This study examined the reliability of 31phosphorus-magnetic resonance spectroscopy (31P-MRS) to measure parameters of liver metabolic function in the intact animals. These parameters can help us to evaluate the severity and prognosis of liver fibrosis. In addition, 31P-MRS was also used to examine the protective effects of melatonin on liver mitochondria. An animal model of liver fibrosis was established via intraperitoneal administration of thioacetamide (TAA) to rats. Rats were scanned at baseline, week 3 and 6 after TAA treatment, respectively, to measure the longitudinal changes of phosphorus metabolite levels by 31P-MRS at 9.4 T. The results showed a consistent decline in the levels of phosphorus metabolites (inorganic phosphate, α-ATP, γ-ATP and NADH) in rats with fibrosis. Impaired mitochondrial respiration capacity, collagen accumulation and the extent of fibrosis in liver were markedly associated with decreased concentrations of phosphorus metabolites. Melatonin-pretreated mitochondria transferring efficiently prevented TAA-induced liver damage mainly by restoring mitochondrial function. In conclusion, the levels of phosphorus metabolites could serve as the indicators of mitochondrial oxidative capacity and thus provides a novel tool to evaluate mitochondrial integrity in the in vivo condition by using 31P-MRS in the setting of liver fibrosis.
Background Virus-associated haemophagocytic syndrome (VAHS) is a fatal complication of viral infections, such as Epstein–Barr virus and H5N1 influenza, that results from macrophage activation and proinflammatory cytokine injuries. The high comorbidity and mortality of current therapy urgently demands an ideal agent based on VAHS pathogenesis. Peroxisome proliferator activated receptor (PPAR) agonists, regulators of metabolic syndrome, can exhibit immunomodulatory effects on macrophage activation and cytokine secretion. Methods In this study, we adopted rosiglitazone, a PPAR-γ agonist, for VAHS control in a Herpesvirus papio (HVP)-infected rabbit model. Various doses of rosiglitazone were orally administered to rabbits on day 7 or day 20 after intravenous challenge with 5x10 7 copies of HVP. Results The rabbits that received 4 mg/day rosiglitazone had significantly increased survival when treated at an early stage of infection ( P<0.01), whereas a higher dose (8 mg/day) was required at the advanced stage of the disease ( P<0.05). All rosiglitazone-treated rabbits had significantly improved laboratory parameters and plasma tumour necrosis factor-α levels. Importantly, rosiglitazone could also inhibit viral replication in vitro and in vivo. Conclusions PPAR agonists could represent a potentially new agent for the therapy of VAHS.
Abstract Background: Thoracic empyema is a serious infectious disease worldwide. Video-assisted thoracoscopic surgery is strongly recommended as a treatment, and pleural fluid and tissue cultures can be obtained intraoperatively. The combination of a pleural peels tissue culture and a pleural fluid culture improves the positive culture rate. We aimed to investigate the role of respiratory secretion cultures to determine the optimal management for improving surgical outcome. Methods: This retrospective study identified 1197 patients with phase II or III thoracic empyema from our institution. Patients who underwent decortication of the pleura from April 2011 to May 2022 with a positive pleural culture were included. Results: There were 225 empyema patients with either a positive pleural fluid culture or a positive pleural peel tissue culture. Of these, 76 patients had positive respiratory secretion culture findings during hospitalization. The most common species of pathogens were Pseudomonas aeruginosa (44%), Klebsiella pneumoniae (16%), and Staphylococcus aureus (10%) in the respiratory secretion cultures and Streptococcus spp. (38%), Klebsiella pneumoniae (12%), and Staphylococcus aureus (11%) in the pleural cultures. There were 30 patients who had a common pathogen in a respiratory secretion culture and in the pleural fluid/tissue culture. Poor outcome measures were found in these patients, including the longer use of antibiotics preoperatively (19.03 ± 37.66 days versus 9.59 ± 27.09 days, p = 0.006) and a higher mortality rate during hospitalization (40.0% versus 17.4%, p = 0.002). Conclusions: The respiratory secretion culture plays an essential role in prediction of surgical outcome in bacterial empyema. Obtaining the respiratory secretion specimen promptly through proper methods helps to improve the survival of empyema patients.
We tested the hypothesis that extracorporeal shockwave treatment (ESWT) can abolish inflammation and restore urothelial barrier integrity in acute interstitial cystitis by upregulating the fatty acid receptor GPR120. A total of 30 female Sprague-Dawley rats were categorized into five groups: (1) sham-operated rats (SC); (2) rats treated with ESWT (SC + ESWT); (3) rats with bladder irritation using 150 mg/kg cyclophosphamide through intraperitoneal injection; (4) cyclophosphamide rats treated with ESWT (cyclophosphamide+ESWT); (5) cyclophosphamide rats treated with GPR120 agonist (cyclophosphamide+GW9508). On Day 3, urine and bladder specimens were collected for biochemical, histopathological, immunological, and immunoblotting analysis. Following stimulation with cyclophosphamide, the inhibition of the elevated levels of TAK1/NF-κB and phospho-TAK1/NF-κB by ESWT and GPR120 agonists in RT4 cells was associated with a suppression of NF-κB translocation from the cytosol to the nucleus. Accordingly, this anti-inflammatory effect was abolished by GPR120 antagonist and knockdown of GPR120. Histologically, bladder inflammation in cyclophosphamide-treated rats was suppressed by GW9508 or ESWT. Masson's trichrome and Sirius red staining revealed that cyclophosphamide treatment enhanced synthesis of extracellular matrix in rats that was reversed by GW9508 or ESWT. Upregulated pro-inflammatory mediators and cytokines in the cyclophosphamide-treated rats were also suppressed in the GW9508- or ESWT-treated rats. The significantly increased inflammatory cell infiltration as well as the impaired urothelial integrity of the bladder after cyclophosphamide treatment were reversed by treatment with GW9508 or ESWT. These findings suggest that GPR120, the sensing receptor for ESWT, may be useful in the treatment of interstitial cystitis by inhibiting inflammatory response in bladder cells.
Abstract Silicosis is the most prevalent and fatal occupational disease with no effective therapeutics, and currently used drugs cannot reverse the disease progress. Worse still, there are still challenges to be addressed to fully decipher the intricated pathogenesis. Thus, specifying the essential mechanisms and targets in silicosis progression then exploring anti-silicosis pharmacuticals are desperately needed. In this work, multi-omics atlas was constructed to depict the pivotal abnormalities of silicosis and develop targeted agents. By utilizing an unbiased and time-resolved analysis of the transcriptome, proteome and phosphoproteome of a silicosis mouse model, we have verified the significant differences in transcript, protein, kinase activity and signaling pathway level during silicosis progression, in which the importance of essential biological processes such as macrophage activation, chemotaxis, immune cell recruitment and chronic inflammation were emphasized. Notably, the phosphorylation of EGFR (p-EGFR) and SYK (p-SYK) were identified as potential therapeutic targets in the progression of silicosis. To inhibit and validate these targets, we tested fostamatinib (targeting SYK) and Gefitinib (targeting EGFR), and both drugs effectively ameliorated pulmonary dysfunction and inhibited the progression of inflammation and fibrosis. Overall, our drug discovery with multi-omics approach provides novel and viable therapeutic strategies for the treatment of silicosis.
This paper proposes a novel AC-DC power supply with features of power-factor correction (PFC) and cost-effectiveness for indoor LED lighting applications. The proposed AC-DC power supply combines an inverse buck-boost converter with a lossless snubber, and also includes input-current shaping. An 1SW(60V/0.3A)-rated prototype power supply has been successfully developed and implemented for operating with an input utility-line voltage of 110 V. Satisfactory results have demonstrated the functionality of the presented AC-DC power supply and its suitability for indoor LED lighting applications.
This study tested the hypothesis that circulating microparticles (MPs) exacerbated vascular wall (VW) remodeling after endothelial denudation by 0.014 wire in a rat model. Adult male Sprague Dawley rats (n = 40) were equally categorized into group 1 [sham-control (SC); 3.0 mL saline intravenous injection], group 2 [SC + intravenous MPs (1.0 × 107) derived from patients with carotid artery stenosis (CAS)], group 3 [femoral arterial endothelial denudation (FAED)], group 4 (FAED + MPs derived from healthy subjects), and group 5 (FAED + CAS-derived MPs). Animals were euthanized by day 28 after FAED procedure. The results demonstrated that neointimal area (NIA) (mm2), medial area, and number of infiltrated cells in medial layer were highest in group 5 and lowest in groups 1 and 2, and significantly higher in group 4 than those in group 3 (all P<0.0001), but no differences were noted between groups 1 and 2. However, the ratio of luminal area to VW area showed an opposite pattern compared to that of NIA among five groups (P<0.0001). Immunofluorescent study showed an identical pattern of changes in the numbers of inflammatory (F4/80, CD14, CD40, IL-β) and proliferative (Ki-67, Cx43) cells in VW compared to that of NIA among the five groups (all P<0.00). The mNRA expressions of inflammatory (MMP-9, NF-κB, TNF-α, IL-1β, iNOS, PDGF) and cell activation (c-Fos, c-Myc, osteopontin, PCNA) biomarkers showed an identical pattern compared to that of NIA among all groups (all P<0.001). Take altogether, CAS-derived MPs further aggravated MP-mediated VW remodeling after endothelial damage compared to that observed after administration of MPS derived from healthy subjects.
Tartary buckwheat sprouts have a high nutritional value and are gluten-free, and polyphenols are their main active constituents. However, information regarding the active constituents' difference of Tartary buckwheat sprouts grown from seeds with different morphology, at different developmental stages and environments is limited. Here, we developed a LC-MS-based targeted metabolomics approach to analyze polyphenols (46 flavonoids and 6 anthraquinones) in 40 Tartary buckwheat sprouts varieties. Both flavonoids and anthraquinones contributed to significant differences in sprouts grown from seed with different color or shape. Twenty-seven differential compounds were all at a higher level in 3-day-old sprouts, and the fold change from 3-day-old to 8-day-old sprouts was 1.42-6.64. A total of 25 differential compounds were all significantly upregulated upon UV-B radiation, especially for epicatechin. This study is valuable not only for better breeding cultivars of Tartary buckwheat sprouts, but also assessing their metabolic quality.
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