Therapeutic potential of toosendanin: Novel applications of an old ascaris repellent as a drug candidate.

Toosendanin (TSN), extracted from Melia. toosendan Sieb.et Zucc. and Melia. azedarach L., has been developed into an ascaris repellent in China. However, with the improvement of public health protection, the incidence of ascariasis has been reduced considerably, resulting in limited medical application of TSN. Therefore, it is questionable whether this old ascaris repellent can develop into a drug candidate. Modern studies have shown that TSN has strong pharmacological activities, including anti-tumor, anti-botulinum, anti-viral and anti-parasitic potentials. It also can regulate fat formation and improve inflammation. These researches indicate that TSN has great potential to be developed into a corresponding medical product. In order to better development and application of TSN, the availability, pharmacodynamics, pharmacokinetics and toxicology of TSN are summarized systematically. In addition, this review discusses shortcomings in the current researches and provides useful suggestions about how TSN developed into a drug candidate. Therefore, this paper illustrates the possibility of developing TSN as a medical product, aimed to provide directions for the clinical application and further research of TSN.

Novel wine in an old bottle: Preventive and therapeutic potentials of andrographolide in atherosclerotic cardiovascular diseases.

Atherosclerotic cardiovascular disease (ASCVD) frequently results in sudden death and poses a serious threat to public health worldwide. The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets. Therefore, the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention. Andrographolide (AG) is a diterpenoid lactone compound extracted from Andrographis paniculata. In addition to its use in conditions such as sore throat, AG can be used to prevent and treat ASCVD. It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity, diabetes, hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis (AS) including lipid accumulation, inflammation, oxidative stress and cellular abnormalities by regulating various targets and pathways. However, the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated, which may hinder its clinical development and application. Therefore, this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD. The findings support the use of the old pharmacological compound ('old bottle') as a novel drug ('novel wine') for the prevention and treatment of ASCVD. Additionally, this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG, aiming to provide more information regarding the clinical application and further research and development of AG.

A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury.

Acute kidney injury (AKI) exhibits high morbidity and mortality. Kidney injury molecule-1 (KIM1) is dramatically upregulated in renal tubules upon injury, and acts as a biomarker for various renal diseases. However, the exact role and underlying mechanism of KIM1 in the progression of AKI remain elusive. Herein, we report that renal tubular specific knockout of Kim1 attenuates cisplatin- or ischemia/reperfusion-induced AKI in male mice. Mechanistically, transcription factor Yin Yang 1 (YY1), which is downregulated upon AKI, binds to the promoter of KIM1 and represses its expression. Injury-induced KIM1 binds to the ECD domain of death receptor 5 (DR5), which activates DR5 and the following caspase cascade by promoting its multimerization, thus induces renal cell apoptosis and exacerbates AKI. Blocking the KIM1-DR5 interaction with rationally designed peptides exhibit reno-protective effects against AKI. Here, we reveal a YY1-KIM1-DR5 axis in the progression of AKI, which warrants future exploration as therapeutic targets.

Insight into the enhancing mechanism of exogenous electron mediators on biological denitrification in microbial electrolytic cell.

Sustained nitrate accumulation in surface water ecosystem was continuously grabbing public attention. Autotrophic denitrification by electron supplement has been applied to overcome the requirement of carbon source, thus the new problem that how to improve the efficiency of extracellular electrons transfer to denitrifiers comes to us. The addition of exogenous electron mediators has been considered as an important strategy to promote extracellular electrons transfer in reductive metabolism. To date, knowledge is lacking about the promoting effects and pathways in nitrate removal by electron mediators. Here, we fully investigated the performance of nitrogen removal as well as quantified the characteristics of biofilms with six electron mediators (riboflavin, flavin mononucleotide, AQS, AQDS, biochar and Nano-Fe3O4) treating in microbial electrolytic cell system. The six electron mediators promoted nitrate removal rate by 76.03-90.43 % with electron supplement. The growth and activity of cathodic biofilm, conductive nanowires generation and electrochemically active substance synthesis of extracellular polymeric substances were facilitated by electron mediator addition. Electrochemical analysis revealed that conductivity and redox capacity of cathodic biofilm was increased for accelerating electron transfer. Moreover, they upregulated the abundance of denitrifying communities and denitrifying genes accordingly. Their denitrification efficiency varied due to their promotion ability in the above different strategies and conductive characteristics, and the efficiency could be concluded as: Nano-Fe3O4 > riboflavin > flavin mononucleotide > AQS ≈ AQDS > biochar. This study revealed how addition of electron mediators promoted denitrification with electron supplement, and compared their promoting efficiency in several main aspects.

Efficacy of Tailor-Made Notched Music Training Versus Tinnitus Retraining Therapy in Adults With Chronic Subjective Tinnitus: A Randomized Controlled Clinical Trial.

OBJECTIVES: Chronic subjective tinnitus can have a serious effect on daily life, even causing serious psychological disorders. Currently there are no specific effective solutions or cures. Tailor-made notched music training (TMNMT) is a recently proposed sound therapy that has simpler processes and a higher compliance rate than tinnitus retraining therapy (TRT), a widely used treatment for chronic subjective tinnitus. This study explores the therapeutic effect of TMNMT in comparison to TRT to highlight its clinical value. DESIGN: The study was a randomized controlled, single-blinded clinical trial. One hundred twenty eligible participants were randomly assigned to receive TMNMT (n = 60) or TRT (n = 60) for 3 mo with concurrent follow-up. It should be noted that the duration of sound treatment in TRT was modified to 2 hr per day for better feasibility in practice. The primary outcome was mean change in tinnitus handicap inventory (THI) measured at baseline ( T0 ), 1 mo ( T1 ) and 3 mo ( T2 ) after intervention. Change in visual analog scale (VAS) was measured as a secondary outcome. A comparison of therapeutic effectiveness between TMNMT and TRT was evaluated by repeated measure analysis of variance. RESULTS: One hundred and twelve (93%) of participants took part in the study, of which 64 were men and 48 women. Mean (SD) age was 42.80 (12.91) years. Fifty-eight were allocated to receive TMNMT and 54 to receive TRT. The between-group difference in primary outcome was -6.90 points (95% confidence interval [CI], -13.53 to -0.27) at T1 and -6.17 points (95% CI, -13.04 to 0.71) at T2 . These results closely reached to clinical significance of tinnitus-related effective relief. For the secondary outcome, the mean value in the TMNMT group was 0.83 points (95% CI, 0.12 to 1.54), significantly lower than the mean value of the TRT group. The differences in THI and VAS between the two groups were statistically significant after intervention. Further analysis showed that age and baseline THI and VAS scores were associated with change in THI and VAS scores after interventions. CONCLUSIONS: Both TMNMT and TRT were able to alleviate chronic subjective tinnitus effectively after a 3 month intervention. When the two forms of therapy were compared TMNMT appeared to be more effective and consequently potentially superior to TRT for reducing tinnitus loudness and functional and emotional disturbance associated with chronic subjective tinnitus.

Vitamin D3 decreases TNF-α-induced inflammation in lung epithelial cells through a reduction in mitochondrial fission and mitophagy.

Previous work has shown an association between vitamin D3 deficiency and an increased risk for acquiring various inflammatory diseases. Vitamin D3 can reduce morbidity and mortality in these patients via different mechanisms. Lung inflammation is an important event in the initiation and development of respiratory disorders. However, the anti-inflammatory effects of vitamin D3 and the underlying mechanisms remained to be determined. The purpose of this study was to examine the effects and mechanisms of action of vitamin D3 (Vit. D) on the expression of intercellular adhesion molecule-1 (ICAM-1) in vitro and in vivo with or without tumor necrosis factor α (TNF-α) treatment. Pretreatment with Vit. D reduced the expression of ICAM-1 and leukocyte adhesion in TNF-α-treated A549 cells. TNF-α increased the accumulation of mitochondrial reactive oxygen species (mtROS), while Vit. D reduced this effect. Pretreatment with Vit. D attenuated TNF-α-induced mitochondrial fission, as shown by the increased expression of mitochondrial fission factor (Mff), phosphorylated dynamin-related protein 1 (p-DRP1), and mitophagy-related proteins (BCL2/adenovirus E1B 19 kDa protein-interacting protein 3, Bnip3) in A549 cells. Inhibition of DRP1 or Mff significantly decreased ICAM-1 expression. In addition, we found that Vit. D decreased TNF-α-induced ICAM-1 expression, mitochondrial fission, and mitophagy via the AKT and NF-κB pathways. Moreover, ICAM-1 expression, mitochondrial fission, and mitophagy were increased in the lung tissues of TNF-α-treated mice, while Vit. D supplementation reduced these effects. In this study, we elucidated the mechanisms by which Vit. D reduces the expression of adhesion molecules in models of airway inflammation. Vit. D might be served as a novel therapeutic agent for the targeting of epithelial activation in lung inflammation. Graphical Headlights: • The expression of DRP1 and Mff, mitochondrial fission-related proteins, was increased in TNF-α-treated A549 cells. • The expression of Bnip3 and LC3B, mitophagy-related proteins, was increased in TNF-α-treated A549 cells. • Vit. D pretreatment decreased TNF-α-induced inflammation through the reduction of mitochondrial fission and mitophagy in A549 cells.

Molecular responses to inorganic and organic phosphorus sources in the growth and toxin formation of Microcystis aeruginosa.

Toxic cyanobacteria bloom is a ubiquitous phenomenon worldwide in eutrophic lakes or reservoirs. Microcystis, is a cosmopolitan genus in cyanobacteria and exists in many different forms. Microcystis aeruginosa (M. aeruginosa) can produce microcystins (MCs) with strong liver toxicity during its growth and decomposition. Phosphorus (P) is a typical growth limiting factor of M. aeruginosa. Though different forms and concentrations of P are common in natural water, the molecular responses in the growth and MCs formation of M. aeruginosa remain unclear. In this study, laboratory experiments were conducted to determine the uptake of P, cell activity, MCs release, and related gene expression under different concentrations of dissolved inorganic phosphorus (DIP) and dissolved organic phosphorus (DOP). We found that the growth of M. aeruginosa was promoted by increasing DIP concentration but coerced under high concentration (0.6 and 1.0 mg P/L) of DOP after P starvation. The growth stress was not related to the alkaline phosphatase activity (APA). Although alkaline phosphatase (AP) could convert DOP into algae absorbable DIP, the growth status of M. aeruginosa mainly depended on the response mechanism of phosphate transporter expression to the extracellular P concentration. High-concentration DIP promoted MCs production in M. aeruginosa, while high-concentration DOP triggered the release of intracellular MCs rather than affecting MCs production. Our study revealed the molecular responses of algal growth and toxin formation under different P sources, and provided a theoretical basis and novel idea for risk management of eutrophic lakes and reservoirs.

Metal chloride-loaded biochar for phosphorus recovery: Noteworthy roles of inherent minerals in precursor.

Phosphorus (P) is a valuable resource, while it is vastly lost with wastewater causing eutrophication. In this study, to recover P, composite biochars were prepared by pyrolyzing biowaste impregnated with FeCl3 or MgCl2. It was found that inherent mineral profiles in the biowastes played important roles in interacting with metal chlorides and determined P sorption and precipitation. Specifically, two biowastes containing distinct mineral contents, sawdust and sediment, were selected as model components, being alone or mixed at 1:1 (w/w) to prepare biochars with low, moderate and high mineral contents. Results showed that biochar itself could not absorb P, while loading FeCl3 or MgCl2 achieved P recovery rates of approximate 60-100% and 50-100%, respectively, via electrostatic attraction or ligand exchange of PO43- with -OH/-COOH, which was attributed to the enhanced positive charges and -OH/-COOH on the materials by these metal chlorides. Inherent minerals inhibited FeCl3 transforming into Fe3O4 in pyrolysis and promoted generation of Fe4(PO4)3(OH)3 in P sorption, thus high-mineral content was more appropriate for FeCl3 loading; however, precursors with low-mineral content was suitable for MgCl2 loading, since the bulk-C in biochar acted as porous structure to support MgO crystals with high superficial area (∼255.85 m2 g-1). Besides, FeCl3 and MgCl2 both drove dissolution of inherent minerals significantly, while inherent minerals inhibited release of soluble Fe and Mg2+ into solution, which minimized secondary pollution. This study implied that in constructing composite biochar for catching P, the type of metal chloride should match the inherent minerals in biowastes to maximize P recovery and minimize secondary pollution.

Expression of Telomeric Repeat-Containing RNA Decreases in Sarcopenia and Increases after Exercise and Nutrition Intervention.

Sarcopenia is defined as aging-related loss of muscle mass and function. Telomere length in chromosomes shortens with age and is modulated by telomeric repeat-containing RNA (TERRA). This study aimed to explore the impact of aging and sarcopenia on telomere length and TERRA expression, and changes following strengthening exercise and nutrition intervention (supplement of branched-chain amino acids, calcium and vitamin D3) for 12 weeks in the sarcopenic population. Older adults (≥65 years old) were divided into non-sarcopenic controls (n = 36) and sarcopenic individuals (n = 36) after measurement of grip strength and body composition. The relative telomere length of leukocytes in all research participants was evaluated using the T/S ratio (telomere/single copy gene), and relative TERRA expression of leukocytes was determined by reverse-transcription qPCR (RT-qPCR). Generalized estimating equation (GEE) was used to analyze the influence of sarcopenia and intervention on the outcomes. There was no significant difference in telomere length between control subjects and participants with sarcopenia. TERRA expression was lower in sarcopenic participants compared to that in non-sarcopenic controls (5.18 ± 2.98 vs. 2.51 ± 1.89; p < 0.001). In the sarcopenic group, intervention significantly increased TERRA expression, but not telomere length. The GEE analysis demonstrated that TERRA expression was negatively associated with sarcopenia (ß coefficient = -2.705, p < 0.001) but positively associated with intervention (ß coefficient = 1.599, p = 0.023). Sarcopenia is associated with a decrease in TERRA expression in leukocytes. Rebound TERRA expression (returning to the level similar to the non-sarcopenic controls) was observed in the sarcopenic group after exercise and nutrition intervention. Future studies are warranted to examine the potential of TERRA as a biomarker for sarcopenia and its subsequent responses to intervention.

Altered hypothalamic functional connectivity in post-traumatic headache after mild traumatic brain injury.

BACKGROUND: Post-traumatic headache (PTH) is one of the most frequent symptoms following mild traumatic brain injury (mTBI). Neuroimaging studies implicate hypothalamic function connectivity (FC) disruption as an important factor in pain disorders. However, it is unknown whether there are alterations in the hypothalamus-based resting state FC within PTH following mTBI at the acute stage and its relationship with headache symptom measurement. METHODS: Forty-four mTBI patients with PTH, 27 mTBI patients without PTH and 43 healthy controls who were well matched for age, gender, and years of education were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (fMRI) scanning as well as headache symptom measurement and cognitive assessment. Hypothalamic resting state networks were characterized by using a standard seed-based whole-brain correlation method. The bilateral hypothalamic FC was compared among the three groups. Furthermore, the correlations between hypothalamic resting state networks and headache frequency, headache intensity and MoCA scores was investigated in mTBI patients with PTH using Pearson rank correlation. RESULTS: Compared with mTBI patients without PTH, mTBI patients with PTH at the acute stage presented significantly decreased left hypothalamus-based FC with the right middle frontal gyrus (MFG) and right medial superior frontal gyrus (mSFG), and significantly decreased right hypothalamus-based FC with the right MFG. Decreased FC of the right MFG was significantly positively associated with headache frequency and headache intensity (r = 0.339, p = 0.024; r = 0.408, p = 0.006, respectively). Decreased FC of the right mSFG was significantly positively associated with headache frequency and headache intensity (r = 0.740, p < 0.0001; r = 0.655, p < 0.0001, respectively). CONCLUSION: Our data provided evidence of disrupted hypothalamic FC in patients with acute mTBI with PTH, while abnormal FC significantly correlated with headache symptom measurement. Taken together, these changes may play an essential role in the neuropathological mechanism of mTBI patients with PTH.

Impaired intrinsic functional connectivity between the thalamus and visual cortex in migraine without aura.

BACKGROUND: Resting-state functional magnetic resonance imaging (fMRI) has confirmed disrupted visual network connectivity in migraine without aura (MwoA). The thalamus plays a pivotal role in a number of pain conditions, including migraine. However, the significance of altered thalamo-visual functional connectivity (FC) in migraine remains unknown. The goal of this study was to explore thalamo-visual FC integrity in patients with MwoA and investigate its clinical significance. METHODS: Resting-state fMRI data were acquired from 33 patients with MwoA and 22 well-matched healthy controls. After identifying the visual network by independent component analysis, we compared neural activation in the visual network and thalamo-visual FC and assessed whether these changes were linked to clinical characteristics. We used voxel-based morphometry to determine whether functional differences were dependent on structural differences. RESULTS: The visual network exhibited significant differences in regions (bilateral cunei, right lingual gyrus and left calcarine sulcus) by inter-group comparison. The patients with MwoA showed significantly increased FC between the left thalami and bilateral cunei and between the right thalamus and the contralateral calcarine sulcus and right cuneus. Furthermore, the neural activation of the left calcarine sulcus was positively correlated with visual analogue scale scores (r = 0.319, p = 0.043), and enhanced FC between the left thalamus and right cuneus in migraine patients was negatively correlated with Generalized Anxiety Disorder scores (r = - 0.617, p = 0.005). CONCLUSION: Our data suggest that migraine distress is exacerbated by aberrant feedback projections to the visual network, playing a crucial role in migraine physiological mechanisms. The current study provides further insights into the complex scenario of migraine mechanisms.

Adequate rectal preparation reduces hospital admission for urosepsis after transrectal ultrasound - guided prostate biopsy

ABSTRACT Objectives: Previous studies have compared infectious outcomes on the basis of whether rectal preparation was performed; however, they failed to evaluate the quality of each rectal preparation, which may have led to confounding results. This study aimed to compare hospitalizations for urosepsis within 1 month after transrectal ultrasound-guided prostate biopsy between patients with adequate and traditional rectal preparations. Materials and Methods: Between January 2011 and December 2016, a total of 510 patients who underwent transrectal ultrasound - guided prostate biopsy at our institutions and were orally administered prophylactic antibiotics (levofloxacin) were included. Two rectal preparations were performed: (1) adequate rectal preparation confirmed by digital rectal examination and transrectal ultrasound (Group A, n = 310) and (2) traditional rectal preparation (Group B, n = 200). All patient characteristics were recorded. A logistic regression model was used to assess the effects of the two different rectal preparations on urosepsis, adjusted by patient characteristics. Results: There were a total of three and nine hospitalizations for urosepsis in Groups A and B, respectively. Differences in the demographic data between the two groups were insignificant. Logistic regression showed that adequate rectal preparation before biopsy significantly decreased the risk for urosepsis after biopsy (adjusted odds ratio: 0.2; 95% confidence interval: 0.05 - 0.78; P = 0.021). Conclusions: Adequate rectal preparation could significantly reduce hospitalizations for urosepsis within 1 month after transrectal ultrasound-guided prostate biopsy. The quality of rectal preparation should be evaluated before biopsy. If adequate rectal preparation is not achieved, postponing the biopsy and adjusting the rectal preparation regimen are suggested.

Adequate rectal preparation reduces hospital admission for urosepsis after transrectal ultrasound - guided prostate biopsy.

OBJECTIVES: Previous studies have compared infectious outcomes on the basis of whether rectal preparation was performed; however, they failed to evaluate the quality of each rectal preparation, which may have led to confounding results. This study aimed to compare hospitalizations for urosepsis within 1 month after transrectal ultrasound-guided prostate biopsy between patients with adequate and traditional rectal preparations. MATERIALS AND METHODS: Between January 2011 and December 2016, a total of 510 patients who underwent transrectal ultrasound - guided prostate biopsy at our institutions and were orally administered prophylactic antibiotics (levofloxacin) were included. Two rectal preparations were performed: (1) adequate rectal preparation confirmed by digital rectal examination and transrectal ultrasound (Group A, n = 310) and (2) traditional rectal preparation (Group B, n = 200). All patient characteristics were recorded. A logistic regression model was used to assess the effects of the two different rectal preparations on urosepsis, adjusted by patient characteristics. RESULTS: There were a total of three and nine hospitalizations for urosepsis in Groups A and B, respectively. Differences in the demographic data between the two groups were insignificant. Logistic regression showed that adequate rectal preparation before biopsy significantly decreased the risk for urosepsis after biopsy (adjusted odds ratio: 0.2; 95% confidence interval: 0.05 - 0.78; P = 0.021). CONCLUSIONS: Adequate rectal preparation could significantly reduce hospitalizations for urosepsis within 1 month after transrectal ultrasound-guided prostate biopsy. The quality of rectal preparation should be evaluated before biopsy. If adequate rectal preparation is not achieved, postponing the biopsy and adjusting the rectal preparation regimen are suggested.

Curcumin accelerates cutaneous wound healing via multiple biological actions: The involvement of TNF-α, MMP-9, α-SMA, and collagen.

Curcumin, a constituent of the turmeric plant, has antitumor, anti-inflammatory, and antioxidative effects, but its effects on wound healing are unclear. We created back wounds in 72 mice and treated them with or without topical curcumin (0.2 mg/mL) in Pluronic F127 gel (20%) daily for 3, 5, 7, 9, and 12 days. Healing in wounds was evaluated from gross appearance, microscopically by haematoxylin and eosin staining, by immunohistochemistry for tumour necrosis factor alpha and alpha smooth muscle actin, and by polymerase chain reaction amplification of mRNA expression levels. Treatment caused fast wound closure with well-formed granulation tissue dominated by collagen deposition and regenerating epithelium. Curcumin increased the levels of tumour necrosis factor alpha mRNA and protein in the early phase of healing, which then decreased significantly. However, these levels remained high in controls. Levels of collagen were significantly higher in curcumin-treated wounds. Immunohistochemical staining for alpha smooth muscle actin was increased in curcumin-treated mice on days 7 and 12. Curcumin treatment significantly suppressed matrix metallopeptidase-9 and stimulated alpha smooth muscle levels in tumour necrosis factor alpha-treated fibroblasts via nuclear factor kappa B signalling. Thus, topical curcumin accelerated wound healing in mice by regulating the levels of various cytokines.

The effects of wild bitter gourd fruit extracts on ICAM-1 expression in pulmonary epithelial cells of C57BL/6J mice and microRNA-221/222 knockout mice: Involvement of the miR-221/-222/PI3K/AKT/NF-κB pathway.

BACKGROUND: The extracts from wild bitter gourd fruit (WBGE) were reported to possess numerous pharmacological activities. However, the anti-inflammatory effects of WBGE on human lung epithelial cells and the underlying mechanisms have not been determined. PURPOSE: To evaluate the molecular basis of the effects of WBGE on intercellular adhesion molecule-1 (ICAM-1) expression in alveolar epithelial (A549) cells, C57BL/6 wild-type (WT) mice and microRNA (miR)-221/-222 knockout (KO) mice with or without tumor necrosis factor (TNF-α; 3 ng/ml) treatment. STUDY DESIGN/METHODS: WT mice and miR-221/-222 KO mice were fed a control diet and divided into four groups (C: control mice; T: treated with TNF-α alone; WBGE/T: pretreated with WBGE and then stimulated with TNF-α; WBGE: treated with WBGE alone). The effects of WBGE on ICAM-1 expression and the related signals in A549 cells and mice with or without TNF-α treatment were examined by Western blot and immunofluorescent staining. RESULTS: WBGE significantly decreased the TNF-α-induced ICAM-1 expression in A549 cells through the inhibition of phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ nuclear factor- kappa B (NF-κB)/ inhibitor of NF-κB (IκB) phosphorylation and decreased leukocyte adhesion. In addition, WBGE reduced endogenous ICAM-1 expression and upregulated miR-221/-222 expression. The overexpression of miR-222 decreased PI3K/AKT/NF-κB/IκB and ICAM-1 expression, which resulted in reducing monocyte adhesion. Moreover, WBGE reduced ICAM-1 expression in lung tissues of WT mice with or without TNF-α treatment and upregulated miR-221/222. WBGE did not affect the miR-221/-222 level and had little effect on ICAM-1 expression in miR-221/-222 KO mice. CONCLUSIONS: These results suggest that WBGE reduced ICAM-1 expression both under in vitro and in vivo conditions. The protective effects were mediated partly through the miR-221/-222/PI3K/AKT/NF-κB pathway.

Caenorhabditis elegans as a model system for target identification and drug screening against neurodegenerative diseases.

Over the past decades, Caenorhabditis elegans (C. elegans) has been widely used as a model system because of its small size, transparent body, short generation time and lifespan (~3 days and 3 weeks, respectively), completely sequenced genome and tractability to genetic manipulation. Protein misfolding and aggregation are key pathological features in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Animal models, including C. elegans, have been extensively used to discover and validate new drugs against neurodegenerative diseases. The well-defined and genetically tractable nervous system of C. elegans offers an effective model to explore basic mechanistic pathways of neurodegenerative diseases. Recent progress in high-throughput drug screening also provides a powerful approach for identifying chemical modulators of biological processes. Here, we summarize the latest progress of using C. elegans as a model system for target identification and drug screening in neurodegenerative diseases.

Crocus sativus L. protects against SDS­induced intestinal damage and extends lifespan in Drosophila melanogaster.

Medicinal plants are important sources of potentially therapeutic biochemical drugs. Crocus sativus L. has been used to treat various diseases in China, the Republic of Korea and Japan. The present study investigated the protective effect of C. sativus L. extract in Drosophila melanogaster intestinal immunity. Wild­type flies were fed standard cornmeal­yeast medium and used as controls, and flies supplemented with 1% C. sativus L. aqueous extract in standard medium were used as the experimental group. Following the ingestion of the various toxic compounds, the survival rate of the flies was determined. Cell viability and levels of reactive oxygen species (ROS) were detected using 7­amino­actinomycin D and dihydroethidium staining, respectively. The present study demonstrated that aqueous extracts of C. sativus L. may significantly increase the lifespan and survival rate of adult flies. Additionally, C. sativus L. may decrease epithelial cell death and ROS levels, resulting in improved intestinal morphology. These findings indicated that C. sativus L. had a protective effect against intestinal injury and may extend the lifespan of Drosophila. Therefore, the findings of the present study may improve the understanding of clinical researchers on the complex effects of C. sativus L. in intestinal disorders.

Identification of the protective effects of traditional medicinal plants against SDS-induced Drosophila gut damage.

Traditional medicinal plants are widely used as immunomodulatory medicines that help improve health. A total of 50 different plants used for the treatment of toxicity were screened for their in vivo protective effects. Flies were fed a standard cornmeal-yeast medium (control group) or the standard medium containing medicinal plant extracts (experimental groups). Assessment of the survival rate was performed by feeding flies with toxic compounds. Gut epithelial cells were analyzed for cell proliferation and death by green fluorescent protein antibodies and 7-aminoactinomycin D staining under the microscope. The expression of antimicrobial peptides (AMPs) was evaluated by the quantitative polymerase chain reaction and the results revealed that after feeding the flies with toxic compounds, aqueous extracts from Codonopsis pilosula (Franch.) Nannf (C. pilosula), Saussurea lappa (Decne.) C.B.Clarke (S. lappa), Imperata cylindrica Beauv.var.major (Nees) C.E. Hubb. (I. cylindrical var. major) and Melia toosendan Sied. Et Zucc. (M.toosendan) increased the fly survival rate, reduced epithelial cell death and improved gut morphology. In addition, C. pilosula extracts induced the antimicrobial peptide levels (Dpt and Mtk) following treatment with sodium dodecyl sulfate (SDS). However, these extracts were not observed to increase SDS-induced cell proliferation in vivo. These results indicate that there are strong protective effects in extracts of C. pilosula, S. lappa, I. cylindrical var. major and M. toosendan on Drosophila intestinal cells among 50 medicinal plants.

Thalamic resting-state functional connectivity: disruption in patients with type 2 diabetes.

To explore the disrupted thalamic functional connectivity and its relationships with cognitive dysfunction in type 2 diabetes mellitus (T2DM) by using resting-state functional magnetic resonance imaging (fMRI). A total of 38 T2DM patients and 39 well-matched healthy controls participated in the resting-state fMRI and T1-weighted imaging scans. The thalamic functional connectivity was characterized by using a seed-based whole-brain correlation method and compared T2DM patients with healthy controls. Pearson correlation analysis was performed between thalamic functional connectivity and clinical data. When compared with healthy controls, T2DM showed significantly decreased functional connectivity of the thalamus mainly in the right middle temporal gyrus (MTG), right precentral gyrus and bilateral occipital cortex; Increased functional connectivity of the thalamus was detected in the left cerebellum, bilateral middle frontal gyrus and middle cingulate gyrus (p < 0.05, corrected for AlphaSim). In T2DM patients, the decreased thalamic functional connectivity of the right MTG was positively associated with the Verbal Fluency Test score (r = 0.438, p = 0.006). Meanwhile, the decreased thalamic functional connectivity of the right cuneus was positively correlated with the Complex Figure Test-delayed score and negatively correlated with the Trail Making Test-B score, respectively (r = 0.492, p = 0.002; r = -0.504, p = 0.001). Moreover, there was no structural damage in the thalamus of T2DM patients. T2DM patients develop disrupted thalamocortical functional connectivity, which is associated with cognitive impairment in selected brain regions. Resting-state thalamocortical connectivity disturbance may play a central role in the underlying neuropathological process of T2DM-related cognitive dysfunction.