ABSTRACT
OBJECTIVE: This study was performed to explore the treatment of the injury caused by traumatic limb amputation. METHODS: From October 2002 to October 2021, 30 cases were enrolled in the present study. The reasons for injury were as follows: 8 cases with single hydraulic column crush injury, 12 cases with gear and wire rope stranding, 6 cases with belt avulsion injury, and 4 cases with carbon block smash injury. The present study application of a free or small saphenous vein bypass to reconstruct the injured artery and vein according to the concept of the angiosome model. The defective vessels were bridged with the axial vessels of a flow-through flap, such as a medial calf flap or anterolateral femoral flap, to construct an additional blood supply and drainage vein for the severed limb. The clinical data of 30 cases with traumatic limb amputation of the lower leg and ankle were retrospectively analyzed. RESULTS: In all 30 cases of traumatic limb amputation, the replantation via the adoption of a flow-through flap was successful, and 85.6% of the patients remained in good postoperative condition. There were no symptoms of ischemia in the marginal segment after blood supply reconstruction of the transected limb by axial vascular bridging within the flap. CONCLUSION: Via the adoption of microsurgical techniques, the blood supply to the transected limb can be reconstructed by bridging the defective vessels with the adoption of the axial vessels of the flow-through flap is a feasible and advanced treatment option.
ABSTRACT
The screening of based target compounds supported by LC/MS, MS/MS and Global Natural Products Social (GNPS) used to identify the compounds 1-10 of Butea monsperma. They were evaluated in human malignant embryonic rhabdomyoma cells (RD cells) infected with Human coronavirus OC43 (HCoV-OC43) and showed significant inhibitory activity. Target inhibition tests showed that compounds 6 and 8 inhibited the proteolytic enzyme 3CLpro, which is widely present in coronavirus and plays an important role in the replication process, with an effective IC50 value. The study confirmed that dioxymethylene of compound 8 may be a key active fragment in inhibiting coronavirus (EC50 7.2 µM, SI > 139.1). The results have led to identifying natural bioactive compounds for possible inhibiting HCoV-OC43 and developing drug for Traditional Chinese Medicine (TCM).
Subject(s)
Antiviral Agents , Coronavirus OC43, Human , Flavonoids , Humans , Flavonoids/pharmacology , Flavonoids/isolation & purification , Flavonoids/chemistry , Chromatography, Liquid , Molecular Structure , Coronavirus OC43, Human/isolation & purification , Coronavirus OC43, Human/drug effects , Antiviral Agents/pharmacology , Antiviral Agents/isolation & purification , Tandem Mass Spectrometry , Cell Line, Tumor , Coronavirus 3C Proteases/antagonists & inhibitors , Biological Products/pharmacology , Biological Products/isolation & purification , Biological Products/chemistryABSTRACT
As a photophilous plant, rice is susceptible to low-light stress during its growth. The Sichuan Basin is a typical low-light rice-producing area. In this study, eight rice varieties with different shade tolerances were studied from 2021 to 2022. The physiological adaptability and yield formation characteristics of rice were studied with respect to photosynthetic physiological characteristics and dry matter accumulation characteristics, and the response mechanism of rice to low light stress was revealed. The results showed that the shading treatment significantly increased the chlorophyll a, chlorophyll b, and total chlorophyll contents in the leaves of direct-seeded rice after heading, and the total chlorophyll content increased by 1.68-29.70%. Nitrate reductase (NR) activity first increased and then decreased under each treatment, and the shading treatment reduced the NR activity of direct-seeded rice. Compared to the control treatment, the peroxidase (POD) activity of each variety increased from 7 to 24 d after the shading treatment. The transketolase (TK) activity in direct-seeded hybrid rice increased under low light stress. Compared with the control, shading treatment significantly reduced the aboveground dry matter, grain number per panicle, and seed setting rate of direct-seeded rice at the full heading stage and maturity stage, thus reducing the yield of direct-seeded rice by 26.10-34.11%. However, under the shading treatment, Zhenliangyou 2018 and Jingliangyou 534 maintained higher chlorophyll content and related enzyme activities, accumulated more photosynthetic products, and reduced yield. In general, Zhenliangyou 2018 and Jingliangyou 534 still had a yield of 7.06-8.33 t·hm-2 under low light. It indicated that Zhenliangyou 2018 and Jingliangyou 534 had better stability and stronger tolerance to weak light stress and had a higher yield potential in weak light areas such as Sichuan.
ABSTRACT
Spontaneous subarachnoid hemorrhage (SAH) is an acute neurologic emergency with poor outcomes, and mitochondrial dysfunction is known as one of the key pathological mechanisms underlying the SAH-induced early brain injury (EBI). 1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate (T817MA) is a newly synthesized neurotrophic compound that has been demonstrated to exert protective effects against brain injury. Here, we investigated the effect of T817MA in neuronal injury following experimental SAH both in vitro and in vivo. Primary cultured cortical neurons were treated with oxyhemoglobin (OxyHb) to mimic SAH in vitro, and T817MA at concentrations higher than 0.1 µM reduced OxyHb-induced neuronal injury. T817MA treatment significantly inhibited lipid peroxidation, reduced neuronal apoptosis and attenuated mitochondrial fragmentation. The results of western blot showed that T817MA markedly reduced the expression of mitochondrial fission proteins, fission protein 1 (Fis-1) and dynamin-related GTPase-1 (Drp-1), but prolonged the expression of the postsynaptic protein activity-regulated cytoskeleton-associated protein (Arc). In addition, T817MA significantly increased the expression of sirtuin 1 (Sirt1), which was accompanied by preserved enzymatic of isocitrate dehydrogenase (IDH2) and superoxide dismutase (SOD). Knockdown of Sirt1 and Arc via small interfere RNA (siRNA) transfection partially prevented the T817MA-induced protection in cortical neurons. Furthermore, treatment with T817MA in vivo significantly reduced brain damage and preserved neurological function in rats. The decreased expression of Fis-1 and Drp-1, as well as the increased expression of Arc and Sirt1 were also observed in vivo. Taken together, these data indicate that the neuroprotective agent T817MA protects against SAH-induced brain injury via Sirt1- and Arc-mediated regulation of mitochondrial dynamics.
Subject(s)
Brain Injuries , Neuroprotective Agents , Subarachnoid Hemorrhage , Rats , Animals , Rats, Sprague-Dawley , Sirtuin 1/metabolism , Subarachnoid Hemorrhage/drug therapy , Subarachnoid Hemorrhage/metabolism , Mitochondrial Dynamics , Neuroprotective Agents/pharmacology , Brain Injuries/pathology , ApoptosisABSTRACT
To investigate changes in the yield and physiological characteristics of indica hybrid rice varieties sown on different dates, we evaluated appropriate hybrid rice varieties and their optimal sowing dates in the hilly areas of Sichuan. Three popular indica rice varieties were used as experimental materials, and five sowing dates were set uniformly locally [16 May (SD1), 23 May (SD2), 30 May (SD3), 6 June (SD4), and 13 June (SD5)] to investigate differences in the yield characteristics, growth period, and dry matter accumulation. The results showed that, over the two years, the sowing-to-heading period and overall growth period of the three varieties shortened as the sowing date was delayed, and the difference in yield between the SD1 and SD2 treatments was not significant, owing to higher material accumulation after flowering and higher assimilative material transport capacity. These varieties are both photosensitive and tolerant to low temperatures. Among the three varieties tested, the Huangyouyuehesimiao (V3) cultivar had the highest yield, with 10.75 t ha-1 under the SD2 treatment. The impact of shifting the sowing date on yield components varied. Delaying the sowing date increased and then decreased the number of effective panicles, and the number of grains per panicle and the seed setting rate decreased by differing degrees. In summary, a high yield of indica hybrid rice can be maintained by sowing between 16 and 23 May each year in the study area. It indicated that indica hybrid rice in the hilly rice-producing region of Sichuan is highly adaptable to different sowing dates.
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Objective: This study was designed to investigate the effect of endocrine metabolic factors on hemocyte parameters, tumor markers, and blood electrolytes in patients with hyperglycemia. Methods: In this study, 1791 patients with hyperglycemia were recruited and grouped according to different testing indexes, and their medical records and laboratory indexes were recorded and analyzed. Results: In adult patients with hyperglycemia, we found that high-density lipoprotein cholesterol (HDL-C) was negatively correlated with white blood cell (WBC) and could exert an effect on WBC; triglyceride (TG) level was positively associated with lymphocyte (LYM#); age, TG, and P affected the level of LYM#; and uric acid (UA) level was positively related to eosinophil (EO#). Besides, age was positively correlated with red blood cell distribution width-coefficient of variation (RDW-CV) level; fasting blood glucose (FBG) and serum phosphorus (P) were negatively correlated with RDW-CV level; and age, creatinine (Cre), FBG, HDL-C, and P were influencing factors of RDW-CV level in adult hyperglycemic patients. HDL-C was negatively correlated with fibrinogen (Fib) level, and age, HDL-C, serum kalium (K), serum sodium (Na), and body mass index (BMI) were the influencing factors of Fib levels. TG was positively associated with neuron-specific enolase (NSE) level and affected the NSE level. Serum magnesium (Mg) was negatively related to carcinoembryonic antigen (CEA) level, and sex, age, FBG, Mg, and BMI could have an effect on CEA level. As well, age and FBG were positively associated with carbohydrate antigen 50 (CA50) levels, UA was negatively correlated with CA50 levels, and age, aspartate aminotransferase (AST), UA, and FBG were the influencing factors of CA50 levels. FBG was negatively related to Mg levels; K, serum zinc (Zn), and fasting C-peptide (C-P) were positively correlated with Mg levels; and FBG, K, Zn, and C-P had an effect on Mg levels. Conclusion: Endocrine metabolic factors are closely related to hemocyte parameters, tumor markers, and blood electrolytes in patients with hyperglycemia.
Subject(s)
Cholesterol, HDL , Electrolytes , Hyperglycemia , Biomarkers, Tumor , Hyperglycemia/blood , Electrolytes/blood , Hemocytes , Cholesterol, HDL/bloodABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The buds of Vaccinium dunalianum Wight are used as folk medicine in the Yi settlement of the Yunnan Province, China. It has long been used as herbal tea in the local area owing to its effects of lowering blood lipids and body weight. However, there are only a few studies on its antihyperlipidemic effects, effective substances and mechanisms, especially its effectiveness in diet-induced hyperlipidemia. AIM OF THE STUDY: This study aimed to elucidate the therapeutic effects, pharmacodynamic material bases, and mechanisms of V. dunalianum buds on diet-induced hyperlipidemia. MATERIALS AND METHODS: A high-fat diet-induced hyperlipidemic Sprague-Dawley (SD) rat model was established. Rats were gavaged with different doses of aqueous extract of V. dunalianum(VDW) for 8 weeks and their sera and organ samples were collected. The antihyperlipidemic effect of VDW on SD rats was evaluated based on the biochemical indices and histopathological outcomes. Liquid chromatography-mass spectrometry(LC-MS) was used to determine the main components in VDW, which were separated and purified using sequential chromatographic methods. Their chemical structures were determined using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. 6'-O-caffeoyl-arbutin, as the principal component of VDW, was also evaluated for its antihyperlipidemic activity using an approach similar to that used for VDW. Lastly, the potential targets of VDW and 6'-O-caffeoyl-arbutin in lowering blood lipids were screened out using network pharmacology, and the selected targets were docked with arbutin derivatives. The expression of target proteins was determined using western blotting to illustrate the antihyperlipidemic mechanisms of VDW and 6'-O-caffeoyl-arbutin. RESULTS: VDW reduced triglyceride, total cholesterol, low-density lipoprotein, alanine transaminase, and aspartate transaminase levels in the serum of modeled rats, and increased high-density lipoprotein levels. There was an improvement in steatoses, and lipid droplet accumulation decreased in vivo after VDW intervention. LC-MS revealed that VDW mainly contained arbutin and chlorogenic acid derivatives. Sixteen compounds were isolated and identified. 6'-O-caffeoyl-arbutin was the main compound of VDW (>21.67%) that showed obvious antihyperlipidemic effect with low hepatic damage at different doses. PTGS2, ADH1C, and MAOB were screened out using network pharmacology and they showed strong correlations with arbutin derivative through molecular docking. Results from WB showed that VDW and 6'-O-caffeoyl-arbutin could reduce blood lipid levels by reducing the protein expression of PTGS2, ADH1C, and MAOB. CONCLUSIONS: 6'-O-caffeoyl-arbutin was the main component of V. dunalianum buds. VDW and 6'-O-caffeoyl-arbutin could regulate blood lipid levels in the high-fat diet-induced rat model of hyperlipidemia without damaging their vital organs. Furthermore, they could regulate the expression of PTGS2, ADH1C, and MAOB proteins and play a role in lowering blood lipids. The findings of this study lay a foundation for the further development of V. dunalianum and 6'-O-caffeoyl-arbutin as health supplements or drugs for the management of hyperlipidemia.
Subject(s)
Hyperlipidemias , Vaccinium , Rats , Animals , Hypolipidemic Agents/pharmacology , Chromatography, Liquid , Vaccinium/chemistry , Arbutin/chemistry , Cyclooxygenase 2 , Molecular Docking Simulation , Rats, Sprague-Dawley , Tandem Mass Spectrometry , China , Hyperlipidemias/drug therapy , Lipids , Diet, High-FatABSTRACT
Sexually dimorphic plumage coloration is widespread in birds in which the male plumage is brighter than the female. This phenomenon is related to the environmental constraints on sexual selection or intraspecific competition between males and females in birds. The physiological factors and genetic regulation mechanism affecting the color of sexual dimorphism plumages in birds have always attracted significant attention in research. Understanding the diversity of sexually dimorphic traits provides insights into the mating strategies of the sexes and their behavior, ecology, and evolution. Interestingly, the ASIP, MC1R, TYRP1, and BCO2 genes have been identified to play a potential role in the coloration of melanin and carotenoids in bird sexual dimorphism plumages, either by controlling the rate and type of melanin or carotene synthesis or degradation by exerting an effect on the pigment biosynthetic pathway. In this review, we systematically summarize the biological significance, the direct causes (chemical and physical color), and the influence of sex hormones in sexually dimorphic plumage coloration. We also investigate the molecular mechanism underlying the roles of some genes on sexual dimorphism coloration, thereby providing a reference for in-depth understanding on the formation mechanism(s) of sexual dimorphic coloration in birds.
Subject(s)
Feathers , Sex Characteristics , Animals , Birds/genetics , Birds/metabolism , Color , Feathers/metabolism , Female , Male , Melanins/genetics , Pigmentation/geneticsABSTRACT
Tabernaemontana corymbosa is a traditional folk medicine. In our research, six monoterpene indole N-oxide alkaloids and their parent alkaloids were obtained from the stem bark of T. corymbosa, including seven new alkaloids (1-7) and five known alkaloids (8-12). Their structures and absolute configurations were elucidated by extensive spectroscopy, quantum chemical calculations, and DP4+ probability analyses. The antimicrobial activity of the obtained compounds was evaluated, among which alkaloids 4, 8, 12 showed significant antimicrobial activity against Staphylococcus aureus with an MIC value of 6.25 µg/mL, while alkaloids 11, 12 showed moderate antimicrobial activity against Bacillus subtilis with an MIC value of 25 µg/mL.
Subject(s)
Alkaloids , Tabernaemontana , Alkaloids/pharmacology , Indole Alkaloids/chemistry , Indole Alkaloids/pharmacology , Indoles , Molecular Structure , Monoterpenes/pharmacology , Oxides , Tabernaemontana/chemistryABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium hypoglaucum (Kunmingshanhaitang in Chinese) is a plant of the genus Tripterygium which have been used as anti-tumor folk medicines in Yi and Bai ethnic groups in Yunnan province, China for hundreds of years. Terpenoids from T. hypoglaucum presented therapeutic effects on multiple tumors. But there were few studies about pancreatic cancer treatment of these terpenoids. Pancreatic cancer is an aggressive malignancy and lacked of specific drugs. Currently, anti-tumor drugs have poor therapeutic effect and prognosis for pancreatic cancer. AIM OF THE STUDY: This study aimed to elucidate the terpenoids from T. hypoglaucum and illuminate their anti-pancreatic cancer bioactivities. MATERIAL AND METHODS: Terpenoids were obtained through sequential chromatographic methods including silica gel, MCI gel, Sephadex LH-20, and preparative HPLC. Their structures were determined by HRESIMS, 1D and 2D NMR spectroscopic analysis. The absolute configurations of some new diterpenoids were assigned through comparison of experimental and calculated circular dichroism spectra. The cytotoxicity of isolates was measured using the MTT method on human pancreatic cancer cells SW1990. The effects on expressions of AKT, Erk1/2, p-AKT, p-Erk1/2, and Bax proteins in human pancreatic cancer cells SW1990 of these compounds were determined by western blotting assays. RESULTS: Eleven new (compounds 1â¼11) and fourteen known terpenoids (compounds 12â¼25) were isolated from the underground parts of T. hypoglaucum. These compounds were belonged to abietane diterpenoids, isoprimara diterpenoids, ent-kaurane diterpenoids, oleanane triterpenoids, and friedelane triterpenoids. Compounds 5, 7, 8, 9, 16, 18, 22, 24, and 25 possessed significant cytotoxicity against SW1990 cells with IC50 values of 19.28 ± 4.39, 9.91 ± 2.23, 27.32 ± 5.89, 56.43 ± 6.92, 0.16 ± 0.05, 0.58 ± 0.15, 0.81 ± 0.04, 0.48 ± 0.11, and 10.01 ± 1.39 µM respectively. After compounds 16, 22, and 24 been treated with the pancreatic cancer cells in medium and high doses, the protein expressions of AKT, p-AKT, Erk, and p-Erk were not remarkably reduced and the expressions of Bax protein were significantly increased. CONCLUSION: This study indicated that terpenoids from T. hypoglaucum could inhibit human pancreatic cancer cells SW1990. Especially, compounds 16, 22, and 24 possessed significant cytotoxicity against SW1990 cells with low IC50 values and could increase the expressions of Bax protein. These compounds shared a wide variety of structural characteristics which provided us more candidate molecules for the development of anti-pancreatic cancer drugs and further prompted us to investigate their anti-pancreatic mechanisms.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Pancreatic Neoplasms/drug therapy , Terpenes/pharmacology , Tripterygium/chemistry , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , Humans , Inhibitory Concentration 50 , Terpenes/administration & dosage , Terpenes/isolation & purification , bcl-2-Associated X Protein/geneticsABSTRACT
Tabernaecorymine A, an 18-normonoterpenoid indole alkaloid with conjugated (E)-3-aminoacrylaldehyde fragment was obtained from the stem bark of Tabernaemontana corymbosa. Its structure was elucidated by extensive spectroscopic data analyses, and further verified by ACD/structure elucidator, electronic circular dichroism (ECD) analyses and density functional theory (DFT) chemical shift predictions. The compound exhibited significant antibacterial bioactivity against Streptococcus dysgalactiae with an MIC value of 3.12 µg/mL, which is better than the plant drug berberine.
Subject(s)
Anti-Bacterial Agents/pharmacology , Plant Extracts/pharmacology , Secologanin Tryptamine Alkaloids/pharmacology , Tabernaemontana/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Bacillus subtilis/drug effects , Circular Dichroism , Escherichia coli/drug effects , Microbial Sensitivity Tests , Plant Bark/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Secologanin Tryptamine Alkaloids/chemistry , Secologanin Tryptamine Alkaloids/isolation & purification , Staphylococcus aureus/drug effects , Streptococcus/drug effectsABSTRACT
Background: Hepatocellular carcinoma (HCC) is a lethal malignancy lacking effective treatment. The Cyclin-dependent kinases 4/6 (CDK4/6) and PI3K/AKT signal pathways play pivotal roles in carcinogenesis and are promising therapeutic targets for HCC. Here we identified a new CDK4/6 and PI3K/AKT multi-kinase inhibitor for the treatment of HCC. Methods: Using a repurposing and ensemble docking methodology, we screened a library of worldwide approved drugs to identify candidate CDK4/6 inhibitors. By MTT, apoptosis, and flow cytometry analysis, we investigated the effects of candidate drug in reducing cell-viability,inducing apoptosis, and causing cell-cycle arrest. The drug combination and thermal proteomic profiling (TPP) method were used to investigate whether the candidate drug produced antagonistic effect. The in vivo anti-cancer effect was performed in BALB/C nude mice subcutaneously xenografted with Huh7 cells. Results: We demonstrated for the first time that the anti-plasmodium drug aminoquinol is a new CDK4/6 and PI3K/AKT inhibitor. Aminoquinol significantly decreased cell viability, induced apoptosis, increased the percentage of cells in G1 phase. Drug combination screening indicated that aminoquinol could produce antagonistic effect with the PI3K inhibitor LY294002. TPP analysis confirmed that aminoquinol significantly stabilized CDK4, CDK6, PI3K and AKT proteins. Finally, in vivo study in Huh7 cells xenografted nude mice demonstrated that aminoquinol exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil with the combination treatment showed the highest therapeutic effect. Conclusion: The present study indicates for the first time the discovery of a new CDK4/6 and PI3K/AKT multi-kinase inhibitor aminoquinol. It could be used alone or as a combination therapeutic strategy for the treatment of HCC.
ABSTRACT
OBJECTIVE: To develop a pirarubicin (THP) and vinorelbine (VRL) codelivery nano-micellar system (T+V-CS micelles) of pirarubicin (THP) and vinorelbine (VRL) by using chondroitin sulfate-cholesterol polymers (CS-Chol) and DSPE-mPEG 2000 and to evaluate the therapeutic efficacy of the codelivery nano-micelles in breast cancer treatment. METHODS: T+V-CS micelles were prepared by ultrasonic-dialysis method, and the physicochemical characterization were evaluated using multiple technological means. The anti-tumor efficacy of T+V-CS micelles in vitro was evaluated by MTT assay and cell cycle arrest analysis. Evaluation of the therapeutic effect of T+V-CS micelles in vivo was carried out on xenograft 4T1 murine breast cancer bearing BALB/c mice model. RESULTS: T+V-CS micelles displayed a nearly spherical shape when observed through transmission electron microscope. The particle size and polydispersity indexes (PDI) of T+V-CS micelles was (155.5±4.5) nm and 0.170±0.003 respectively, while the Zeta potential was (-23.0±0.9) mV. Meanwhile, T+V-CS micelles demonstrated high encapsulation efficiency of (81.87±2.56)% for THP and (87.54±2.82)% for VRL and a high overall drug loading efficiency of (10.20±1.20)%. In vitro and in vivo studies of the therapeutic efficacy of breast cancer showed that T+V-CS micelles had synergistic anti-tumor effect and induced increased G 2/M cell cycle arrest in 4T1 cells, which could significantly inhibit tumor growth and prolong survival compared with the therapeutic efficacy of micelles loaded with a single kind of drug or free drug solutions. CONCLUSION: The study showed that T+V-CS micelles had excellent anti-tumor effect, offering a reference to the clinical treatment of breast cancer.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Animals , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Cell Line, Tumor , Doxorubicin/analogs & derivatives , Drug Carriers , Female , Humans , Mice , Mice, Inbred BALB C , Micelles , Polyethylene Glycols/therapeutic use , Vinorelbine/therapeutic useABSTRACT
Alstoscholarisine K, an indole alkaloid with eight chiral carbons and featuring a novel 6/5/6/6/6/6/6/5 octacyclic architecture, was found to be specific to the gall-infected leaves of Alstonia scholaris. Its structure was elucidated by spectroscopy, computational analysis, and single-crystal X-ray diffraction. The unusual highly fused cage-like pyrrolo[1,2-a]pyrimidine structure with an additional -C4N unit is possibly derived from a combination of monoterpenoid indole and polyamine pathways. The fascinating compound exhibited significant antibacterial bioactivities by targeting cell membranes.
Subject(s)
Alstonia/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Indole Alkaloids/chemistry , Indole Alkaloids/pharmacology , Monoterpenes/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Crystallography, X-Ray , Indole Alkaloids/isolation & purification , Magnetic Resonance Spectroscopy , Molecular Structure , Monoterpenes/chemistry , Monoterpenes/isolation & purification , Plant Leaves/chemistryABSTRACT
Laggera pterodonta (DC.) Benth, a folk herb widely distributes in southwest China, especially in Yunnan Province, demonstrates anti-pathogenic microorganisms, anti-inflammatory, inhibition of Helicobacter pylori activities in vitro et al. Interestingly, previous studies have shown that pterodontic acid (1), a eudesmane-type sesquiterpene isolated from L. pterodonta (DC.), displays excellent selective antiviral activity to H1N1 subtype of influenza A virus. At the same time, our group also discovered that the antiviral activity of 1 was relatively close to that activity of post-marketed ribavirin. Therefore, we consider that the synthesis of pterodontic acid (1) derivatives and evaluation of their anti-influenza A virus (H1N1) activities is of potential clinical significance. In this manuscript, a series of pterodontic acid derivatives were prepared and demonstrated significantly improved anti-influenza A virus (H1N1) activities, providing more opportunities for the treatment of respiratory viral diseases.
Subject(s)
Antiviral Agents/pharmacology , Asteraceae/chemistry , Influenza A Virus, H1N1 Subtype/drug effects , Sesquiterpenes/pharmacology , Animals , Antiviral Agents/chemical synthesis , China , Dogs , Madin Darby Canine Kidney Cells , Molecular Structure , Sesquiterpenes/chemical synthesisABSTRACT
The composition of microorganisms in the gastrointestinal tract is closely related to the intestinal microenvironments and the exterior growth environments of host. In this study, 16S rDNA sequencing technology was adopted to investigate the influence of fermentation bed on the cecum microorganisms of ducks. Two feeding density treatment groups were set up, including group A (n = 4brids/m2) and group B (n = 6brids/m2). Samples were collected from the intermediate core fermentation layer (10-20 cm) of the fermented mattress materials and from the intestinal contents of ducks at 4, 6 and 8 weeks, respectively. Results showed that Bacteroidetes (20.12-27.17%) and Ruminococcaceae UCG-014 (2.97-10.1%) were the predominant microorganisms in duck cecum, while the Truepera (5.08-6.29%), Pricia (4.44-5.44%) and Luteimonas (3.62-4.99%) were the dominant microorganisms in fermentation mattress material. The cecum bacteria exhibited great difference among different growth periods of the ducks. Increasing the stocking density of ducks had a negative effect on the beneficial bacteria in the cecum. The microbial populations in fermentation mattress material were very different from that in the cecal. In summary, our findings can provide a scientific data for the rational use of fermentation bed feeding mode in poultry production.
Subject(s)
Animal Husbandry , Cecum , Ducks , Fermentation , Floors and Floorcoverings , Gastrointestinal Microbiome , Animal Husbandry/methods , Animals , Bacteria/genetics , Bacteria/metabolism , Bacteroidetes/genetics , Cecum/microbiology , Ducks/genetics , Ducks/microbiology , Gastrointestinal Microbiome/physiology , Gastrointestinal Tract/microbiology , RNA, Ribosomal, 16S/geneticsABSTRACT
OBJECTIVES: To explore the possible mechanism of Yunaconitine poisoning by studying the changes of urine metabolic profile in rats chronically poisoned by Yunaconitine via non-targeted metabolomics. METHODS: A rat model of Yunaconitine poisoning was established, and a metabolomics method based on UPLC-QTOF-MS technology was used to obtain the urine metabolic profile. Principal component analysis (PCA), orthogonal projections to latent structures-discriminant analysis (OPLS-DA), variable importance in projection (VIP) value greater than 1, fold change (FC) value greater than 3 or less than 0.33 and P value less than 0.05 were used to screen potential biomarkers related to the toxicity of Yunaconitine. The metabolic pathway analysis was performed through the MetaboAnalyst website and pathological changes of related tissues were observed. RESULTS: Sixteen potential biomarkers including L-isoleucine were screened, which mainly involved six metabolic pathways including the biosynthesis and degradation of valine, leucine and isoleucine, pentose and glucuronate interconversions, and propanoate metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism. Pathological studies showed that rat toxic change in nervous system, liver and cardiac caused by Yunaconitine. CONCLUSIONS: Yunaconitine may cause neurotoxicity, hepatotoxicity and cardiotoxicity by affecting amino acid and glucose metabolism.
Subject(s)
Metabolome , Metabolomics , Aconitine/analogs & derivatives , Animals , Biomarkers/metabolism , Chromatography, High Pressure Liquid , RatsABSTRACT
AIM: To investigate the protective effects and possible mechanisms of action of resina draconis (RD) on acute liver injury and liver regeneration after 2/3 partial hepatectomy (PH) in mice. METHODS: 2/3 PH was used to induce acute liver injury. Mice were divided into three groups: sham, vehicle + 2/3 PH, and RD + 2/3 PH. Resina draconis was administered intragastrically after 2/3 PH into the RD + 2/3 PH group, and the same volume of vehicle (1% sodium carboxymethyl cellulose) was injected into the vehicle + 2/3 PH group and sham group mice. The index of liver to body weight (ILBW) and proliferating cell nuclear antigen (PCNA) were assayed to evaluate liver regeneration. Blood and liver tissues were collected for serological and western blotting analysis. RESULTS: Resina draconis protected against 2/3 PH-induced acute severe liver injury and promoted liver regeneration as shown by significantly increased ILBW compared with that of controls. 2/3 PH increased serum AST and ALT levels, which were significantly decreased by RD treatment, while 2/3 PH decreased serum TP and ALB, which were increased by RD treatment. In the RD + 2/3 PH group, PCNA expression was significantly increased compared with the 2/3 PH group. Further, hepatocyte growth factor (HGF), TNFα, and EGFR levels were increased in the RD group at postoperative days 2 and 4 compared with the those in the 2/3 PH group. CONCLUSION: Our results suggest that RD ameliorates acute hepatic injury and promotes liver cell proliferation, liver weight restoration, and liver function after 2/3 PH, probably via HGF, TNFα, and EGFR signaling.
ABSTRACT
Spatial learning and memory are typically assessed to evaluate hippocampus-dependent cognitive and memory functions in vivo. Protein phosphorylation and dephosphorylation by kinases and phosphatases play critical roles in spatial learning and memory. Here we report that the Wip1 phosphatase is essential for spatial learning, with knockout mice lacking Wip1 phosphatase exhibiting dysfunctional spatial cognition. Aberrant phosphorylation of the Wip1 substrates p38, ATM, and p53 were observed in the hippocampi of Wip1-/- mice, but only p38 inhibition reversed impairments in long-term potentiation in Wip1-knockout mice. p38 inhibition consistently ameliorated the spatial learning dysfunction caused by Wip1 deficiency. Our results demonstrate that deletion of Wip1 phosphatase impairs hippocampus-dependent spatial learning and memory, with aberrant downstream p38 phosphorylation involved in this process and providing a potential therapeutic target.
Subject(s)
Memory , Protein Phosphatase 2C/physiology , Spatial Learning , Animals , Hippocampus/enzymology , Hippocampus/physiology , Long-Term Potentiation , Male , Mice, Knockout , Morris Water Maze Test , Phosphorylation , Protein Phosphatase 2C/genetics , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Human behavior has a major impact on the spread of the disease during an epidemic. At the same time, the spread of disease has an impact on human behavior. In this paper, we propose a coupled model of human behavior and disease transmission, take into account both individual-based risk assessment and neighbor-based replicator dynamics. The transmission threshold of epidemic disease and the stability of disease-free equilibrium point are analyzed. Some numerical simulations are carried out for the system. Three kinds of return matrices are considered and analyzed one by one. The simulation results show that the change of human behavior can effectively inhibit the spread of the disease, individual-based risk assessments had a stronger effect on disease suppression, but also more hitchhikers. This work contributes to the study of the relationship between human behavior and disease epidemics.