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PURPOSE: Cinchoninze hydrochloride solves the problem of the low solubility of cinchonine, but it is unstable and susceptible to deliquescence. In this study, we designed and prepared cinchonine cocrystal salts or cinchonine salts with better stability, solubility and antioxidant activity than cinchonine. METHOD: We successfully synthesized and characterized three cinchonine salts, namely, cinchonine-fumaric acid, cinchonine-isoferulic acid, and cinchonine-malic acid. The high humidity (92.5% RH) and high temperature (60°C) tests were conducted to determine the physical stability and hygroscopicity of cinchonine hydrochloride, cinchonine and three cinchonine salts. And the ultraviolet spectrophotometry was conducted to determine the equilibrium solubility and intrinsic dissolution rate of cinchonine and salts. Moreover, the DPPH, ABTS, and FRAP assays determined the antioxidant activity of cinchonine and salts. RESULT: Compared with cinchonine hydrochloride and cinchonine, all three cinchonine salts exhibited good physical stability over 15 days under high humidity (92.5% RH) and high temperature (60°C) conditions. While cinchonine and cinchonine hydrochloride are categorized as hygroscopic and deliquescent, respectively, three cinchonine salts are classified as slightly hygroscopic, meaning that they have a lower hygroscopicity than cinchonine and cinchonine hydrochloride. And three cinchonine salts had higher equilibrium solubility, faster intrinsic dissolution rates, and higher antioxidant activity in comparison to cinchonine. Moreover, they showed a "spring and parachute" pattern in the phosphate buffer (pH = 6.8). CONCLUSION: Cocrystallization technology is a viable option for improving cinchonine's poor physicochemical qualities.
Subject(s)
Antioxidants , Crystallization , Drug Stability , Solubility , Antioxidants/chemistry , Antioxidants/pharmacology , Wettability , Chemistry, Pharmaceutical/methods , Humidity , Salts/chemistryABSTRACT
Motivated by the driving force to address global water scarcity, industrial water resources, as the second largest consumption of water resources, its security assessment plays a crucial role in improving the current situation. Hence, this paper proposes a novel methodology to conduct the industrial water resources security (IWRS) assessment. Firstly, a more targeted assessment system based on the framework of the Pressure-State-Response (P-S-R) on IWRS is established. Then, enhanced with a double hierarchy hesitant fuzzy linguistic term set (DHHFLTS), the Best-Worst Method (BWM) now determines subjective weights through DHHFLTS-BWM (DF-BWM). By introducing the Criteria Importance Through Intercriteria Correlation (CRITIC) method, which considers the indicator interactions, objective weights are obtained to modify the subjective weights. Furthermore, the global dominance of all alternatives is calculated by a TODIMSort method and grading them. Moreover, 16 cities in Anhui Province are taken as examples to assess IWRS in the decade from 2011 to 2020. Comparative analysis with original BWM, time series analysis, sensitivity analysis on loss attenuation coefficient, coupling and coordination analysis and obstacle analysis on all indicators are conducted to verify the rationality, effectiveness, and stability of the proposed assessment methodology. Simultaneously, explore the existing issues within IWRS. It can be seen from the results that the performance of Lu'an and Huainan cities is relatively better, while Ma'anshan city shows relatively poorer performance. In addition, per capita water resources and wastewater treatment facilities have a significant impact on the IWRS. Finally, some management suggestions are proposed to enhance the scientific and effective management of industrial water resources and ensure their sustainable utilization.
Subject(s)
Fuzzy Logic , Water Resources , China , Industry , Water SupplyABSTRACT
A novel, to the best of our knowledge, photodetector with a metalens packaging module used as the visible light communication (VLC) receiver is proposed and designed. An LED consisting of red, green, blue, and yellow chips (RGBY-LED) is adopted as the transmitter for intensity modulation direct detection VLC systems. A metalens array with a numerical aperture (NA) of 0.707 used as a polarization-insensitive planar lens of the VLC system receiver is designed at wavelengths of 457, 523, 592, and 623 nm corresponding to blue, green, yellow, and red for high efficiency. Compared with a traditional Fresnel lens positive-intrinsic-negative (PIN) photodetector module as the VLC receiver, the introduction of a metalens module can decrease the form factor of the VLC receiver module and, in particular, it is much thinner. The combination of the multi-color LED transmitter and photodetector metalens packaging module receiver can increase the modulation bandwidth due to four different wavelengths used for the VLC system. Finite-difference time domain (FDTD) simulations are performed to validate the performance of the photodetector with a metalens module. It is revealed that the corresponding efficiencies of 57.5%, 55.4%, 57%, and 56.3% were achieved at wavelengths of 623, 592, 523, and 457 nm, respectively, based on a metalens array with a 0.707 NA and 2.5 µm radius of the active area of the photodetector. It is a promising technology for indoor VLC systems such as those for smart phones and other Internet of Things devices due to the need for compact packaging for the receiver.
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Inhibition of methyl-coenzyme M reductase can suppress the activity of ruminal methanogens, thereby reducing enteric methane emissions of ruminants. However, developing specific and environmentally friendly inhibitors is a challenging endeavor. To identify a natural and effective methane inhibitor that specifically targets methyl-coenzyme M reductase, molecular docking technology was employed to screen a library of phytogenic compounds. A total of 52 candidate compounds were obtained through molecular docking technique. Rosmarinic acid (RA) was one of the compounds that could traverse a narrow channel and bind to the active sites of methyl-coenzyme M reductase, with a calculated binding free energy of -9.355 kcal/mol. Furthermore, the effects of rosmarinic acid supplementation on methane production, rumen fermentation, and the microorganism's community in dairy cows were investigated through in vitro rumen fermentation simulations according to a random design. Supplementation of RA resulted in a 15% decrease in methane production compared with the control. In addition, RA increased the molar proportion of acetate and propionate, whereas the sum of acetate and butyrate divided by propionate was decreased. At the bacterial level, the relative abundance of Rikenellaceae RC9 gut group, Christensenellaceae R7 group, Candidatus Saccharimonas, Desulfovibrio, and Lachnospiraceae FE2018 group decreased with RA supplementation. Conversely, the addition of RA significantly increased the relative abundance of DNF00809 (a genus from Eggerthellaceae), Denitrobacterium, an unclassified genus from Eggerthellaceae, an unclassified genus from Bacteroidales, and an unclassified genus from Atopobiaceae. At the archaeal level, the relative abundance of Methanobrevibacter decreased, while that of Methanosphaera increased with the RA supplementation. These findings suggested that RA has the potential to be used as a novel natural additive for inhibiting ruminal methane production.
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The intricate and protracted process of dentin formation has been extensively explored, thanks to the significant advancements facilitated by the use of animal models and related techniques. Despite variations in their effectiveness, taking into account factors such as sensitivity, visibility, and reliability, these models or techniques are indispensable tools for investigating the complexities of dentin formation. This article focuses on the latest advances in animal models and related technologies, shedding light on the key molecular mechanisms that are essential in dentin formation. A deeper understanding of this phenomenon enables the careful selection of appropriate animal models, considering their suitability in unraveling the underlying molecular intricacies. These insights are crucial for the advancement of clinical drugs targeting dentin-related ailments and the development of comprehensive treatment strategies throughout the duration of the disease.
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Colorectal cancer (CRC) remains a significant global health issue. In this study, the role of T-cell exhaustion-related genes (TEXs) in CRC was investigated using single-cell and bulk RNA-seq analysis. This research involved extensive data analysis using multiple databases, including the TCGA-COAD cohort, GSE14333, and GSE39582. Through single-cell analysis, distinct cell populations within CRC samples were identified and classified T-cells into four subgroups: regulatory T-cells (Tregs), conventional CD4+ T-cells (CD4+ T conv), CD8+ T, and CD8+ T exhausted cells. Intercellular communication networks and signaling pathways associated with TEXs using computational tools such as CellChat and PROGENy. Additionally, TEX-related alterations in tumor gene pathways were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Prognostic models were developed, and their correlation with immune infiltration was assessed. The study revealed the presence of distinct cell populations within CRC, with TEXs playing a crucial role in the tumor microenvironment. CD8+ T exhausted cells exhibited expression of specific markers, indicating their involvement in tumor immune evasion. CellChat and PROGENy analyses revealed intricate communication networks and signaling pathways associated with TEXs, including RNA splicing and viral carcinogenesis. Furthermore, the prognostic risk model developed on the basis of TEXs demonstrated its efficacy in stratifying CRC patients. This risk model exhibited strong correlations with immune infiltration by various effector immune cells, highlighting the influence of TEXs on the tumor immune response. The complex interactions and signaling pathways underlying TEX-associated immune dysregulation in CRC were revealed by employing advanced analytical approaches. The development of a prognostic risk model based on TEXs offers a promising tool for prognostic stratification in patients with CRC. Furthermore, the correlations observed between TEXs and immune infiltration provide valuable insights into the potential of TEXs as therapeutic targets and highlight the need for further investigation into TEX-mediated immune evasion mechanisms. This study thus provides valuable insights into the role of TEXs in CRC.
Subject(s)
Colorectal Neoplasms , T-Cell Exhaustion , Humans , Carcinogenesis , Computational Biology , Gene Ontology , Colorectal Neoplasms/genetics , Tumor Microenvironment/geneticsABSTRACT
Enterocytozoon hepatopenaei (EHP) is a common parasite that invades the epithelial cytoplasm in the hepatopancreas of shrimp Litopenaeus vannamei and results in slow growth of the host shrimps to cause significant economic loss in shrimp aquaculture. In this study, a TaqMan probe-based qPCR for quantitative detection of EHP was established. A pair of specific primers and a TaqMan probe were designed based on the sequence of cysteine desulfurase gene (NFS1) of EHP. The standard curve between cycle threshold (Ct) and the logarithmic starting quantity (SQ) of the template was determined as Ct = - 3.231 lg (SQ) + 40.638, with a correlation coefficient (R2) of 0.998 and an amplification efficiency of 103.9%. The lower limit of quantification was 1.67 × 101 copies/µL for this TaqMan probe-based qPCR and 1.67 × 103 copies/µL for the conventional PCR. The TaqMan probe-based qPCR established in the research was 100 times more sensitive than the conventional PCR method. In addition, the results of clinical sample detection indicated that the present technique was efficient in detecting EHP in the hepatopancreas, feces, water, and pond bottom mud samples. Therefore, the established TaqMan probe-based qPCR is a suitable technique for detecting EHP in both shrimp and aquatic environment samples.
Subject(s)
Enterocytozoon , Penaeidae , Animals , Enterocytozoon/genetics , Hepatopancreas , Real-Time Polymerase Chain ReactionABSTRACT
BACKGROUND: Dens invaginatus (DI) is a developmental anomaly, Oehlers Type III DI is the most complex type and early diagnosis and treatment is complicated and challenging. This report presents a rare case of a type IIIb DI associated with a periapical lesion in bilateral immature permanent mandibular central incisors. CASE PRESENTATION: An eight-year-old boy referred to our clinic manifesting with pain along with swelling in the mandibular incisors for the past one month. Radiographic examination showed periapical radiolucency exhibiting a scantly defined border, as well as an invagination which had a central invaginated canal extending from the pulp chamber throughout the apical foramen in both mandibular central incisors. We performed two different treatment procedures on the basis of the condition of the main pulp of the mandibular central incisors. in which only the invagination root canal was treated in the right mandibular central incisor, while the invagination and main root canals were treated in the left mandibular central incisor. During the 18-month follow-up period, the teeth were clinically asymptomatic. Imaging examinations indicated complete healing of the periapical lesion and revealed that the wall of the root canal was thickened and the open apex was closed. CONCLUSION: For young permanent teeth with type III Dens invaginatus, it is particularly important to keep pulp vitality, which could maintain root development and allow a good long-term prognosis.
Subject(s)
Dens in Dente , Incisor , Child , Dens in Dente/complications , Dens in Dente/diagnostic imaging , Dens in Dente/therapy , Dental Pulp Cavity/pathology , Humans , Incisor/abnormalities , Incisor/diagnostic imaging , Male , Root Canal Therapy/methods , Tooth Apex/pathologyABSTRACT
In the period of Corona Virus Disease 2019 (COVID-19), millions of people participate in the discussion of COVID-19 on the Internet, which can easily trigger public opinion and threaten social stability. This paper creatively proposes a multi-stage risk grading model of Internet public opinion for public health emergencies. On the basis of general public opinion risk grading analysis, the model continuously pays attention to the risk level of Internet public opinion based on the time scale of regular or major information updates. This model combines Analytic Hierarchy Process Sort II (AHPSort II) and Swing Weighting (SW) methods and proposes a new Multi-Criteria Decision Making (MCDM) method - AHPSort II-SW. Intuitionistic fuzzy number and linguistic fuzzy number are introduced into the model to evaluate the criteria that cannot be quantified. The multi-stage model is tested using more than 2,000 textual data about COVID-19 collected from Microblog, a leading social media platform in China. Seven public opinion risk assessments were conducted from January 23 to April 8, 2020. The empirical results show that in the early COVID-19 outbreak, the risk of public opinion is more serious on macroscopic view. In details, the risk of public opinion decreases slowly with time, but the emergence of important events may still increase the risk of public opinion. The analysis results are in line with the actual situation and verify the effectiveness of the method. Comparative analysis indicates the improved method is proved to be superior and effective, sensitivity analysis confirms its stability. Finally, management suggestions was provided, this study contributes to the literature on public opinion risk assessment and provides implications for practice.
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Introduction: In dental treatments, the reason for secondary caries and the failure of root canal treatment is the microbial infection, which concerns most dentists. The challenge of how to reduce the number of bacteria at the filling materials and the number of residual bacteria in the root canal has become a research hotspot. In this study, the bacterial adhesion properties of several common dental materials were compared to provide a theoretical basis for the selection of antibacterial properties of dental materials. Methodology. Three commonly used dental restorative materials and five sealers in root canal treatment were selected. Each material block was immersed in the corresponding supragingival (Streptococcus mutans and Actinomyces viscosus) or subgingival (Porphyromonas gingivalis and Enterococcus faecalis) bacterial solution and cultured under anaerobic conditions at 37°C for 2, 4, 6, 8, 12, 16, 20, and 24 h. The adhesion of bacteria was observed, and the number of different bacteria adhering to various material model disks was calculated at different time intervals under a scanning electron microscope. The adherent CFU load of the materials was determined by colony counting. Results: Streptococcus mutans and Actinomyces viscosus exhibited the strongest adhesion ability to the resin material blocks. Porphyromonas gingivalis and Enterococcus faecalis exhibited the highest adhesion ability to the AH-Plus sealer block. Conclusions: In dental treatments, dental materials should be selected based on the chemical, physical, and biological properties of materials. In addition, it is necessary to develop new antibacterial dental materials.
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Motivated by the realistic demand of controlling the Internet public opinion risk caused by the local outbreak of COVID-19, this paper creatively proposes a COVID-19 local outbreak Internet public opinion risk grading research framework. The SMAA-FAHPSort II method combining Analytic Hierarchy Process Sort II (AHPSort II) method with Stochastic Multicriteria Acceptability Analysis (SMAA-2) method is introduced into this framework, to evaluate the Internet public opinion risk level of social media during the local outbreak of COVID-19. In addition, this framework is applied to a case of Internet public opinion risk evaluation on Microblog platform of China. According to the number of new cases per day in mainland China, this paper divides the period from May 7, 2020 to September 3, 2021 into seven stages. A total of more than 10,000 Microblog hot topics were collected, after screening and preprocessing, 5422 related topics are remained to help complete the Internet public opinion risk evaluation. The case study analysis results show that the number of days classified as moderate risk and above has reached more than 280. This proves that the local outbreak of COVID-19 will indeed increase the risk of Internet public opinion, and correlation analysis confirms that the level of public opinion risk is positively correlated with the severity of the epidemic in the real world. Furthermore, the effectiveness and advantages of the proposed method are verified by comparative analysis and sensitivity analysis. Finally, some effective public opinion management suggestions have been put forward. This paper can provide reference for the government to formulate or improve relevant strategies, and also has great significance for reducing the risk of Internet public opinion in social media.
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OBJECTIVE: Microbial exposure is critical to neonatal and infant development, growth and immunity. However, whether a microbiome is present in the fetal gut prior to birth remains debated. In this study, lambs delivered by aseptic hysterectomy at full term were used as an animal model to investigate the presence of a microbiome in the prenatal gut using a multiomics approach. DESIGN: Lambs were euthanised immediately after aseptic caesarean section and their cecal content and umbilical cord blood samples were aseptically acquired. Cecal content samples were assessed using metagenomic and metatranscriptomic sequencing to characterise any existing microbiome. Both sample types were analysed using metabolomics in order to detect microbial metabolites. RESULTS: We detected a low-diversity and low-biomass microbiome in the prenatal fetal gut, which was mainly composed of bacteria belonging to the phyla Proteobacteria, Actinobacteria and Firmicutes. Escherichia coli was the most abundant species in the prenatal fetal gut. We also detected multiple microbial metabolites including short chain fatty acids, deoxynojirimycin, mitomycin and tobramycin, further indicating the presence of metabolically active microbiota. Additionally, bacteriophage phiX174 and Orf virus, as well as antibiotic resistance genes, were detected in the fetal gut, suggesting that bacteriophage, viruses and bacteria carrying antibiotic resistance genes can be transmitted from the mother to the fetus during the gestation period. CONCLUSIONS: This study provides strong evidence that the prenatal gut harbours a microbiome and that microbial colonisation of the fetal gut commences in utero.
Subject(s)
Fetus/metabolism , Fetus/microbiology , Gastrointestinal Microbiome/genetics , Sheep/genetics , Sheep/microbiology , Animals , Female , Gene Expression Profiling , Metabolomics , Metagenomics , Models, Animal , PregnancyABSTRACT
China has a long history of Salviae Miltiorrhizae Radix et Rhizoma processing with multiple methods available. The pre-sent study collated and summarized the Salviae Miltiorrhizae Radix et Rhizoma processing methods recorded in 23 related herbal medicine books, all editions of Chinese Pharmacopoeia, the 1988 edition of National Regulations for Processing of Chinese Medicine, and 20 current local processing specifications and standards. The results demonstrated various processing methods of Salviae Miltiorrhizae Radix et Rhizoma, such as removing residual part of stem, plantlet, or soil, smashing, filing, cutting, decocting, washing with wine, soaking in wine, and stir-frying with wine or blood from pig heart, while raw and wine-processed products are mainly used in modern times. Due to the lack of unified standards, the phenomena of multiple methods adopted in one place and different methods in different places have led to uneven quality of Salviae Miltiorrhizae Radix et Rhizoma pieces, even affecting the safety and effectiveness of its clinical medication. This study is expected to provide a reference for the development of Salviae Miltiorrhizae Radix et Rhizoma processing and its rational medication.
Subject(s)
Drugs, Chinese Herbal , Salvia miltiorrhiza , Animals , China , Plant Roots , Rhizome , SwineABSTRACT
Lysine (Lys) is majorly metabolized in the liver. The liver functional consequences of a dietary Lys deficiency in young Holstein calves are unknown. This study aimed to investigate the effects of Lys deficiency in Holstein calf livers using RNA-sequencing and untargeted LC-MS metabolomics. Calves (n = 36; initial body weight 101.2 ± 10.8 kg; 90-day-old) were fed restricted diets, for 90 days, containing 19.2% crude protein that varied in Lys content (PC group 1.21%; PC-Lys group 0.85%; dry matter basis) for 90 days. Body weight, average daily gain, gain/feed, and Lys intake were significantly decreased in response to Lys deficiency (P < 0.05). Dry matter intake was not altered (P > 0.05). Network and pathway analyses revealed that noradrenaline, adenosine 5'-monophosphate, acetyl-CoA, and coenzyme A were significantly decreased. Regulating of lipolysis in adipocytes pathway and fatty acid degradation pathway were downregulated. We also identified eight significantly differentially expressed genes (SDEGs), among which adrenoceptor beta 2 (ADRB2), WAP four-disulfide core domain 2 (WFDC2), and claudin-4 (CLDN4) were associated with inhibition of lipolysis, and carbon catabolite repression 4-like (CCRN4L), FOS like 2 (FOSL2), and arginase 2 (ARG2) were associated with inhibiting lipid synthesis. Correlation tests showed that coenzyme A was strongly correlated with SDEGs (0.82 ≤|r|≤ 0.96). Acetyl-CoA and adenosine 5'-monophosphate were strongly correlated with CCRN4L (0.90 ≤|r|≤ 0.92), indicating a strong correlation between the changes in SDEGs and these metabolites. In conclusion, Lys deficiency caused dysplasia and affected lipid metabolism in the liver by inhibiting lipolysis and lipid synthesis in calves.
Subject(s)
Animal Feed/analysis , Diet/veterinary , Liver/metabolism , Lysine/deficiency , Metabolome , Transcriptome , Animal Nutritional Physiological Phenomena , Animals , Animals, Newborn , Cattle , Chromatography, Liquid , Female , Mass Spectrometry , RNA-SeqABSTRACT
This study aimed to evaluate the effects of partial reducing rumen-protected Lys (RPLys) on rumen fermentation and microbial composition in heifers. Three ruminal fistulated Holstein Friesian bulls were used to determine the effective degradability of RPLys using an in situ method at incubation times of 0, 2, 6, 12, 16, 24, 36, and 48 h. Thereafter, 36 Holstein heifers at 90 days of age were assigned to one of two dietary treatments: a theoretically balanced amino acid diet (PC group; 1.21% Lys, 0.4% Met) or a 30% Lys-reduced diet (PCLys group, 0.85% Lys, 0.4% Met). Rumen fluid samples from five heifers in each group were extracted using esophageal tubing on day 90 to determine pH, microprotein, ammonia, volatile fatty acids, and microbial communities. Results showed that the effective ruminal degradability was 25.76%. Furthermore, differences in rumen fermentation parameters and alpha diversity of the microbiota between the two groups were not significant, but beta diversity was significant. Based upon relative abundance analysis, short-chain fatty acid-producing bacteria, including Sharpea, Syntrophococcus, [Ruminococcus]_gauvreauii_group, Acetitomaculum, and [Eubacterium]_nadotum_group belonging to Firmicutes, were significantly decreased in the PCLys group. Spearman's analysis revealed a positive correlation between the butyrate molar proportion and the relative abundance of butyrate-producing bacteria such as [Eubacterium]_nadotum_group, Coprococcus_1, Ruminococcaceae_UCG_013, Pseudoramibacter, and Lachnospiraceae_UCG_010. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis further validated that RPLys deduction influenced energy metabolism. Together, our findings highlight the role of RPLys or Lys in butyrate-producing bacteria. However, the number of bacteria affected by Lys was very limited and insufficient to alter rumen fermentation. Key Points ⢠Reducing 30% Lys via rumen-protected Lys did not affect rumen fermentation parameters and alpha diversity of microbiota of Holstein heifers. It meant that the ruminal fermentation pattern was not changed. ⢠Reducing 30% Lys via rumen-protected lysine significantly decreased relative abundance of short-chain fatty acid-producing bacteria belonging to Firmicutes. ⢠Functions of microorganisms were changed by reducing 30% Lys via rumen-protected Lys, especially amino acid metabolism. It may affect the amino acid composition of microprotein.
Subject(s)
Animal Feed/analysis , Bacteria/metabolism , Fermentation , Gastrointestinal Microbiome , Lysine/metabolism , Rumen/chemistry , Rumen/microbiology , Animals , Bacteria/classification , Cattle , Dietary Supplements/analysis , Energy Metabolism , Female , MaleABSTRACT
Acute kidney injury (AKI) is a common adverse reaction of the anticancer drug. Among these chemotherapeutic agents, cisplatin, an effective chemotherapeutic drug, is extensively applied to the treatment of solid tumours, yet various adverse reactions, especially AKI, often limit their use. However, the pathogenesis of AKI caused by cisplatin remains poorly clarified. Therefore, we tested whether microRNAs, which have been certified as key regulators of disease are involved in this process. AKI mouse and HK2 cells were treated with cisplatin. Annexin V/PI staining and cleaved caspase-3 were used to assess apoptosis. Western blot analyses and qRT-PCR were used to evaluate the protein and mRNA level of TRPC6 and DRP1. miR-26a was remarkably decreased in cisplatin-induced AKI and in cisplatin co-cultured HK2 cells. Furthermore, we used a miR-26a mimics in vitro and found that apoptosis was alleviated than that in the control cells. We further verified that miR-26a protected against cisplatin-induced cell apoptosis by acting on transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamin-related protein 1 (DRP1), thus inhibited the mitochondrial apoptosis pathway. Therefore, the study unveiled that miR-26a/TRPC6/DRP1 is a novel protective pathway in cisplatin-induced AKI and may be targeted for the prevention and treatment of drug-related renal injury. SIGNIFICANCE OF THE STUDY: Our study found that miR-26a was significantly downregulated during cisplatin-induced AKI and during cisplatin co-cultured HK2 cells. Further, in vitro we used miR-26a mimic to intervene cells and found that apoptosis alleviated compared with control group. We further verified that miR-26a protected cisplatin-induced apoptosis by target transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamic-related protein 1 (DRP1) and inhibit the mitochondrial apoptosis pathway. Thus, miR-26a/TRPC6/DRP1 is a new protective pathway in cisplatin-induced AKI and may be targeted for the prevention and treatment of drug-related acute kidney injury.
Subject(s)
Acute Kidney Injury/metabolism , Apoptosis/drug effects , Cisplatin/adverse effects , Dynamins/metabolism , Epithelial Cells/metabolism , Kidney Tubules/metabolism , MicroRNAs/metabolism , TRPC6 Cation Channel/metabolism , Acute Kidney Injury/chemically induced , Acute Kidney Injury/pathology , Animals , Cell Line , Cisplatin/pharmacology , Epithelial Cells/pathology , Humans , Kidney Tubules/pathology , Male , MiceABSTRACT
BACKGROUND This study aimed to provide precise material selection guidance for proper clinical restoration and treatment of plaque-related oral diseases, such as dental caries and periodontal diseases. MATERIAL AND METHODS Four groups (n=24) of restorative material sheets (n=24) were prepared using 3M Z350 composite resin (ZR), zinc phosphate cement (ZPC), glass-ionomer (GI), and ICON permeable resin (IPR). Six volunteers wore a plaque-collection device equipped with the 4 restorative material sheets for 48 hours. Plaque samples were collected, and Miseq sequencing was applied to obtain template DNA fragments for microbial diversity analysis. The data were analyzed with nonparametric tests. RESULTS The microbial diversity on the ZPC surface was significantly lower than that on GI and IPR surfaces. The abundance of Firmicutes and Streptococcus on the ZPC surface was significantly higher than on the surfaces of GI and IPR. In contrast, the abundance of Porphyromonas on the surface of ZPC was significantly lower than that on GI and IPR surfaces. (P<0.05). CONCLUSIONS The results of the present study might serve as a basis for material selection under different oral microbial conditions to provide more accurate treatments and restorative procedures in the oral cavity.
Subject(s)
Dental Caries/microbiology , Dental Materials/adverse effects , Dental Plaque/microbiology , Adult , Bacteria/genetics , Composite Resins/adverse effects , DNA, Ribosomal/genetics , Dental Materials/pharmacology , Female , Glass Ionomer Cements/adverse effects , Humans , Male , Materials Testing/methods , RNA, Ribosomal, 16S/genetics , Resin Cements/adverse effectsABSTRACT
Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are orally active first-in-class new generation drugs for renal anemia. This extensive meta-analysis of randomized controlled trials (RCTs) was designed to provide clear information on the efficacy and safety of HIF-PHIs on anemia in chronic kidney disease (CKD) patients. Searches included PubMed, Web of Science, Ovid MEDLINE, and Cochrane Library database up to October 2019. RCTs of patients with CKD comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in the treatment of anemia. The primary outcome was hemoglobin change from baseline (Hb CFB); the secondary outcomes included iron-related parameters and the occurrence of each adverse event. 26 trials in 17 articles were included, with a total of 2804 dialysis or patients with CKD. HIF-PHIs treatment produced a significant beneficial effect on Hb CFB compared with the placebo group (MD, 0.69; 95% CI, 0.36 to 1.02). However, this favored effect of HIF-PHIs treatment was not observed in subgroup analysis among trials compared with ESAs (MD, 0.06; 95% CI, -0.20 to 0.31). The significant reduction in hepcidin by HIF-PHIs was observed in all subgroups when compared with the placebo group, whereas this effect was observed only in NDD-CKD patients when compared with ESAs. HIF-PHIs increased the risk of nausea (RR, 2.20; 95% CI, 1.06 to 4.53) and diarrhea (RR, 1.75; 95% CI, 1.06 to 2.92). We conclude that orally given HIF-PHIs are at least as efficacious as ESAs treatment to correct anemia short term in patients with CKD. In addition, HIF-PHIs improved iron metabolism and utilization in patients with CKD.
Subject(s)
Anemia/drug therapy , Hematinics/pharmacology , Prolyl-Hydroxylase Inhibitors/administration & dosage , Renal Insufficiency, Chronic/therapy , Anemia/etiology , Erythropoietin/metabolism , Hepcidins/drug effects , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors , Prolyl-Hydroxylase Inhibitors/adverse effects , Prolyl-Hydroxylase Inhibitors/pharmacology , Randomized Controlled Trials as Topic , Renal Dialysis , Renal Insufficiency, Chronic/complicationsABSTRACT
The requirement of net protein (NP) and metabolizable protein (MP) by Dorper crossbred ewe lambs grown from 35 to 50 kg of body weight (BW) was assessed by comparative slaughter experiment. Thirty-five ewe lambs (33.5 ± 0.6 kg BW) of F1 crosses of Dorper × thin-tailed Han sheep were used: 7 lambs were slaughtered as reference animals at the start of the trial, and the remaining 28 lambs were randomly divided into 4 groups of 7 lambs each. Three of the 4 groups were fed a pelleted mixed diet (concentrate/roughage = 44:56, dry matter basis) for ad libitum intake or 65% or 45% of ad libitum intake, and they were all slaughtered when the lambs that were fed ad libitum reached 50 kg BW. The lambs from the fourth group were also fed ad libitum and slaughtered at 43 kg BW as the intermediate group. The intake of MP by the animals of these 4 groups was estimated, and their total body protein and protein retention were measured. The daily requirements of NP and MP for maintenance were 1.52 and 3.98 g/kg BW0.75 , respectively, with a partial efficiency of MP utilization for maintenance of 0.38. The MP requirement for growth ranged from 77.4 to 124.5 g/day for average daily gains from 100 to 250 g BW, and the partial efficiency of MP utilization for growth was 0.66. The Dorper crossbred ewe lambs required more MP for both maintenance and growth in comparison with the recommendations of the US nutritional system.
Subject(s)
Animal Feed/analysis , Diet/veterinary , Dietary Proteins/administration & dosage , Sheep/physiology , Animal Nutritional Physiological Phenomena , Animals , Female , Nutritional Requirements , Sheep/geneticsABSTRACT
OBJECTIVE: The study was conducted to investigate the effects of Broussonetia papyrifera L.(B. papyrifera) silage on growth performance, serum biochemical parameters, meat quality, and meat amino acids and fatty acids compositions in beef cattle. METHODS: Sixty-four male Angus beef cattle were assigned to 4 groups with 4 pens in each group and 4 beef cattle in each pen, and fed with the total mixed ration supplemented with 0%, 5%, 10%, or 15% B. papyrifera silage for 100 days (control group, 5% group, 10% group and 15% group) separately. RESULTS: Beef cattle had significantly higher final body weight (BW) in 15% group, higher average daily gain (ADG) and dry matter intake (DMI) in 5% group, 10% group and 15% group, and higher feed conversion ratio (FCR) in 10% group and 15% group. Significantly higher blood superoxide dismutase (SOD) concentration was noted in 15% group, higher blood total antioxidant capacity (TAC) in 10% group and 15% group, lower 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) in 15% group. Meat had lower pH in 15% group, higher Commission International DeI'Eclairage (CIE) L* in 5% group, 10% group, and 15% group, and lower drip loss in 15% group. Greater concentration of meat polyunsaturated fatty acids (PUFA) was observed in 10% group and 15% group, and docosahexaenoic acid (DHA) in 15% group. CONCLUSION: Diet with 15% B. papyrifera silage could improve performance and increase final BW, ADG, DMI, and FCR, enhance the antioxidant functions by decreasing blood 8-OHdG and MDA and increasing blood SOD and TAC, improve the meat quality by lowing pH and drip loss and increasing CIE L*, increase the meat PUFA and DHA concentration. Polyphenols and flavonoids might be the main components responsible for the antioxidant activity and anti-biohydrogenation in the B. papyrifera silage. And B. papyrifera silage could be used as a new feedstuff in beef cattle nutrition.