Engineered Selenium/Human Serum Albumin Nanoparticles for Efficient Targeted Treatment of Parkinson's Disease via Oral Gavage.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopamine (DA) neurons in the midbrain substantia nigra pars compacta (SNpc). While existing therapeutic strategies can alleviate PD symptoms, they cannot inhibit DA neuron loss. Herein, a tailor-made human serum albumin (HSA)-based selenium nanosystem (HSA/Se nanoparticles, HSA/Se NPs) to treat PD that can overcome the intestinal epithelial barrier (IEB) and blood-brain barrier (BBB) is described. HSA, a transporter for drug delivery, has superior biological characteristics that make it an ideal potential drug delivery substance. Findings reveal that HSA/Se NPs have lower toxicity and higher efficacy than other selenium species and the ability to overcome the IEB and BBB to enrich DA neurons, which then protect MN9D cells from MPP+-induced neurotoxicity and ameliorate both behavioral deficits and DA neuronal death in MPTP-model mice. Thus, a therapeutic drug delivery system composed of orally gavaged HSA/Se NPs for the treatment of PD is described.

Secondary metabolites from Aspergillus terreus F6-3, a marine fungus associated with Johnius belengerii.

Two new terrein derivatives asperterreinones A-B (1-2), one new octahydrocoumarin derivative (±)-asperterreinin A (6), along with seventeen known compounds, were isolated from Aspergillus terreus F6-3, a marine fungus associated with Johnius belengerii. The structures of 1, 2, and 6 were established on the basis of 1D and 2D NMR, mass spectroscopy, comparative electronic circular dichroism (ECD) spectra analysis, density functional theory calculation of 13C NMR, and DP4+ probability analysis. Among all the isolates, eurylene (7), a constituent of the Malaysian medicinal plant Eurycoma longifolia, was obtained from a microbial source for first time. In the in vitro bioassay, 11 and 13 showed potent inhibitory activity against the Escherichia coli ß-glucuronidase (EcGUS) with IC50 values of 27.75 ± 0.73 and 17.73 ± 0.81 µM, respectively. It was the first time that questinol (11) and (±)-aspertertone B (13) were reported as potent EcGUS inhibitors.

Structures of L-proline trans-hydroxylase reveal the catalytic specificity and provide deeper insight into AKG-dependent hydroxylation.

L-Proline hydroxylase is a member of the non-heme Fe2+/α-ketoglutarate (AKG)-dependent hydroxylase family that catalyzes the reaction from L-proline to hydroxy-L-proline, which is widely used in drug synthesis, biochemistry, food supplementation and cosmetic industries. Here, the first crystal structure of L-proline trans-hydroxylase and its complexes with substrate and product are reported, which reveal the structural basis of trans-cis proline hydroxylation selectivity. Structure comparison with other AKG-dependent hydroxylases identifies conserved amino acid residues, which may serve as signatures of in-line or off-line AKG binding modes in the AKG-dependent enzyme family.

A Noval Established Cuproptosis-Associated LncRNA Signature for Prognosis Prediction in Primary Hepatic Carcinoma.

The copper ion content in the body maintains homeostasis, and when dysregulated, it can produce cytotoxicity and induce cell death through a variety of pathways. Cuproptosis refers to copper ions combining directly with acylated molecules, leading to the accumulation of oligomerization of lipoylated protein and subsequent downregulation of iron-sulfur cluster proteins; this induces proteotoxic stress and cell death. This study on the relationship between cuproptosis-related lncRNAs (CRLns) and the prognosis of primary hepatic carcinoma (PHC) has important clinical guiding significance for the diagnosis and treatment of PHC. Prognosis-related CRLRs were identified via rank-sum tests, correlational analyses, and univariate Cox regression, and a CRLR risk-scoring model (CRLRSM) was constructed using LASSO Cox regression. Patients were divided into high-risk and low-risk groups based on the median CRLRSM scores. Variance analysis for cuproptosis-related genes, gene set enrichment analysis, and correlational analysis for risk and immunity were performed using boxplots. Quantitative polymerase chain reactions were used to verify the CRLR levels in PHC cell lines. The study results showed that patients in the CRLRSM high-risk group had worse survival rates than those in the low-risk group. The PHC stage and risk score were independent prognostic factors for hepatocellular carcinoma. There were 7 CRLRs (MIR210HG, AC099850.3, AL031985.3, AC012073.1, MKLN1-AS, KDM4A-AS1, and PLBD1-AS1) associated with PHC prognosis, primarily through cellular metabolism, growth, proliferation, apoptosis, and immunity. In conclusion, the overexpression of 7 CRLRs in patients with PHC indicates a poor prognosis.

Study on a novel enzymatic colon-targeted particle of total saponins of Pulsatilla by mechanical grinding technology in a solvent free system.

Oral colon-targeting preparation can achieve targeted drug release in the lesion site and have a great application prospect. In this study, we presented the principle of particle design in the field of materials science into the preparation of colon-targeting preparation. Enzymatic Pulsatilla saponins Colon-targeting composite Microparticles (EPCM) were prepared by mechanical grinding without any organic solvent. Firstly, Response Surface Methodology (RSM) designed by Box-Behnken was used to optimize the preparation process of EPCM, and the structure of EPCM was characterized. All-Atomic and Molecular Dynamics (AAMD) was used to calculate the compatibility between drugs and coating materials before and after release, so as to explain the principle of colon- targeted drug release in this method. Then, colon-targeting characteristics of EPCM in vitro and in vivo were investigated by experiments. Finally, the pharmacodynamics effects of this composite microparticles on Ulcerative Colitis (UC) induced by DSS in C57BL/6 mice were evaluated. The results demonstrated that the colon-targeting composite microparticles could be prepared by mechanical grinding based on particle design principle. The composite microparticles have appropriate colon-targeting drug release performance in vitro and in vivo, and have good anti-ulcerative colitis effect. This study provides a new idea for the preparation of oral colon-targeting preparation of Traditional Chinese medicine, and has evident reference value for the study of coating isolation and powder modification of traditional Chinese medicine for other purposes.

Analysis of the Effect of Holistic Nursing in the Operating Room Based on PDCA and Evidence-Based Nursing in the Otorhinolaryngology Operating Room: Based on a Retrospective Case-Control Study.

Objective: Based on a retrospective case-control study, this study aims to explore the effect of holistic nursing in operating room based on PDCA (plan, do, check, and action) process and evidence-based nursing (EBN) in a ear, nose, and throat operating room. Methods: About 200 patients who underwent otorhinolaryngology surgery in our hospital from January 2019 to September 2021 were enrolled. According to the difference of nursing mode, patients were assigned into a control group and study group; holistic nursing in operating room was included in control group, and holistic nursing in the operating room based on PDCA and EBN was included in study group. Nursing satisfaction, hypothermia, chills, restlessness, related indexes of operating room, nursing quality scores of operating room, and individual quality control scores were compared. Results: First of all, we compared the nursing satisfaction, the study group was very satisfied in 69 cases, satisfactory in 30 cases, general in 1 case, the satisfaction rate was 100.00%, while in the control group, 46 cases were very satisfied, 34 cases were satisfied, 13 cases were general, and 7 cases were dissatisfied, the satisfaction rate was 93.00%. The nursing satisfaction of the study group was higher compared to the control group (P < 0.05). Second, we compared the incidence of hypothermia, chills and restlessness. The incidence of hypothermia, chills, and restlessness in the study group was lower compared to the control group (P < 0.05). The time of tracheal tube extubation, PACU stay time, postoperative hospitalization time, hospitalization cost, and operation time in the study group was significantly lower compared to the control group (P < 0.05). In terms of the scores of nursing quality in the operating room, the instruments and equipment management, equipment preparation, nurses' cooperation skills, disinfection and isolation quality, and total score in the study group were higher compared to the control group (P < 0.05). Finally, we compared the scores of individual quality control examination. The scores of ward management, rescue, therapeutic articles, drug management, first-level nursing, nursing documents, and head nurse management in the study group were higher compared to the control group (P < 0.05). Conclusion: Incorporating the concepts of PDCA and EBN into the overall care of the operating theatre is effective for patients in the ENT operating theatre. Our results show that this care can be effective in improving patients' surgical indicators, reducing the incidence of postoperative infections, shortening postoperative resuscitation and length of stay, reducing hospital costs, and promoting surgical patient satisfaction. While further multicenter studies are necessary, this series of nursing interventions remains worthy of replication in the clinical setting.

Therapeutic efficacy of early photobiomodulation therapy on the zones of stasis in burns: An experimental rat model study.

This study aimed to investigate the role of photobiomodulation therapy in preventing zones of stasis in burn wounds. We hypothesized that photobiomodulation therapy could promote tissue formation and release of nitric oxide (NO), and reduce inflammatory responses, thereby dilating local microvessels, reducing necrosis and apoptosis. Thirty rats were randomly divided into control group (CG) and laser group (LG). The zone of stasis was formed by applying a brass comb to the skin resulting in four rectangular burns separated by three unburned interspaces. The left side was laser wound (LW), while the right side was shielded wound (SW). The LW of LG was immediately subjected to photobiomodulation therapy, followed by once-daily 30-minutes photobiomodulation therapy sessions. Skin ultrasound and Doppler angiography analyses were used to evaluate the statuses of the zones of stasis at 1, 24, and 96 hours after injury. Harvested burn wound tissue was subjected to hematoxylin-eosin staining and HMGB1, caspase 3, and thrombomodulin immunohistochemistry, and the contents of NO and TNF-α were measured in stasis tissue. Thrombomodulin, HMGB1, and caspase 3 immunohistochemistry revealed significantly lower positive staining rates in the LW of LG rats relative to the others at 96 hours (p < 0.05), as well as a significantly higher skin blood flow relative to the others (p < 0.05). The NO content was significantly higher in the LW of LG, compared with other wounds, at 24 and 96 hours after injury (p < 0.05). The TNF-α level was significantly lower in the LW of LG than in other wounds at 96 hours (p < 0.05). Early, local photobiomodulation therapy can effectively ameliorate injury progression in the zone of stasis. However, these beneficial effects are limited to the directly irradiated sites.

[Clinical observation on treatment of type 2 cardiac and kidney syndrome by combination of traditional Chinese and Western medicines].

Clinical observation on treatment of type 2 cardiac and kidney syndrome by combination of traditional Chinese and Western medicine. The patients were divided into two groups： the simple Western medicine treatment group (control group) and the traditional Chinese medicine and Western medicine treatment group (treatment group). The patients in the two groups were treated with conventional western medicine.The treatment group was given based on Buxin Yishen decoction, a total of three courses of treatment to observe the two groups of patients before and after treatment of total efficacy, cardiac function indicators, changes in renal function indicators. The total efficacy of the treatment group and the control group were 91.80% and 72.41%, respectively. There were significant differences between the two groups (P<0.01). The cardiac function indexes and renal function indexes of the treatment group and the control group before and after treatment (P<0.01). Compared with the two groups, the left ventricular function, Hematuria natriuretic peptide, serum creatinine, urea nitrogen, cystatin-C were improved, and the treatment group (P<0.05~0.01). The results showed that the combination of traditional Chinese and Western medicine treatment can improve the clinical efficacy of type 2 heart and kidney syndrome, significantly improve heart and kidney function, better than conventional Western medicine treatment, and has good safety.

[Diversity of agronomic traits of Paris polyphylla var. chinensis and their correlation with rhizome yield and active compositions].

The supply deficiency of crude medicinal plant of Paris polyphylla var. chinensis has become a bottleneck for related medicinal industry. An important approach to increase herbal production is to breed high-yield cultivated variety, which characterized ideal plant morphology. In the present study, we collected 99 wild germplasm resources of P. polyphylla and then measured their 12 main agronomic traits and contents of polyphyllin Ⅶ,Ⅵ,Ⅱ,Ⅰ. Followed analyses were used to characterize those traits and explore the potential connection with herbal yield or quality. The results showed that: ①There was ample morphological diversity in wild P. polyphylla, whose variation of agronomic traits reduced according to followed order: content of polyphyllin, weight of dry rhizome, petiole length, stem length, petal length, pedicel length, sepal length, leaf width, leaf length, sepal width, leaf number, stamen number, petal number. ② Most of those traits were significantly correlated to each other and generally represented the characterization of photosynthetic organs or reproductive organ. ③The total content of polyphyllin Ⅶ,Ⅵ,Ⅱ,Ⅰvaried between 0.02% and 0.87% and averagedat 0.13%, which showed no significant correlation with any agronomic trait. ④Plant breeders should play more attention on those germplasm resources with large leaves, large sepals and high stem.

MicroRNA-328 is involved in the effect of selenium on hydrogen peroxide-induced injury in H9c2 cells.

Oxidative stress induces apoptosis in cardiac cells, and antioxidants attenuate the injury. MicroRNAs (miRNAs) are also involved in cell death; therefore, this study aimed to investigate the role of miRNAs in the effect of selenium on oxidative stress-induced apoptosis. The effects of sodium selenite were analyzed via cell viability, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) concentration. Flow cytometry was used to evaluate cell apoptosis. Fura-2AM was used to calculate intracellular Ca2+ concentration. Sodium selenite could ameliorate hydrogen peroxide (H2 O2 )-induced cell apoptosis and improve expression levels of glutathione peroxidase and thioredoxin reductase. Pretreatment with sodium selenite improved SOD activity and reduced MDA concentration. Treatments with H2 O2 or sodium selenite decreased miR-328 levels. MiR-328 overexpression enhanced cell apoptosis, reduced ATP2A2 levels, and increased intracellular Ca2+ concentration, while inhibition produced opposite effects. MiR-328 might be involved in the effect of sodium selenite on H2 O2 -induced cell death in H9c2 cells.

Zinc levels in seminal plasma and their correlation with male infertility: A systematic review and meta-analysis.

Zinc is an essential trace mineral for the normal functioning of the male reproductive system. Current studies have investigated the relationship between seminal plasma zinc and male infertility but have shown inconsistent results. Hence, we systematically searched PubMed, EMBASE, Science Direct/Elsevier, CNKI and the Cochrane Library for studies that examined the relationship between seminal plasma zinc and male infertility, as well as the effects of zinc supplementation on sperm parameters. Twenty studies were identified, including 2,600 cases and 867 controls. Our meta-analysis results indicated that the seminal plasma zinc concentrations from infertile males were significantly lower than those from normal controls (SMD (standard mean differences) [95% CI] -0.64 [-1.01, -0.28]). Zinc supplementation was found to significantly increase the semen volume, sperm motility and the percentage of normal sperm morphology (SMD [95% CI]: -0.99 [-1.60, -0.38], -1.82 [-2.63, -1.01], and -0.75 [-1.37, -0.14], respectively). The present study showed that the zinc level in the seminal plasma of infertile males was significantly lower than that of normal males. Zinc supplementation could significantly increase the sperm quality of infertile males. However, further studies are needed to better elucidate the correlation between seminal plasma zinc and male infertility.

[Determination of benzyl glucosinolate in Lepidium meyenii from different regions by HPLC].

The content of benzyl isothiocyanate (BITC) which as the enzymatic hydrolysis product of benzyl glucosinolate through thioglucosidase was determined by HPLC. The content of benzyl isothiocyanate (BITC) which as the enzymatic hydrolysis product of benzyl glucosinolate through thioglucosidase was determined by HPLC. The chromatography condition was as follows: Kaseisorb LC ODS 2000 (4.6 mm x 150 mm, 5 min) column with the mobile phase of acetonitrile(A)-water( B) under gradient elution (0-5 min, 3%-8% A; 5-9 min, 8%-48% A; 9-23 min, 48%-62% A; 23-28 min, 62%-99% A); the flow rate was 1.0 mL x min(-1) with 10 microL injection volume; detection wavelength was 246 nm and temperature of column was 40 degrees C. The content of benzyl glucosinolate was in the range of 10.76-17.91 g x L(-1). The method is simple, accurate and good reproducibility which can be used for the determination of benzyl glucosinolate in Lepidium meyenii, effectively.

Notolutesins A-J, dolabrane-type diterpenoids from the Chinese liverwort Notoscyphus lutescens.

Ten new dolabrane-type diterpenoids, notolutesins A-J (1-10), were isolated from the Chinese liverwort Notoscyphus lutescens, along with four known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic data, and that of 1 was confirmed by single-crystal X-ray crystallography. The absolute configuration of 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. All of the isolates were evaluated for their cytotoxicity against a small panel of human cancer cell lines, and compound 1 exhibited an IC50 value of 6.2 µM against the PC3 human prostate cancer cell line.

[Particle settling characteristics of alcohol precipitation mixture of Paeoniae Radix rubra extract and models establishment of settling velocity].

OBJECTIVE: To understand the particle settling characteristics of alcohol precipitation mixture of Paeoniae Radix rubra extract and establish models of the sedimentation rate. METHODS: Focusing on the particle settling characteristics such as particle settling curve, particle settling velocity (PSV), particle volume index (PVI), the particle settling process of alcohol precipitation was investigated. The effect of three key process factors on the settling process was discussed and mathematical models for describing the particle settling velocity were developed. RESULTS: Controlling of higher final alcohol concentration, higher density of Paeoniae Radix rubra extract, or lower initial alcohol concentration, was conducive to settlement of alcohol precipitation particles. In the constant speed phase, an empirical calculation formula of v(0) was established, with both the variables PSV and PVI (v(0)=-0.236PSV+0.022PVI+7.521). Another developed model was applied to predict the settling velocity in decelerated phase and the simulation was very good [v=k(1-n(1)X)(4)exp(-n(2)X)/X]. CONCLUSION: The results of this work will contribute to a better control and optimization of alcohol precipitation process, and help to implementation of accuracy control in the manufacture of botanical medicines.

[Fingerprint of Angelica polymorpha by HPLC].

OBJECTIVE: To establish the HPLC fingerprint of Angelica polymorpha. METHOD: The 10 batches of A. polymorpha were measured by HPLC with isoimperatorin as a reference substance and the chromatographic experients were performed on Kromasil 100A C18 column (4.6 mm x 250 mm, 5 microm), eluted with acetonitrile and water as mobile phase in gradient mode. The flow rate was 1.0 m x min(-1) and the detection wavelength was 254 nm. RESULT: The common mode of the HPLC fingerprints were set up. There were 8 common peaks in the fingerprint of 10 samples, and the similarity of the 10 samples was more than 0.9. CONCLUSION: The method is simple, accurate and have a good reaptability. The quality of A. polymorpha can be controlled effectively by the HPLC fingerprint.

Determination of organophosphorus pesticide residues in vegetables by an enzyme inhibition method using α-naphthyl acetate esterase extracted from wheat flour.

The widespread use of organophosphorus pesticides (OPs) poses a great threat to human health and has made the detection of OP residues in food an important task, especially in view of the fact that easy and rapid detection methods are needed. Because OPs have inhibitory effects on the activity of α-naphthyl acetate esterase (ANAE) in plants, in this work we evaluated the possibility of detecting OPs in vegetables with ANAE extracted from commercial flour. The limits of detection (LODs) obtained for methamidophos, dichlorvos, phoxim, dimethoate, and malathion in lettuce samples with crude ANAE were 0.17, 0.11, 0.11, 0.96, and 1.70 mg/kg, respectively. Based on the maximum residue limits (MRLs) for OPs in food stipulated by Chinese laws which are 0.05, 0.20, 0.05, 1.00, and 8.00 mg/kg for methamidophos, dichlorvos, phoxim, dimethoate, and malathion, respectively, the esterase inhibition method with crude ANAE had sufficient sensitivity to detect the residues of dichlorvos, dimethoate, and malathion in lettuce, but it could not be used to guarantee the safety of the same samples if methamidophos or phoxim residue was present. The sensitivity of the method was improved by the use of esterase purified by ammonium sulfate salting-out. The LODs obtained for methamidophos and phoxim with purified esterase were lower than the MRLs for these OPs in food. This is a very promising method for the detection of OP residues in vegetables using crude or purified esterase because of its cheapness, sensitivity, and convenience.

[Fast analytical method on content and transfer rate of marker component in ethanol precipitation of cinobufacini by near infrared spectroscopy].

The method of near infrared spectroscopy was established to analyze the content and transfer rate of the marker component, indole alkaloids, of cinobufacini in the process of ethanol precipitation. The samples of cinobufacini were collected, and the concentration of indole alkaloids was determined by the reference method, UV-vis spectroscopy. After the rejection of abnormal samples, the pretreatment of spectra and the choice of the corresponding wave band, the multivariate calibration models were established using PLS algorithm between spectra and the UV values. The samples in ethanol precipitation, which did not participate in modeling, were used to examine the performance of the models. The correlation coefficient of the calibration model was 0.9613. Root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) were 0.172 and 0.169, respectively. Furthermore, residual predictive deviation (RPD) of the model was 4.13, which meant quantity analysis was feasible. It is concluded that near infrared spectroscopy can be considered as a fast, effective and non-destructive analysis method applied in the process of ethanol precipitation for traditional Chinese medicine.

[Studies on chemical constituents of Dendranthema indicum var. aromaticum].

OBJECTIVE: To study chemical constituents of Dendranthema indicum var. aromaticum. METHODS: The constituents were separated and purified by column chromatography with silica gel and Semi-preparative HPLC. Their structures were identified on the basis of physical-chemical properties and spectral data. RESULTS: Seven compounds were isolated and identified as acacetin, apignein, acacetin-7-O-beta-D-glucopy ranoside, apignein-7-O-beta-D-glucopy ranosids, luteolin, beta-sitosterol and daucosterol. CONCLUSION: Apigenin, acacetin-7-O-beta-D-glucopy ranoside and apignein-7-O-beta-D-glucopy ranoside are obtained from the plant for the first time.

Studies on the anti-psoriasis constituents of Oplopanax elatus Nakai.

Seven compounds were isolated from roots and stems of Oplopanax elatus, of which compounds 3, 4, 5 and 6 were isolated for the first time from the title plant; compounds 1 and 2 are new compounds and characterised to be 3,3'-dimethoxy-4,9,9'-trihydroxy-4',7-epoxy-5'8-lignan-4,9-bis-O-beta-D-glucopyranoside and 5-methoxylariciresinol-4-O-beta-D-glucopyranoside on the basis of NMR spectra and CD spectrum.

Ginsenoside Rg3 promotes beta-amyloid peptide degradation by enhancing gene expression of neprilysin.

OBJECTIVES: It has been hypothesized that the accumulation of beta-amyloid peptide (Abeta) in the brain is a triggering event leading to the pathological cascade of Alzheimer's disease. The steady-state levels of Abeta are determined by the metabolic balance between anabolic and catabolic activity and the dysregulation of this activity leads to Alzheimer's disease. Recent evidence has shown that neprilysin (NEP) is the rate-limiting enzyme in the Abeta degradation in the brain. Ginseng, the root of Panax ginseng C.A. Meyer, is widely used as a tonic for the prevention and treatment of age-related disorders in China. We aimed to investigate the basis of this use. METHODS: In this study, we investigated the effect of ginsenoside Rg3, one of the major active components of ginseng, on the metabolism of Abeta40 and Abeta42 in SK-N-SH cells transfected with Swedish mutant beta-amyloid precursor protein (SweAPP). RESULTS: The ELISA result showed that Rg3 significantly reduced the levels of Abeta40 and Abeta42, 19.65 +/- 6.05%, 23.61 +/- 6.74%, respectively (P < 0.01). The Western blot analysis showed that Rg3 reduced the levels of Abeta40 and Abeta42 through enhancing NEP gene expression, and real-time PCR assay showed that 50 microM Rg3 could significantly enhance NEP gene expression (2.9 fold at 48 h). CONCLUSIONS: Our findings suggest that the Rg3 compound of ginseng may be useful for treating patients suffering with Alzheimer's disease.