Modulation of entorhinal cortex-hippocampus connectivity and recognition memory following electroacupuncture on 3×Tg-AD model: Evidence from multimodal MRI and electrophysiological recordings.

Memory loss and aberrant neuronal network activity are part of the earliest hallmarks of Alzheimer's disease (AD). Electroacupuncture (EA) has been recognized as a cognitive stimulation for its effects on memory disorder, but whether different brain regions or neural circuits contribute to memory recovery in AD remains unknown. Here, we found that memory deficit was ameliorated in 3×Tg-AD mice with EA-treatment, as shown by the increased number of exploring and time spent in the novel object. In addition, reduced locomotor activity was observed in 3×Tg-AD mice, but no significant alteration was seen in the EA-treated mice. Based on the functional magnetic resonance imaging, the regional spontaneous activity alterations of 3×Tg-AD were mainly concentrated in the accumbens nucleus, auditory cortex, caudate putamen, entorhinal cortex (EC), hippocampus, insular cortex, subiculum, temporal cortex, visual cortex, and so on. While EA-treatment prevented the chaos of brain activity in parts of the above regions, such as the auditory cortex, EC, hippocampus, subiculum, and temporal cortex. And then we used the whole-cell voltage-clamp recording to reveal the neurotransmission in the hippocampus, and found that EA-treatment reversed the synaptic spontaneous release. Since the hippocampus receives most of the projections of the EC, the hippocampus-EC circuit is one of the neural circuits related to memory impairment. We further applied diffusion tensor imaging (DTI) tracking and functional connectivity, and found that hypo-connected between the hippocampus and EC with EA-treatment. These data indicate that the hippocampus-EC connectivity is responsible for the recognition memory deficit in the AD mice with EA-treatment, and provide novel insight into potential therapies for memory loss in AD.

Target arm affinities determine preclinical efficacy and safety of anti-HER2/CD3 bispecific antibody.

Systemic cytokine release and on-target/off-tumor toxicity to normal tissues are the main adverse effects limiting the clinical utility of T cell-redirecting therapies. This study was designed to determine how binding affinity for CD3 and tumor target HER2 impact the efficacy and nonclinical safety of anti-HER2/CD3 T cell-dependent antibodies (TDBs). Affinity was found to be a major determinant for the overall tolerability. Higher affinity for CD3 associated with rapidly elevated peripheral cytokine concentrations, weight loss in mice, and poor tolerability in cynomolgus monkeys. A TDB with lower CD3 affinity was better tolerated in cynomolgus monkeys compared with a higher CD3-affinity TDB. In contrast to tolerability, T cell binding affinity had only limited impact on in vitro and in vivo antitumor activity. High affinity for HER2 was critical for the tumor-killing activity of anti-HER2/CD3 TDBs, but higher HER2 affinity also associated with a more severe toxicity profile, including cytokine release and damage to HER2-expressing tissues. The tolerability of the anti-HER2/CD3 was improved by implementing a dose-fractionation strategy. Fine-tuning the affinities for both the tumor target and CD3 is likely a valuable strategy for achieving maximal therapeutic index of CD3 bispecific antibodies.

Total Glycosides of Peony Protects Against Inflammatory Bowel Disease by Regulating IL-23/IL-17 Axis and Th17/Treg Balance.

Inflammatory bowel disease (IBD) is a group of autoimmune diseases, including ulcerative colitis and Crohn's disease, characterized by nonspecific inflammation in the gut. Total glycoside of peony (TGP) has been widely used for treatment of autoimmune diseases because of its pharmacological effects. However, it is lack of depth in whether TGP regulate T helper 17 cell (Th17) / T regulatory cell (Treg) immune balance or interleukin 23 (IL-23) / IL-17 axis to achieve the goal of treating IBD. Hence, the aim of this study was to investigate the effects of TGP on experimental colitis mice and the related mechanisms. In the present study, we demonstrated that administration of TGP effectively attenuates colonic inflammation of TNBS-induced colitis mice, mainly reflected in significantly improved clinical parameters, reduced inflammatory response and myeloperoxidase (MPO) activity, even stronger systemic immune ability and effective improvement of Th17/Treg immune disorders. In addition, there was a stronger immunosuppressive ability in a positive cluster of differentiation 4 (CD4 + ) T-lymphocytes from the TGP treated mouse colon, characterized by the inhibition of high levels of inflammatory factors and increased regulatory T cells. Importantly, high-dose TGP has similar therapeutic effects as salicylazosulfapyridine (SASP) on IBD treatment. The potential mechanisms might be, at least in part, related to the adjustment of imbalance of Th17/Treg cells and the inhibition of IL-23/IL17 inflammatory signal axis.

Characterization of the chemical composition of white chrysanthemum flowers of Hangzhou by using high-performance ion trap mass spectrometry.

In this study, high-performance liquid chromatography coupled with amaZon SL high-performance ion trap mass spectrometry was used to analyze the target components in white chrysanthemum flowers of Hangzhou. Twenty-one components were detected and identified in both white chrysanthemum flowers of Hangzhou samples by using target compound analysis. Furthermore, seven new compounds in white chrysanthemum flowers of Hangzhou were found and identified by analyzing the fragment ion behavior in the mass spectra. The established method can be expedient for the global quality investigation of complex components in herbal medicines and food.

[Sedum sarmentosun bunge extraction ameliorated severe acute pancreatitis-induced lung injury: an experimental research]].

OBJECTIVE: To explore the effect of Sedum sarmentosum Bunge Extract (SSBE) on severe acute pancreatitis (SAP) induced acute lung injury (ALI) model rats and their excessive inflammatory reactions. METHODS: Forty-two healthy adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups, the sham-operated control group (C), the SAP group (SAP), and the SSBE treated group (SSBE), 14 in each group. SAP induced ALl rat model was induced by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct. SSBE (100 m/kg) was administrated subcutaneously after the establishment of the SAP model. Equal dose of SSBE was injected again 12 h later. Equal volume of normal saline was administrated in the same way for rats in the C group and the SAP group. Rats were sacrificed after successful modeling and samples taken at 12 and 24 h. Pathological changes in the pancreas and the lung tissue were observed under light microscope. The ascites, serum amylase (AMS), wet/dry proportion (W/D) of the lung tissue, activities of myeloperoxidase (MPO), interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were also measured. RESULTS: Ascites and serum AMS activities significantly increased; MPO, IL-1, IL-6, TNF-alpha contents, and W/D ratio also significantly increased in the SAP group, when compared with the C group (P<0.05). Compared with the SAP group, those parameters were all attenuated in the SSBE group at 12 and 24 h (P<0.05, P<0.01). Pathological changes in the pancreas and the lung tissue were alleviated in the SSBE group under light microscope. The injury degree ranged between that of the C group and the SAP group. CONCLUSION: SSBE could relieve the ALl in SAP model rats, which could be achieved through alleviating inflammation responses of SAP rats.

Ultra-performance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry analysis of the impact of bran-processing on the chemical profile of Radix Paeoniae Alba (Baishao).

In this study, a rapid and versatile ultra-performance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry-based chemical profiling approach was applied to evaluate chemical constitution of crude and processed Radix Paeoniae Alba (RPA) samples. A total of 44 compounds were identified, among which the contents of 9 compounds in processed samples were obviously decreased and 8 compounds were increased. Furthermore, compound 28 was not found in RPA sample after stir-frying with wheat bran. The proposed method provided a chemical basis for exploring the processed mechanism of herbal medicine.

Rapid identif ication and comparative analysis of chemical constituents in herbal medicine Fufang decoction by ultra-high-pressure liquid chromatography coupled with a hybrid linear ion trap-high-resolution mass spectrometry.

This study was conducted to reveal the relation between herbal medicine Fufang decoction and a single drug in terms of material base. Da-Cheng-Qi decoction (DCQD) was used as a model. Ultrahigh-pressure liquid chromatography coupled with a hybrid linear ion trap-high-resolution mass spectrometry (UHPLC-LTQ-Orbitrap) was applied to detect and identify the main chemical compounds. This technique was also employed to determine the different chemical components. Under optimized liquid chromatography and mass spectrometry conditions, 64 components, including iridoids, flavonoids, anthraquinones and coumarins, were separated and tentatively characterized in Da-Cheng-Qi decoction. After decoction, the contents of 18 compounds were markedly changed, and two components were no longer detected in Fufang decoction compared with single-medicine decoction. The established method provided a good example for the rapid identification of complicated polar constituents in herbal medicine prescriptions.

Static headspace-multicapillary column with gas chromatography coupled to ion mobility spectrometry as a simple approach for the discrimination of crude and processed traditional Chinese medicines.

The processing procedure can alter the nature and chemical transformation of traditional Chinese medicine to accommodate different clinical dispensing and preparation requirements. In this study, static headspace-multicapillary column with gas chromatography coupled to ion mobility spectrometry was developed for the rapid and sensitive discrimination of crude and processed traditional Chinese medicine. Using Radix Paeoniae Alba as a traditional Chinese medicine model, the combined power of this approach was illustrated by classifying the crude and processed Radix Paeoniae Alba samples into two main categories. The contents of the main components in Radix Paeoniae Alba varied significantly. The established method could promote the use of ion mobility spectrometry in intrinsic quality control and differentiation of herbal medicines from other processed products or preparations.

Analysis of the influence of processing of stir-baking with glycyrrhizae on the main components of Euodiae Fructus by high-performance liquid chromatography with diode array detector.

Euodiae Fructus is one of the most commonly used Chinese herbs in China. Specifically, the crude Euodiae Fructus and its processed products of Gancao Zhi Pin are used clinically for the treatment of different diseases. In order to improve the quality control standard and evaluate the crude and processed Euodiae Fructus, in this study, a simple and sensitive high-performance liquid chromatography-diode array detector method was developed for the simultaneous determination of five major compounds in Euodiae Fructus. The results indicated that the five components had significant linear relation (r(2) ≥ 0.9997) between the peak area and the injected concentration. The average recoveries of the five components were in the range from 97.38% to 102.56%. Overall intra- and inter-day variations were less than 1.36%. The developed method can be applied to the intrinsic quality control of crude and processed Euodiae Fructus.

Hepatoprotective effect of superfine particles of herbal medicine against CCl4-induced acute liver damage in rats.

This study aimed to examine the hepatoprotective effects of the superfine particles of Radix Tetrastigma (SPRT) against CCl4-induced acute liver damage in rats. Animals were treated with SPRT (0.3, 0.6, and 1.2 g/kg) and showed remarkable hepatoprotection against CCl4-induced hepatotoxicity. CCl4 altered various biochemical parameters in rat liver, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD), histopathological changes, and Bax and caspase-3 expressions. SPRT significantly prevented increases in ALT and AST levels, reduced MDA level, decreased Bax and caspase-3 protein expression, enhanced SOD activity, and provided significant amelioration in the histopathological lesions. These findings suggested that SPRT has significant protective effect against acute hepatotoxicity induced by CCl4 in rats.

Capture and identification of the volatile components in crude and processed herbal medicines through on-line purge and trap technique coupled with GC × GC-TOF MS.

This work aimed to investigate the volatile components in crude and processed herbal medicines (HMs). Using Atractylodis Macrocephalae Rhizoma (AMR) as a model HM, the volatile components were captured through on-line purge and trap technique and identified by using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF MS) system. A total of 224 and 171 volatile compounds were identified in crude and processed AMR samples, respectively. After frying with honey-bran, 52 compounds which were found in crude AMR samples disappeared in processed AMR samples, and 15 compounds were newly generated in processed AMR. The established method can be applied in different research areas such as HM and food processing.

Quantitative analysis coupled with toxic evaluation to investigate the influence of sulfur-fumigation on the quality of Chrysanthemum morifolium.

In the present study, quantitative analysis coupled with toxic evaluation was applied to investigate the influence of sulfur-fumigation on the quality of Chrysanthemum morifolium. The results showed that the average contents of six flavonoids (cynaroside, hyperoside, isoquercitrin, luteolin, apigenin, and diosmetin) in sulfur-fumigated C. morifolium samples decreased by about 6.2%, 3.5%, 22.0%, 33.3%, 26.0%, and 36.9%, respectively, while the average contents of two organic acids (chlorogenic acid and isochlorogenic acid A) in sulfur-fumigated C. morifolium samples increased by about 16.8% and 7.6%, respectively. Furthermore, high dosage sulfur-fumigated C. morifolium could induce hydropic degeneration in epithelial cells of the renal tubule and interstitial edema. This indicates that sulfur-fumigated C. morifolium may lead to renal toxicity.

Growth hormone and insulin-like growth factor of naked carp (Gymnocypris przewalskii) in Lake Qinghai: expression in different water environments.

Here, we report the cloning and characterization of growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-II from naked carp (Gymnocypris przewalskii), a native teleost fish of Lake Qinghai in the Qinghai-Tibet Plateau of China. The GH of naked carp encodes for a predicted amino acid sequence showing identities of 63%, 63%, 91% and 94% with cherry salmon, rainbow trout, zebrafish and grass carp, respectively. Compared to common carp and goldfish, evolutionary analysis showed that genome duplication has had less influence on the relaxation of purifying selection in the evolution of naked carp GH. Sequence analysis of naked carp IGF-I (ncIGF-I) and ncIGF-II showed a high degree of homology with known fish IGF-I and IGF-II. To investigate effects of salinity and ionic composition of the aquatic environment on the GH-IGF axis in naked carp, male fish held in river water were assigned randomly to 4 groups: RW (river-water), RW+Na (NaCl in RW), RW+Mg (MgCl(2) in RW) and LW (lake-water) groups. The concentrations of Na(+) in RW+Na and Mg(2+) in RW+Mg were equal to the concentrations of these ions in lake-water. After 2 days of exposure, the plasma IGF-I levels in the RW+Na and LW groups were significantly higher than the control group (RW), and the plasma GH levels of the LW group were also significantly higher than the RW group. The somatostatin (SS) levels in the hypothalamus significantly increased in the RW+Na group. After 5 days of exposure, these hormone levels did not differ significantly among groups. These results indicate that while the plasma GH and IGF-I levels are osmosensitive, the absence of a change in GH secretion in RW+Na might be partly due to a transiently increased release of hypothalamic SS induced by the stress of neutral-saline water. This is the first report of a salinity-induced increase of GH-IGF-I circulating levels in Cypriniformes.