using the patient-generated subjective global assessment (PG-SGA), albumin (ALB), prealbumin (PA), and hemoglobin (Hb), as well as lung function, including forced expiratory volume in the first second (FEV1) and maximum voluntary ventilation (MVV), in the patient population following the Piper intervention. RESULTS: In the study group, the times to first defecation and getting out of bed, the duration of thoracic drainage tube indwelling, and the length of hospital stay were shorter than those in the control group. The VAS scores on the 2nd and 3rd postoperative days were lower in the study group than in the control group (P < .05). Medication compliance was higher in the study group compared to the control group (P < .05). Post-intervention, the PG-SGA scores in the study group were lower, while PA, ALB, and Hb levels were higher than those in the control group (P < .05). The MVV, FEV1, and FVC values were higher in the study group than in the control group after the intervention (P < .05). The PFS and mMRC scores were lower in the study group compared to the control group after the intervention, and the QLQ-C30 scores were higher (P < .05). The incidence of complications was 6.98% in the study group, which was not significantly different from 11.90% in the control group (P > .05). CONCLUSION: The exercise-nutrition management model, based on the ERAS concept, exhibits significant perioperative effects in patients undergoing thoracoscopic radical resection of lung cancer, improving their nutritional status and reducing complications.

Aloe-Emodin Derivative, an Anthraquinone Compound, Attenuates Pyroptosis by Targeting NLRP3 Inflammasome in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DCM) is widely recognized as a major contributing factor to the development of heart failure in patients with diabetes. Previous studies have demonstrated the potential benefits of traditional herbal medicine for alleviating the symptoms of cardiomyopathy. We have chemically designed and synthesized a novel compound called aloe-emodin derivative (AED), which belongs to the aloe-emodin (AE) family of compounds. AED was formed by covalent binding of monomethyl succinate to the anthraquinone mother nucleus of AE using chemical synthesis techniques. The purpose of this study was to investigate the effects and mechanisms of AED in treating DCM. We induced type 2 diabetes in Sprague-Dawley (SD) rats by administering a high-fat diet and streptozotocin (STZ) injections. The rats were randomly divided into six groups: control, DCM, AED low concentration (50 mg/kg/day), AED high concentration (100 mg/kg/day), AE (100 mg/kg/day), and positive control (glyburide, 2 mg/kg/day) groups. There were eight rats in each group. The rats that attained fasting blood glucose of ˃16.7 mmol/L were considered successful models. We observed significant improvements in cardiac function in the DCM rats with both AED and AE following four weeks of intragastric treatment. However, AED had a more pronounced therapeutic effect on DCM compared to AE. AED exhibited an inhibitory effect on the inflammatory response in the hearts of DCM rats and high-glucose-treated H9C2 cells by suppressing the pyroptosis pathway mediated by the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain 3 (NLRP3) inflammasome. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes showed a significant enrichment in the NOD-like receptor signaling pathway compared to the high-glucose group. Furthermore, overexpression of NLRP3 effectively reversed the anti-pyroptosis effects of AED in high-glucose-treated H9C2 cells. This study is the first to demonstrate that AED possesses the ability to inhibit myocardial pyroptosis in DCM. Targeting the pyroptosis pathway mediated by the NLRP3 inflammasome could provide a promising therapeutic strategy to enhance our understanding and treatment of DCM.

Neotuberostemonine and tuberostemonine ameliorate pulmonary fibrosis through suppressing TGF-ß and SDF-1 secreted by macrophages and fibroblasts via the PI3K-dependent AKT and ERK pathways.

Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-ß and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg-1 bleomycin and orally administered with 30 mg·kg-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-ß and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-ß1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-ß through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-ß and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.

Synergistic effect of constituent drugs of Baibutang on improving Yin-deficiency pulmonary fibrosis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Baibutang (BBT) is an ancient prescription for the treatment of pulmonary fibrosis. Previous experiments have shown that BBT had a good therapeutic effect on pulmonary fibrosis. However, there had been no study on the synergy between drugs composed of BBT. Due to the interaction between the constituent drugs, exploring their synergy profile is of great significance for explaining the essence of BBT's efficacy in improving pulmonary fibrosis. AIM OF THE STUDY: Based on the pharmacodynamic value, this study aimed to explore a method for the evaluation of the synergy profile between constituent drugs in traditional Chinese medicine (TCM) compounds. MATERIALS AND METHODS: Nine herbs of BBT were divided into Zhikeqingre (ZK), Yangyinyiqi (YY) and Lishijianpi (LS) groups. A rat model of Yin-deficiency pulmonary fibrosis induced by thyroxine-bleomycin was used to evaluate the effects of BBT and the three groups. The pathological changes of lung tissue and the changes of biomarkers associated with fibrosis, Yin-deficiency and water-fluid metabolism were detected. After standardization of pharmacodynamics value (PV), the compatibility coefficient (CC) of the three groups, the relative PV (RPV) and contribution value (CV) of each group on every index were calculated. RESULTS: The average CC on fibrosis indexes was 0.44, indicating that 44% of the efficacy of BBT came from the synergistic effect of the three groups. ZK group had the highest RPV (0.80) in improving fibrosis indexes such as histopathological changes, α-SMA, collagen-I and renin-angiotensin system. The average CC on Yin-deficiency indexes was 0.25, and YY group had the highest RPV (0.96) in improving deficiency indexes such as body temperature, cAMP/cGMP ratio, and PDEs, PGE2 and COX-2 levels. The average CC on water-fluid metabolism indexes was 0.15, and LS group had the highest RPV (1.52) in improving water-fluid metabolism indexes such as aquaporins, mucins, and surfactant proteins. The results also showed that 29% of the improvement effect of BBT on all indexes came from the synergistic effect of the three groups, and the contribution of ZK, YY and LS groups to the efficacy of BBT were 25%, 25% and 21%, respectively. CONCLUSION: The established semiquantitative method can clearly and simply evaluate the synergy of the three groups in BBT, which will help to promote the research on the synergy of TCM compounds and other multiple-components combinations.

The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer.

Artemisinin (ART) is a bioactive molecule derived from the Chinese medicinal plant Artemisia annua (Asteraceae). ART and artemisinin derivatives (ARTs) have been effectively used for antimalaria treatment. The structure of ART is composed of a sesquiterpene lactone, including a peroxide internal bridge that is essential for its activity. In addition to their well-known antimalarial effects, ARTs have been shown recently to resist a wide range of tumors. The antineoplastic mechanisms of ART mainly include cell cycle inhibition, inhibition of tumor angiogenesis, DNA damage, and ferroptosis. In particular, ferroptosis is a novel nonapoptotic type of programmed cell death. However, the antitumor mechanisms of ARTs by regulating ferroptosis remain unclear. Through this review, we focus on the potential antitumor function of ARTs by acting on ferroptosis, including the regulation of iron metabolism, generation of reactive oxygen species (ROS), and activation of endoplasmic reticulum stress (ERS). This article systematically reviews the recent progress in ferroptosis research and provides a basis for ARTs as an anticancer drug in clinical practice.

Photothermal-Chemotherapy Enhancing Tumor Immunotherapy by Multifunctional Metal-Organic Framework Based Drug Delivery System.

Immunotherapy holds great promise for patients undergoing tumor treatment. However, the clinical effect of immunotherapy is limited because of tumor immunogenicity and its immunosuppressive microenvironment. Herein, the metal-organic framework (MIL-100) loaded with chemotherapeutic agent mitoxantrone (MTO) was combined with photothermal-chemotherapy for enhancing immunogenic cell death. MIL-100 loaded with MTO and hyaluronic acid as nanoparticles (MMH NPs) yielded an NP with two therapeutic properties (photothermal and chemotherapy) with dual imaging modes (photoacoustic and thermal). When MMH NPs were coinjected with an anti-OX40 antibody in colorectal cancer, the highest antitumor efficacy and a robust immune effect were achieved. This work provides a novel combined therapeutic strategy, which will hold great promise in future tumor therapy.

Quantification of sorafenib, lenvatinib, and apatinib in human plasma for therapeutic drug monitoring by UPLC-MS/MS.

Sorafenib, lenvatinib, and apatinib, as multi-targeted tyrosine kinase inhibitors with anti-proliferative and anti-angiogenic effects, are widely used for systemic therapy in advanced hepatocellular carcinoma patients. Nevertheless, insufficient efficacy or adverse effects often appear due to the significant inter-individual variability of plasma concentration for these drugs. In order to carry out therapeutic drug monitoring of these drugs and then ensure the effectiveness and safety of the medical treatment, the first method allowing to quantify sorafenib, lenvatinib, and apatinib simultaneously in human plasma was developed in this study. The analysis was performed by UPLC-MS/MS system and the chromatographic separation was achieved on a C18 column using a gradient elution of water-acetonitrile in 3.5 min. This method presented satisfactory results in terms of specificity, precision (coefficient of variation of intra-day and inter-day:1.4-6.6 %), accuracy (92.6-105.4 %), matrix effects (96.9-107.2 %), extraction recovery (90.5-99.4 %), as well as stability in human plasma and even whole blood under certain conditions. This sensitive, rapid and simple method was successfully applied to the analysis of sorafenib, lenvatinib and apatinib for therapeutic drug monitoring in hepatocellular carcinoma patients, and it was expected to be applied to further study about clarifying the concentration- efficacy and concentration-toxic relationship of sorafenib, lenvatinib, and apatinib in hepatocellular carcinoma patients.

[Therapeutic effect of acupuncture combined with medication on chronic prostatitis of damp and heat stasis].

OBJECTIVE: To observe the clinical therapeutic effect of electroacupuncture (EA) combined with tamsulosin hydrochloride sustained release capsule on chronic prostatitis (CP) of damp and heat stasis. METHODS: A total of 70 patients with CP of damp and heat stasis were randomized into an acupuncture plus medication group (35 cases, 4 cases dropped off) and a medication group (35 cases, 5 cases dropped off). In the medication group, tamsulosin hydrochloride sustained release capsule was given orally, 0.2 mg a time, once each night. On the basis of treatment in the medication group, EA was applied at Guanyuan (CV 4), Sanyinjiao (SP 6) and Yinglingquan (SP 9), with disperse-dense wave, 5 mA in intensity for 30 min. Treatment for 30 days was as one course, and totally 3 courses were required in both groups. Before treatment, 1, 2, 3 months into treatment and at the follow-up of 2 months after treatment, the TCM syndrome score and National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score were observed, and the clinical efficacy was evaluated in both groups. RESULTS: Compared before treatment, the TCM syndrome scores of 3 months into treatment and follow-up were decreased in the acupuncture plus medication group (P<0.01), and were lower than those in the medication group (P<0.05). Compared before treatment, the NIH-CPSI scores of 3 months into treatment and follow-up were decreased in both groups (P<0.01), and those in the acupuncture plus medication group were lower than the medication group (P<0.05). The total effective rate was 90.3% (28/31) in the acupuncture plus medication group, which was superior to 80.0% (24/30) in the medication group (P<0.05). CONCLUSION: Acupuncture combined with medication can improve the clinical symptoms in patients with CP of damp and heat stasis, and its therapeutic effect is superior to simple western medication.

Notoginsenoside R1 Protects Against the Acrylamide-Induced Neurotoxicity via Upregulating Trx-1-Mediated ITGAV Expression: Involvement of Autophagy.

Acrylamide (ACR) is a common chemical used in various industries and it said to have chronic neurotoxic effects. It is produced during tobacco smoking and is also generated in high-starch foods during heat processing. Notoginsenoside R1 (NR1) is a traditional Chinese medicine, which is used to improve the blood circulation and clotting. The objective of this study was to investigate the mechanism of ACR-triggered neurotoxicity and to identify the protective role of NR1 by upregulating thioredoxin-1 (Trx-1). Our results have shown that NR1 could block the spatial and cognitive impairment caused by ACR administration. Bioinformatics analysis revealed that Trx-1 regulated autophagy via Integrin alpha V (ITGAV). NR1 could resist the ACR-induced neurotoxicity by upregulating thioredoxin-1 in PC12 cells and mice. The autophagy-related proteins like autophagy-related gene (ATG) 4B, Cathepsin D, LC3 II, lysosomal-associated membrane protein 2a (LAMP2a), and ITGAV were restored to normal levels by NR1 treatment in both PC12 cells and mice. Besides, we also found that overexpression of Trx-1 resisted ACR-induced autophagy in PC12 cells and downregulation of Trx-1 triggered autophagy induced by ACR in PC12 cells. Therefore, it could be concluded that Trx-1 was involved in the autophagy pathway. Besides, we also found that ITGAV was an intermediate node linking Trx-1 and the autophagy pathway.

Highly Enhanced Antitumor Immunity by a Three-Barreled Strategy of the l-Arginine-Promoted Nanovaccine and Gene-Mediated PD-L1 Blockade.

Weak T cell responses and immune checkpoints within tumors could be two key factors for limiting antitumor efficacy in the field of cancer immunotherapy. Thus, the combined strategy of tumor vaccines and immune checkpoint blockade has been widely studied and expected to boost antitumor immune responses. Herein, we first developed a two-barreled strategy to combine the nanovaccine with a gene-mediated PD-L1 blockade. On the one hand, polyethyleneimine (PEI) worked as a vaccine carrier to codeliver the antigen ovalbumin (OVA) and the adjuvant unmethylated cytosine-phosphate-guanine (CpG) to formulate the PEI/OVA/CpG nanovaccine through electrostatic binding, which realized both dendritic cell activation and antigen cross-presentation enhancement. On the other hand, the PD-L1 silence gene was loaded by PEI to form PEI/pshPD-L1 complexes, which were further in situ shielded by aldehyde-modified polyethylene glycol (OHC-PEG-CHO) via pH-responsive Schiff base bonds. The formed pshPD-L1@NPs could decrease PD-L1 expression on the tumor cells. However, such a combined two-barreled strategy improved feebly for tumor inhibition in comparison with monotherapy, exhibiting the antagonistic effect, which might be due to the limited T cell response enhancement in the tumor microenvironment. To solve this problem, we have further developed a three-barreled strategy to combine oral administration of l-arginine, which worked as an amplifier to induce robust T cell response enhancement, without causing the upregulation of other negative immune regulators. Superior antitumor behavior and tumor rechallenge protection were realized by the three-barreled strategy in B16F10-OVA (B16-OVA)-bearing mice. The unique three-barreled strategy we developed might offer a novel clinical therapeutic treatment.

Emodin improves glucose metabolism by targeting microRNA-20b in insulin-resistant skeletal muscle.

BACKGROUND: Emerging evidence has indicated the therapeutic potential of emodin with its multiple pharmacological effects. PURPOSE: To evaluate role of emodin in regulating insulin resistance (IR) and to elucidate the underlying molecular mechanisms. STUDY DESIGN/METHODS: Fasting blood glucose (FBG) and lipid levels were measured before and after intragastric administration of emodin in type 2 diabetes mellitus (T2DM) rats. Glucose consumption was determined in L6 cells to investigate the effect of emodin on glucose metabolism. Expression of miR-20b and SMAD7 was quantified by real-time PCR for mRNAs or western blot analysis for proteins. RESULTS: Emodin ameliorated hyperglycemia and dyslipidemia in T2DM rats, and glucose metabolism in a concentration- and time-dependent manner. MiR-20b was markedly upregulated in the setting of IR and overexpression of miR-20b disrupted glucose metabolism by repressing SMAD7 in L6 cells. Knockdown of this miRNA produced the opposite effects. Emodin abolished the abnormal upregulation of miR-20b and indirectly upregulated SMAD7. CONCLUSION: Emodin improves glucose metabolism to produce anti-IR effects, and downregulation of miR-20b thereby upregulation of SMAD7 is an underlying mechanism for the beneficial effects of emodin.

A newborn with seizures born to a mother diagnosed with primary carnitine deficiency.

BACKGROUND: Maternofetal carnitine transport through the placenta is the main route of fetal carnitine uptake. Decreased free carnitine levels discovered by newborn screening has identified many asymptomatic adult women with systemic primary carnitine deficiency (PCD). Here, we presented amplitude integrated electroencephalogram (aEEG) and magnetic resonance imaging (MRI) findings from a neonate with epilepsy whose mother was carnitine deficient. CASE PRESENTATION: A one-day-old female newborn was admitted after experiencing seizures for half a day; status epilepticus was found on the continuous normal voltage background pattern with immature sleep-wake cycling during aEEG monitoring. On T1-weighted, T2-weighted, FLAIR, and DWI head MRI, there were various degrees of hyperintense signals and diffusion restrictions in the deep white matter of the right hemisphere. Tandem mass spectrometry discovered carnitine deficiency on the second day, which elevated to normal by the 9th day before L-carnitine supplementation was started. The patient was treated with phenobarbital after admission. No further seizures were noted by day 5. It was confirmed that the patient's mother had a low level of serum-free carnitine. Gene analyses revealed that the newborn had heterozygote mutations on c.1400C > G of the SLC22A5 gene, and her mother had homozygous mutations on c.1400C > G. The patient had a good outcome at the 8-month follow up. CONCLUSIONS: Maternal carnitine deficiency that occurs during the perinatal period may manifest as secondary epilepsy with cerebral injury in neonates. The short-term neurodevelopmental outcomes were good. Early diagnosis of asymptomatic PCD in female patients can provide guidance for future pregnancies.

Effects of Enhanced Exercise and Combined Vitamin D and Calcium Supplementation on Muscle Strength and Fracture Risk in Postmenopausal Chinese Women.

Objective To observe the effects of enhanced exercise and combined vitamin D and calcium supplementation on muscular strength and fracture occurrence in postmenopausal women with a high risk of osteoporosis.Methods Totally 614 postmenopausal women at high risk factors of osteoporosis were enrolled in Dongcheng district of Beijing and randomized into four groups:group A(control group,n=173),group B(regular Tai Chi exercise,n=171),group C(calcium 600 mg/d+VitD3 800 U/d,n=139),and group D[calcium 600 mg/d+25 hydroxyl vitamin D(25OHD) 0.25 µg/d,n=131].Muscular strength was measured at baseline and one and two years after intervention.Bone turnover markers were measured at baseline and during the two-year follow-up.Falls and fractures were recorded.Results The incidence of 25OHD<50 nmol/L was approximately 92.6%.During the follow-up,the left grip strength decreased significantly two years after intervention(t=-3.252,P=0.001)in group A.Right grip strength decreased significantly in group B(t=2.460,P=0.015)while left grip strength improved significantly in group C(t=-2.051,P=0.043)one year after intervention.In group D,muscular strength in both 12-month and 24-month did not change compared with baseline(both P>0.05).Furthermore,serum procollagen type I N-terminal propeptide elevated significantly in group A(t=-2.962,P=0.004),group B(t=-2.888,P=0.005),and group C(t=-2.441,P=0.016),whereas ß-C-terminal telopeptide of type I collagen decreased significantly in group B(t=2.285,P=0.024)and group D(t=2.596,P=0.011)two years after intervention.Conclusion Enhanced exercise and combined calcium vitamin D supplementation may help sustain muscle strength in postmenopausal women,while calcium and vitamin D supplementation may improve muscular strength within a short period of time.

Geodermatophilus daqingensis sp. nov., isolated from petroleum-contaminated soil.

A novel Gram-positive actinobacterium, designated WT-2-1T, was isolated from a sample of petroleum-contaminated soil collected in Daqing, Heilongjiang province, China and characterised using a polyphasic taxonomic approach. The optimal growth for strain WT-2-1T was found to be at 25-35 °C and at pH 6.0-9.0 and with 0-4% (w/v) NaCl, forming blackish green-coloured colonies. Chemotaxonomic and molecular characteristics of the isolate match those described for members of the genus Geodermatophilus. The peptidoglycan was found to contain meso-diaminopimelic acid; galactose, glucose and xylose were detected as diagnostic sugars. The main phospholipids were identified as diphosphatidylglycerol, phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine and phosphatidylglycerol; MK-9(H4) was the dominant menaquinone present. The major cellular fatty acids were identified as iso-C16:0 and iso-C15:0. 16S rRNA gene sequence analysis showed that strain WT-2-1T is a member of the genus Geodermatophilus, with high sequence similarities to Geodermatophilus aquaeductus BMG801T (98.4%), Geodermatophilus saharensis CF5/5T (98.4%), Geodermatophilus bullaregiensis BMG841T (98.3%) and Geodermatophilus normandii CF5/3T (98.3%). Based on the phenotypic characteristics, phylogenetic data and DNA-DNA hybridization results, the isolate is concluded to represent a novel species of the genus Geodermatophilus, for which the name Geodermatophilus daqingensis sp. nov. is proposed. The type strain is WT-2-1T (=CGMCC 4.7381T = DSM 104001T).

Ultraviolet B Inhibits IL-17A/TNF-α-Stimulated Activation of Human Dermal Fibroblasts by Decreasing the Expression of IL-17RA and IL-17RC on Fibroblasts.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease, and a mixed Th1/Th17 cytokine environment plays a critical role in the pathogenesis of psoriasis. Dermal fibroblasts secrete certain cytokines such as IL-6, IL-8, and CXCL-1, contributing to the hyperproliferative state of the epidermis in psoriatic skin. Ultraviolet B (UVB) phototherapy is one of the most commonly used treatments in psoriasis but the influence of UVB on human dermal fibroblasts (HDFs) in psoriasis treatment is not completely understood. OBJECTIVES: We conducted this study to mimic a psoriatic microenvironment in order to investigate and illustrate the combined effects of UVB, IL-17A, and TNF-α on HDFs. METHODS: The cultured HDFs were obtained from foreskin samples and divided into four groups, as follows: control; IL-17A/TNF-α; UVB; and IL-17A/TNF-α + UVB. Cultured HDFs were irradiated with 30 mJ/cm2 UVB followed by addition of IL-17A/TNF-α and incubated for 24 h. We used real-time quantitative PCR, Western blot, ELISA analysis, and flow cytometry to examine gene and protein expression of related pro-inflammatory cytokines and chemokines and receptors. RESULTS: HDFs produced significant IL-6, IL-8, and CXCL-1 in response to IL-17A/TNF-α stimulation and UVB irradiation but UVB irradiation inhibited IL-17A/TNF-α-induced IL-6, IL-8, and CXCL-1 expression and downregulated the expression of IL-17RA and IL-17RC at both gene and protein levels. Additionally, UVB irradiation induced significant TGF-ß1 protein secretion and expression of Smad3 mRNA and protein by HDFs. TGF-ß1 significantly induced the expression of Smad3 mRNA and downregulated the IL-17RA and IL-17RC expression on HDFs. CONCLUSION: UVB irradiation inhibits IL-17A/TNF-α-induced IL-6, IL-8, and CXCL-1 production in HDFs by decreasing the expression of IL-17RA and IL-17RC on fibroblasts through TGF-ß1/Smad3 signaling pathway, which reveals a new mechanism of the therapeutic action of UVB on psoriasis.

Systemic abnormalities of psoriatic patients: a retrospective study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease related to the metabolic syndrome, cardiovascular disease, and other comorbidities. However, so far there has been no specific research concerning systemic abnormalities in psoriatic patients. OBJECTIVE: A retrospective study was conducted focusing on the detailed systemic abnormalities in psoriatic patients. METHODS: Psoriatic inpatients data was collected from July 2009 to September 2015. The inclusion criteria were first-time hospitalization and without administration of systemic drug therapy or exposure to phototherapy for psoriasis for at least 1 month. Detailed systemic indexes were mainly evaluated. RESULTS: The abnormality rates of blood routine examination, urine examination, blood biochemical examination and chest X-ray of 43 psoriatic patients were significantly higher than those of 44 non-psoriasis controls, and psoriasis patients significantly had higher absolute values of leukocytes and neutrophils, and significantly lower values of lymphocytes. Compared with psoriasis vulgaris, erythrodermic psoriasis had significantly higher abnormality rates of blood biochemical examination and serum electrolyte analysis. Erythrodermic psoriasis had significantly higher absolute values of blood leukocytes, neutrophils, and lower serum calcium compared with those of psoriasis vulgaris. The neutrophil-to-lymphocyte ratio of controls was significantly lower than that of psoriatic patients, and neutrophil-to-lymphocyte ratio of erythrodermic psoriasis was significantly higher in comparison with psoriasis vulgaris. CONCLUSION: This study is the first report in relation to a detailed assessment of systemic abnormalities in psoriatic patients prior to onset of systemic treatment. The systemic condition of psoriatic patients should be observed by clinicians before systemic therapy.

Expression of Codon-Optimized Plant Glycosyltransferase UGT72B14 in Escherichia coli Enhances Salidroside Production.

Salidroside, a plant secondary metabolite in Rhodiola, has been demonstrated to have several adaptogenic properties as a medicinal herb. Due to the limitation of plant source, microbial production of salidroside by expression of plant uridine diphosphate glycosyltransferase (UGT) is promising. However, glycoside production usually remains hampered by poor expression of plant UGTs in microorganisms. Herein, we achieved salidroside production by expression of Rhodiola UGT72B14 in Escherichia coli (E. coli) and codon optimization was accordingly applied. UGT72B14 expression was optimized by changing 278 nucleotides and decreasing the G+C content to 51.05% without altering the amino acid sequence. The effect of codon optimization on UGT72B14 catalysis for salidroside production was assessed both in vitro and in vivo. In vitro, salidroside production by codon-optimized UGT72B14 is enhanced because of a significantly improved protein yield (increased by 4.8-fold) and an equivalently high activity as demonstrated by similar kinetic parameters (K M and V max), compared to that by wild-type protein. In vivo, both batch and fed-batch cultivation using the codon-optimized gene resulted in a significant increase in salidroside production, which was up to 6.7 mg/L increasing 3.2-fold over the wild-type UGT72B14.

Shensong Yangxin Capsule prevents diabetic myocardial fibrosis by inhibiting TGF-ß1/Smad signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Shensong Yangxin Capsule (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the effect of SSYX on interstitial fibrosis in diabetic cardiomyopathy is unknown. The objective of this study was to investigate the effects of SSYX on myocardial fibrosis in diabetic rats. MATERIALS AND METHODS: The antifibrotic effect of SSYX was investigated in streptozocin (STZ)-induced diabetic rats with high fat-diet (HFD). Fasting blood glucose, heart weight/body weight (HW/BW) ratio, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were measured. Echocardiography and histology examination were carried out to evaluate heart function. Expressions of Smad7, TGF-ß1, collagen I (col-1), collagen III (col-3), MMP-2, MMP-9 and α-SMA mRNA in heart tissues were measured by real time polymerase chain reaction (PCR). TGF-ß1, Smad2/3, p-Smad2/3 and Smad7 protein levels were measured by western blot analysis. Proliferation of cardiac fibroblast was detected via immunofluorescence. RESULTS: SSYX markedly decreased HW/BW ratio and improved the impaired cardiac function of type-2 diabetes mellitus (T2DM) rats. Transmission electron microscopy (TEM), haematoxylin and eosin (HE) and Masson staining results showed that SSYX attenuated cardiac fibrosis and collagen deposition in T2DM rats. Moreover, mRNA levels of TGF-ß1, col-1, col-3, MMP-2, MMP-9 and α-SMA were downregulated, whereas Smad7 expression was upregulated after treatment with SSYX in rats with cardiac fibrosis. Furthermore, SSYX decreased protein levels of TGF-ß1 and p-Smad2/3, and increased Smad7 expression. CONCLUSION: TGF-ß1/Smad signaling is involved in the cardiac fibrosis in diabetic cardiomyopathy and SSYX inhibits fibrosis and improves cardiac function via suppressing this pathway. Therefore, SSYX might be considered as an alternative therapeutic remedy for diabetic cardiomyopathy.

Isolation and characterization of an α-glucosidase inhibitor from Musa spp. (Baxijiao) flowers.

The use of α-glucosidase inhibitors is considered to be an effective strategy in the treatment of diabetes. Using a bioassay-guided fractionation technique, five Bacillus stearothermophilus α-glucosidase inhibitors were isolated from the flowers of Musa spp. (Baxijiao). Using NMR spectroscopy analysis they were identified as vanillic acid (1), ferulic acid (2), ß-sitosterol (3), daucosterol (4) and 9-(4'-hydroxyphenyl)-2-methoxyphenalen-1-one (5). The half maximal inhibitory concentration (IC50) values of compounds 1-5 were 2004.58, 1258.35, 283.67, 247.35 and 3.86 mg/L, respectively. Compared to a known α-glucosidase inhibitor (acarbose, IC50=999.31 mg/L), compounds 3, 4 and 5 showed a strong α-glucosidase inhibitory effect. A Lineweaver-Burk plot indicated that compound 5 is a mixed-competitive inhibitor, while compounds 3 and 4 are competitive inhibitors. The inhibition constants (Ki) of compounds 3, 4 and 5 were 20.09, 2.34 and 4.40 mg/L, respectively. Taken together, these data show that the compounds 3, 4 and 5 are potent α-glucosidase inhibitors.

Effect of low-dose alendronate treatment on bone mineral density and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis.

OBJECTIVE: The aim of this study was to evaluate the effect of low-dose alendronate (ALN) treatment on bone mineral density (BMD) and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis. METHODS: This study was a large-sample, randomized, open-label, prospective, multicenter, clinical trial with a 12-month follow-up. A total of 639 postmenopausal women (aged 62.2 ± 7.0 y) with osteopenia or osteoporosis were randomized into two groups: low-dose ALN (70 mg every two weeks) and standard-dose ALN (70 mg weekly). All patients were also supplemented with calcium (600 mg) and vitamin D3 (125 IU) daily. BMD (measured by dual-energy x-ray absorptiometry; Hologic and Lunar) and levels of serum bone turnover markers (bone resorption marker, carboxy-telopeptide of type I collagen; bone formation marker, alkaline phosphatase) were assessed at baseline and at 3, 6, and 12 months of treatment. BMD and bone turnover markers were compared between the baseline and the end of treatment, and the changes in BMD and bone turnover markers were also compared between the low-dose ALN group and the standard-dose ALN group. RESULTS: No significant differences in age, years since menopause, body mass index, BMD, 25-hydroxy vitamin D level, and serum biochemical markers were found at baseline between the two dose groups. A total of 558 (87.3%) and 540 (84.5%) women completed the treatment at the 6th and 12th months, respectively. After the 12-month treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly in both of the treatment groups (P < 0.01), and no differences in percentage changes in BMD at the lumbar spine, femoral neck, and hip were found between the low-dose group (5.60%, 3.87%, and 3.28%, respectively) and the standard-dose group (5.07%, 2.93%, and 3.80%, respectively; P > 0.05). However, levels of serum alkaline phosphatase and carboxy-telopeptide of type I collagen in the standard-dose group decreased moderately compared with those in the low-dose group (P < 0.05 and P < 0.01). The women tolerated the two doses of ALN quite well. Adverse effects were similar in the two groups. CONCLUSIONS: Treatment with low-dose ALN (70 mg every two weeks) in women with postmenopausal osteopenia or osteoporosis effectively increases lumbar spine and hip BMD, similar to treatment with standard-dose ALN. Low-dose ALN may be a cost-effective and safe protocol for treating osteopenia or osteoporosis in Chinese women.