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Objectives: Based on the data during the outbreak of COVID-19 in Wuxi city in China, we explored the relationship between laboratory variables and clinical features in patients hospitalized with COVID-19 after non-mRNA vaccination, and attempted to identify the significant impact of vaccination and COVID-19 infection on humans. Methods: A retrospective observational cohort study was carried out. Patients who received non-mRNA COVID-19 vaccines and were hospitalized with COVID-19 between June 28, 2022, and July 24, 2022 were included. The correlation between different vaccine statuses, the time to negative PCR test, and biochemical parameters were investigated. Results: All patients had a mild COVID-19 disease. The number of vaccine doses exerted no effects on the time to negative PCR test (P = 0.559). No differences were evident among inactivated, adenoviral-vectored, and recombinant subunit vaccines in the time to negative PCR test.Patients who just received one dose had significantly lower blood glucose levels than those who received three doses (P = 0.024), whereas two doses had no effect on blood glucose levels (one dose vs. two doses, P = 0.223; two doses vs. three doses, P = 0.457).Body temperature (ß = 0.168, P = 0.011) and the percentage of lymphocytes (ß = -0.219, P = 0.001) were substantially correlated with the time to COVID-19 negative PCR test. The prolonged stay was linked to a rise in GOT that fell within the usual range (P = 0.025).The percentage of lymphocytes (P = 0.007) and serum potassium (P = 0.004) were concordant with the marked change in body temperature. Conclusions: The dose and type of vaccination had no effect on the time to COVID-19 negative PCR test in patients with mild COVID-19. Comparing the first dose with the booster dose, the blood glucose levels increased within the normal range. The period at which the COVID-19 nucleic acid turned negative correlated with body temperature, the proportion of lymphocytes, GOT, and serum potassium.
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Microbial communities are the key component to maintaining the structure and function of forest soil ecosystems. The vertical distribution of bacterial communities on the soil profile has an important impact on forest soil carbon pools and soil nutrient cycling. Using Illumina MiSeq high-throughput sequencing technology, we analyzed the characteristics of bacterial communities in the humus layer and 0-80 cm soil layer of Larix principis-rupprechtii in Luya Mountain, China, to explore the driving mechanisms affecting the structure of bacterial communities in soil profiles. The results showed that the α diversity of bacterial communities decreased significantly with increasing soil depth, and community structure differed significantly across soil profiles. The relative abundance of Actinobacteria and Proteobacteria decreased with increased soil depth, whereas the relative abundance of Acidobacteria and Chloroflexi increased with the increase in soil depth. The results of RDA analysis showed that soil NH+4, TC, TS, WCS, pH, NO-3, and TP were important factors determining the bacterial community structure of the soil profile, among which soil pH had the most significant effect. Molecular ecological network analysis showed that the complexity of bacterial communities in the litter layer and subsurface soil (10-20 cm) was relatively high, whereas the complexity of bacterial communities in deep soil (40-80 cm) was relatively low. Proteobacteria, Acidobacteria, Chloroflexi, and Actinobacteria played important roles in the structure and stability of soil bacterial communities in Larch. The species function prediction of Tax4Fun showed a gradual decline in microbial metabolic capacity along the soil profile. In conclusion, soil bacterial community structure showed a certain distribution pattern along the vertical profile of soil, the community complexity gradually decreased, and the unique bacterial groups of deep soil and surface soil were significantly different.
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Actinobacteria , Larix , Microbiota , Bacterias , Bosques , Acidobacteria , Proteobacteria , SueloRESUMEN
To reveal the assembly mechanisms of soil protozoan community in subalpine forest ecosystems, we analyzed the composition and diversity of protozoan communities and their drivers at the six strata (the litter profile, humus profile, 0-10 cm, 10-20 cm, 20-40 cm and 40-80 cm) of soil profiles in subalpine Larix principis-rupprechtii forest in Luya Mountain using Illumina Miseq high-throughput sequencing technology. The results showed that protozoa in the soil profiles belonged to 335 genera, 206 families, 114 orders, 57 classes, 21 phyla, and 8 kingdoms. There were five dominant phyla (relative abundance >1%) and 10 dominant families (relative abundance >5%). The α diversity decreased significantly with increasing soil depth. Results of PCoA analysis showed that the spatial composition and structure of protozoan community differed significantly across soil depths. The results of RDA analysis showed that soil pH and soil water content were important factors driving protozoan community structure across soil profile. Null model analysis suggested that the heterogeneous selection dominated the processes of protozoan community assemblage. Molecular ecological network analysis revealed that the complexity of soil proto-zoan communities decreased continuously with increasing depth. These results elucidate the assembly mechanism of soil microbial community in subalpine forest ecosystem.
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Larix , Microbiota , Humanos , Suelo , Bosques , China , Microbiología del SueloRESUMEN
Although excessive salt consumption appears to hasten intestinal aging and increases susceptibility to cardiovascular disease, the molecular mechanism is unknown. In this study, mutual validation of high salt (HS) and aging fecal microbiota transplantation (FMT) in C56BL/6 mice was used to clarify the molecular mechanism by which excessive salt consumption causes intestinal aging. Firstly, we observed HS causes vascular endothelial damage and can accelerate intestinal aging associated with decreased colon and serum expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and increased malondialdehyde (MDA); after transplantation with HS fecal microbiota in mice, vascular endothelial damage and intestinal aging can also occur. Secondly, we also found intestinal aging and vascular endothelial damage in older mice aged 14 months; and after transplantation of the older mice fecal microbiota, the same effect was observed in mice aged 6-8 weeks. Meanwhile, HS and aging significantly changed gut microbial diversity and composition, which was transferable by FMT. Eventually, based on the core genera both in HS and the aging gut microbiota network, a machine learning model was constructed which could predict HS susceptibility to intestinal aging. Further investigation revealed that the process of HS-related intestinal aging was highly linked to the signal transduction mediated by various bacteria. In conclusion, the present study provides an experimental basis of potential microbial evidence in the process of HS related intestinal aging. Even, avoiding excessive salt consumption and actively intervening in gut microbiota alteration may assist to delay the aging state that drives HS-related intestinal aging in clinical practice.
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BACKGROUND: This study was designed to provide additional insights into the incidence of appendectomy complications in patients with appendicitis. METHODS: A total of 619 patients who underwent appendectomy for appendicitis between 2014 and 2020 were recruited. Preoperative patient data and details of postoperative complications were collected. Comparisons between simple and complex appendicitis were obtained via univariate and multivariate analyses of the outcomes. RESULTS: Simple and complex appendicitis was diagnosed in 192 and 427 patients, respectively. Twenty-eight patients with simple appendicitis developed complications, and 14 of these were infectious complications. In patients with complex appendicitis, 65 patients developed complications, and 55 of these were infectious complications. Infectious complications were identified as the largest proportion of complications. The significant risk factor for infectious complications in simple appendicitis was American Society of Anesthesiologists (ASA) grade [odds ratio (OR) =7.843, 95% confidence interval (CI): 1.987-30.955, P=0.003]. ASA grade (OR =1.992, P=0.032) and positive bacterial culture (OR =4.019, 95% CI: 1.809-8.933, P=0.001) were significantly related to infectious complication in complex appendicitis. CONCLUSIONS: This study showed that appendectomy is not always a routine operation with few complications. There was a relatively high rate of complications in patients with appendicitis, which were mostly infectious complications. A higher ASA grade correlated with infectious complication. In some cases of complex appendicitis, patients with positive bacterial culture may have had a greater risk of infectious complications.
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Apendicectomía , Apendicitis , Apendicectomía/efectos adversos , Apendicitis/cirugía , Humanos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied. METHODS: Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was detected using flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cell proliferation and p65 expression was examined using flow cytometry. P65 nuclear translocation was analyzed using IF. IL-10, TGF-ß, IFN-γ, perforin and granzyme B were detected using real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with a CD137 agonist in vitro. Apoptosis of primary GC cells was detected using flow cytometry. RESULTS: Our data demonstrated that GC tumors showed characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. The CD137 agonist promoted CD8+ T cell proliferation and increased the secretion of IFN-γ, perforin and granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that the CD137 agonist induced NF-κB nuclear translocation in CD8+ T cells. CONCLUSION: Our results demonstrated that a CD137 agonist induced primary GC cell apoptosis by enhancing CD8+ T cells via activation of NF-κB signaling.
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The level of sun ultraviolet ray reaching the surface of the earth is increasing severely due to the rapid development of the society and environmental destruction. Excessive exposure to ultraviolet radiation causes skin damage and photoaging. Therefore, it is emerged to develop effective sunscreen to prevent ultraviolet-induced skin damage. This study was aimed at investigating the effects of Coenzyme Q10 (CoQ10) sunscreen on the prevention of ultraviolet B radiation- (UVB-) induced mouse skin damage. Three-month-old female mice were used, and they were randomly divided into four groups: control, model, CoQ10, and titanium dioxide (TiO2; positive control) groups. Our results showed that body weight, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and DNA (cytosine-5)-methyltransferase 1 (DNMT1) protein expression were significantly decreased, while malondialdehyde (MDA) activity and metalloproteinase-1 (MMP-1) level were increased in UVB-treated mice. Besides, the stratum corneum was shed from the skin surface in the model group compared with the control group. In contrast, CoQ10 sunscreen prevented from UVB-induced skin damage, as well as reversing SOD, GSH-Px, and MDA activities, and MMP-1 and DNMT1 levels. Taken together, the current study provided further evidence on the prevention of UVB-induced skin damage by CoQ10 and its underlying mechanisms.
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Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Protectores Solares/farmacología , Ubiquinona/análogos & derivados , Rayos Ultravioleta/efectos adversos , Animales , Catalasa/metabolismo , Epidermis/efectos de los fármacos , Epidermis/metabolismo , Femenino , Glutatión Peroxidasa/metabolismo , Malondialdehído/metabolismo , Ratones , Modelos Animales , Estrés Oxidativo/efectos de los fármacos , Piel/metabolismo , Superóxido Dismutasa/metabolismo , Ubiquinona/farmacologíaRESUMEN
Understanding the coagulation process is critical to developing treatments for trauma and coagulopathies. Clinical studies on tranexamic acid (TXA) have resulted in mixed reports on its efficacy in improving outcomes in trauma patients. The largest study, CRASH-2, reported that TXA improved outcomes in patients who received treatment prior to 3 hours after the injury, but worsened outcomes in patients who received treatment after 3 hours. No consensus has been reached about the mechanism behind the duality of these results. In this paper we use a computational model for coagulation and fibrinolysis to propose that deficiencies or depletions of key anti-fibrinolytic proteins, specifically antiplasmin, a1-antitrypsin and a2-macroglobulin, can lead to worsened outcomes through urokinase-mediated hyperfibrinolysis.
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Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Ácido Tranexámico/uso terapéutico , Activador de Plasminógeno de Tipo Uroquinasa/genética , Heridas y Lesiones/tratamiento farmacológico , Antifibrinolíticos/uso terapéutico , Coagulación Sanguínea/genética , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/genética , Trastornos de la Coagulación Sanguínea/patología , Simulación por Computador , Fibrina/genética , Tiempo de Lisis del Coágulo de Fibrina , Fibrinolisina/genética , Fibrinólisis/efectos de los fármacos , Hemorragia/sangre , Hemorragia/tratamiento farmacológico , Hemorragia/genética , Humanos , Proteínas de la Membrana/genética , Mortalidad , alfa 2-Macroglobulinas Asociadas al Embarazo/genética , Trombina/genética , Trombina/metabolismo , Heridas y Lesiones/sangre , Heridas y Lesiones/genética , Heridas y Lesiones/patología , alfa 1-Antitripsina/genéticaRESUMEN
Sinibotia lani, a new botiid loach is described from the Zuojiang River, located in Guangxi Autonomous Region, China. The species differs from other members of Sinibotia by a combination of the following morphological characters: body depth 17.5-21.1% SL; snout length shorter than postorbital length of head; eye diameter 10.2-13.2% HL; interorbital width 16.0-18.6% HL; suborbital spine reaching or extending beyond postorbital margin of eye; lower lip with pair of fleshy button-like clusters of papillae; dorsal-fin origin opposite to pelvic-fin origin, pelvic fin not reaching anus; includes six dark vertical bars on the body. A key to the species of Sinibotia is provided.
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Cipriniformes , Animales , China , RíosRESUMEN
A new spined loach of the genus Cobitis Linnaeus is described from the Buquan River, located in Guangxi Zhuang Autonomous Region, China. The species differs from other members of Cobitis in China by a combination of morphological characters, none of them unique: body depth 14.3â18.4% SL; lamina circularis long and knife-shaped; Gambetta zones present on the dorsolateral sides of the body (L1âL5); 8â11 large transverse elongated blotches on L5; 9â12 large transverse elongated blotches on L1; maxillary barbels longer than eye diameter; 4â5 narrow rows of dark spots on the caudal fin; caudal fin with 14 branched rays; a rectangular spot slightly smaller than eye diameter on the upper side of caudal fin base; and caudal-peduncle depth 79.5â93.1% its length.
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Escarabajos , Cipriniformes , Animales , China , RíosRESUMEN
Spinal disorders often require surgical treatment called spinal fusion to restore a stabilized spine where bone grafts are implanted for the fusion of adjacent vertebras. In this study, we developed a bioactive composite scaffold incorporated with salvianolic acid B (SB), an active component extracted from Danshen. This study aimed to evaluate the effects of SB-incorporated porous scaffold on spinal fusion models. The composite scaffolds composed of poly (lactic-co-glycolic acid) and tricalcium phosphate (PLGA/ß-TCP) were fabricated with low-temperature rapid prototyping technique, which incorporated SB at low (SB-L), middle (SB-M), high (SB-H) doses, and pure PLGA/ß-TCP as blank control (Con). The release profile of SB from the scaffolds was determined by high performance liquid chromatography. Osteoconductive and osteoinductive properties of the scaffolds were reflected by the osteogenic differentiation ability of rat primary mesenchymal stem cells. The angiogenesis was determined by the forming of tube-like structures resembling capillaries using endothelial cell line (EA hy9.26). A well-established spinal fusion model was used to evaluate the in vivo bony fusion. Animals were transplanted with scaffolds, or autografts from iliac crest as positive controls. Micro-computed tomography (CT) analysis, CT-based angiography, manual palpation test, histomorphometry, and histology were performed after 8 weeks of transplantation. Results revealed that incorporated SB was steadily released from the scaffolds. The aliquot of released SB promoted osteogenesis and angiogenesis in vitro in a dose-dependent manner. In animal study, a dose-dependent effect of SB on new bone formation, mineral apposition rate, and vessel density within the scaffold were demonstrated. Manual palpation test showed little numerical improvement in fusion rate when compared with the blank controls. In summary, our results suggested that SB-incorporated PLGA/ß-TCP composite scaffold could enhance bony fusion through the promotion of osteogenesis and angiogenesis.
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Benzofuranos/farmacología , Fosfatos de Calcio/química , Neovascularización Fisiológica/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ácido Poliglicólico/química , Fusión Vertebral , Andamios del Tejido/química , Animales , Materiales Biocompatibles/farmacología , Diferenciación Celular/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Modelos Animales de Enfermedad , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/patología , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/ultraestructura , Ratas Sprague-Dawley , Cicatrización de Heridas/efectos de los fármacos , Microtomografía por Rayos XRESUMEN
Osteoporosis (OP) is a systemic skeletal disorder, manifesting with a reduction in bone mass and deterioration of the microarchitecture. Mesenchymal stem cells (MSCs) have an innate ability to differentiate into several cell types, including osteoblasts (OB). Ginsenoside Rb1 (GRb1) is an ethanol extract from ginseng and contains a highly concentrated form of ginsenoside. GRb1 shows extensive beneficial health effects such as anti-oxidative and anti-inflammatory functions, modulating the immune system and inhibiting osteoclastogenesis. We hypothesized that GRb1 can promote MSC differentiation into OBs and inhibit bone loss. In the present study, we aimed to address two questions: (1) Will GRb1 have a positive effect on osteogenic differentiation of MSCs? and (2) Will GRb1 halt bone loss in ovariectomized (OVX) rats? We investigated the effects of GRb1 on viability and osteogenic differentiation of rat mesenchymal stem cells (rMSCs). Our results showed that GRb1 at concentrations of 10-8 M and 10-6 M can increase alkaline phosphatase activity, mineralization and the expression of osteogenic related proteins, such as osteopontin and osteoprotegerin, while incubating rMSCs with osteogenic induction medium and GRb1. Adding GRb1 into the medium can prevent rMSCs from Oxidative damage at the concentration of 25µM H2O2. Furthermore, 40 4-month-old rats were assigned to 5 groups(8 rats per group): the basal group, the sham group, the OVX group, the high dose of GRb1 group (6 mg/kg/day) and the low dose of GRb1 group (3 mg/kg/day). Rats recrived treatment 3days after surgery and last for 14 weeks. Examinations included serum analysis, mechanical testing, Masson-Goldner trichrome staining and bone histomorphometry analysis. The results showed that OVX can lead to dyslipidemia and excessive oxidative stress, whereas GRb1 cannot significantly halt dyslipidemia and excessive oxidative stress in OVX rats. In addition, the bone density of the lumbar vertebra and femur were decreased significantly in the OVX rats, and GRb1 could not inhibit bone loss. Bone histomorphometry analysis showed that the number and width of bone trabecula of the tibia were reduced in OVX rats, and GRb1 could not prevent their occurrence. A bone biomechanics assay showed that GRb1 cannot improve the ability of bone structure to resist fracture of the femur in OVX rats. The current study demonstrated that GRb1 has an obvious effect on osteogenic differentiation in rMSCs but no obvious effect on bone loss in OVX rats. These findings indicate GRb1 has a positive effect on rMSCs but does not have an effect on bone loss in OVX rats at the concentration we used.
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Conservadores de la Densidad Ósea/farmacología , Ginsenósidos/farmacología , Osteoporosis/tratamiento farmacológico , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ovariectomía , Ratas Sprague-Dawley , Organismos Libres de Patógenos Específicos , Insuficiencia del TratamientoRESUMEN
Sepsis-induced skeletal muscle wasting may lead to various severe clinical consequences. Understanding molecular mechanisms of the regulation of the loss of skeletal muscle mass in septic patients remains a significant clinical challenge. The current study was conducted to establish septic mice models to explore the relationship between microRNA (miR)-351 and the transcription element apical (TEA) domain transcription factor (Tead)-4 gene and to investigate its effects on the skeletal muscle through mediating the Hippo signaling pathway in mice with acute sepsis. A total of 60 mice were collected to establish mouse models of acute sepsis. The positive expression rate of Tead-4 and the apoptotic index (AI) were measured. A dual-luciferase reporter gene assay was conducted to verify the targeting relationship between miR-351 and Tead-4. Furthermore, the muscle fiber diameter (MFD) and area (MFA) and the content of 3-methylhistidine (3-MH) and tyrosine (Tyr) were assessed. The expression levels of miR-351, p38-MAPK, Yes-associated protein, Tead-4, B-cell lymphoma X protein (Bax), and Caspase-3 were determined with quantitative RT-PCR and Western blot analysis. Finally, cell viability, apoptosis, and levels of inflammatory factors, including IL-1ß, IL-6, IGF-1, TNF-α, and monocyte chemoattractant protein-1 were detected by 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and ELISA. Initially, Tead-4 protein expression was higher in skeletal muscle tissues of mice with acute sepsis. Tead-4 was identified to negatively regulate miR-351. Upregulation of miR-351 increased MFA and MFD, muscle weight water content, Bcl-2 expression levels, and cell viability. Up-regulation of miR-351 reduced AI; 3-MH and Tyr content; positive expression of Tead-4 protein; the expression levels of p38-MAPK, Yap, Tead-4, Bax, and Caspase-3; apoptosis; and inflammatory responses. The current study demonstrated that up-regulation of miR-351 inhibits the degradation of skeletal muscle protein and the atrophy of skeletal muscle in mice with acute sepsis by targeting Tead-4 through suppression of the Hippo signaling pathway. Thus, miR-351 overexpression may be a future therapeutic strategy for acute sepsis.-Zhang, L.-N., Tian, H., Zhou, X.-L., Tian, S.-C., Zhang, X.-H., Wu, T.-J. Upregulation of microRNA-351 exerts protective effects during sepsis by ameliorating skeletal muscle wasting through the Tead-4-mediated blockade of the Hippo signaling pathway.
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The onset of acute traumatic coagulopathy in trauma patients exacerbates hemorrhaging and dramatically increases mortality. The disease is characterized by increased localized bleeding, and the mechanism for its onset is not yet known. We propose that the fibrinolytic response, specifically the release of tissue-plasminogen activator (t-PA), within vessels of different sizes leads to a variable susceptibility to local coagulopathy through hyperfibrinolysis which can explain many of the clinical observations in the early stages from severely injured coagulopathic patients. We use a partial differential equation model to examine the consequences of vessel geometry and extent of injury on fibrinolysis profiles. In addition, we simulate the efficacy of tranexamic acid treatment on coagulopathy initiated through endothelial t-PA release, and are able to reproduce the time-sensitive nature of the efficacy of this treatment as observed in clinical studies.
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Coagulación Intravascular Diseminada , Fibrinólisis , Modelos Cardiovasculares , Activador de Tejido Plasminógeno/metabolismo , Ácido Tranexámico/farmacología , Heridas y Lesiones , Enfermedad Aguda , Coagulación Intravascular Diseminada/tratamiento farmacológico , Coagulación Intravascular Diseminada/patología , Coagulación Intravascular Diseminada/fisiopatología , Humanos , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/patología , Heridas y Lesiones/fisiopatologíaRESUMEN
A new cave-dwelling fish, Triplophysa anshuiensis, is described here based on specimens collected from a karst cave in Guangxi Zhuang Autonomous Region, China, interconnected with the Hongshui River system, a tributary of the Xijiang River in the Pearl River (Zhu Jiang) Drainage. The species can be distinguished from its congeners by a combination of morphological characters. A key to the cave-dwelling species of Triplophysa in the Xijiang River is provided.
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DESCRIPTION: Two new ruthenium(II) complexes containing guanidinium as ligands, [Ru(dip)2 (L1)]3+ (Ru1) and [Ru(dip)2(L2)]3+ (Ru2) (dip=4,7-diphenyl-1,10-phenanthroline; L1=1-(4-(1H-imidazo[4,5- f][1,10]phenanthrolin-2-yl)phenyl)guanidine cation; L2 = 1-(3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl) phenyl)guanidine cation) have been synthesized and characterized. Both complexes display higher cytotoxicity against several cancer cell lines compared to cisplatin and are less cytotoxic on the nontumorigenic cell line LO2. Intracellular distribution studies show that these complexes are selectively localized in the cytoplasm. FINDINGS: Further analysis revealed that Ru1 and Ru2 had no obvious effects on the cell cycle and induced apoptosis in HeLa cells via the mitochondrial pathway, which involved reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and Bcl-2 family member activation. Taken together, the two complexes have the potential to be utilized as anticancer agents.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Complejos de Coordinación/farmacología , Guanidina/farmacología , Rutenio/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Guanidina/química , Humanos , Ligandos , Estructura Molecular , Rutenio/química , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
The aim of the present study was to investigate the effect of salvianolic acid B (Sal B) and danshensu (DSU) on the osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) and the mechanisms of the effects. The osteogenic differentiation of MSCs in culture was assessed by measuring alkaline phosphatase (ALP) activity, osteocalcin (OCN) production, nitric oxide (NO) production and the mRNA expression levels of osteoprotegerin (OPG) and its ligand by MSCs. MSCs were successfully induced to differentiate into osteoblasts and adipocytes. Sal B and DSU increased the ALP activity and the production of OCN in the absence of an ossification inducer. The increase in ALP activity was more pronounced when induction was combined with the osteogenic inducer, Sal B, which enhanced the expression of OPG; however, Sal B reduced the expression of receptor activator of nuclear factor-κB ligand (RANKL) by MSCs. Sal B reversed the inhibitory effect of N-nitro L-arginine methylester on the MSCs and increased ALP activity, OCN content and the OPG/RANKL ratio. Based on these results, it was concluded that Sal B increases the osteogenic differentiation of MSCs, most likely by regulating the nitric oxide pathway.
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Chemotherapy is used as a primary approach in cancer treatment after routine surgery. However, chemo-resistance tends to occur when chemotherapy is used clinically, resulting in poor prognosis and recurrence. Currently, Chinese medicine may provide insight into the design of new therapies to overcome chemo-resistance. Furanodiene, as a heat-sensitive sesquiterpene, is isolated from the essential oil of Rhizoma Curcumae. Even though mounting evidence claiming that furanodiene possesses anti-cancer activities in various types of cancers, the underlying mechanisms against chemo-resistant cancer are not fully clear. Our study found that furanodiene could display anti-cancer effects by inhibiting cell viability, inducing cell cytotoxicity, and suppressing cell proliferation in doxorubicin-resistant MCF-7 breast cancer cells. Furthermore, furanodiene preferentially causes apoptosis by interfering with intrinsic/extrinsic-dependent and NF-κB-independent pathways in doxorubicin-resistant MCF-7 cells. These observations also prompt that furanodiene may be developed as a promising natural product for multidrug-resistant cancer therapy in the future.
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CONTEXT: Hyperoside was used to treat cardiovascular disease for many years in China. It was shown great effect on regulation of lipid metabolism. But there is lack of reports about the effects of hyperoside on liver diseases. OBJECTIVE: This study was designed to investigate the potentially protective effects of hyperoside and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation on Carbon Tetrachloride (CCl4)-induced chronic liver fibrosis in mice. MATERIALS AND METHODS: All mice were divided into six groups containing 6 animals per group. Mice in different group were given relative processing for 4 weeks. The potentially protective effects of hyperoside on CCl4-induced chronic liver fibrosis in mice were depicted histologically and biochemically. RESULTS: CCl4 administration caused a marked increase in the levels of serum aminotransferases, serum monoamine oxidase (MAO) and lipid peroxidation, MAO in mouse liver homogenates. Also decreased activities of cellular antioxidant defense enzymes were found after CCl4 exposure. Histopathological changes induced by CCl4 including regenerative nodules, deteriorated parenchyma. Hyperoside and silymarin reduced these changes and attenuated the pathological effects of CCl4 induced liver injury. In addition, hyperoside exhibited antioxidant effects in vitro. In Western blot analysis, the protein level of Nrf2 was downregulated after CCl4 administration and reversed by hyperoside. CONCLUSION: Hyperoside increased the activity of the antioxidant and phase II detoxifying enzymes through the activation of Nrf2 nuclear translocated in the CCl4-induced liver fibrosis mice.