Integrated Serum Pharmacochemistry and Network Pharmacological Analysis Used To Explore Possible Anti-Aging Mechanisms of the Ginsenosides

BACKGROUND: Although constitutive ginsenosides are credited with ginseng's remarkable anti-aging efficacy, the mechanism of action and bioactive components of ginsenosides are unclear. OBJECTIVE: The goal of the study was to examine the effect of ginsenosides on D-galactose (D-gal)-induced aging in rats and to figure out the underlying molecular mechanism using serum pharmacochemistry and network pharmacology. METHODS: Using behavioral, biochemical indexes, and histological analysis, ginsenosides were evaluated for their anti-aging effects in rats induced by D-gal, and effective ingredients absorbed in the blood were examined by ultra-performance liquid chromatography quadrupole time of flight coupled with mass spectrometry (UPLC-Q/TOF-MS) before being subjected to network pharmacology analysis. RESULTS: As well as improving spatial learning and memory skills, Ginsenosides are known to regulate malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity. In addition, it improved the ultrastructure of neurons in D-gal-induced rats' hippocampus. Seventy-four absorption components and metabolites of ginsenosides were identified in aging rat serum. According to a network pharmacology study, ginsenosides have anti-aging properties by modulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinases (MAPK) signaling pathways. CONCLUSION: The potential mechanisms of the anti-aging effect of ginsenosides involve multiple components, targets, and pathways. These findings serve as a foundation for further research into the processes behind ginsenoside's anti-aging impact.

Adrenomedullin in paraventricular nucleus attenuates adipose afferent reflex and sympathoexcitation via receptors mediated nitric oxide-gamma-aminobutyric acid A type receptor pathway in rats with obesity-related hypertension.

BACKGROUND: Hypothalamic paraventricular nucleus (PVN) is an important central site for the control of the adipose afferent reflex (AAR) that increases sympathetic outflow and blood pressure in obesity-related hypertension (OH). METHOD: In this study, we investigated the effects of nitric oxide (NO) and cardiovascular bioactive polypeptide adrenomedullin (ADM) in the PVN on AAR and sympathetic nerve activity (SNA) in OH rats induced by a high-fat diet. RESULTS: The results showed that ADM, total neuronal NO synthase (nNOS) and phosphorylated-nNOS protein expression levels in the PVN of the OH rats were down-regulated compared to the control rats. The enhanced AAR in OH rats was attenuated by PVN acute application of NO donor sodium nitroprusside (SNP), but was strengthened by the nNOS inhibitor nNOS-I, guanylyl cyclase inhibitor (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) and gamma-aminobutyric acid A type receptor (GABAA) antagonist Bicuculline. Moreover, PVN ADM microinjection not only decreased basal SNA but also attenuated the enhanced AAR in OH rats, which were effectively inhibited by ADM receptor antagonist ADM22-52, nNOS-I, ODQ or Bicuculline pretreatment. Bilateral PVN acute microinjection of ADM also caused greater increases in NO and cyclic guanosine monophosphate (cGMP) levels, and nNOS phosphorylation. Adeno-associated virus vectors encoding ADM (AAV-ADM) transfection in the PVN of OH rats not only decreased the elevated AAR, basal SNA and blood pressure (BP), but also increased the expression and activation of nNOS. Furthermore, AAV-ADM transfection improved vascular remodeling in OH rats. CONCLUSION: Taken together, our data highlight the roles of ADM in improving sympathetic overactivation, enhanced AAR and hypertension, and its related mechanisms associated with receptors mediated NO-cGMP-GABAA pathway in OH condition.

Ribosome-inactivating protein MAP30 isolated from Momordica charantia L. induces apoptosis in hepatocellular carcinoma cells.

BACKGROUND: Ribosome-inactivating proteins (RIPs) have been reported to exert anti-tumor and anti-virus activities. A recent patent CN202011568116.7 has developed a new method to prepare Momordica anti-HIV protein of 30 kDa (MAP30). MAP30 is a type I RIP, which kills various tumor cells through the N-glycosidase activity and irreversibly inhibits protein synthesis. OBJECTIVE: To assess the potential role of MAP30 in inducing apoptosis of human hepatocellular carcinoma HCC-LM3 cells and elucidate the molecular mechanism of MAP30. METHODS: CC-8 assay was used to assess the proliferation of HCC-LM3 cells. Flow cytometry was used to measure the cycle, the level of ROS and apoptosis in HCC-LM3 cells. Western blots were used to measure protein levels Results: Treatment with MAP30 reduced survival and proliferation of human liver cancer HCC-LM3 cells in a dose-dependent manner. PI staining showed cell cycle arrest in G0/G1 phase. Furthermore, MAP30 increased the level of ROS in HCC-LM3 cells in 24 h treatment. To further confirm the role of MAP30 in inducing cell apoptosis, immunoblotting was carried out to detect the change of apoptosis-related proteins including PARP poly (ADP-ribose) polymerase (PARP-1), Casepase3 and Cleaved-Caspase9. We found that PARP-1 and Caspase-3 were downregulated, whereas Cleaved-Caspase9 were up-regulated in HCC-LM3 cells treated with MAP30. CONCLUSION: This study indicated that MAP30 has the potential to be a novel therapeutic agent for human hepatocellular carcinoma.

Challenges and strategies in high-accuracy manufacturing of the world's largest SiC aspheric mirror.

In the process of manufacturing the world's largest silicon carbide (SiC) aspheric mirror, the primary difficulties are mirror blank preparation, asphere fabrication, and testing, as well as cladding and coating. Specifically, the challenges include the homogeneity of the complicated structure casting, accuracy and efficiency of the fabrication process, print-through effect, fidelity and precision of test procedure, stress and denseness of cladding process, the dynamic range of interferometric measurement, and air turbulence error due to the long optical path. To break through such a barrier of difficulties, we proposed the water-soluble room temperature vanishing mold and gel casting technology, homogeneous microstructure reaction-formed joint technology, nano-accuracy efficient compound fabrication, gravity unloading technology, high-denseness low-defect physical vapor deposition (PVD) Si-cladding technology, test data fusion method, and time-domain averaging method, etc. Based on the proposed technologies and methods, we have accomplished the world's largest SiC aspheric mirror with a size of ⌀4.03 m. The impressive performance of the SiC aspheric mirror is validated by the characteristics of the fabricated SiC aspheric mirror. The aerial density of the SiC blank is less than 120 kg/m2, surface shape test accuracy is better than 6 nm RMS, thickness inhomogeneity of the cladding layer is less than 5%, and the final surface figure error and roughness are 15.2 nm RMS and 0.8 nm RMS, respectively.

Crossed Andreev reflection in zigzag phosphorene nanoribbon based ferromagnet/superconductor/ferromagnet junctions.

We study the crossed Andreev reflection in zigzag phosphorene nanoribbon based ferromagnet/superconductor/ferromagnet junction. Only edge states, which are entirely detached from the bulk gap, involved in the transport processes. The perfect crossed Andreev reflection, with the maximal nonlocal conductance [Formula: see text], is addressed by setting the electric potentials of the leads and device properly. At this situation, the local Andreev reflection and the electron tunneling are completely eliminated, the incoming electrons can only be reflected as electrons or transmitted as holes, corresponding to the electron reflection and the crossed Andreev reflection respectively.The nonlocal conductance oscillates periodically with the length and the electric potential of the superconductor. Our study shows that the phosphorene based junction can be used as the quantum device to generate entangled-electrons.

Management of Postoperative Pain after Elective Craniotomy: A Prospective Randomized Controlled Trial of a Neurosurgical Enhanced Recovery after Surgery (ERAS) Program.

Objective: To prospectively evaluate the efficacy of a neurosurgical enhanced recovery after surgery (ERAS) protocol on the management of postoperative pain after elective craniotomies. Methods: This randomized controlled trial was conducted in the neurosurgical center of Tangdu Hospital (Fourth Military Medical University, Xi'an, China). A total of 129 patients undergoing craniotomies between October 2016 and July 2017 were enrolled in a randomized clinical trial comparing an ERAS protocol to a conventional postoperative care regimen. The primary outcome was the postoperative pain score assessed by a verbal numerical rating scale (NRS). Results: Patients in the ERAS group had a significant reduction in their postoperative pain scores on POD 1 compared to patients in the control group (p < 0.05). More patients (n = 44, 68.8%) in the ERAS group experienced mild pain (NRS: 1 to 3) on POD1 compared with patients (n = 23, 35.4%) in the control group (p < 0.05). A further reduction in pain scores was also observed on POD 2 and maintained on POD 3 in the ERAS group compared with that in the control group. In addition, the median postoperative length of hospital stay was significantly decreased with the incorporation of the ERAS protocol compared to controls (ERAS: 4 days, control: 7 days, P<0.001). Conclusion: The implementation of a neurosurgical ERAS protocol for elective craniotomy patients has significant benefits in alleviating postoperative pain and enhancing recovery leading to early discharge after surgery compared to conventional care. Further evaluation of this protocol in larger, multi-center studies is warranted.

Ambulatory Surgery Protocol for Endoscopic Endonasal Resection of Pituitary Adenomas: A Prospective Single-arm Trial with Initial Implementation Experience.

Endoscopic endonasal transsphenoidal resection has been accepted as a routine therapy for pituitary adenoma, but the postoperative hospital stay is typically several days long. With the advantages of reduced cost and improved patient satisfaction, the application of ambulatory surgery (AS) has developed rapidly. However, AS was still rarely adopted in neurosurgery. Here we designed an AS treatment protocol for pituitary adenoma with the endoscopic endonasal approach (EEA), and reported our initial experiences regarding the safety and efficacy of the AS protocol. 63 patients who presented with pituitary adenoma were screened at the Department of Neurosurgery, Tangdu Hospital from July to September, 2017. A total of 20 pituitary adenoma patients who met the inclusion criteria underwent EEA surgery using this evidence-based AS protocol, which emphasized adequate assessment for eligibility, full preparation to minimize invasiveness, enhanced recovery, and active perioperative patient education. Of the 20 patients enrolled, 18 were discharged on the afternoon of the operation day with a median total length of stay (LOS) of 31 hours (range, 29-32) hours. The median LOS after surgery was 6.5 (range, 5-8) hours. Two patients were transferred from the AS protocol to conventional care due to intraoperative cerebrospinal fluid leakage (one case) and an unsatisfying post-anesthetic discharge score (one case). Complications included transient and reversible mild postoperative nausea and vomiting [visual analog scale (VAS) score <3], headache (VAS score <3) after the operation or early after discharge. No patient was readmitted. Our results supported the safety and efficacy of the AS protocol for pituitary adenoma patients undergoing EEA resection among eligible patients, and further evaluation of this protocol in controlled studies with a larger sample size is warranted.

Mechanism of antidiabetic and synergistic effects of ginseng polysaccharide and ginsenoside Rb1 on diabetic rat model.

Ginseng polysaccharides (GP) have been reported to modulate gut microbiota, and ginsenoside Rb1 is known to display significant hypoglycemic activity. However, the synergistic effect of Rb1 and GP when applied to diabetic treatment remains largely unknown. Male rats were divided into ten groups: blank group (B-Group), model group (D-Group), Rb1 group (Rb1-Group), CK group (CK-Group), GP groups and GP + Rb1 groups in dosage of high, middle and low (H-Group, M-Group, L-Group, H-Rb1-Group, M-Rb1-Group, and L-Rb1-Group). CK-Group, GP groups and Rb1 group were fed CK, GP and Rb1 for 30 days, respectively. GP + Rb1 groups were fed GP on the initial 15 days and GP and Rb1 on the final 15 days. The fasting glucose of all groups was measured every five days. The transformation of Rb1 in vitro by rat intestinal microflora, which was collected from the B-Group, D-Group and GP groups on the 15th day, was investigated using HPLC and RRLC-Q-TOF/MS. Analyses the of 16S rRNA gene of the fecal bacterial population and fecal ß-glucosidase activity were conducted among the B-Group, D-Group and H-Group. Compared with those of rats in the D-Group, the fasting glucose levels of rats in the CK-Group and H-Rb1-Group decreased highest. During transformation of Rb1 by diabetic rat intestinal microflora, five transformed products, including ginsenoside Rd, F2, CK, gypenoside XVII (G-XVII), and LXXV (G-LXXV), as well as three transformation pathways, were identified. When a high dose of GP was fed to diabetic rats for 15 days, the formation of intermediates, including G-XVII and G-LXXV was inhibited, and only one pathway (Rb1→Rd→F2→CK) was identified. Moreover, the biotransformation rate of CK increased from 14.0% to 86.7% after 8 h of cultivation. GP reinstated the perturbed holistic gut microbiota and promoted fecal ß-d-glucosidase activity. Ginsenoside Rb1 and GP shows synergistic effects when applied to diabetic treatment and may be developed as a potential antidiabetic drug.

Safety and efficacy of a novel neurosurgical enhanced recovery after surgery protocol for elective craniotomy: a prospective randomized controlled trial.

OBJECTIVEAlthough enhanced recovery after surgery (ERAS) programs have gained acceptance in various surgical specialties, no established neurosurgical ERAS protocol for patients undergoing elective craniotomy has been reported in the literature. Here, the authors describe the design, implementation, safety, and efficacy of a novel neurosurgical ERAS protocol for elective craniotomy in a tertiary care medical center located in China.METHODSA multidisciplinary neurosurgical ERAS protocol for elective craniotomy was developed based on the best available evidence. A total of 140 patients undergoing elective craniotomy between October 2016 and May 2017 were enrolled in a randomized clinical trial comparing this novel protocol to conventional neurosurgical perioperative management. The primary endpoint of this study was the postoperative hospital length of stay (LOS). Postoperative morbidity, perioperative complications, postoperative pain scores, postoperative nausea and vomiting, duration of urinary catheterization, time to first solid meal, and patient satisfaction were secondary endpoints.RESULTSThe median postoperative hospital LOS (4 days) was significantly shorter with the incorporation of the ERAS protocol than that with conventional perioperative management (7 days, p < 0.0001). No 30-day readmission or reoperation occurred in either group. More patients in the ERAS group reported mild pain (visual analog scale score 1-3) on postoperative day 1 than those in the control group (79% vs. 33%, OR 7.49, 95% CI 3.51-15.99, p < 0.0001). Similarly, more patients in the ERAS group had a shortened duration of pain (1-2 days; 53% vs. 17%, OR 0.64, 95% CI 0.29-1.37, p = 0.0001). The urinary catheter was removed within 6 hours after surgery in 74% patients in the ERAS group (OR 400.1, 95% CI 23.56-6796, p < 0.0001). The time to first oral liquid intake was a median of 8 hours in the ERAS group compared to 11 hours in the control group (p < 0.0001), and solid food intake occurred at a median of 24 hours in the ERAS group compared to 72 hours in the control group (p < 0.0001).CONCLUSIONSThis multidisciplinary, evidence-based, neurosurgical ERAS protocol for elective craniotomy appears to have significant benefits over conventional perioperative management. Implementation of ERAS is associated with a significant reduction in the postoperative hospital stay and an acceleration in recovery, without increasing complication rates related to elective craniotomy. Further evaluation of this protocol in large multicenter studies is warranted.Clinical trial registration no.: ChiCTR-INR-16009662 (chictr.org.cn).

Neurosurgical Site Infection Prevention: Single Institute Experience.

AIM: To estimate the effect of a multimodal prevention program on controlling surgical site infection (SSI) risk among neurosurgical patients. MATERIAL AND METHODS: This prospective study was conducted among adult patients who have undergone neurosurgical procedures in a tertiary-care university-affiliated hospital during January 2008 to December 2013 since the implementation of an infection control program. SSI cases among inpatients were identified by daily active searches, whereas post-discharge surveillance was performed for outpatients through telephone contact 30-35 days after surgery, according to the definition proposed by the Center for Disease Control. The variation of SSI rate during the study period was analyzed by Cochran-Armitage trend test. RESULTS: Overall, a total of 3042 patients were enrolled and 112 SSI cases were identified during the studied period. SSI more likely occurred in patients with older age (t=5.16, p < 0.01), undergoing emergency operations (x2=50.5, p < 0.01), having higher American Society of Anesthesiologists (ASA) scores (x2=7.2, p=0.01) and clean contaminated wound or above (x2=53.8, p < 0.01). The annual incidence rate of SSI was 6.21%, 5.01%, 3.89%, 3.06%, 2.38% and 2.28%, respectively, showing a significant decreasing trend (z=3.96, p < 0.01). CONCLUSION: The results provide evidence of a significant decreasing trend in the SSI rate following the infection prevention program, demonstrating the role of multimodal approach in controlling SSI.

Passively athermalized broadband optical design using doublet combinations.

In this paper we propose a method for broadband achromatic and passive athermal optical system design using a combination of three doublets. In the implementation of this method, the first-order color dispersion is corrected by distributing proper power to the elements inside the doublets; the thermal and secondary color dispersion are corrected by distributing proper power to the doublet group units. The theoretical deviation is given and we summarize the power distribution equations. A design of an example system using this method, which covers the 350-1200 nm wavelength band, is given and the image quality evaluation is presented. It is shown that the example system maintains high imaging qualities over the required wavelength and temperature range, which proves the effectiveness of the method.

A novel organic-inorganic hybrid monolithic column prepared in-situ in a microchip and its application for the determination of 2-amino-4-chlorophenol in chlorzoxazone tablets.

γ-Alumina nanoparticles (γ-Al2O3) were introduced to the conventional poly(methacrylic acid-co-ethylene glycol dimethacrylate) (MAA-co-EGDMA) monolith to prepare a novel organic-inorganic hybrid monolith, poly(MAA-co-EGDMA)-Al2O3 monolith. The polymerization was induced in-situ with UV irradiation in an ultraviolet transparent polymethyl methacrylate (PMMA) microfluidic chip. The monolith-based solid phase microextraction system was used for the on-line determination of 2-amino-4-chlorophenol (ACP) in chlorzoxazone tablets coupled with an optical fiber spectrophotometer. Several parameters affecting the adsorption/desorption, including sample pH value, sample flow rate, sampling time, eluent flow rate, and eluting time, were investigated in detail. Under the optimized conditions, limit of detection (LOD) and limit of quantification (LOQ) of the method were calculated to be 2.8 and 9.1 µg L(-1), respectively, with the relative standard deviation (RSD) of 3.1%.