[An experimental study of acute toxicity and pharmacology of fermented Platycodonis Radix].

This study investigated the acute toxicity of fermented Platycodonis Radix on mice and its effect on coughing in mice infected with Mycoplasma pneumoniae. The maximum dosage(MAD) was used in the acute toxicity experiment on mice to observe the signs of mice. After 14 days, dissection, blood biochemical examination, and pathological tissue section observation were conducted. In the pharmacological experiment of fermented Platycodonis Radix, 60 healthy BALB/c mice, 30 males and 30 females, were randomly divided into a blank group, a model group, a carbetapentane group(0.013 g·kg~(-1)·d~(-1)), and high-, medium-, and low-dose fermented Platycodonis Radix groups(5.2, 2.6, and 1.3 g·kg~(-1)·d~(-1)), with 10 mice in each group. Except for the blank group, the mice in the other five groups underwent model induction by intranasally instilling 20 µL of 1×10~6 CCU M. pneumoniae for 3 days, and the mice in each group were orally administered the corresponding drugs for 7 days. Cough induction experiment was conducted to observe and record the cough latency and total cough count within 3 min for each group. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes in lung tissues. Immunohistochemistry was performed to observe the protein expression of transient receptor potential A1(TRPA1), calcitonin gene-related peptide(CGRP), and substance P(SP) in the lung tissues of mice in each group. Real-time fluorescence-based quantitative polymerase chain reaction(qRT-PCR) was used to elucidate the changes in the mRNA levels of cough-related factors TRPA1, CGRP, and SP in mice treated with fermented Platycodonis Radix. No mice died in the acute toxicity experiment, and there were no changes in general behavior and major organ histopathological examinations. Compared with the blank group, there were no statistically significant differences in blood biochemical indexes. In the pharmacological experiment of fermented Platycodonis Radix, compared with the model group, the high-and medium-dose fermented Platycodonis Radix groups showed improved lung tissue structure of mice, with clear structure and regular tissue morphology. The qRT-PCR and immunohistochemical detection showed a decrease in the expression of TRPA1, CGRP, and SP in the fermented Platycodonis Radix groups. Fermented Platycodonis Radix can exert an inhibitory effect on cough by suppressing the expression of TRPA1, CGRP, and SP in lung tissues, thereby identifying the target of the drug.

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia.

Hyperlipidemia has become a leading risk factor for cardiovascular diseases and liver injury worldwide. Fructus Phyllanthi (FP) is an effective drug against hyperlipidemia in Traditional Chinese Medicine (TCM) and Indian Medicine theories, however the potential mechanism requires further exploration. The present research aims to reveal the mechanism of FP against hyperlipidemia based on an integrated strategy combining network pharmacology prediction with metabolomics validation. A high-fat diet (HFD)-induced mice model was established by evaluating the plasma lipid levels, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Network pharmacology was applied to find out the active ingredients of FP and potential targets against hyperlipidemia. Metabolomics of plasma and liver were performed to identify differential metabolites and their corresponding pathways among the normal group, model group, and intervention group. The relationship between network pharmacology and metabolomics was further constructed to obtain a comprehensive view of the process of FP against hyperlipidemia. The obtained key target proteins were verified by molecular docking. These results reflected that FP improved the plasma lipid levels and liver injury of hyperlipidemia induced by a HFD. Gallic acid, quercetin, and beta-sitosterol in FP were demonstrated as the key active compounds. A total of 16 and six potential differential metabolites in plasma and liver, respectively, were found to be involved in the therapeutic effects of FP against hyperlipidemia by metabolomics. Further, integration analysis indicated that the intervention effects were associated with CYP1A1, AChE, and MGAM, as well as the adjustment of L-kynurenine, corticosterone, acetylcholine, and raffinose, mainly involving tryptophan metabolism pathway. Molecular docking ensured that the above ingredients acting on hyperlipidemia-related protein targets played a key role in lowering lipids. In summary, this research provided a new possibility for preventing and treating hyperlipidemia.

Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma.

Glioblastoma (GBM) is the most malignant tumor of the central nervous system in adults. Irradiation (IR) and temozolomide (TMZ) play an extremely important role in the treatment of GBM. However, major impediments to effective treatment are postoperative tumor recurrence and acquired resistance to chemoradiotherapy. Our previous studies confirm that Yin Yang 1 (YY1) is highly expressed in GBM, whereby it is associated with cell dedifferentiation, survival, and therapeutic resistance. Targeted delivery of small interfering RNA (siRNA) without blood-brain barrier (BBB) restriction for eradication of GBM represents a promising approach for therapeutic interventions. In this study, we utilize the engineering technology to generate T7 peptide-decorated exosome (T7-exo). T7 is a peptide specifically binding to the transferrin receptor. T7-exo shows excellent packaging and protection of cholesterol-modified Cy3-siYY1 while quickly releasing payloads in a cytoplasmic reductive environment. The engineered exosomes T7-siYY1-exo could deliver more effciently to GBM cells both in vitro and in vivo. Notably, in vitro experiments demonstrate that T7-siYY1-exo can enhance chemoradiotherapy sensitivity and reverse therapeutic resistance. Moreover, T7-siYY1-exo and TMZ/IR exert synergistic anti-GBM effect and significantly improves the survival time of GBM bearing mice. Our findings indicate that T7-siYY1-exo may be a potential approach to reverse the chemoradiotherapy resistance in GBM.

Vinylmethylsiloxanes in Municipal Wastewater Treatment Plant and Biosolid-Amended Soils: Their Distribution and Backbone/Vinyl Branch Degradation.

This study is the first to investigate the emission and environmental fate of one type of modified methylsiloxane with double-bond (vinyl) groups. During 2018-2020, 2,4,6-trimethyl-2,4,6-trivinylcyclotrisiloxane (V3), 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane (V4), and 2,4,6,8,10-pentavinyl-2,4,6,8,10-pentamethylcyclopentasiloxane (V5) were found in aqueous (

Temporal and spatial variation, input fluxes and risk assessment of cyclic methylsiloxanes in Rivers-Bohai Sea System.

In the present study, the total concentrations of three cyclic methylsiloxanes (ΣCMSs), including octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6), in surface water and sediment samples of five main rivers draining into the Bohai Sea were in the range of 1.62-1.39 × 103 ng/L and 1.92-1.69 × 103 ng/g dw, respectively. Riverine input had great influence on the coastal distribution of siloxanes in the Bohai Sea. The concentrations of ΣCMSs in coastal sediments farthest away (40-50 Km) from the estuaries were only 4-33% of those close to the estuaries. But surprisingly, compared with those in coastal sediments (1.03-1.44 × 103 ng/g dw), the concentrations of CMSs (1.56-2.67 × 103 ng/g dw) in some deep-sea sediments were higher, and certain positive correlation existed between sediment ΣCMSs in this area with the total petroleum hydrocarbons concentration (R2 = 0.92, p < 0.05) suggested offshore oil exploitation as one important emission source of siloxanes. Overall, calculated based on their sediment concentrations, D4-D6 had negligible ecological risks to the benthic organisms in river-Bohai Sea system, i.e. HQs < 1. However, sediment-accumulation of siloxanes should be paid attention, especially for some deep-sea sediments nearby drilling platforms, where it will take only less than 1 year for D4 to reach its threshold.

Recent advances of tanshinone in regulating autophagy for medicinal research.

Initially described as an ancient and highly conserved catabolic biofunction, autophagy plays a significant role in disease pathogenesis and progression. As the bioactive ingredient of Salvia miltiorrhiza, tanshinone has recently shown profound effects in alleviating and treating various diseases by regulating autophagy. However, compared to the remarkable achievements in the known pharmacological effects of this traditional Chinese medicine, there is a lack of a concise and comprehensive review deciphering the mechanism by which tanshinone regulates autophagy for medicinal research. In this context, we concisely review the advances of tanshinone in regulating autophagy for medicinal research, including human cancer, the nervous system, and cardiovascular diseases. The pharmacological effects of tanshinone targeting autophagy involve the regulation of autophagy-related proteins, such as Beclin-1, LC3-II, P62, ULK1, Bax, ATG3, ATG5, ATG7, ATG9, and ATG12; the regulation of the PI3K/Akt/mTOR, MEK/ERK/mTOR, Beclin-1-related, and AMPK-related signaling pathways; the accumulation of reactive oxygen species (ROS); and the activation of AMPK. Notably, we found that tanshinone played a dual role in human cancers in an autophagic manner, which may provide a new avenue for potential clinical application. In brief, these findings on autophagic tanshinone and its derivatives provide a new clue for expediting medicinal research related to tanshinone compounds and autophagy.

Salvianolic acid A relieves cognitive disorder after chronic cerebral ischemia: Involvement of Drd2/Cryab/NF-κB pathway.

Chronic cerebral ischemia (CCI) refers to long-term hypoperfusion of cerebral blood flow with the main clinical manifestations of progressive cognitive impairment. The pathological mechanism of CCI is complex, and there is a lack of effective treatments. Salvianolic acid A (SalA) is a neuroprotective extract of Salvia miltiorrhiza with the effects of anti-inflammation and anti-apoptosis. In this study, the effect of SalA on cognitive function and Drd2/Cryab/NF-κB signaling pathway in rats with CCI was investigated. Morris water maze and open field test were used to observe the effects of SalA on the cognitive function of CCI rats. The pathological changes in the brain were observed by HE, Nissl, and LFB staining. TUNEL staining, enzyme-linked immunosorbent assay, and western blot analysis were used to detect the inflammatory and apoptosis in the cortex and hippocampus. The expression of Drd2/Cryab/NF-κB pathway-related molecules and Drd2 localization were detected by western blotting and dual immunofluorescence, respectively. SH-SY5Y cells were exposed to chronic hypoglycemic and hypoxic injury in vitro, and Drd2 inhibitor haloperidol was used to verify the involved pathway. The results showed that SalA could improve the cognitive function of CCI rats, reduce pathological damage of cortex and hippocampus, inhibit neuroinflammation and apoptosis, and suppress the activation of NF-κB by regulating Drd2/Cryab pathway. And SalA inhibited NF-κB activation and nuclear translocation in SH-SY5Y cells by upregulating Drd2/Cryab pathway, which was reversed by haloperidol interference. In conclusion, SalA could relieve CCI-induced cognitive impairment in rats, at least partly through the Drd2/Cryab/NF-κB pathway.

Xiao-Xu-Ming decoction prevented hemorrhagic transformation induced by acute hyperglycemia through inhibiting AGE-RAGE-mediated neuroinflammation.

Stroke is one of the leading causes of death worldwide. Hemorrhagic transformation (HT) is a common serious complication of ischemic stroke (IS) and is related to poor prognosis. Hyperglycemia after stroke is associated with the occurrence of HT and seriously affects the clinical treatment of stroke. Our previous experiments demonstrated that the Xiao-Xu-Ming decoction effective components group (XXMD), which is a Chinese medicine formula reconstituted by active ingredients, has multiple pharmacological effects in the treatment of IS. However, the effects of XXMD on HT after IS remain unclear. Thus, we investigated the preventive effects of XXMD on hyperglycemia-induced HT and further explored the underlying mechanism. Acute hyperglycemia combined with the electrocoagulation cerebral ischemia model was used to establish the HT model. XXMD (37.5, 75, 150 mg/kg/d) was given by gavage for 5 days. Network pharmacology was used to predict potential targets and pathways of XXMD in HT occurrence, and further studies confirmed the related targets. The results showed that hyperglycemia aggravated neurological deficits and blood-brain barrier (BBB) disruption, leading to intracerebral hemorrhage. Pretreatment with XXMD improved neurological function and BBB integrity and inhibited HT occurrence. Network pharmacology revealed that AGE-RAGE-mediated neuroinflammation may be associated with hyperglycemia-induced HT. Further studies confirmed that hyperglycemia activated the AGE-RAGE signaling pathway, increased the expression of HMGB1, TLR4 and p-p65, and induced the release of inflammatory factors and neutrophil infiltration, leading to HT. XXMD could inhibit AGE-RAGE-mediated neuroinflammation. These findings indicated that pretreatment with XXMD alleviated hyperglycemia-induced HT, which may be associated with the inhibition of AGE-RAGE-mediated neuroinflammation. Therefore, XXMD may be a potential therapeutic drug for HT.

Atorvastatin reverses high cholesterol-induced cardiac remodelling and regulates mitochondrial quality-control in a cholesterol-independent manner: An experimental study.

Mitochondria are key regulators of cell fate, maintaining self-stability by a fine-tuned quality-control network including mitophagy, biogenesis, fission and fusion processes. Myocardial mitochondria can be impaired by hypercholesterolemia. Statins, such as atorvastatin, are considered the cornerstone in the management of hypercholesterolaemia primarily due to their marked cholesterol-lowering ability. The direct effect of atorvastatin on myocardial mitochondria remains unclear. We aimed to explore whether atorvastatin could attenuate myocardial mitochondrial defects induced by high cholesterol, and whether cycloastragenol, a potent telomerase activator, could be used as a potential complementary bioactive compound for obesity and hypercholesterolaemia treatment. We found that atorvastatin at a low dose (3 mg/kg) did not reduce elevated serum cholesterol, but reversed cardiac remodelling and dysfunction in C57BL/6J mice fed with high-fat diet (HFD). Atorvastatin reversed the upregulated mitophagy, mitochondrial fission and fusion, accompanied by mitochondrial biogenesis activation in HFD-fed mice hearts. Mitochondrial structural impairments were attenuated by atorvastatin in HFD-fed mice and oxidized low-density lipoprotein (ox-LDL) exposed HL-1 cardiomyocytes. The depolarized mitochondrial membrane potential and increased mitochondrial oxygen consumption rates in ox-LDL exposed HL-1 cells were recovered by atorvastatin. Furthermore, atorvastatin co-treated with cycloastragenol had better effects on reducing body weight, improving cardiac remodelling and dysfunction, and protecting mitochondria in high cholesterol. Conclusively, low-dose atorvastatin exhibited a cholesterol-independent cardioprotective effect through improving the mitochondrial quality-control network and repairing mitochondrial ultrastructure in high cholesterol. Atorvastatin plus cycloastragenol supplement therapy has a better effect on treating obesity and hypercholesterolaemia.

Methylsiloxanes in petroleum refinery facility: Their sources, emissions, environmental distributions and occupational exposure.

High concentrations (1.08 ng/g-3.61 mg/g) of methylsiloxanes, including cyclic analogs [octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6)], and linear analogs with 3-14 silicon atoms (L3-L14), have been detected in crude oil, additives and petroleum products from one petroleum refinery facility in China. Overall, the total mass load of Σmethylsiloxanes (1320 kg/day) in crude oil and additives was 1.5 times higher than that in petroleum products (857 kg/day), indicating their potential emissions in this facility, which were further confirmed by the find of their obvious emission through exhaust-gas (89.4 kg/day) and wastewater (4.70 kg/day). Σmethylsiloxanes emission from exhaust-gas discharge outlets of deep catalytic cracking units (60.6 kg/day) took up 68% of their total emission from all gas outlets. Overall, Σmethylsiloxanes in air (17.1-743 µg/m3) and soil samples [311 ng/g dw (dry weight) - 34.2 µg/g dw] from this facility were up to four orders of magnitude greater than those from surrounding areas, and plasma concentrations of Σmethylsiloxanes in current workers from this facility (7.4-609 ng/mL) were up to two orders of magnitude larger than those from reference group (

Synaptic Protein Phosphorylation Networks Are Associated With Electroacupuncture-Induced Circadian Control in the Suprachiasmatic Nucleus.

Phosphorylation is one of the most important posttranslational modifications and regulates the physiological process. While recent studies highlight a major role of phosphorylation in the regulation of sleep-wake cycles to a lesser extent, the phosphoproteome in the suprachiasmatic nucleus (SCN) is not well-understood. Herein, we reported that the EA treatment elicits partial reparation of circadian rhythmicity when mice were exposure to constant darkness for long time. We investigated the effects of EA on circadian rhythms in constant darkness between EA stimulation and free-running control. Next, mass spectrometry-based phosphoproteome was utilized to explore the molecular characteristics of EA-induced phosphorylation modification in the SCN. A total of 6,192 distinct phosphosites on 2,488 proteins were quantified. Functional annotation analysis and protein-protein interaction networks demonstrated the most significant enriched phosphor-proteins and phosphosites involved in postsynapse and glutamatergic synapse. The current data indicated that most of the altered molecules are structural proteins. The target proteins, NMDAR and CAMK2, were selected for verification, consistent with the results of LC-MS/MS. These findings revealed a complete profile of phosphorylation modification in response to EA.

Stability of pure oxygen aeration-activated sludge system under non-steady food-to-microorganism ratio conditions during petrochemical wastewater treatment.

This study investigates the stability of a pure oxygen aeration-activated sludge system for petrochemical wastewater treatment under high organic concentration and non-steady food-to-microorganism (F/M) ratio conditions. Sludge settling characteristics maintained relatively stable conditions with an F/M ratio variation from 0.15 ± 0.04 to 0.33 ± 0.07 kg COD/kg MLSS⋅d, while the excess F/M ratio (0.44 ± 0.16 kg COD/kg MLSS⋅d) resulted in deterioration of the organic removal and sludge-water separation performances. Loosely bound extracellular polymeric substances (EPS) showed more significant effect on sludge settleability than the tightly bound EPS. The genus Hydrogenophaga was related to organic removal performance, while Zoogloea and Chitinophaga were related to the effluent quality of suspended solids. The excess F/M ratio also caused an increase in Zoogloea and Chitinophaga, whereas the toxicity of petrochemical wastewater resulted in decreased abundance of Hydrogenophaga. These changes caused deterioration of the organic removal and sludge-water separation performances.

Salvianolic acid A prevented cerebrovascular endothelial injury caused by acute ischemic stroke through inhibiting the Src signaling pathway.

Stroke is an acute cerebrovascular disease caused by ruptured or blocked blood vessels. For the prevention of ischemic stroke, the coagulation state of blood and cerebrovascular protection should be considered. Our previous study has shown that salvianolic acid A (SAA), which is a water-soluble component from the root of Salvia Miltiorrhiza Bge, prevents thrombosis with a mild inhibitory effect on platelet aggregation. In this study we investigated the preventive effects of SAA on cerebrovascular endothelial injury caused by ischemia in vivo and oxygen-glucose deprivation (OGD) in vitro, and explored the underlying mechanisms. An autologous thrombus stroke model was established in SD rats by electrocoagulation. SAA (10 mg/kg) was orally administered twice a day for 5 days before the operation. The rats were sacrificed at 24 h after the operation. We showed that pretreatment with SAA significantly improved the neurological deficits, intracerebral hemorrhage, BBB disruption, and vascular endothelial dysfunction as compared with model group. In human brain microvascular endothelial cells (HBMECs), pretreatment with SAA (10 µM) significantly inhibited OGD-induced cell viability reduction and degradation of tight junction proteins (ZO-1, occludin, claudin-5). Furthermore, we found that SAA inhibited the upregulation of Src signaling pathway in vivo and vitro and reversed the increased expression of matrix metalloproteinases (MMPs) after ischemic stroke. In conclusion, our results suggest that SAA protects cerebrovascular endothelial cells against ischemia and OGD injury via suppressing Src signaling pathway. These findings show that pretreatment with SAA is a potential therapeutic strategy for the prevention of ischemic stroke.

Simultaneous calcium recordings of hippocampal CA1 and primary motor cortex M1 and their relations to behavioral activities in freely moving epileptic mice.

Epilepsy is a common neurological disorder characterized by recurrent epileptic seizures. The cause of most cases of epilepsy is unknown. Although changes of calcium events in a single brain region during seizures have been reported before, there have been few studies on relations between calcium events of two different brain regions and epileptic behaviors in freely moving mice. To analyze calcium events simultaneously recorded in hippocampal CA1 (CA1) and primary motor cortex M1 (M1), and to explore their relations to various epileptic behaviors in freely moving epileptic models. Epileptic models were induced by Kainic acid (KA), a direct agonist of glutamatergic receptor, on adult male C57/BL6J mice. Calcium events of neurons and glia in CA1 and M1 labeled by a calcium indicator dye were recorded simultaneously with a multi-channel fiber photometry system. Three typical types of calcium events associated with KA-induced seizures were observed, including calcium baseline-rising, cortical spreading depression (CSD) and calcium flashing with a steady rate. Our results showed that the calcium baseline-rising occurred in CA1 was synchronized with that in M1, but the CSD waves were not. However, synchronization of calcium flashing in the two areas was uncertain, because it was only detected in CA1. We also observed that different calcium events happened with different epileptic behaviors. Baseline-rising events were accompanied by clonus of forelimbs or trembling, CSD waves were closely related to head movements (15 out of 18, 6 mice). Calcium flashing occurred definitely with drastic convulsive motor seizures (CMS, 6 mice). The results prove that the synchronization of calcium event exists in CA1 and M1, and different calcium events are related with different seizure behaviors. Our results suggest that calcium events involve in the synchronization of neural network and behaviors in epilepsy.

The Roles of Skin Fibroblasts at Local Acupoints in Chrono-Acupuncture.

Objective: The aim of this study was to demonstrate the peripheral mechanisms of chrono-acupuncture by observing acupuncture at different time points affecting relative proteins to regulate the cytoskeleton of fibroblasts differently. Methods: A total of 108 male SD rats (180-220 g) that have basic pain threshold within 3-10 s were selected and randomly divided into group A (n = 72) and control group (n = 36). After the succession of modeling with CFA injection, the rats in group A were randomly divided into model group and acupuncture group, each group containing 36 rats. Then according to the different treatment time, each group was randomly classified into 6 subgroups (ZT0, ZT4, ZT8, ZT12, ZT16, and ZT20), each subgroup containing 6 rats (n = 6). On the second day of successful modeling, the rats in the acupuncture group received acupuncture treatment at the corresponding time point, while the control group and the model group were only tied up at the corresponding time point without any treatments. Methods of operation: use 0.5-inch needles, puncture the rats' "Zusanli" on the affected limb, with Twirling manipulation for a minute after every five minutes; the treatment lasts thirty minutes in total. After 7 days of treatments, the skin and subcutaneous tissue of rats' acupoint area of "Zusanli" on the affected limb were taken and then stained by immunofluorescence double staining method to observe the expression of the fibroblast cytoskeleton F-actin and ß-tubulin under the LSCM while using western blot to observe the expression of P38MAPK/P-P38MAPK. Results: The expression of the cytoskeleton F-actin and ß-tubulin at acupoint area in the acupuncture group was significantly higher than that in the control and model group. The effect of acupuncture on the restructure of the fibroblast cytoskeleton is different at different time points, the most effective time point was at ZT12 while the least at ZT16. Acupuncture can decrease the high expression of P-P38MAPK/P38MAPK in the model group, and the effect has time differences. The expression of P-P38MAPK/P38MAPK increased more significantly at ZT16 than ZT12. Conclusion: The remodeling difference of fibroblast cytoskeleton after receiving acupuncture treatment could be one of the peripheral bases of the chrono-acupuncture.

DDR2-CYR61-MMP1 Signaling Pathway Promotes Bone Erosion in Rheumatoid Arthritis Through Regulating Migration and Invasion of Fibroblast-Like Synoviocytes.

Regulation of matrix metalloproteinases (MMPs) by collagen in the fibroblast-like synoviocytes (FLSs) plays a critical role in joint destruction in rheumatoid arthritis (RA). Our previous study indicated that discoidin receptor 2 (DDR2) mediated collagen upregulation of MMPs. However, the precise underlying mechanism remains unclear. We report here that CYR61, a secreted, extracellular matrix-associated signaling protein which is capable of regulating a broad range of cellular activities, including cell adhesion, migration, proliferation, and apoptosis, is significantly upregulated in collagen II-stimulated RA FLS. Further studies found that collagen II-activated phosphorylated-DDR2 induces CYR61 through activation of transcription factor activator protein 1 (AP-1). The elevated CYR61, in turn, accelerates MMP1 production via ETS1 (ETS proto-oncogene 1). In addition, CYR61 significantly promotes FLS invasion and migration. Blockade of CYR61 by an adenovirus expressing CYR61 shRNA (Ad-shCYR61) in vivo remarkably ameliorated the severity of arthritis, reduced inflammatory cytokine secretion, and attenuated bone erosion as detected by micro-computed tomography (µCT), in collagen-induced arthritis (CIA) rats. Taken together, we uncovered the Collagen II-DDR2-AP-1-CYR61-ETS1-MMP1 loop in RA FLS. In which, CYR61 acts as a hinge to promote cartilage damage through regulating FLS invasion, migration, and MMP1 production and the inflammatory cascade in RA. Thus, CYR61 may be a promising diagnostic and therapeutic target for RA treatment. © 2016 American Society for Bone and Mineral Research.

Functional "Janus" Annulus in Confined Channels.

Scattered Au 3D nanoparticles form distinct functional regions with an uncovered internal surface in confined channels, named the "Janus" annulus. Electrochemical impedance spectroscopy responses to the variations in DNA self-assembly and hybridization in the channels decorated by the "Janus" annulus are presented. Single nucleotide mutations are further detected in a linear DNA chain, including terminal base polymorphisms.

[Changes of lung, spleen and kidney aquaporin-1 in rats with Kidney Yang Deficiency: the "water metabolism theory" in traditional Chinese medicine].

OBJECTIVE: To explore the experimental basis of the "water metabolism theory" in traditional Chinese medicine by observing the changes of aquaporin-1 in the lung, spleen and kidney. METHODS: Rat models of Kidney Yang Deficiency induced by gavage with 2% adenine suspension for 4 weeks were treated with cistanches decoction for 6 weeks. Urinary 17-hydroxy cortisol, urine creatinine, urine osmolality value content, and aquaporin-1 mRNA and protein expressions in the lung, spleen and kidney tissues were detected after the treatment. RESULTS: Treatment with adenine induced Kidney Yang Deficiency in rats by causing a reduction in urinary 17-hydroxy cortisol, urine creatinine and urine osmolality. Aquaporin-1 mRNA expression in the spleen and kidney were down-regulated after adenine treatment. Compared with the rat models, intervention with cistanche significantly increased aquaporin-1 mRNA expression in the lung and kidney tissues. Adenine resulted in increased aquaporin-1 protein expression in the lung, spleen and kidney of the rats, while cistanche intervention lowered its expression in lung and kidney tissues. CONCLUSION: The lung, spleen, kidneys are involved in water metabolism, and aquaporin-1 is one of its molecular basis. Cistanche can increase aquaporin-1 expressions, which is also regulated by other factors.

[GTW-induced abnormal expressions of testicular reproduction-related genes and intervention with kidney-tonifying Chinese herbs].

OBJECTIVE: To explore the abnormal expressions of testicular reproduction-related genes induced by glycosides of Tripterygium wilfordii (GTW) and the intervention with kidney-tonifying Chinese herbs. METHODS: Adult Balb/C male mice were fed on GTW at 30 mg per kg per d for 3 weeks to establish a model of reproductive dysfunction. The model mice were divided into different groups to receive intragastrical administration of saline (0.25 ml/d), GTW (30 mg per kg per d), Cistanche (10 g per kg per d), Rehmannia (10 g per kg per d), and Rehmannia + Cistanche (20 g per kg per d), respectively, once a day for 3 weeks. And a Cistanches pretreatment group was treated with GTW (30 mg per kg per d) and Cistanche (10 g per kg per d) for the same length of time. Then we detected the changed expressions of testicular reproduction-related genes Dzip1, Fas, c-jun and Wnt4 in each group. RESULTS: The model mice showed an obviously down-regulated expression of the Y chromosome microdeletion-related gene Dzip1, and up-regulated expressions of the germ cell apoptosis-related gene Fas, proto-oncogene c-jun, and signal transduction-related gene Wnt4. Intervention with Chinese herbs achieved different degrees of improvement of the mice's reproductivity, and the most obvious efficacy was observed with the combined use of kidney-yang tonifying Cistanche and kidney-yin nourishing Rehmannia. CONCLUSION: GTW exerts significant impact on reproduction-related genes. Both the kidney-yang tonifying drug Cistanche and kidney-yin nourishing drug Rehmannia can counteract some of the reproductive toxicity of GTW, while the combination of the two can further enhance the effect.

Effect of Feining on bleomycin-induced pulmonary injuries in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The flowers of Gentiana veitchiorum has been widely used in decoction form in the traditional medicine of Tibet against tussis, tracheitis, angina for their anti-inflammatory, antimicrobial and alexipharmic properties. AIM OF THE STUDY: The aim of current study was to evaluate the therapeutic effects of Feining, a Chinese herbal formula (national invention patent: ZL200510042636.3) against pulmonary injuries and to clarify the mechanisms involved. MATERIALS AND METHODS: Experimental pulmonary injuries were induced by bleomycin (BLM) in rats with or without subsequent treatment of Feining or prednisone as positive control. The pulmonary injuries were evaluated by histological analysis. Also, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) and hydroxyproline (Hyp) in the lung tissue were determined. To clarify one of the possible active principles responsible for Feining, high performance liquid chromatography-diode array detector-mass spectrometry (HPLC-DAD-MS) method was applied to identify the components of Gentiana veitchiorum, one of major ingredients of Feining. RESULTS: Feining significantly improved lung alveolitis scores and reduced the Hyp content of lungs, which is an index of collagen accumulation. Moreover, Feining played a role against the oxidative damages by decreasing the MDA level, whereas increasing SOD and GSH activity, which correlated with oxidation resistance and scavenging of free radicals. In addition, Feining alleviated inflammatory lung injury by decreasing tumor necrosis factor-α (TNF-α) expression. HPLC-DAD-MS analysis revealed that there was 1.97% gentiopicroside in Gentiana veitchiorum. CONCLUSION: Feining has certain therapeutic effects against pulmonary injuries.