A High-Saturated-Fat, High-Sucrose Diet Aggravates Bone Loss in Ovariectomized Female Rats.

BACKGROUND: Estrogen deficiency in women and high-saturated fat, high-sucrose (HFS) diets have both been recognized as risk factors for metabolic syndrome. Studies on the combined actions of these 2 detrimental factors on the bone in females are limited. OBJECTIVE: We sought to determine the interactive actions of estrogen deficiency and an HFS diet on bone properties and to investigate the underlying mechanisms. METHODS: Six-month-old Sprague Dawley sham or ovariectomized (OVX) rats were pair fed the same amount of either a low-saturated-fat, low-sucrose (LFS) diet (13% fat calories; 15% sucrose calories) or an HFS diet (42% fat calories; 30% sucrose calories) for 12 wk. Blood, liver, and bone were collected for correspondent parameters measurement. RESULTS: Ovariectomy decreased bone mineral density in the tibia head (TH) by 62% and the femoral end (FE) by 49% (P < 0.0001). The HFS diet aggravated bone loss in OVX rats by an additional 41% in the TH and 37% in the FE (P < 0.05). Bone loss in the HFS-OVX rats was accompanied by increased urinary deoxypyridinoline concentrations by 28% (P < 0.05). The HFS diet induced cathepsin K by 145% but reduced osteoprotegerin mRNA expression at the FE of the HFS-sham rats by 71% (P < 0.05). Ovariectomy significantly increased peroxisome proliferator-activated receptor γ mRNA expression by 136% and 170% at the FE of the LFS- and HFS-OVX rats, respectively (P < 0.05). The HFS diet aggravated ovariectomy-induced lipid deposition and oxidative stress (OS) in rat livers (P < 0.05). Trabecular bone mineral density at the FE was negatively correlated with rat liver malondialdehyde concentrations (R(2) = 0.39; P < 0.01). CONCLUSIONS: The detrimental actions of the HFS diet and ovariectomy on bone properties in rats occurred mainly in cancellous bones and were characterized by a high degree of bone resorption and alterations in OS.

Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis.

Rhizoma Drynariae (RD), as one of the most common clinically used folk medicines, has been reported to exert potent anti-osteoporotic activity. The bioactive ingredients and mechanisms that account for its bone protective effects are under active investigation. Here we adopt a novel in silico target fishing method to reveal the target profile of RD. Cathepsin K (Ctsk) is one of the cysteine proteases that is over-expressed in osteoclasts and accounts for the increase in bone resorption in metabolic bone disorders such as postmenopausal osteoporosis. It has been the focus of target based drug discovery in recent years. We have identified two components in RD, Kushennol F and Sophoraflavanone G, that can potentially interact with Ctsk. Biological studies were performed to verify the effects of these compounds on Ctsk and its related bone resorption process, which include the use of in vitro fluorescence-based Ctsk enzyme assay, bone resorption pit formation assay, as well as Receptor Activator of Nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis using murine RAW264.7 cells. Finally, the binding mode and stability of these two compounds that interact with Ctsk were determined by molecular docking and dynamics methods. The results showed that the in silico target fishing method could successfully identify two components from RD that show inhibitory effects on the bone resorption process related to protease Ctsk.

A New Feature Extraction Method of Near-Infrared Spectra Based on the Addition of Historical Data.

In traditional qualitative analysis of near-infrared (NIR) spectra, the stability of recognition models is decreased when new varieties of samples are added into the model. In order to improve the robustness of the model, a new feature extraction method based on the addition of historical data was put forward. The NIR training samples will be collected first, after that the historical data of the same species is added to constitute a larger and richer dataset. Then, the pretreated data of these training samples is projected to the feature space, which is constructed by feature extraction using partial least squares (PLS) based on the above dataset. Subsequently, orthogonal linear discriminant analysis (OLDA) is employed to extract features of the projected data. 18 varieties of corn seeds were taken as study subject, the comparative experiments with and without historical data are implemented respectively, and then the biomimetic pattern recognition (BPR) method is applied to verify the efficiency of the method proposed. The results suggest that the method adopted can improve the robustness of recognition model more effectively compared with the method without historical data. It maintains the high correct recognition ratios when new varieties are added into the model. Besides that, the recognition effect on test sets of the different days remains the same basically in the condition of same PLS dimensions. Therefore, the dimension of feature extraction can be set to some fixed values in recognition software. In this way, it can keep out of the trouble of manually modifying the optimal PLS parameter in recognition software if new varieties need to be added into the model. The experiment results of the thesis manifested the effectiveness of the proposed method.

Sodium tanshinone IIA sulfonate attenuates radiation-induced fibrosis damage in cardiac fibroblasts.

The main pathological change in radiation-induced heart disease is fibrosis. Emerging evidence has indicated that sodium tanshinone IIA sulfonate (STS) was used for treating fibrosis diseases. The present study was undertaken to characterize the effect of STS on radiation-induced cardiac fibrosis (RICF) on cultured cardiac fibroblasts (CFs). CFs were irradiated with 1 or 2 Gy X-rays, and the expression of TGF-ß1 and collagen I (Col-1) increased, indicating that low-dose X-rays promoted fibrosis damage effect. The fibrosis damage was accompanied by morphologic changes in the endoplasmic reticulum (ER), as well as an increase in the expression of the ER stress-related molecules, GRP78 and CHOP. Administration of STS reduced ROS production and decreased the expression of Col-1, TGF-ß1, p-Smad2/3, GRP78, and CHOP in irradiated CFs, thus weakening the radiation-induced fibrosis damage and ER stress. Radiation-induced fibrosis damage was observed on a cellular level. The involvement of ER stress in radiation-induced fibrosis damage was demonstrated for the first time. STS attenuated the fibrosis damage effect in CFs and this effect may be related to its antioxidant action, and also related to its inhibition of ER stress and TGF-ß1-Smad pathway. These results suggest that STS shows a good prospect in clinical prevention and treatment of RICF.

[Study on spectral calibration of discrimination of corn variety using near-infrared spectra based on DS algorithm].

From the perspective of calibration, the present paper studies the model stability problem in qualitative analysis of NIR. Aiming at the issue of model failure caused by different data acquisition time, 13 varieties of corn were used as experimental material, and learning from the idea of model calibration transfer between the two instruments in quantitative analysis of NIR, the DS (direct standardization) algorithm was used to calibrate the spectra acquired at different times with the same instrument, that made the varieties identification model established one time able to be applied to identify the test data at different acquisition time. First, transfer set was selected from the master spectrum set by Kennard/Stone algorithm, the corresponding number spectrums in slave spectrum set were selected, and then DS algorithm was applied to transfer set to calculate the transformation function between the two sets of data. Finally, the remaining slave spectrums were transformed so that they could apply to the model. This study does some experiment to discuss the impact of the number of transfer set and the location of calibration on the calibration results. Respectively, the experiment results were analyzed from two aspects, one is the correct discrimination rate in qualitative analysis, and the other is the distribution distance between master spectrums and slave spectrums before and after calibration. The experiment results indicate that this approach is effective to solve the spectra drift produced by sampling over time, can bring higher recognition rate on different sampling time test sets, also improves the robustness and application scope of the identification model, and the experiment results also indicate that the best result can be obtained with calibration locating after feature extraction.

Baohuoside I suppresses the NLRP3 inflammasome activation via targeting GPER to fight against Parkinson's disease.

BACKGROUND: Accumulating evidence indicates the crucial role of microglia-mediated inflammation and the NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis in the pathogenesis of Parkinson's disease (PD). Baohuoside I, a natural flavonoid extracted from Herba Epimedii, has been shown to possess anti-inflammatory effects, but its potential neuroprotective effects and mechanism against PD have not been documented. STUDY DESIGN AND METHODS: The anti-inflammatory effects of Baohuoside I were evaluated by LPS-induced BV2 cells or primary microglia isolated from wide type or G protein-coupled estrogen receptor (GPER) gene knockout mice. The underlying mechanism related to GPER-mediated NLRP3 inflammasome inhibition was further explored using LPS-induced GPER+/+ or GPER-/- mouse models of PD. The neuroprotective effects of Baohuoside I were detected through western blot analysis, real-time PCR, molecular docking, mouse behavioral tests, immunofluorescence, and immunohistochemistry. RESULTS: Baohuoside I significantly alleviated LPS-induced neuroinflammation by inhibiting the activation of NF-κB signal and the increase of pyroptosis levels as evidenced by the downregulated expression of pyroptosis-related proteins (NLRP3, ASC, pro-Caspase-1, IL-1ß) in microglia cells. Intragastric administration of Baohuoside I protected against LPS-induced motor dysfunction and loss of dopaminergic neurons, reduced pro-inflammatory cytokines expressions, and inhibited microglial (Iba-1) and astrocyte (GFAP) activation in the nigrostriatal pathway in LPS-induced mouse model of PD. Pretreatment with GPER antagonist G15 in microglia cells or GPER gene deletion in mice significantly blocked the inhibitory effects of Baohuoside I on LPS-induced neuroinflammation and activation of the NLRP3/ASC/Caspase-1 pathway. Molecular docking further indicated that Baohuoside I might bind to GPER directly with a binding energy of -10.4 kcal/mol. CONCLUSION: Baohuoside I provides neuroprotective effects against PD by inhibiting the activation of the NF-κB signal and NLRP3/ASC/Caspase-1 pathway. The molecular target for its anti-inflammatory effects is proved to be GPER in the PD mouse model. Baohuoside I may be a valuable anti-neuroinflammatory agent and a drug with well-defined target for the treatment of PD.

Inhibition of calcium-sensing receptor by its antagonist promotes gastrointestinal motility in a Parkinson's disease mouse model.

BACKGROUND: The Calcium-sensing receptor (CaSR) participates in the regulation of gastrointestinal (GI) motility under normal conditions and might be involved in the regulation of GI dysmotility in patients with Parkinson's disease (PD). METHODS: CaSR antagonist-NPS-2143 was applied in in vivo and ex vivo experiments to study the effect and underlying mechanisms of CaSR inhibition on GI dysmotility in the MPTP-induced PD mouse model. FINDINGS: Oral intake of NPS-2143 promoted GI motility in PD mice as shown by the increased gastric emptying rate and shortened whole gut transit time together with improved weight and water content in the feces of PD mice, and the lack of influence on normal mice. Meanwhile, the number of cholinergic neurons, the proportion of serotonergic neurons, as well as the levels of acetylcholine and serotonin increased, but the numbers of nitrergic and tyrosine hydroxylase immunoreactive neurons, and the levels of nitric oxide synthase and dopamine decreased in the myenteric plexus in the gastric antrum and colon of PD mice in response to NPS-2143 treatment. Furthermore, the numbers of c-fos positive neurons in the nucleus tractus solitarius (NTS) and cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) increased in NPS-2143 treated PD mice, suggesting the involvement of both the enteric (ENS) and central (CNS) nervous systems. However, ex vivo results showed that NPS-2143 directly inhibited the contractility of antral and colonic strips in PD mice via a non-ENS mediated mechanism. Further studies revealed that NPS-2143 directly inhibited the voltage gated Ca2+ channels, which might, at least in part, explain its direct inhibitory effects on the GI muscle strips. INTERPRETATION: CaSR inhibition by its antagonist ameliorated GI dysmotility in PD mice via coordinated neuronal regulation by both ENS and CNS in vivo, although the direct effects of CaSR inhibition on GI muscle strips were suppressive.

Complete mitogenome sequences of four flatfishes (Pleuronectiformes) reveal a novel gene arrangement of L-strand coding genes.

BACKGROUND: Few mitochondrial gene rearrangements are found in vertebrates and large-scale changes in these genomes occur even less frequently. It is difficult, therefore, to propose a mechanism to account for observed changes in mitogenome structure. Mitochondrial gene rearrangements are usually explained by the recombination model or tandem duplication and random loss model. RESULTS: In this study, the complete mitochondrial genomes of four flatfishes, Crossorhombus azureus (blue flounder), Grammatobothus krempfi, Pleuronichthys cornutus, and Platichthys stellatus were determined. A striking finding is that eight genes in the C. azureus mitogenome are located in a novel position, differing from that of available vertebrate mitogenomes. Specifically, the ND6 and seven tRNA genes (the Q, A, C, Y, S1, E, P genes) encoded by the L-strand have been translocated to a position between tRNA-T and tRNA-F though the original order of the genes is maintained. CONCLUSIONS: These special features are used to suggest a mechanism for C. azureus mitogenome rearrangement. First, a dimeric molecule was formed by two monomers linked head-to-tail, then one of the two sets of promoters lost function and the genes controlled by the disabled promoters became pseudogenes, non-coding sequences, and even were lost from the genome. This study provides a new gene-rearrangement model that accounts for the events of gene-rearrangement in a vertebrate mitogenome.

[Effect of acupuncture combined language training on cerebral palsy children with language retardation].

OBJECTIVE: To observe effects of acupuncture combined speech therapy for cerebral palsy children with linguistic retardation. METHODS: Totally 132 cerebral palsy children were randomly assigned to the speech training group (Group A, 44 cases) and the routine acupuncture combined speech training group (Group B, 44 cases), and the acupuncture combined speech training group (Group C, 44 cases). Patients in Group A received one to one training including game therapy, therapy of communication attitudes, and so on. Those in the other two groups were needed at Baihui (GV20), Sishencong (EX-HN1), the first language zone, the second language zone, and the third language zone. Those in Group B were treated with electric needling and then speech training. Those in Group C were treated with language training, while needling with needle maintaining for 40 min. All patients were treated once daily, 5 times per week, 20 times as one course of treatment, 6 courses in total. The efficacy was assessed using S-S phonetic speech developmental retardation examination (CRRC version). The development quotient (DQ) was observed referring to the Gesell intellectual development scale before treatment, after 3 and 6 treatment courses. RESULTS: Compared with Group A (the total effective rate: 51.3%, DQ value: 58.1 +/- 13.3), better effects were obtained in Group B (the total effective rate: 77.5%, DQ value: 60.4 +/- 13.5) and Group C (the total effective rate: 81.0%, DQ value: 64.0 +/- 11.6) (all P < 0.05). There was no statistical difference in the total effective rate or post-treatment DQ value between Group B and Group C (P > 0.05). CONCLUSION: Acupuncture combined speech therapy showed obvious effects on cerebral palsy children with linguistic retardation.

Low and high doses of oral maslinic acid protect against Parkinson's disease via distinct gut microbiota-related mechanisms.

The use of oral agents that can modify the gut microbiota (GM) could be a novel preventative or therapeutic option for Parkinson's disease (PD). Maslinic acid (MA), a pentacyclic triterpene acid with GM-dependent biological activities when it is taken orally, has not yet been reported to be effective against PD. The present study found both low and high dose MA treatment significantly prevented dopaminergic neuronal loss in a classical chronic PD mouse model by ameliorating motor functions and improving tyrosine hydroxylase expressions in the substantia nigra pars compacta (SNpc) and increasing dopamine and its metabolite homovanillic acid levels in the striatum. However, the effects of MA in PD mice were not dose-responsive, since similar beneficial effects for low and high doses of MA were observed. Further mechanism studies indicated that low dose MA administration favored probiotic bacterial growth in PD mice, which helped to increase striatal serotonin, 5-hydroxyindole acetic acid, and γ-aminobutyric acid levels. High dose MA treatment did not influence GM composition in PD mice but significantly inhibited neuroinflammation as indicated by reduced levels of tumor necrosis factor alpha and interleukin 1ß in the SNpc; moreover, these effects were mainly mediated by microbially-derived acetic acid in the colon. In conclusion, oral MA at different doses protected against PD via distinct mechanisms related to GM. Nevertheless, our study lacked in-depth investigations of the underlying mechanisms involved; future studies will be designed to further delineate the signaling pathways involved in the interactive actions between different doses of MA and GM.

Improvement of calcium balance by Fructus Ligustri Lucidi extract in mature female rats was associated with the induction of serum parathyroid hormone levels.

Fructus Ligustri Lucidi (FLL) is a commonly prescribed herb in many kidney-tonifying Traditional Chinese Medicinal formulae for the treatment of osteoporosis. The present study aimed to identify the active fractions in FLL and to characterise its effects on Ca balance, calciotropic hormone levels as well as bone properties in mature female rats fed diets containing different levels of Ca. In the present study, 4-month-old Sprague-Dawley female rats were treated with either FLL ethanol extract (EE), ethyl acetate-soluble fraction of EE (EAF), water-soluble fraction of EE (WF) or their vehicle for 12 weeks on a medium-Ca diet (MCD, 0·6 % Ca, 0·65 % P). Then, the Sprague-Dawley female rats treated with WF or its vehicle for 12 weeks were fed diets containing different levels of dietary Ca (low-Ca diet (LCD), 0·1 % Ca, 0·65 % P; MCD; high-Ca diet (HCD), 1·2 % Ca, 0·65 % P). The results demonstrated that WF from EE but not EAF exerted a prominent effect on Ca balance by inhibiting urinary and faecal Ca excretion. WF significantly increased Ca balance in rats fed MCD or HCD with an associated increase in serum parathyroid hormone (PTH) levels. WF did not alter bone mineral density or bone mineral content of the tibia in all the rats fed with different levels of dietary Ca. In conclusion, WF was responsible for the positive actions of FLL on Ca absorption and balance. The regulation of Ca balance by WF might involve its action in stimulating PTH production in the mature female rats.

Epimedin B exerts neuroprotective effect against MPTP-induced mouse model of Parkinson's disease: GPER as a potential target.

Mitochondrial dysfunction and oxidative stress play important roles in the neuropathogenesis of Parkinson's disease (PD). Epimedin B, the second highest active ingredient in the flavonoids of Herba Epimedii, has been proven effective in treating osteoporosis and oxaliplatin-induced peripheral neuropathy. The present study aims to investigate the neuroprotective effects of Epimedin B in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced mouse model of PD, and the involvement of G protein-coupled estrogen receptor (GPER)-mediated anti-apoptosis as well as anti-endoplasmic reticulum stress. Molecular docking revealed that Epimedin B could directly bind to GPER at the same site as GPER agonist G1 and the binding energy was - 7.3 kcal/mol. Epimedin B treatment ameliorated MPTP-induced motor dysfunction and alleviated the decreased contents of DA with its metabolites in the striatum and the loss of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantial nigra pars compacta (SNpc). Epimedin B treatment markedly prevented MPTP-induced changes in apoptosis-related protein Bcl-2 and Bax as well as endoplasmic reticulum stress-related protein glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). Pharmacological blockade with GPER antagonist G15 could antagonize these neuroprotective effects of Epimedin B on the nigrostriatal system. Moreover, the anti-apoptosis and anti-endoplasmic reticulum stress effects of Epimedin B against MPTP toxicity were significantly reduced in GPER knockout (GPER-/-) mice. The present study provides the first evidence that Epimedin B can protect against MPTP-induced PD mice model. GPER may be a potential target for the neuroprotective effect of Epimedin B against PD.

Polymannuronic acid prebiotic plus Lacticaseibacillus rhamnosus GG probiotic as a novel synbiotic promoted their separate neuroprotection against Parkinson's disease.

Gut microbiota (GM) dysbiosis plays key roles in aggravating Parkinson's disease (PD) and discovery of agents targeting GM may open new avenues for PD therapy. This study aims to investigate the potentially neuroprotective effects and underlying mechanisms of polymannuronic acid (PM) or Lacticaseibacillus rhamnosus GG (LGG), or their combination in a chronic PD mice model. Our results found oral administration of prebiotic PM or LGG separately or in combination for 5 weeks could prevent dopaminergic neuronal loss via improving reduced walking distance and activity or weakened muscle strength in behavior tests by enhancing tyrosine hydroxylase (TH) gene and/or protein expressions in the midbrain and striatum of PD mice. Strikingly, PM and LGG in combination had a much better neuroprotective effects than separate PM or LGG. PM provided neuroprotection via a short chain fatty acids (SCFAs)-mediated anti-inflammation and anti-apoptosis mechanism. The neuroprotective effects of LGG might be associated with its ability to improve the expression of striatal glial cell-derived neurotrophic factor (GDNF) and to increase bacteria abundance of Clostridiales. When PD mice were administered with PM + LGG, PM as prebiotic favored bacterial growth (from Bacilli class to Lactobacillus genus) in the colon, which helped to improve blood brain barrier (BBB) integrity and increase brain-derived neurotrophic factor (BDNF) and GDNF expressions, thereby inhibiting apoptosis in the striatum. In conclusion, PM and LGG in combination promoted their separate neuroprotection against PD. Our study discovered and testified a novel synbiotic that might be one of the ideal oral agents for PD therapy.

Solid-state-cultured mycelium of Antrodia camphorata exerts potential neuroprotective activities against 6-hydroxydopamine-induced toxicity in PC12 cells.

Antrodia camphorata (A. camphorata) is an edible fungus containing various bioactive compounds generally used for health benefits. This study aimed to explore the potential neuroprotective activities of solid-state-cultured mycelium of A. camphorata (SCMAC) against Parkinson's disease (PD), as well as the underlying mechanism using an in vitro 6-hydroxydopamine (6-OHDA)-induced PC12 cell model. The results showed that SCMAC extracts alleviated cell toxicity induced by 6-OHDA and the loss of dopaminergic neurons, which was confirmed by the increase of cell viabilities, inhibition of cell apoptosis, the upregulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels and the downregulation of α-Synuclein level. After purification, 11 compounds were identified by the NMR technique, including a quinone, four phenolic acid derivatives, three ubiquinone derivatives, two alkaloids, and a triterpenoid. The present study suggests that SCMAC could be an attractive candidate for the prevention or treatment of PD. PRACTICAL APPLICATIONS: Parkinson's disease seriously affects the lifetime and quality of the elder population for a long history. Long-term consumption of L-DOPA will result in side effects, such as developing abnormal involuntary movements called dyskinesia. This study showed that natural SCMAC extracts could be a potential therapeutic agent for the treatment of neurodegenerative disorder.

Alginate and its Two Components Acted Differently Against Dopaminergic Neuronal Loss in Parkinson's Disease Mice Model.

SCOPE: This study aims to investigate and compare the potentially neuroprotective effects and underlying mechanisms for brown seaweed polysaccharides (PS) of Alginate (Alg) and its two components, including polymannuronic acid (PM) and polyguluronic acid (PG), against Parkinson's disease (PD) pathogenesis. METHODS AND RESULTS: Model mice of PD are pretreated with Alg or PM or PG, separately via oral gavage once per day for four weeks. Our results found PM improved motor functions of PD mice, but Alg or PG did not. PM or PG, but not Alg, can prevent dopaminergic neuronal loss by increasing tyrosine hydroxylase (TH) expressions in midbrain of PD mice. The neuroprotective effects of PM rely on its anti-inflammation effects and its ability to improve striatal neurotransmitters (serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA)) levels in PD mice. PM inhibits inflammation, but PG or Alg induces inflammation in systemic circulation of PD mice. The neuroprotection provided by PG might be related to its ability to increase striatal neurotransmitter of 5-hydroxyindole acetic acid levels in PD mice. CONCLUSION: PM plays better than PG to provide neuroprotection, but Alg did not show any neuroprotection against PD. Alg and its two components acted differently in preventing dopaminergic neuronal loss in PD mice.

An Investigation of the Risk Factors Associated With Anti-Tuberculosis Drug-Induced Liver Injury or Abnormal Liver Functioning in 757 Patients With Pulmonary Tuberculosis.

Objectives: To identify the risk factors associated with anti-tuberculosis drug-induced liver injury (AT-DILI) or abnormal living functioning from 757 patients with pulmonary tuberculosis (TB) registered at Nanshan Center for Chronic Disease Control (Nanshan CCDC), Shenzhen, Guangdong Province, China. Design and methods: We identified 757 TB patients who met our inclusion criteria by screening the Hospital Information System (HIS) at Nanshan CCDC. Next, we identified positive cases of AT-DILI or abnormal liver functioning based on results of the first-time liver function tests (LFTs) after taking anti-TB drugs. The χ2 test was used to relate the positive rate with a variety of factors. A logistic regression model was also used to identify statistically significant risk factors. Results: Of the 757 patients, the positive rate of AT-DILI or abnormal liver functioning was 37.9% (287/757). Univariate analysis revealed that the positive rate was 42.91% (212/494) for males and 28.52% (75/263) for females. The positive rate was significantly higher in males (p <0.001). Patients with an annual income of 9,231-13,845 USD had a significantly higher positive rate (67.35%; 33/49) than those with an income of 1,540-4616 USD (37.97%; 30/79) (p = 0.022). The most frequent prescription regime among positive cases was a 2 months supply of fixed dose combination Ethambutol Hydrochloride, Pyrazinamide, Rifampicin and Isoniazid Tablets (Ⅱ) 450 mg) followed by a 4 months supply of fixed dose combination Rifampin and Isoniazid Capsules (2FDC-HRZE half/4FDC-HR) at 56.03% (144/257). The least frequent prescription regime was a 2 months supply of fixed dose combination Rifampin, Isoniazid and Pyrazinamide Capsules with Ethambutol independently followed by a 4 months supply of fixed dose combination Rifampin and Isoniazid Capsules (2FDC-HRZ + EMB/4FDC-HR) at 24.27% (25/103). The difference between these two different regimes was significant (p = 0.022). With an increase in the duration of medication, patients under various prescription regimes all showed a gradual increase in the positive rate of AT-DILI or abnormal liver functioning. Conclusion: We identified several risk factors for the occurrence of AT-DILI or abnormal liver functioning, including gender, annual income, prescription regime, dosage, and treatment time.

Colonic Dopaminergic Neurons Changed Reversely With Those in the Midbrain via Gut Microbiota-Mediated Autophagy in a Chronic Parkinson's Disease Mice Model.

The role of gut-brain axis in the pathogenesis of Parkinson's disease (PD) have become a research hotspot, appropriate animal model to study gut-brain axis in PD is yet to be confirmed. Our study employed a classical PD mice model achieved by chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) injection to study concurrent changes of dopaminergic neurons in the midbrain and the colon of mice. Our results showed such a PD model exhibited apparent locomotor deficits but not gastrointestinal dysfunction. Tyrosine hydroxylase expressions and dopamine content reduced greatly in the substantia nigra pars compacta (SNpc) or striatum, but increased in the colon of PD mice. Mechanism investigation indicated autophagy activity and apoptosis were stimulated in the SNpc, but inhibited in the colon of PD mice. Interplay of gut microbiota (GM) and autophagy in response to chronic MPTP injection led to GM dysbiosis and defective autophagy in mice colon. Meanwhile, fecal short chain fatty acids (SCFAs), acetate and propionate in particular, declined greatly in PD mice, which could be attributed to the decreased bacteria abundance of phylum Bacteroidetes, but increased abundance of phylum Firmicutes. GM dysbiosis derived fecal SCFAs might be one of the mediators of downregulated autophagy in the colon of PD mice. In conclusion, colonic dopaminergic neurons changed in the opposition direction with those in the midbrain via GM dysbiosis-mediated autophagy inhibition followed by suppressed apoptosis in response to chronic MPTP injection. Such a chronic PD mice model might not be an ideal model to study role of gut-brain axis in PD progression.

Methane-dependent selenate reduction by a bacterial consortium.

Methanotrophic microorganisms play a critical role in controlling the flux of methane from natural sediments into the atmosphere. Methanotrophs have been shown to couple the oxidation of methane to the reduction of diverse electron acceptors (e.g., oxygen, sulfate, nitrate, and metal oxides), either independently or in consortia with other microbial partners. Although several studies have reported the phenomenon of methane oxidation linked to selenate reduction, neither the microorganisms involved nor the underlying trophic interaction has been clearly identified. Here, we provide the first detailed evidence for interspecies electron transfer between bacterial populations in a bioreactor community where the reduction of selenate is linked to methane oxidation. Metagenomic and metaproteomic analyses of the community revealed a novel species of Methylocystis as the most abundant methanotroph, which actively expressed proteins for oxygen-dependent methane oxidation and fermentation pathways, but lacked the genetic potential for selenate reduction. Pseudoxanthomonas, Piscinibacter, and Rhodocyclaceae populations appeared to be responsible for the observed selenate reduction using proteins initially annotated as periplasmic nitrate reductases, with fermentation by-products released by the methanotrophs as electron donors. The ability for the annotated nitrate reductases to reduce selenate was confirmed by gene knockout studies in an isolate of Pseudoxanthomonas. Overall, this study provides novel insights into the metabolic flexibility of the aerobic methanotrophs that likely allows them to thrive across natural oxygen gradients, and highlights the potential role for similar microbial consortia in linking methane and other biogeochemical cycles in environments where oxygen is limited.

[Effects of BNP preconditioning on myocardial cell apoptosis and expressions of bcl-2 and Bax during myocardial ischemia-reperfusion injury in rats].

OBJECTIVE: To study the effects of B-type natriuretic peptide (BNP) preconditioning on the apoptosis and expressions of Bcl-2 and Bax in rat cardiomyocytes during myocardial ischemia-reperfusion. METHODS: Twenty-one male Sprague-Dawley rats weighing (250 ± 50) g were randomly divided into 3 groups of sham operation (SHAM), ischemia-reperfusion (I/R) and B-type natriuretic peptide (BNP). A rat model of in vivo myocardial ischemia-reperfusion injury was established by ligating the left anterior descending coronary artery for 35 minutes and then reperfusing for 240 minutes. The apoptosis of myocardial cell was determined by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end-labeling (TUNEL) method. Real-time polymerase chain reaction and Western blot were used to detect the expression changes of Bcl-2 and Bax in rat ischemia myocardium. RESULTS: The apoptotic indices of SHAM, BNP and I/R groups were 5.4% ± 4.2%, 22.5% ± 9.5% and 45.2% ± 13.0% respectively (P < 0.05). The Bcl-2 protein expression of SHAM, BNP and I/R groups were 0.87 ± 0.09, 0.70 ± 0.07 and 0.38 ± 0.09 respectively (P < 0.05). The Bax protein expression of SHAM, BNP and I/R groups were 0.08 ± 0.04, 0.39 ± 0.09 and 0.71 ± 0.18 respectively (P < 0.01). The Bcl-2/Bax mRNA ratio of SHAN, BNP and I/R groups were 0.763 ± 0.154, 0.099 ± 0.025 and 0.022 ± 0.024 respectively (P < 0.05). CONCLUSION: The BNP preconditioning can decrease the myocardial apoptosis induced by ischemia-reperfusion injury. The mechanisms may be associated with an elevated expression of Bcl-2, an increased ratio of Bcl-2/Bax and a lowered expression of Bax.

Chuanxiong (Rhizome of Ligusticum chuanxiong) Protects Ovariectomized Hyperlipidemic Rats from Bone Loss.

Oxidative stress (OS) is the common mechanism for age-related diseases. The co-occurrence of osteoporosis (OP) and cardiovascular disease (CVD) in postmenopausal women makes it warranted to find a holistic approach for treatment of multiple diseases or conditions. The rhizome of Ligusticum chuanxiong Hort. (CX), which has high anti-oxidant properties and is widely used for CVD treatment in China, might be the potential candidate. In the present study, CX ethanol extract (CXE) was applied to H2O2 induced MG63 cells to study its effects and mechanisms on osteoblastogenesis against OS. CXE was then administered to six-month-old Sprague Dawley sham or ovariectomized (OVX) rats fed either a low saturated fat-sucrose (LFS) or a high fat-sucrose (HFS) diet for 12 weeks, to confirm its anti-osteoporotic effects. The results demonstrated that CXE directly improved proliferation and differentiation in vitro in an H2O2-induced osteoblast cell model by attenuating cellular reactive oxygen species levels and inhibiting osteoblast apoptosis via PI3K/Akt signaling pathway. CXE significantly improved bone properties as revealed by the increase in trabecular bone mineral density and decrease in trabecular separation at proximal metaphysis of the tibia (PT) in HFS-fed OVX rats but not in LFS-fed OVX rats. CXE ameliorated dyslipidemia, greatly reduced lipid deposition and malondialdehyde levels, improved activities of superoxide dismutase, catalase and glutathione peroxidase in the livers of HFS-fed OVX rats. In conclusion, CXE could favor osteoblastogenesis against OS. The ability of CXE to reduce bone loss in HFS-fed OVX rats was associated with its abilities to correct dyslipidemia, and reduce lipid deposition and OS levels.