Indole Propionic Acid Disturbs the Normal Function of Tryptophanyl-tRNA Synthetase in Mycobacterium tuberculosis.

Tuberculosis (TB) is the leading infectious disease caused by Mycobacterium tuberculosis and the second-most contagious killer after COVID-19. The emergence of drug-resistant TB has caused a great need to identify and develop new anti-TB drugs with novel targets. Indole propionic acid (IPA), a structural analog of tryptophan (Trp), is active against M. tuberculosis in vitro and in vivo. It has been verified that IPA exerts its antimicrobial effect by mimicking Trp as an allosteric inhibitor of TrpE, which is the first enzyme in the Trp synthesis pathway of M. tuberculosis. However, other Trp structural analogs, such as indolmycin, also target tryptophanyl-tRNA synthetase (TrpRS), which has two functions in bacteria: synthesis of tryptophanyl-AMP by catalyzing ATP + Trp and producing Trp-tRNATrp by transferring Trp to tRNATrp. So, we speculate that IPA may also target TrpRS. In this study, we found that IPA can dock into the Trp binding pocket of M. tuberculosis TrpRS (TrpRSMtb), which was further confirmed by isothermal titration calorimetry (ITC) assay. The biochemical analysis proved that TrpRS can catalyze the reaction between IPA and ATP to generate pyrophosphate (PPi) without Trp as a substrate. Overexpression of wild-type trpS in M. tuberculosis increased the MIC of IPA to 32-fold, and knock-down trpS in Mycolicibacterium smegmatis made it more sensitive to IPA. The supplementation of Trp in the medium abrogated the inhibition of M. tuberculosis by IPA. We demonstrated that IPA can interfere with the function of TrpRS by mimicking Trp, thereby impeding protein synthesis and exerting its anti-TB effect.

miR828a-CsMYB114 Module Negatively Regulates the Biosynthesis of Theobromine in Camellia sinensis.

Theobromine is an important quality component in tea plants (Camellia sinensis), which is produced from 7-methylxanthine by theobromine synthase (CsTbS), the key rate-limiting enzyme in theobromine biosynthetic pathway. Our transcriptomics and widely targeted metabolomics analyses suggested that CsMYB114 acted as a potential hub gene involved in the regulation of theobromine biosynthesis. The inhibition of CsMYB114 expression using antisense oligonucleotides (ASO) led to a 70.21% reduction of theobromine level in leaves of the tea plant, which verified the involvement of CsMYB114 in theobromine biosynthesis. Furthermore, we found that CsMYB114 was located in the nucleus of the cells and showed the characteristic of a transcription factor. The dual luciferase analysis, a yeast one-hybrid assay, and an electrophoretic mobility shift assay (EMSA) showed that CsMYB114 activated the transcription of CsTbS, through binding to CsTbS promoter. In addition, a microRNA, miR828a, was identified that directly cleaved the mRNA of CsMYB114. Therefore, we conclude that CsMYB114, as a transcription factor of CsTbS, promotes the production of theobromine, which is inhibited by miR828a through cleaving the mRNA of CsMYB114.

Chromosome-scale genome assembly of sweet tea (Lithocarpus polystachyus Rehder).

Lithocarpus, with >320 species, is the second largest genus of Fagaceae. However, the lack of a reference genome limits the molecular biology and functional study of Lithocarpus species. Here, we report the chromosome-scale genome assembly of sweet tea (Lithocarpus polystachyus Rehder), the first Lithocarpus species to be sequenced to date. Sweet tea has a 952-Mb genome, with a 21.4-Mb contig N50 value and 98.6% complete BUSCO score. In addition, the per-base consensus accuracy and completeness of the genome were estimated at 60.6 and 81.4, respectively. Genome annotation predicted 37,396 protein-coding genes, with repetitive sequences accounting for 64.2% of the genome. The genome did not undergo whole-genome duplication after the gamma (γ) hexaploidy event. Phylogenetic analysis showed that sweet tea diverged from the genus Quercus approximately at 59 million years ago. The high-quality genome assembly and gene annotation resources enrich the genomics of sweet tea, and will facilitate functional genomic studies in sweet tea and other Fagaceae species.

[Cost-benefit analysis on the intervention of application iron-fortified soy sauce for anemia in Deqing 15-54 years women, Zhejiang].

OBJECTIVE: To make a cost-benefit analysis on anemia intervention with iron-fortified soy sauce in 15-54 years old women. METHODS: The study was conducted in Deqing county, Zhejiang province in 2012-2013. A total 585 women as sampling size were estimated with statistical model and randomly selected by probability proportionate to size sampling. Hemoglobin were measured before intervention and after 15 months. The cost of the intervention project were collected with manpower, communication and other invest. The benefit was estimated with profiling model. RESULTS: After the intervention, the anemia prevalence of sampled women decreased from 31.1% to 21.9%(P<0.01). The major cost of the project was 156 400 RMB, and total benefits result ing from projects were 1 448 485 RMB. The cost-benefit ratio of the project is 1∶9.49. If investing one yuan can produce economic benefits of nearly 9.49 yuan, therefore, the intervention projectis worth to be scaling up. Sensitivity analysis showed the result of this study was stable. CONCLUSION: The intervention can significantly reduce the prevalence of anemia in women, and reduce the economic burden of the diseases. .

Raman spectroscopic and microscopic monitoring of on-site and in-situ remediation dynamics in petroleum contaminated soil and groundwater.

The mechanistic study of soil and groundwater remediation in petroleum contaminated lands significantly demands rapid qualitative and quantitative identification of petroleum substances. However, most traditional detection methods cannot provide the on-site or in-situ information of petroleum compositions and contents simultaneously even with multi-spot sampling and complex sample preparation. In this work, we developed a strategy for the on-site detection of petroleum compositions and in-situ monitoring of petroleum contents in soil and groundwater using dual-excitation Raman spectroscopy and microscopy. The detection time was 0.5 h for the Extraction-Raman spectroscopy method and one minute for the Fiber-Raman spectroscopy method. The limit of detection was 94 ppm for the soil samples and 0.46 ppm for the groundwater samples. Meanwhile, the petroleum changes at the soil-groundwater interface were successfully observed by Raman microscopy during the in-situ chemical oxidation remediation processes. The results revealed that hydrogen peroxide oxidation released petroleum from the interior to the surface of soil particles and then to groundwater during the remediation process, while persulfate oxidation only degraded petroleum on the soil surface and in groundwater. This Raman spectroscopic and microscopic method can shed light on the petroleum degradation mechanism in contaminated lands, and facilitate the selection of suitable soil and groundwater remediation plans.

Taohong Siwu Decoction enhances human bone marrow mesenchymal stem cells proliferation, migration and osteogenic differentiation via VEGF-FAK signaling in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (THSWD) is a conventional traditional Chinese prescription aiming at promoting blood circulation and alleviating blood stasis. It is widely prescribed in instances of ischemic strokes, cardiovascular diseases, osteoporosis and bone fracture. However, its molecular functions in bone formation remain uncharacterized. AIM OF STUDY: This study aims to explore the potential effects of THSWD treatment on human bone marrow mesenchymal stem cells (BMSCs) proliferation, osteogenic differentiation, and migration. MATERIALS AND METHODS: BMSCs undergo osteogenic, adipogenic, and chondrogenic differentiation to determine cell stemness. BMSCs were treated with low dose (200 µg/ml), medium dose (400 µg/ml) and high dose (600 µg/ml) THSWD. The cell viability was determined by CCK-8 assays, the osteogenic differentiation ability was determined by alizarin red staining and ALP staining, and cell migration was determined by wound healing and transwell assays. The effect of THSWD on the vascular endothelial growth factor (VEGF)/focal adhesion kinase (FAK) pathway was determined by immunoblotting. RESULTS: THSWD time-dependently and dose-dependently promoted BMSC viability. Moreover, THSWD also promoted BMSC osteogenic differentiation and migration. As opposed to THSWD, VEGF receptor inhibitor Bevacizumab suppressed BMSC osteogenic differentiation and migration. In BMSCs that have been co-treated with THSWD and Bevacizumab, THSWD effects on BMSC functions were partially eliminated by Bevacizumab. Moreover, THSWD treatment boosted VEGF content in the supernatant and was conducive to the phosphorylation of FAK and Src, whereas Bevacizumab exerted opposite effects; similarly, Bevacizumab partially abolished THSWD effects on VEGF and FAK (Tyr397) and Src (Tyr418) phosphorylation. CONCLUSION: THSWD enhances the capacities of BMSCs to proliferate, differentiate, and migrate, possibly through VEGF and the FAK-Src, thereby improving fracture healing.

Prevalence of anemia and related nutrient deficiencies after sleeve gastrectomy: A systematic review and meta-analysis.

This study aimed to investigate the prevalence of anemia and related nutrient deficiencies after sleeve gastrectomy (SG). Four online databases were searched for relevant articles. Thirty-one studies with 7639 patients were included in the meta-analysis. The pooled anemia prevalence was 7%, 6%, 9%, 10%, 12%, 25%, 20%, and 18% at baseline, 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months, respectively. Although the prevalence of vitamin B12 and folate deficiencies remained low postoperatively, the prevalence of ferritin deficiency steadily increased from 6% at baseline to 27% at 60 months. The prevalence of serum iron deficiency decreased from 13% at baseline to 6% at 24 months and increased to 20% at 60 months. Anemia and ferritin deficiency were strongly correlated (Pearson correlation coefficient = 0.774, p = 0.041). Subgroup analysis suggested that age ≤40 years, preoperative anemia, and insufficient iron supplementations were high-risk factors for postoperative anemia. SG is associated with an increased risk of anemia and decreased iron storage over long-term observation. Routine iron supplementations may reduce anemia after SG; however, the dosages recommended by current guidelines may be insufficient. More strict monitoring schedules and supplementation strategies should be established for the timely detection and management of postoperative anemia.

Taohong Siwu Decoction Promotes Osteo-Angiogenesis in Fractures by Regulating the HIF-1α Signaling Pathway.

Background: Vascular damage is a major consequence of bone fracture. Taohong Siwu decoction (TSD) can raise the expression of vascular endothelial growth factor (VEGF) in fracture healing. However, its molecular mechanism in promoting angiogenesis is still unknown. The aim of this study was to investigate the potential mechanisms of TSD in the regulation of osteo-angiogenesis in fracture healing. Methods: A rat tibial fracture model was established. After low- (4.5 g·kg-1), medium- (9 g·kg-1), and high-dose TSD (18 g·kg-1) and panax notoginsenoside (25 mg kg-1) treatment, hematoxylin-eosin staining was employed to visualize pathological changes in bone tissues. The levels of cytokines (interleukin (IL)-2, tumor necrosis factor-α (TNF-α), IL-6, and IL-1ß), thromboxane B2 (TXB2), and 6 ketone prostaglandin F1α (6-Keto-PGF1α) were quantified by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to identify the rat aortic endothelial cells (RAECs). Control serum, 10% TSD-containing serum, and 10% TSD-containing serum combined with hypoxia-inducible factor-1α (HIF-1α) inhibitor were used to treat the RAECs and rat osteoblasts. Transwell migration assay was utilized to examine the migration of the RAECs. The Matrigel tubulogenesis assay was used for the assessment of angiogenesis. The expression of angiogenesis- (von Hippel-Lindau tumor suppressor (VHL), HIF-1α, VEGF, angiopoietin-2 (Ang-2), and pVHL) and osteogenesis-related (alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteopontin-1 (OPN-1)) protein and gene was detected by western blot and quantitative real-time PCR (qRT-PCR). Results: Compared with the model group, TSD increased the trabecular bone areas, numbers, and thicknesses in fractured rats. In the plasma, the levels of cytokines and TXB2 in the middle- and high-dose TSD group were significantly lower than those in the model group (P < 0.01). The 6-keto-PGF1α content was increased by middle- and high-dose TSD intervention (P < 0.01). Compared to the control serum group, the angiogenesis and migration of the RAECs were enhanced in the TSD group (P < 0.001). The expression of HIF-1α, VEGF, and Ang-2 in the TSD group upregulated significantly (P < 0.001). VHL and pVHL were inhibited under TSD-containing serum treatment (P < 0.001). ALP, Runx2, and OPN-1 were increased obviously in the TSD group (P < 0.001). Nevertheless, the HIF-1α inhibitor reversed these changes (P < 0.001). Conclusion: TSD promotes angiogenesis and osteogenesis by regulating the HIF-1α signaling pathway. Meanwhile, it can effectively reduce the risk of inflammation and improve blood circulation.

Mitochondrial regulation of acute extrafollicular B-cell responses to COVID-19 severity.

BACKGROUND: Patients with COVID-19 display a broad spectrum of manifestations from asymptomatic to life-threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive. METHODS: We investigated a total of 137 APs infected with SARS-CoV-2. Patients were divided into mild and severe patient groups based on their requirement of oxygen supplementation. All blood samples from APs were collected within three weeks after symptom onset. Freshly isolated PBMCs were investigated for B cell subsets, their homing potential, activation state, mitochondrial functionality and proliferative response. Plasma samples were tested for cytokine concentration, and titer of Nabs, RBD-, S1-, SSA/Ro- and dsDNA-specific IgG. RESULTS: While critically ill patients displayed predominantly extrafollicular B cell activation with elevated inflammation, mild patients counteracted the disease through the timely induction of mitochondrial dysfunction in B cells within the first week post symptom onset. Rapidly increased mitochondrial dysfunction, which was caused by infection-induced excessive intracellular calcium accumulation, suppressed excessive extrafollicular responses, leading to increased neutralizing potency index and decreased inflammatory cytokine production. Patients who received prior COVID-19 vaccines before infection displayed significantly decreased extrafollicular B cell responses and mild disease. CONCLUSION: Our results reveal an immune mechanism that controls SARS-CoV-2-induced detrimental B cell responses and COVID-19 severity, which may have implications for viral pathogenesis, therapeutic interventions and vaccine development.

Effect of vitamin D on oxidative stress and serum inflammatory factors in the patients with type 2 diabetes.

The type 2 diabetes mellitus (T2DM) is an urgent global health problem. T2DM patients are in a state of high oxidative stress and inflammation. Vitamin D and glutathione (GSH) play crucial roles in antioxidation and anti-inflammation. However, T2DM patients have lower vitamin D and GSH levels than healthy persons. A randomized controlled trial was conducted to see the effect of the vitamin D supplementation on oxidative stress and inflammatory factors in T2DM patients. In this study, a total of 178 T2DM patients were randomly enrolled, 92 patients received regular treatment (T2DM group) and 86 patients in Vitamin D group received extra vitamin D 400 IU per day in addition to regular treatment. Serum vitamin D, GSH, GSH metabolic enzyme GCLC and GR, inflammatory factor MCP-1, and IL-8 levels were investigated. We found that the T2DM group has significantly higher concentrations of MCP-1 and IL-8 than those in the healthy donor group. After vitamin D supplementation for 90 days, T2DM patients had a 2-fold increase of GSH levels, from 2.72 ± 0.84 to 5.76 ± 3.19 µmol/ml, the concentration of MCP-1 decreased from 51.11 ± 20.86 to 25.42 ± 13.06 pg/ml, and IL-8 also decreased from 38.21 ± 21.76 to 16.05 ± 8.99 pg/ml. In conclusion, our study demonstrated that vitamin D could regulate the production of GSH, thereby reducing the serum levels of MCP-1 and IL-8, alleviating oxidative stress and inflammation, providing evidence of the necessity and feasibility of adjuvant vitamin D treatment among patients with T2DM. On the other hand, vitamin D and GSH levels have important diagnostic and prognostic values in T2DM patients.

Physical and chemical properties of dust in the Pre-Aral region of Uzbekistan.

The aim of this work is study of physical and chemical properties of dust of the Pre-Aral region of Uzbekistan such as Karakalpakstan and Khorezm that are located near the three deserts such as the Aralkum, Karakum, and Kyzylkum. The dust particles fell on glass have been collected in Karakalpakstan and Khorezm and studied systematically by employing wide range of methods. Particle volume vs size distribution has been measured with maximum around 600 nm and ~ 10 µm. The major and minor constituent materials present in the dust have been studied systematically by X-ray fluorescence spectroscopy, energy dispersive X-ray diffraction, and inductively coupled plasma optical emission spectroscopy. Main characteristic absorption bands corresponding to Si-O, Si-O-Si bonding in quartz and Fe-O bonds in hematite Fe2O3 have been identified by infrared and Raman spectroscopy. Quartz, hematite, lime, corundum, magnesia, and several other trace minerals have been identified in the dust particles. X-ray diffraction peaks corresponding to quartz, hematite, and corundum are sharp and are found to be more crystalline with some level of disorder. Analysis of the particle size and crystallinity on human being has been performed: disordered or crystalline quartz can create the lung disease; the particles in the size of 0.5-0.7 µm may produce diseases such as chronic silicosis, silicosis, and silica tuberculosis whereas hematite might create lung disease. Dust particles worsen optical transmittance of glass of the panels.

Optimization of primary prevention strategies of birth defects in Zhejiang Province by Delphi method / 预防医学

Objective @#To optimize the primary prevention strategies of birth defects in Zhejiang Province by Delphi method, so as to promote the capacity of birth defects prevention. @*Methods@#The expert consultation questionnaire was developed based on the relevant policies of Zhejiang Province and literature. Ten experts from medical institutions and health administrative departments were employed for one round Delphi expert consultation. The weighted scores and priorities of ten measures for the primary prevention of birth defects in Zhejiang Province were determined, as well as the suggestions of optimizing the current policies. @*Results @# The response rate of the experts was 90.91%; the coefficient of authority was 0.92; the coefficients of variation of ten measures were all less than 0.25; the coefficient of coordination was 0.31 ( P<0.05 ) , which indicated the opinions of the experts tended to be consistent. In the order of priority, ten primary prevention measures of birth defects were the improvement of birth defects surveillance network ( province, city and county level ) , the training of birth defects prevention talents, the construction of genetic consultation clinics, health education and publicity, the reproduction outpatient service construction for older people, free premarital medical examination, free pre-pregnancy eugenics test, the construction of drug consultation clinics, career planning and training of birth defect prevention and control consultants and free folic acid supplement to the whole population. Nine experts suggested that the following policies need to be optimized: birth defects surveillance system, free premarital medical examination, and health education and publicity.@*Conclusion@#In the primary prevention of birth defects in Zhejiang Province, the most urgent problem to be solved is the improvement of the three-level birth defects surveillance network.

Acupuncture for treatment of anxiety, an overview of systematic reviews.

PURPOSE: To evaluate the methodological quality and summarize evidence of important outcomes of systematic reviews (SRs)/Meta analyses (MAs) of acupuncture for anxiety. METHODS: We conducted a comprehensive literature search for SRs/MAs in PubMed, EMBASE, Cochrane library, Chinese Biomedical Databases (CBM), Wanfang database and China National Knowledge Infrastructure (CNKI) until November 30, 2018. Three reviewers independently extracted data and assessed the methodological quality of the reviews according to the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to rate the quality of evidence. In the pre-experiment, we used the intra-class correlation coefficient (ICC) to assess reviewer agreement, the ICC value for overall score was 0.978. RESULTS: Ten reviews were included. The assessment results of AMSTAR-2 showed that the methodological quality of all included studies was critically low. The lowest score were item "provide a list of excluded studies and justify the exclusions" and item "report sources of funding for the included studies", none of studies provided information about the above two items, followed by the "providing a priori design" item with only two (20%) studies conforming to this item. For GRADE, of the 7 outcomes, high quality evidence was provided in only 1 (14.3%), moderate in 2 (28.6.7%), and low in 4 (57.1%). CONCLUSION: Although most of the included reviews indicated that acupuncture group was more effective than control group in the treatment of anxiety, more importantly, the methodological quality of the included reviews and the quality of evidence were low. More high-quality evidence is needed to determine whether acupuncture is more effective than other treatments.

Estrogen Receptors Are Involved in the Neuroprotective Effect of Silibinin in Aß1-42-Treated Rats.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by a cascade of pathologic changes. A widely discussed theory indicates that amyloid ß (Aß) peptides are the causative agents of AD. Silibinin, a flavonoid derived from milk thistle, is well known for its hepato-protective activities and we have reported the neuroprotective effects of silibinin. In this study, we investigated the role of estrogen receptors (ERs) in silibinin's neuroprotective effect on Aß1-42-injected rats. Results of Morris water maze and novel object-recognition tests demonstrated that silibinin significantly attenuated Aß1-42-induced memory impairment. Silibinin attenuated ERs and PI3K-Akt pathways, as well as modulated mitogen-activated protein kinases in the hippocampus of Aß1-42-injected rats. Taken together, silibinin is a potential candidate in the treatment of Alzheimer's disease.

Effect of Low-Dose Vitamin D Supplementation on Serum 25(OH)D in School Children and White-Collar Workers.

OBJECTIVE: Our study aimed to investigate the nutritional vitamin D status of school children aged 9-15 years and white-collar workers in Zhejiang province, and evaluate the efficacy of low-dose-oral vitamin D supplementation in both populations. METHODS: We conducted a prospective controlled trial during March 2014 to November 2015, comparing the efficacy of vitamin D supplements (400 IU/day) with non-intervention for 18 months in school children aged 9-15 years. Meanwhile, a before-after study was conducted among white-collar workers for 1 year. Serum 25(OH)D concentration was measured at baseline and after vitamin D supplementation, respectively. RESULTS: At the baseline, 95% of school children and 84% of adult participants had vitamin D deficiency (<20 ng/mL). In school children, no difference was observed between the intervention and control groups with regard to anthropometric data. Serum 25(OH)D concentrations of the school children intervention group, school children control group and white-collar workers were 12.77 ± 3.01 ng/mL, 14.17 ± 3.59 ng/mL and 16.58 ± 3.66 ng/mL at baseline and increased to 17.34 ± 3.78 ng/mL, 18.04 ± 4.01 ng/mL and 17.75 ± 5.36 ng/mL after vitamin D supplementation, respectively. Although, after adjusting for potential confounders, the 400 IU oral vitamin D supplementation increased serum 25(OH)D concentration in school children (ß = 0.81, p = 0.0426) as well as in white-collar workers (p = 0.0839), the prevalence of vitamin D deficiency was still very high among school children (79.23% in intervention group and 72.38% in control group) and white-collar workers (76.00%). CONCLUSIONS: High prevalence of vitamin D deficiency was common in these two study populations. Daily doses of 400 IU oral vitamin D supplementation was not able to adequately increase serum 25(OH)D concentrations. A suitable recommendation regarding the level of vitamin D supplementation is required for this Chinese population.

Influence of sinomenine upon mesenchymal stem cells in osteoclastogenesis.

With the advent of aging, the morbidity rates of such diseases as osteoarthritis, rheumatoid arthritis, and osteoporosis has witnessed a significant increase. As a common rattan drug, sinomenine (SIN) has been widely applied for the treatment of various arthritic diseases in traditional Chinese medicine (TCM) clinics. Given that SIN has been reported to inhibit the expression of Prostaglandin E2 (PGE2) in several types of cells, in this study, the influence of SIN treatment on PGE2 expression in mesenchymal stem cells (MSCs), thereby changing the osteoprotegerin (OPG) receptor/activator for the nuclear factor-κ B ligand (RANKL) ratio, was investigated. Our results showed that, when compared with the untreated cells, treatment with 0.25mM SIN can down-regulate the mRNA and protein expression levels of the Prostaglandin E synthase 3 (PTGES3) or PGE2 and RANKL, while the OPG was up-regulated. After being cultured with SIN treated MSC-conditioned medium (stMSC-CM), the amount of TRAP-positive multinucleated osteoclasts differentiated from RAW264.7 cells was reduced. Also, the expression levels of specific markers for active osteoclasts were decreased when incubated with stMSC-CM. Moreover, these changes were able to be recovered when the exogenous RANKL was added to the MSC-CM culture. This indicates that the increased OPG/RANKL ratio can reduce the osteoclastogenesis of RAW264.7 cells. Our results demonstrated that SIN has an inhibitory effect on osteoclast differentiation through mechanisms involving the inhibition of the PGE2-induced OPG/RANKL ratio. SIN can also serve as a proinflammatory mediator to regulate the MSC immunosuppressive effects. Our findings suggest that SIN can be useful for the treatment of bone diseases associated with over-activity of osteoclasts.

Silibinin ameliorates Aß25-35-induced memory deficits in rats by modulating autophagy and attenuating neuroinflammation as well as oxidative stress.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that inflammatory response, oxidative stress and autophagy are involved in amyloid ß (Aß)-induced memory deficits. Silibinin (silybin), a flavonoid derived from the herb milk thistle, is well known for its hepatoprotective activities. In this study, we investigated the neuroprotective effect of silibinin on Aß25-35-injected rats. Results demonstrated that silibinin significantly attenuated Aß25-35-induced memory deficits in Morris water maze and novel object-recognition tests. Silibinin exerted anxiolytic effect in Aß25-35-injected rats as determined in elevated plus maze test. Silibinin attenuated the inflammatory responses, increased glutathione (GSH) levels and decreased malondialdehyde (MDA) levels, and upregulated autophagy levels in the Aß25-35-injected rats. In conclusion, silibinin is a potential candidate for AD treatment because of its anti-inflammatory, antioxidant and autophagy regulating activities.

[Dietary vitamins intakes status of elderly people of 6 minitoring areas in Zhejiang Province in 2010-2012].

OBJECTIVE: To assess the situations of dietary vitamins intakes among aged 60 years old adults in different areas of Zhejiang Province, and analyze the food sources of vitamins. METHODS: Data were obtained from the 2010-2012 Chinese National Nutrition and Health Survey in Zhejiang Province. Dietary intakes among elderly people of vitamin A, vitamin B_1, vitamin B_2, vitamin C, vitamin E and their sources were acquired by 24-hour dietary recalls for 3 days in different areas. RESULTS: The elderly people' intakes of VA(296. 85(174. 32, 500. 28) µg RAE/d), VB_1(0. 68(0. 47, 0. 96) mg/d), VB2(0. 65(0. 47, 0. 90) mg /d) and VC(54. 54(33. 65, 83. 82) mg/d) were generally low. Intakes of vitamin B_1, vitamin C and vitamin E were significantly different in different areas( χ~2=41. 201, 39. 262 and 19. 474, P<0. 001). The food sources of vitamins were slightly variant. CONCLUSION: The insufficient status of vitamins intakes among elderly people in Zhejiang was serious, and there were differences among elderly people from different areas in intakes and food sources of vitamins.

Protective Effect of Silibinin on Learning and Memory Impairment in LPS-Treated Rats via ROS-BDNF-TrkB Pathway.

Silibinin, a flavonoid derived from the herb milk thistle (Silybum marianum), has been used as a hepato-protectant in the clinical treatment of liver disease. In the present study, the effect of silibinin on lipopolysaccharide (LPS)-induced neuroinflammatory impairment in rats is investigated. Injection of LPS into lateral ventricle caused learning and memory impairment. Rats were treated with silibinin to see the effect in comparison with resveratrol as a positive control. Y-maze and Morris water maze tests showed that silibinin significantly attenuated memory damage caused by LPS treatment. At the molecular analysis, the levels of IL-1ß and of IL-4 in the hippocampus were decreased and enhanced, respectively, by the treatment with silibinin. NF-κB expression was attenuated by silibinin treatment. Furthermore, generation of total reactive oxygen species (ROS) in the hippocampus was elevated in silibinin-treated groups, and so were the expressions of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB). At the same time, LPS-induced reduction of neurons in hippocampus was reversed by silibinin. In conclusion, silibinin ameliorated the impairment of learning and memory of LPS-injection rats, possibly due to the activation of ROS-BDNF-TrkB pathway in the hippocampus as well as the suppression of inflammatory response. This study gives an insight on the beneficial consequences of ROS in central nervous system. Silibinin might be a potential candidate drug for neurodegenerative diseases.

Suppression of Evi1 promotes the osteogenic differentiation and inhibits the adipogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro.

Osteoporosis (OP) is considered a complex disease with a strong genetic impact, mainly affecting post-menopausal women and is also a common cause of fracture. Elucidating the molecular mechanisms that regulate the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) is crucial to developing treatment strategies to combat OP. In the present study, we found that ectopic viral integration site­1 (Evi1) was highly expressed during the process of adipogenesis of rat BMSCs. Notably, Evi1 levels markedly increased on day 3 of adipogenic differentiation following the addition of adipogenic induction supplements. In addition, we interfered with the expression of the Evi1 gene in the adipogenesis of BMSCs by supplementing adenoviral plasmids and measured the expression levels of bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN), peroxisome proliferator­activated receptor γ2 (PPARγ2) and lipoprotein lipase (LPL) by RT-qPCR and western blot analysis. The mRNA and protein levels of osteogenic and adipogenic markers in the BMSCs were up­ and downregulated, respectively following the silencing of siEvi1. Our experimental results substantiate that the suppression of Evi1 in BMSCs by RNA interference inhibits adipogenic differentiation, while it promotes osteogenic differentiation. The results from our study demonstrated that the Evi1 gene may be targeted as a therapeutic strategy for promoting bone formation.