High altitude retinopathy: An overview and new insights.

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.

Astragalus membranaceus and Salvia miltiorrhiza ameliorate diabetic kidney disease via the "gut-kidney axis".

BACKGROUND: The combination of Astragalus membranaceus and Salvia miltiorrhiza (AS) is an effective prescription for treating diabetic kidney disease (DKD) in traditional Chinese medicine. Its efficacy in treating DKD has been confirmed, but the potential regulatory mechanism has not yet been fully clarified. PURPOSE: To explore the mechanism by which AS regulates the "gut-metabolism-transcription" coexpression network under the action of the "gut-kidney axis" to ameliorate DKD. METHODS: SD rats were used to establish the DKD model by injecting STZ. After AS intervention, the structure and function of the kidney and colon were observed. We sequenced the gut microbiota utilizing 16S rDNA, identified serum differential metabolites using LC‒MS/MS, and observed renal mRNA expression by RNA seq. The "gut-metabolism-transcription" coexpression network was further constructed, and the target bacteria, target metabolites, and target genes of AS were ultimately screened and validated. RESULTS: AS improved renal pathology and functional damage and increased the abundance of Akkermansia, Akkermansia_muciniphila, Lactobacillus and Lactobacillus_murinus. Fourteen target metabolites of AS were identified, which were mainly concentrated in 19 KEGG pathways, including sphingolipid metabolism and glycerophospholipid metabolism. Sixty-three target mRNAs of AS were identified. The top 20 pathways were closely related to glycolipid metabolism, and 14 differential mRNAs were expressed in these pathways. Correlation analysis showed that Akkermansia, Akkermansia muciniphila, Lactobacillus and Lactobacillus murinus were closely associated with sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, ascorbate and aldarate metabolism and galactose metabolism. Moreover, the target metabolites and target mRNAs of AS were also enriched in five identical pathways of sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, ascorbate and aldarate metabolism and galactose metabolism, including 8 different metabolites, such as sphingosine, and 5 different genes, such as Kng1. The 8 metabolites had high AUC prediction values, and the validation of the 5 genes was consistent with the sequencing results. CONCLUSION: Our research showed that AS can improve DKD via the "gut-kidney axis". Akkermansia muciniphila and Lactobacillus murinus were the main driving bacteria, and five pathways related to glycolipid metabolism, especially sphingolipid metabolism and glycerophospholipid metabolism, may be important follow-up reactions and regulatory mechanisms.

[Transurethral plasma resection of the prostate for acute urinary retention in patients with advanced prostate cancer].

OBJECTIVE: To compare the safety of transurethral plasma resection of the prostate (TuPkRP) in the treatment of advanced PCa (APC)-related acute urinary retention (AUR) with that in the treatment of BPH-related AUR and investigate the oncologic characteristics of the PCa patient after TuPkRP. METHODS: In this retrospective study, we first compared the baseline data between the patients with APC-related AUR (group A, n = 32) and those with BPH-related AUR (group B, n = 45) as well as their surgical parameters, such as the operation time, pre- and post-operative hemoglobin levels, IPSS at 3 months after TuPkRP and length of postoperative hospital stay. Then, we observed possible TuPkRP-induced tumor progression by comparing the oncologic parameters, such as the PSA level and ECT-manifested bone metastasis, between the APC-AUR patients treated by androgen-deprivation therapy (ADT) + TuPkRP and those treated by ADT only (group C, n = 24). RESULTS: There were no statistically significant differences in the baseline data between the APC-AUR and BPH-AUR patients (P > 0.05). The operation time and postoperative hospital stay were significantly longer in the APC-AUR than in the BPH-AUR group (P < 0.05), but the decreases in the hemoglobin level and IPSS at 3 months after operation showed no significant differences between the two groups of patients (P > 0.05). Besides, no statistically significant differences were observed in the oncologic parameters between the APC-AUR patients treated by ADT + TuPkRP and those by ADT only (P > 0.05). CONCLUSION: The safety of TuPkRP was not significantly lower and the rates of postoperative complications and adverse events were not significantly higher in the patients with APC-related AUR than in those with BPH-related AUR. And this surgical strategy did not significantly improve the progression of APC.

Yi-Shen-Hua-Shi granule ameliorates diabetic kidney disease by the "gut-kidney axis".

ETHNOPHARMACOLOGICAL RELEVANCE: Yi-Shen-Hua-Shi (YSHS) granule is an effective prescription widely used in traditional Chinese medicine to treat diabetic kidney disease (DKD), its exact efficacy in treating DKD has been confirmed but the underlying regulatory mechanism has not been fully elucidated. AIM OF THE STUDY: To explore the mechanism by which YSHS granule regulates intestinal flora and serum metabolites and then regulates renal mRNA expression through the "gut-kidney axis", so as to improve DKD. MATERIALS AND METHODS: 40 rats were divided into five groups: Normal group (N) (normal saline), model group (M) (STZ + normal saline), YSHS granule low-dose group (YL) (STZ + 2.27 g kg-1 d-1), YSHS granule high-dose group (YH) (STZ + 5.54g kg-1 d-1) and valsartan group (V) (STZ + 7.38mg kg-1 d-1). After 6 weeks, changes in blood glucose, blood lipids, and renal function related indexes were observed, as well as pathological changes in the kidney and colon. Intestinal microbiota was sequenced by 16S rDNA, serum differential metabolites were identified by LC-MS/MS, and renal differences in mRNA expression were observed by RNA-seq. Further, through the association analysis of intestinal differential microbiota, serum differential metabolites and kidney differential mRNAs, the target flora, target metabolites and target genes of YSHS granule were screened and verified, and the "gut-metabolism-transcription" co-expression network was constructed. RESULTS: In group M, blood glucose, blood lipid and proteinuria were increased, inflammation, oxidative stress and renal function were aggravated, with the proliferation of mesangial matrix, vacuolar degeneration of renal tubules, accumulation of collagen and lipid, and increased intestinal permeability, and YSHS granule and valsartan improved these disorders to varying degrees. High dose of YSHS granule improved the diversity and abundance of flora, decreased the F/B value, greatly increased the abundance of Lactobacillus and Lactobacillus_murinus, and decreased the abundance of Prevoella UCG_001. 14 target metabolites of YSHS granule were identified, which were mainly enriched in 20 KEGG pathways, such as Glycerophospholipid metabolism, Sphingolipid metabolism and Phenylalanine, tyrosine and tryptophan biosynthesis. 96 target mRNAs of YSHS granule were also identified. The enriched top 20 pathways were closely related to glucose and lipid metabolism, of which a total of 21 differential mRNAs were expressed. Further correlation analysis revealed that Lactobacillus, Lactobacillus_murinus and Prevotella UCG_001 were highly correlated with Glycerophospholipid metabolism, Sphingolipid metabolism and Phenylalanine, tyrosine and tryptophan biosynthesis pathways. At the same time, 6 pathways including Glycerophospholipid metabolism, Arachidonic acid metabolism, Purine metabolism, Primary bile acid biosynthesis, Ascorbate and aldarate metabolism and Galactose metabolism were co-enriched by the target metabolites and the target mRNAs of YSHS granule, including 7 differential metabolites such as phosphatidylethanolamine and 7 differential genes such as Adcy3. The 7 differential metabolites had high predictive value of AUC, and the validation of 7 differential genes were highly consistent with the sequencing results. CONCLUSION: YSHS granule could improve DKD through the "gut-kidney axis". Lactobacillus and Lactobacillus_murinus were the main driving forces. 6 pathways related to glucose and lipid metabolism, especially Glycerophospholipid metabolism, may be an important follow-up response and regulatory mechanism.

Resin-based iron-manganese binary oxide for phosphate selective removal.

Adsorption technology can effectively remove phosphorus from water and realize phosphorus recovery. Hence, it is used to curb the eutrophication of water and alleviate the crisis caused by the shortage of phosphorus resources. Resin has been attracting increasing interest as an ideal adsorption material; however, its practical application is greatly affected by environmental factors. To solve the competitive adsorption and pore blockage caused by humic acid and coexisting ions during the removal of phosphorus by ion-exchange resin, this study has developed an iron-manganese oxide-modified resin composite adsorbent (Fe/Mn-402) based on the nanoconfinement theory. The structural characterization results of XRD, FT-IR, SEM, and XPS showed that the iron-manganese binary oxide was successfully loaded on the skeleton of the strongly alkaline anion resin and showed good stability under both neutral and alkaline conditions. The batch adsorption experiments showed that the maximum adsorption capacity of Fe/Mn-402 for phosphorus can reach up to 50.97 mg g-1 under the optimal raw material ratio (Fe:Mn = 1:1). In addition, Fe/Mn-402 shows good selectivity for phosphorus removal. Fe/Mn-402 can maintain good adsorption performance for phosphate even under high concentrations of SO42-, HCO3-, and humic acid. The regenerated Fe/Mn-402 can be recycled without any obvious change in its treatment capacity. Hence, it is suitable for stable, long-term usage. In general, this work puts forward a new idea for the development of phosphorus-removal adsorbents for the treatment of wastewater containing coexisting ions and HA.

Correlation analysis of carotid artery intima-media thickness, serum 25(OH)D and men with erectile dysfunction.

Our goal is to investigate the connection between serum 25(OH)D and carotid artery intima-media thickness (CIMT) in men with erectile dysfunction (ED).Serum 25(OH)D and CIMT were measured in 124 participants with erectile dysfunction and 39 healthy controls. The relationship between them and different patient-related parameters and disease-related parameters was studied. Compared with the control group and mild ED group, the level of serum 25(OH)D in moderate ED group and severe ED group decreased significantly(P<0.05). The CIMT values of moderate ED group and severe ED group were higher than those of the control group(P<0.05). The CIMT value of severe ED group was significantly higher than that of mild ED group(P<0.05). IIEF-5 score was positively correlated with serum 25(OH)D level, but negatively correlated with CIMT value(P<0.05). After adjusting for the influence of confounding factors, The CIMT values, 25(OH)D and IIEF-5 score were substantially associated(P<0.05). The serum level of 25(OH)D and IIEF-5 score were positively correlated, while the CIMT values and IIEF-5 score were negatively correlated. The level of serum 25(OH)D should be analyzed in men with ED, especially in patients with vasculogenic ED, and supplementation is recommended for those who were with vitamin D deficiency.

Trigonelline Extends the Lifespan of C. Elegans and Delays the Progression of Age-Related Diseases by Activating AMPK, DAF-16, and HSF-1.

Trigonelline is the main alkaloid with bioactivity presented in fenugreek, which was used in traditional medicine in Asian countries for centuries. It is reported that trigonelline has anti-inflammatory, anti-oxidant, and anti-pathogenic effects. We are wondering whether trigonelline have anti-aging effect. We found that 50 µM of trigonelline had the best anti-aging activity and could prolong the lifespan of Caenorhabditis elegans (C. elegans) by about 17.9%. Trigonelline can enhance the oxidative, heat, and pathogenic stress resistance of C. elegans. Trigonelline could also delay the development of neurodegenerative diseases, such as AD, PD, and HD, in models of C. elegans. Trigonelline could not prolong the lifespan of long-lived worms with loss-of-function mutations in genes regulating energy and nutrition, such as clk-1, isp-1, eat-2, and rsks-1. Trigonelline requires daf-16, hsf-1, and aak-2 to extend the lifespan of C. elegans. Trigonelline can also up-regulate the expression of daf-16 and hsf-1 targeted downstream genes, such as sod-3, gst-4, hsp-16.1, and hsp-12.6. Our results can be the basis for developing trigonelline-rich products with health benefits, as well as for further research on the pharmacological usage of trigonelline.

Partitioning of evapotranspiration and the influencing factors of evapotranspiration components in a shrub ecosystem dominated by Artemisia ordosica and Hedysarum fruticosum var. mongolicum in the Mu Us Desert, Northwest China.

Evapotranspiration (ET) is an important part of water cycle and energy flow in ecosystem. Accurate estimation of ET and its components is critical for understanding the impacts of ecophysiological processes on ecosystem water balance and plant water use strategy. Using the eddy-covariance technique and the micro-lysimeter, we measured ET, evaporation (E), transpiration (T) of the Artemisia ordosica-Hedysarum fruticosum var. mongolicum shrubland in the Mu Us Desert during May 20 to September 15, 2019, quantified the ET components, and analyzed the seasonal characteristics and influencing factors of ET and its components. The results showed that T was the main component of ET in the growing season, with a T/ET of 53.1%. T/ET increased and E/ET decreased as precipitation decreased. The partitioning of evapotranspiration was regulated by precipi-tation. At the seasonal scale, the value of E was positively correlated with soil water content at 10 cm depth (SWC10) and net radiation (Rn), while SWC10 was the main factor influencing E. The value of T increased with the increases of Rn and leaf area index (LAI), and increased first and then decreased with the increases of soil water content at 30 cm layer (SWC30). T was affected by SWC30, Rn and LAI. Moisture was the main influencing factor of ET. The ET/P in the growing season was 109.2% and was 250.5% in May, indicating that the water consumption of ET in early growing season was partly from the precipitation in non-growing season.

The effects of extruded endogenous starch on the processing properties of gluten-free Tartary buckwheat noodles.

The lack of gluten in Tartary buckwheat has always been the main limiting factor of their development. This paper explored how to improve the processing quality of gluten-free Tartary buckwheat noodles (GF-TBNs) by introducing extruded starch into Tartary buckwheat flour (TBF) and the underlying mechanism was also elucidated. Extruded Tartary buckwheat starch (ETBS) was obtained under different extrusion conditions. The thermal properties, molecular weight, and viscosity of ETBS were examined to determine the key parameters closely related to the water distribution and rheological properties of the dough sheet, and tensile properties of GF-TBNs. The results showed that ETBS with a low molecular weight and high viscosity contributed greatly to the GF-TBNs with good tensile properties. It is proposed that ETBS with a low molecular weight and high viscosity might form a gel-entrapped network inside GF-TBNs, which was confirmed by the morphology of GF-TBNs.

A network pharmacology perspective for deciphering potential mechanisms of action of Solanum nigrum L. in bladder cancer.

BACKGROUND: Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC). However, there are no previous pharmacological studies on the protective mechanisms of this activity of the plant. Thus, this study aimed to perform a systematic analysis and to predict the potential action mechanisms underlying S. nigrum activity in BC based on network pharmacology. METHODS: Based on network pharmacology, the active ingredients of S. nigrum and the corresponding targets were identified using the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform database, and BC-related genes were screened using GeneCards and the Online Mendelian Inheritance in Man database. In addition, ingredient-target (I-T) and protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, and then the pathways directly related to BC were integrated manually to reveal the pharmacological mechanism underlying S. nigrum-medicated therapeutic effects in BC. RESULTS: Seven active herbal ingredients from 39 components of S. nigrum were identified, which shared 77 common target genes related to BC. I-T network analysis revealed that quercetin was associated with all targets and that NCOA2 was targeted by four ingredients. Besides, interleukin 6 had the highest degree value in the PPI network, indicating a hub role. A subsequent gene enrichment analysis yielded 86 significant GO terms and 89 significant pathways, implying that S. nigrum had therapeutic benefits in BC through multi-pathway effects, including the HIF-1, TNF, P53, MAPK, PI3K/Akt, apoptosis and bladder cancer pathway. CONCLUSIONS: S. nigrum may mediate pharmacological effects in BC through multi-target and various signaling pathways. Further validation is required experimentally. Network pharmacology approach provides a predicative novel strategy to reveal the holistic mechanism of action of herbs.

Astragalus membranaceus and Salvia miltiorrhiza ameliorates cyclosporin A-induced chronic nephrotoxicity through the "gut-kidney axis".

ETHNOPHARMACOLOGICAL RELEVANCE: The combination of Astragalus membranaceus and Salvia miltiorrhiza (AS) is an effective prescription that is widely used to treat chronic kidney disease (CKD) clinically in traditional Chinese medicine. Our previous studies have shown that AS can alleviate early CKD through the "gut-kidney axis", but the regulatory role of AS in the "gut-kidney axis" in the middle and late stages of CKD caused by cyclosporin A-induced chronic nephrotoxicity (CICN) has remained unclear. AIM OF THE STUDY: To explore the protective effect of AS by regulating the intestinal flora to further control the miRNA-mRNA interaction profiles in CICN. MATERIALS AND METHODS: Thirty-two mice were divided into four groups: Normal (N) (olive oil), Model (M) (CsA, 30 mg kg-1 d-1), AS (CsA + AS, 30 + 8.4 g kg-1 d-1) and FMT-AS (CsA + Faeces of AS group, 30 mg + 10 mL kg-1 d-1). The mice were treated for 6 weeks. Changes in renal function related metabolites were detected, pathological changes in the colon and kidney were observed, and 16S rDNA sequencing was performed on mouse faeces. In addition, miRNA and mRNA sequencing were performed on the kidney to construct differential expression (DE) profiles of the other 3 groups compared with group M. The target mRNAs among the DE miRNAs were then predicted, and an integrated analysis was performed with the DE mRNAs to annotate gene function by KEGG. DE miRNAs and DE mRNAs related to CICN in the overlapping top 20 KEGG pathways were screened and verified. RESULTS: Eight metabolites that could worsen renal function were increased in group M, accompanied by thickening of the glomerular basement membrane, vacuolar degeneration of renal tubules, and proliferation of collagen fibres, while AS and FMT-AS intervention amended these changes to varying degrees. Simultaneously, intestinal permeability increased, the abundance and diversity of the flora decreased, and the ratio of Firmicum to Bacteroides (F/B) increased in group M. The AS and FMT-AS treatments reversed the flora disorder and increased probiotics producing butyric acid and lactic acid, especially Akkermansia and Lactobacillus, which might regulate the 12 overlapping top 20 KEGG pathways, such as Butanoate metabolism, Tryptophan metabolism and several RF-related pathways, leading to the remission of renal metabolism. Finally, 15 DE miRNAs and 45 DE mRNAs were screened as the therapeutic targets, and the results coincided with the sequencing results. CONCLUSION: AS could alleviate renal fibrosis and metabolism caused by CICN through the "gut-kidney axis". Probiotics such as Akkermansia and Lactobacillus were the primary driving factors, and the miRNA-mRNA interaction profiles, especially Butanoate metabolism and Tryptophan metabolism, may be an important subsequent response and regulatory mechanism.

HOXD3 was negatively regulated by YY1 recruiting HDAC1 to suppress progression of hepatocellular carcinoma cells via ITGA2 pathway.

OBJECTIVES: HOXD3 is associated with progression of multiple types of cancer. This study aimed to identify the association of YY1 with HOXD3-ITGA2 axis in the progression of hepatocellular carcinoma. MATERIALS AND METHODS: Bioinformatics assay was used to identify the effect of YY1, HOXD3 and ITGA2 expression in HCC tissues. The function of YY1 and HOXD3 in HCCs was determined by qRT-PCR, MTT, apoptosis, Western blotting, colony formation, immunohistochemistry, and wound-healing and transwell invasion assays. The relationship between YY1 and HOXD3 or HOXD3 and ITGA2 was explored by RNA-Seq, ChIP-PCR, dual luciferase reports and Pearson's assays. The interactions between YY1 and HDAC1 were determined by immunofluorescence microscopy and Co-IP. RESULTS: Herein, we showed that the expression of YY1, HOXD3 and ITGA2 associated with the histologic and pathologic stages of HCC. Moreover, YY1, recruiting HDAC1, can directly target HOXD3 to regulate progression of HCCs. The relationship between YY1 and HOXD3 was unknown until uncovered by our present investigation. Furthermore, HOXD3 bound to promoter region of ITGA2 and up-regulated the expression, thus activating the ERK1/2 signalling and inducing HCCs proliferation, metastasis and migration in the vitro and vivo. CONCLUSIONS: Therefore, HOXD3, a target of YY1, facilitates HCC progression via activation of the ERK1/2 signalling by promoting ITGA2. This finding provides a new whole way to HCC therapy by serving YY1-HOXD3-ITGA2 regulatory axis as a potential therapeutic target for HCC therapy.

Study on the Antihypertensive Mechanism of Astragalus membranaceus and Salvia miltiorrhiza Based on Intestinal Flora-Host Metabolism.

Our previous studies have shown that the combination of Astragalus membranaceus and Salvia miltiorrhiza (HD) had a good antihypertensive effect, but its potential mechanism remained unclear. This study aimed to investigate the role of intestinal flora and serum metabolism induced by HD against hypertension. 16 spontaneous hypertensive rats (SHRs) were divided into HD group (5.9 g/kg) and model group (M) (normal saline), with eight Wistar-Kyoto (WKY) rats as control group (W) (normal saline). Rats were fed by gavage once a day for 28 days. The changes of intestinal flora and serum metabolism were analyzed by 16S rDNA sequencing and LC-MS/MS assay. HD decreased blood pressure steadily, improved the structure and composition of imbalance flora in SHRs, increased the abundance and diversity of flora, and decreased flora Firmicutes to Bacteroidetes (F/B) ratio. Rumen bacterium NK4A214, Clostridium sp. MC 40 increased remarkably in M group. Akkermansia, Akkermansia muciniphila, and Lactobacillus intestinalis increased significantly in HD group, which were functionally related to the significant increase of Lachnoclostridium, Faecalibaculum, and Lactobacillus reuteri in W group, which were all probiotics producing butyric acid, lactic acid, and regulating inflammation and other antihypertensive related factors. HD also changed the serum metabolic pattern of SHRs. 16 potential biomarkers related to inflammation, vasodilation, steroid hormones, oxidative stress, and etc. changed significantly, mainly enriched in arachidonic acid metabolism, tryptophan metabolism, steroid hormone biosynthesis, and glutathione metabolism. The correlation analysis demonstrated that the dominant genius and species in three groups were highly correlated with steroid hormone biosynthesis, arachidonic acid metabolism, tryptophan metabolism, and vitamin B6 metabolism. Our research indicated that HD had a good antihypertensive effect, which may be driven by the protective intestinal flora and beneficial metabolites induced by it, and the metabolites were closely related to the changes of intestinal flora. It provided new insights for the antihypertensive mechanism of HD.

Blood Oxygen Level-Dependent Response Changes in the Ipsilateral Primary Somatosensory Cortex and Thalamus of Patients With Moyamoya Disease During Median Nerve Electrical Stimulation.

OBJECTIVE: The objective of this study was to investigate the changes in the blood oxygen level-dependent (BOLD) response in the ipsilateral primary somatosensory cortex (SI) and thalamus of patients with moyamoya disease (MMD) during sensory stimulation. METHODS: Sixty-four MMD patients, and 15 healthy volunteers were enrolled. Thirty-three MMD patients exhibited paroxysmal numbness or hypoesthesia in the unilateral limbs. Fifteen patients with acroparesthesia underwent unilateral encephaloduroarteriosynangiosis (EDAS). All volunteers underwent BOLD functional magnetic resonance imaging (BOLD-fMRI) under median nerve electrical stimulation (MNES). Blood oxygen level-dependent fMRI data were processed to obtain time-signal intensity curves in the activation areas of the bilateral SI and thalamus. Processed dynamic susceptibility contrast-enhanced magnetic resonance imaging data were used to measure the time to peak of the BOLD response in the regions of interest, including the bilateral SI, thalamus, and cerebellum. Changes in the time-signal intensity curve-related hemodynamic parameters in the ipsilateral SI and thalamus were examined between healthy controls, nonacroparesthesia patients, and asymptomatic and symptomatic sides of unilateral acroparesthesia patients during MNES. Changes in these parameters in MMD patients before and after EDAS were examined. RESULTS: Compared with healthy volunteers, 3 groups of MMD patients exhibited an increased peak of the positive BOLD response in the ipsilateral thalamus during MNES (0.65 ± 0.24 vs 0.79 ± 0.35, 0.94 ± 0.57, and 0.89 ± 0.50; P = 0.0335). The positive response peak in the ipsilateral SI markedly increased in MMD patients with acroparesthesia during MNES on the asymptomatic side (0.56 ± 0.37 vs 0.38 ± 0.27, P = 0.0243). The time to peak negative response in the ipsilateral SI was prolonged during MNES on the symptomatic side after EDAS (12.14 ± 8.90 seconds vs 18.86 ± 9.20 seconds, P = 0.0201). CONCLUSIONS: During sensory stimulation treatment, BOLD response changes occurred in the ipsilateral SI and thalamus of MMD patients. These changes enabled the contralateral hemisphere of the brain to better deal with sensory stimuli.

[Cynomorium songaricum improves sperm count and motility and serum testosterone level and promotes proliferation of undifferentiated spermatogonia in oligoasthenospermia rats].

OBJECTIVE: To investigate the effects of cynomorium songaricum (CS) decoction on the testis weight, serum testosterone level, and sperm parameters of rats with oligoasthenospermia (OAS), explore its action mechanism of improving the proliferation of undifferentiated spermatogonial cells, and provide some experimental and theoretical evidence for the development of new Chinese drugs for OAS. METHODS: Thirty 8-week-old male SD rats were randomly divided into five groups of equal number: blank control, model control, high-dose CS, medium-dose CS, and low-dose CS. OAS models were established by intraperitoneal injection of cyclophosphamide and, a month later, treated intragastrically with normal saline or CS at 2, 1, and 0.5 g per kg of the body weight per day, all for 4 weeks. Then, the testes of the animals were harvested to obtain the testicular weight, sperm concentration and motility, and the level of serum testosterone (T), detect the expressions of the transcription factor 1 (Oct4), Thy-1 cell surface antigen (Thy1), promyelocytic leukemia zinc finger (PLZF), KIT proto-oncogene receptor tyrosine kinase (C-kit) and glial cell-derived neurotrophic factor (GDNF) in the testis tissue of the rats in the low-dose CS group by real-time PCR. RESULTS: The testis weights in the blank control, model control, high-dose CS, medium-dose CS, and low-dose CS groups were (1.52±0.06), (1.55±0.06), (1.43±0.30), (1.35±0.40) and (1.34±0.04) g, respectively, not significantly different in the blank and model controls from those in the CS groups (P>0.05). The visual field sperm count per 10 HP was significantly increased in the high-, medium-, and low-dose CS groups (202±20, 196±5 and 216±25) as compared with the blank and model controls (200±15 and 134±30) (P<0.05). The mRNA expressions of the Oct4, Thy1, PLZF and GDNF genes were remarkably higher in the low-dose CS group than in the controls (P<0.05), but that of the C-kit gene showed no significant difference from the latter (P>0.05). The visual field sperm motility per 10 HP was markedly increased in the blank control (ï¼»52.1±5.5ï¼½%), model control (ï¼»38.1±2.5ï¼½%), high-dose CS (ï¼»59.1±9.5ï¼½%), medium-dose CS (ï¼»58.7±9.5ï¼½%), and low-dose CS (ï¼»49.6±1.0ï¼½%) groups, and so was the level of serum testosterone (ï¼»190±87.5ï¼½, ï¼»82.5±25.8ï¼½, ï¼»229±75.6ï¼½, ï¼»331±86.7ï¼½ and ï¼»185±82.4ï¼½ mmol/L), both remarkably higher in the CS groups than in the model controls (P<0.05) but with no statistically significant difference between the CS groups and the blank controls (P>0.05). CONCLUSIONS: CS can significantly improve sperm concentration, sperm motility and serum T level in OAS rats, probably by inducing the expression of GDNF in the rat Sertoli cells, promoting the proliferation of undifferentiated spermatogonial cells, and enhancing spermatogenesis.

In Vitro and In Vivo Antitumor Effects of n-Butanol Extracts of Pterocephalus hookeri on Hep3B Cancer Cell.

Pterocephalus hookeri is a widely applied Tibetan medicinal prescription for treatment of diseases such as flu, rheumatoid arthritis, and enteritis in China. It has been reported that Pterocephalus hookeri has anti-inflammatory and analgesic actions. However, the antitumor activity of Pterocephalus hookeri remains unknown. In the present study, we demonstrate that n-butanol extracts of Pterocephalus hookeri (YSC-ZDC) has a strong antitumor activity against hepatoma carcinoma cell in vitro and in vivo. YSC-ZDC inhibited proliferation of all cancer cell lines and significantly inhibited Hep3B cells proliferation in a dose- and time-dependant manner. Transmission electron microscopy, hoechst 33258 staining, and flow cytometry analysis revealed that YSC-ZDC induced apoptosis in Hep3B cells. YSC-ZDC treatment dramatically inhibited PDK1 and Akt phosphorylation in Hep3B cells. Moreover, YSC-ZDC increased Bax expression and inhibited Bcl-2 expression. In addition, YSC-ZDC inhibited growth hepatoma xenografts in vivo with no effect on body weight and spleen index. Consistent with results in vitro, YSC-ZDC increased Bax expression and inhibited Bcl-2 expression in tumor tissue. Taken together, this study shows YSC-ZDC with an antitumor activity both in vitro and in vivo. Its mechanism underlying is related to blocking of the Akt pathway and regulation of Bcl-2 family proteins expression.

Effects of trehalose supplementation on cell viability and oxidative stress variables in frozen-thawed bovine calf testicular tissue.

Trehalose is widely used for cryopreservation of various cells and tissues. Until now, the effect of trehalose supplementation on cell viability and antioxidant enzyme activity in frozen-thawed bovine calf testicular tissue remains unexplored. The objective of the present study was to compare the effect of varying doses of trehalose in cryomedia on cell viability and key antioxidant enzymes activities in frozen-thawed bovine calf testicular tissue. Bovine calf testicular tissue samples were collected and cryopreserved in the cryomedias containing varying doses (0, 5, 10, 15, 20 and 25%; v/v) of trehalose, respectively. Cell viability, total antioxidant capacity (T-AOC) activity, catalase (CAT) activity, superoxide dismutase (SOD) activity, glutathione (GSH) content and malondialdehyde (MDA) content were measured and analyzed. The results showed that cell viability, T-AOC activity, SOD activity, CAT activity and GSH content of frozen-thawed bovine calf testicular tissue was decreased compared with that of fresh group (P<0.05). MDA content in frozen-thawed bovine calf testicular tissue was significantly increased compared with that of fresh group (P<0.05). The cryomedia added 15% trehalose exhibited the greatest percentage of cell viability and antioxidant enzyme activity (SOD and CAT) among frozen-thawed groups (P<0.05). Meanwhile, GSH content was the lowest among frozen-thawed groups (P<0.05). However, there were no significance differences in MDA content among the groups added 10, 15 and 20% trehalose (P>0.05). In conclusion, the cryomedia added 15% trehalose reduced the oxidative stress and improved the cryoprotective effect of bovine calf testicular tissue. Further studies are required to obtain more concrete results on the determination of antioxidant capacity of trehalose in frozen-thawed bovine calf testicular tissue.

Protective effects of Wusen Erlian granules in experimental model of viral myocarditis.

We wished to study the protective effects of Wusen Erlian granules, a therapy from traditional Chinese medicine, in experimental viral myocarditis (VMC). Sixty mice were divided into six groups: control group, infection group, ribavirin group, and three Wusen Erlian groups, treated with low, intermediate, or high doses (4, 12, or 20 mg/kg) of Wusen Erlian. Control animals were intraperitoneally injected with culture medium, while animals in other groups received intraperinoneal injections of CoxB3 virus. The Wusen Erlian granules were intragastrically administered on days 0, 1, 2, 3, 4, and 5 after virus inoculation. The experiment was terminated 2 h after the final drug administration. The mice were weighed, and specimens were collected for detection of myocardial enzymes, measurement of organ index, and natural killer (NK) cell activity. The levels of creatine kinase isoenzyme, troponin, and myoglobin were significantly increased in infected animals (all p < 0.05). Compared with infection group, the levels of creatine kinase isoenzyme and troponin were significantly (p < 0.05) decreased in animals that received ribavirin, and in animals that received high or intermediate dose of Wusen Erlian. Furthermore, the spleen and thymus indexes were increased in animals treated with ribavirin, or high/intermediate doses of Wusen Erlian, suggesting immunoregulating functions of these drugs. The NK cell activity was also markedly increased in the above three groups. Wusen Erlian alleviates the CoxB3-induced myocardial injury and exhibits immunoregulating features, leading to protective effects toward myocardial cells in experimental VMC.

In vitro cardioprotective effect of Wusen Erlian Granules through the inhibition of Coxsackievirus B3 replication.

Wusen Erlian Granules are a traditional Chinese medicine and we sought to determine the antiviral activity of Wusen Erlian Granules against Coxsackievirus B3 infection. First, cytotoxicity of Wusen Erlian Granules was determined in cultured cardiomyocytes isolated from day-old Wister rat pups. Later, cardiomyocytes were infected with Coxsackievirus B3 and the protective effect of Wusen Erlian Granules against cell injury was compared with that of ribavirin. Cell injury indicators including myoglobin, MB isozyme of Creatine Kinase, and cardiac Troponin were assessed by enzyme-linked immunosorbent assay (ELISA) and antiviral effect was assessed by MTT assay. We found that the 50 %-Toxic (TC50) and 50 %-Effective (EC50) concentrations of Wusen Erlian Granules were 394.05 and 30.26 µg/ml, respectively. Following infection of cardiomyocytes with Coxsackievirus B3, cell injury index of Wusen Erlian Granules, as determined by ELISA, was 125 µg/ml which yielded significant protection from virus-induced cell damage. The antiviral activity of Wusen Erlian Granules i.e., therapeutic index in MTT assay was higher (13.02) than that of ribavirin (6.93). It was, therefore, concluded that the Wusen Erlian Granules exerted better antiviral effect than ribavirin using Coxsackievirus B3 in vitro infection model in terms of rat cardiomyocytes protection from virus-induced cell injury.

Discovery of Helicobacter pylori shikimate kinase inhibitors: bioassay and molecular modeling.

Shikimate kinase (SK) is the fifth enzyme in the shikimate pathway and catalyzes the phosphate transfer from ATP to shikimate in generating shikimate 3-phosphate and ADP. SK has been developed as a promising target for the discovery of antibacterial agents. In this report, two small molecular inhibitors (compound 1, 3-methoxy-4-{[2-({2-methoxy-4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy}methyl)benzyl]oxy}benzaldehyde; compound 2, 5-bromo-2-(5-{[1-(3,4-dichlorophenyl)-3,5-dioxo-4-pyrazolidinylidene]methyl}-2-furyl)benzoic acid) against Helicobacter pylori SK (HpSK) were successfully identified with IC(50) values of 5.5+/-1.2 and 6.4+/-0.4 microM, respectively. The inhibition kinetics shows that compound 1 is a noncompetitive inhibitor with respect to both shikimate and MgATP, and compound 2 is a competitive inhibitor toward shikimate and noncompetitive inhibitor with respect to MgATP. The surface plasmon resonance (SPR) technology based analysis reveals that the equilibrium dissociation constants (K(D)s) of compounds 1 and 2 with HpSK enzyme are 4.39 and 3.74 microM, respectively. The molecular modeling and docking of two inhibitors with HpSK reveals that the active site of HpSK is rather roomy and deep, forming an L-shape channel on the surface of the protein, and compound 1 prefers the corner area of L-shape channel, while compound 2 binds the short arm of the channel of SK in the binding interactions. It is expected that our current work might supply useful information for the development of novel SK inhibitors.