RESUMEN
Alzheimer's disease (AD) is a degenerative dementia illness that causes atrophy of the temporal and frontal lobes of the cerebral cortex. Linggui Zhugan (LGZG), a classic Chinese herbal formula, was initially recognized as a safe and effective treatment of cardiovascular diseases for long history. This study intended to assess the effects and the molecular mechanism of LGZG on AD progress. C57BL/6 mice were divided into six groups: normal mice, amyloid precursor protein/presenilin 1 (APP/PS1) mice (model group), positive control group (model mice treated with donepezil), high, medium and low LGZG group (model mice treated with 7g/kg/d, 3.5g/kg/d or 1.75g/kg/d LGZG respectively). Water maze results showed that the escape latency and path length of high and medium LGZG groups declined compared to the model mice, the decline degree was dose-dependent. The hippocampal slices of six groups were analyzed by Nissl-staining, Perls' iron staining and immunofluorescence assay. The results indicated LGZG could restore morphological anomalies and alleviate iron deposition of AD mice, and the GXP4 positive cells increased significantly. The MDA, Fe2+ and GSH were measured by biochemical testing, whose results illustrated that LGZG could normalize MDA, Fe2+ and GSH levels in AD model compared to un-treated APP/PS1 model. The higher dose of LGZG the mice received, the more intensive effects on those levels of molecules. Western blot results showed that LGZG could affect NeuN, AMPK, p53, SLC7A11 and GPX4 levels in the hippocampus of AD model, which was all proteins related to AMPK pathway. In conclusion, LGZG has a neuroprotective effect on AD through AMPK pathway by alleviating oxidative stress and ferroptosis.
Asunto(s)
Enfermedad de Alzheimer , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Hipocampo , Ratones Endogámicos C57BL , Fármacos Neuroprotectores , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Ratones , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Proteínas Quinasas Activadas por AMP/metabolismo , Transducción de Señal/efectos de los fármacos , Masculino , Ratones Transgénicos , Estrés Oxidativo/efectos de los fármacos , Neuroprotección/efectos de los fármacos , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Aprendizaje por Laberinto/efectos de los fármacosRESUMEN
The root rot disease caused by Fusarium oxysporum f. sp. ginseng is one of the most destructive diseases of ginseng, an economically important herb. However, little is known about the pathogen's toxin biosynthesis or the molecular mechanisms regulating infection of ginseng. In this study we identified and functionally characterized the FoRSR1 gene that encodes a Ras-related (RSR) small GTPase homologous to yeast Rsr1 in F. oxysporum f. sp. ginseng. Disruption of FoRSR1 resulted in a significant reduction in mycelial dry weight in liquid cultures, although vegetative growth rate was not affected on culture plates. Notably, the Forsr1 mutant exhibited blunted and swollen hyphae with multi-nucleated compartments. It produced fewer and morphologically abnormal conidia and was defective in chlamydospore formation. In infection assays with ginseng roots, the Forsr1 mutant was significantly less virulent and caused only limited necrosis at the wounding sites. Deletion of FoRSR1 also affected pigmentation, autophagy, and production of fusaric acid. Furthermore, the expression of many candidate genes involved in secondary metabolism was significantly downregulated in the mutant, suggesting that FoRSR1 is also important for secondary metabolism. Overall, our results indicated that FoRSR1 plays important roles in conidiation, vacuolar morphology, secondary metabolism, and pathogenesis in F. oxysporum f. sp. ginseng.
Asunto(s)
Fusarium , Panax , Virulencia/genética , Ácido Fusárico/metabolismo , Enfermedades de las Plantas , Saccharomyces cerevisiaeRESUMEN
OBJECTIVE: The aim of this study was to investigate the incidence of chromosome anomalies in different types of congenital gastrointestinal obstruction and assess pregnancy outcomes of fetuses with congenital gastrointestinal obstruction. METHODS: A total of 64 cases with gastrointestinal obstruction between January 2014 and December 2020 were enrolled in this study. They were divided into three groups according to sonographic images. Group A: isolated upper gastrointestinal obstruction; Group B: isolated lower gastrointestinal obstruction; Group C: non-isolated gastrointestinal obstruction. The rate of chromosome anomalies in different groups was calculated. Pregnant women with amniocentesis were followed up by medical records and telephone. The follow-up included pregnancy outcomes and development of the live born infants. RESULT: From January 2014 to December 2020, there were 64 fetus with congenital gastrointestinal obstruction underwent chromosome microarray analysis(CMA), the overall detection rate of CMA testing was 14.1%(9/64). The detection rate of Group A, B and C were 16.2%, 0 and 25.0% respectively. 9 fetuses with abnormal CMA results were all terminated. Among 55 fetuses with normal chromosomes, 10(18.2%) fetuses were not found to have any gastrointestinal obstruction after birth. 17(30.9%) fetuses were diagnosed with gastrointestinal obstruction and underwent surgical treatment after birth, one of which had lower gastrointestinal obstruction combined with biliary obstruction and died due to liver cirrhosis. 11(20.0%) pregnancy were terminated due to multiple abnormalities. 5(9.1%) fetuses were intrauterine death. 3(5.5%) fetuses were neonatal deaths. 9(16.4%) fetuses were lost to follow-up. CONCLUSION: It is crucial to understand whether the gastrointestinal tract abnormality is isolated or associated to other findings. The risk of chromosomal abnormalities in fetuses with isolated lower gastrointestinal obstruction is lower than upper gastrointestinal obstruction. While genetic abnormalities excluded, a promising prognosis is expected for fetuses with congenital gastrointestinal obstruction.
Asunto(s)
Obstrucción Intestinal , Resultado del Embarazo , Recién Nacido , Embarazo , Femenino , Humanos , Ultrasonografía Prenatal , Diagnóstico Prenatal/métodos , Aberraciones Cromosómicas , Feto , Cromosomas , Análisis por Micromatrices/métodos , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/genéticaRESUMEN
OBJECTIVE: To analyze the prognosis of fetuses identified with de novo variants of unknown significance (VOUS) by chromosome microarray analysis (CMA). METHODS: A total of 6 826 fetuses who underwent prenatal CMA detection at the Prenatal Diagnosis Center of Drum Tower Hospital from July 2017 to December 2021 were selected as the study subjects. The results of prenatal diagnosis, and outcome of fetuses identified with VOUS of de novo origin were followed up. RESULTS: Among the 6 826 fetuses, 506 have carried VOUS, of which 237 were detected for the parent-of-origin and 24 were found to be de novo. Among the latters, 20 were followed up for 4 to 24 months. Four couples had opted elective abortion, 4 had developed clinical phenotypes after birth, and 12 were normal. CONCLUSION: Fetuses with VOUS should be continuously follow-up, in particular those carrying de novo VOUS, in order to clarify their clinical significance.
Asunto(s)
Variaciones en el Número de Copia de ADN , Diagnóstico Prenatal , Embarazo , Femenino , Humanos , Estudios de Seguimiento , Diagnóstico Prenatal/métodos , Cromosomas , Análisis por Micromatrices/métodos , Feto , Aberraciones CromosómicasRESUMEN
Single-component organic solar cells (SCOSCs) based on conjugated block copolymers (CBCs) by covalently bonding a polymer donor and polymer acceptor become more and more appealing due to the formation of a favorable and stable morphology. Unfortunately, a deep understanding of the effect of the assembly behavior caused by the sequence structure of CBCs on the device performance is still missing. Herein, from the aspect of manipulating the sequence length and distribution regularity of CBCs, we synthesized a series of new CBCs, namely D18(20)-b-PYIT, D18(40)-b-PYIT and D18(60)-b-PYIT by two-pot polymerization, and D18(40)-b-PYIT(r) by traditional one-pot method. It is observed that precise manipulation of sequence length and distribution regularity of the polymer blocks fine-tunes the self-assembly of the CBCs, optimizes film morphology, improves optoelectronic properties, and reduces energy loss, leading to simultaneously improved efficiency and stability. Among these CBCs, the D18(40)-b-PYIT-based device achieves a high efficiency of 13.4 % with enhanced stability, which is an outstanding performance among SCOSCs. Importantly, the regular sequence distribution and suitable sequence length of the CBCs enable a facile film-forming process of the printed device. For the first time, the blade-coated large-area rigid/flexible SCOSCs are fabricated, delivering an impressive efficiency of 11.62 %/10.73 %, much higher than their corresponding binary devices.
RESUMEN
Mammalian female meiosis must be tightly regulated to produce high-quality mature oocytes for subsequent regular fertilization and healthy live birth of the next generation. GTPases control many important signal pathways involved in diverse cellular activities. ADP-ribosylation factor family members (Arfs) in mice possess GTPase activities, and some members have been found to function in meiosis. However, whether other Arfs play a role in meiosis is unknown. In this study, we found that Arl2 and Arf5 are the richest among Arfs in mouse oocytes, and they are more abundant in oocytes than in granular cells. Furthermore, Arl2 and Arf5 depletion both impeded meiotic progression, but by affecting spindles and microfilaments, respectively. Moreover, Arl2 and Arf5 depletion both significantly increased regular reactive oxygen species levels and decreased mitochondrial membrane potential and autophagy, indicating that oocyte quality was damaged by Arl2 and Arf5 depletion. These results suggest that Arl2 and Arf5 are two novel essential GTPases required for oocyte meiosis and quality control.
Asunto(s)
Factores de Ribosilacion-ADP/metabolismo , Proteínas de Unión al GTP/metabolismo , Oocitos/citología , Oocitos/metabolismo , Factores de Ribosilacion-ADP/genética , Citoesqueleto de Actina/metabolismo , Animales , Femenino , Proteínas de Unión al GTP/genética , Meiosis/genética , Meiosis/fisiología , Ratones , Huso Acromático/metabolismoRESUMEN
Alocasia macrorrhiza (L.) Schott, known as Alocasia is found in the Araceae, and is widely planted in southern China for its ornamental and medicinal value. This plant has a wide range of pharmacological effects, and has potential anti-tumor activity (Lei et al. 2013). In July of 2019, leaf spots were observed on A. macrorrhiza in the Xixiangtang Area, Nanning, Guangxi, China. Disease symptoms began with water-soaked yellow-green spots and progressed to form brown, round or oval lesions with yellow halos. Under severe conditions, spots merged into larger irregular lesions. More than 60% of the plants in a 0.5 ha field showed disease symptoms. Symptomatic leaves were collected and cut into small pieces (3×3 mm). Leaf pieces from the margin of the necrotic tissue were surface sterilized in 75% alcohol for 10 s, followed by 2% sodium hypochlorite solution for 2 min, then rinsed three times in sterile distilled water. Tissues were plated on potato dextrose agar (PDA) and incubated at 28°C for 5 days in the dark. Among over 30 isolates, most shared a similar morphology, the isolation rate of these was 86.7% and three of these (GY1-1A, GY1-1B, and GY1-1C) were chosen for single-spore purification and used for fungal morphological characterization and identification. White feathery aerial mycelia with olivaceous gray mycelia below were observed in 7-day cultures. After 14 days, orange conidia were observed. Conidia were hyaline, guttulate, smooth, one-celled, and cylindrical, averaged 13.79 µm × 5.26 µm, 13.89 µm × 5.33 µm and 13.92 µm × 5.42 µm for GY1-1A, GY1-1B and GY1-1C, respectively. Appressoria were mostly irregular in outline, deeply lobed or lightly lobed, gray brown to dark brown, conidial appressoria were 7.93 to 8.74 µm × 5.26 to 5.42 µm, mycelial appressoria were 7.15 to 10.11 µm × 5.60 to 7.44 µm. These morphological characteristics were similar to the C. siamense as previously described (Weir et al. 2012). The partial internal transcribed spacer (ITS) regions, actin (ACT), chitin synthase (CHS-1), glyceraldehydes-3-phosphate dehydrogenase (GAPDH), calmodulin (CAL), ß-tubulin (TUB2), and the intergenic region of apn2 and MAT1-2-1 (ApMAT) were amplified from genomic DNA for the three isolates using primers ITS4/ITS1 (White et al. 1990), ACT-512F/ACT-783R, CHS-79F/CHS-354R, GDF1/GDR1, CL1C/CL2C, Bt2a/Bt2b (Weir et al. 2012), and AM-F/AM-R (Silva et al. 2012) and sequenced. All sequences showed over 99% identity with C. siamense and were deposited in GenBank (ITS, MW040179-MW040181; ACT, MW049220-MW049222; CHS-1, MW049229-MW049231; GAPDH, MW049232-MW049234; CAL, MW049226-MW049228; TUB, MW049235-MW049237; ApMAT, MW049223-MW049225). Maximum Likelihood (ML) phylogenetic tree was constructed with MEGA 5 using the concatenation of multiple sequences (ACT, CHS-1, GAPDH, ITS, TUB2, CAL). According to the phylogenetic tree, all three isolates were found with C. siamense with 95% bootstrap support. To confirm pathogenicity, three sets (three plants per set) of healthy leaves were slightly scratched with autoclaved toothpicks at each of eight locations. Each inoculation location was a cross (2 mm length) and inoculation location was at least 3 cm apart. Ten µl of conidial suspension (106 conidia /ml in 0.1% sterile Tween 20) was applied to the inoculation areas. A control group was mock inoculated with 0.1% sterile Tween 20. Plants were covered with plastic bags to maintain a high humidity environment and placed in a 28°C growth chamber with constant light for 7 days. Inoculated leaves showed yellowish brown spots (0.4 × 0.65 cm), but no symptoms were observed in the control group. The fungus was reisolated from inoculated leaves, and these isolates matched the molecular and morphological characteristics of the original isolates confirming Koch's postulates. Reported hosts of this pathogen include Coffea arabica, Carica papaya, Melilotus indicus and Litchi chinensis (Weir et al. 2012; Qin et al. 2017; Ling et al. 2019) and so on. To our knowledge, this is the first report of C. siamense causing leaf spot on A. macrorrhiza in China. The identification of this pathogen provides a foundation for the management of leaf spot on this medicinal plant.
RESUMEN
Placenta-specific 1 (Plac1) has been found to be essential for placentation, and abnormal Plac1 expression and distribution is highly correlated with preeclampsia and implantation failure; however, its function in mammalian oocytes has not been elucidated. Here, we report that Plac1 was more prominent in mouse oocytes and enriched at the membrane region throughout meiosis. On the one hand, Plac1 knockdown severely disrupted microvillus organization; however, on the other hand, Plac1 significantly decreased oocyte maturation and increased aneuploidy, consequently disrupting normal fertilization. On the basis of immunoprecipitate matrix-assisted laser desorption/ionization, we established a working model, then verified and suggested that, at the germinal vesicle stage, Plac1 enriches the membrane to activate furin, and active furin subsequently activates IGF-1 receptor to maintain regular microvillus organization. Upon meiosis onset, active furin/IGF-1 receptor relocates into the cytoplasm to activate (phosphorylate) Akt to promote meiosis. In summary, our finding suggests that Plac1, a protein that is crucial for placentation, is also essential for oocyte meiosis and fertilization.-Shi, L.-Y., Ma, Y., Zhu, G.-Y., Liu, J.-W., Zhou, C.-X., Chen, L.-J., Wang, Y., Li, R.-C., Yang, Z.-X., Zhang, D. Placenta-specific 1 regulates oocyte meiosis and fertilization through furin.
Asunto(s)
Fertilización/fisiología , Furina/metabolismo , Meiosis/fisiología , Oocitos/metabolismo , Proteínas Gestacionales/metabolismo , Animales , Activación Enzimática/fisiología , Femenino , Furina/genética , Ratones , Ratones Endogámicos ICR , Oocitos/citología , Proteínas Gestacionales/genética , Transporte de Proteínas/fisiología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismoRESUMEN
Enterocytozoon bieneusi is one of the most frequently diagnosed Microsporidia of humans and most animals. However, there is no information on E. bieneusi infection of pigs in Tibet and Henan, China. In this study, 1,190 fecal samples were collected from pigs in Tibet and Henan and screened for the presence of E. bieneusi. The overall prevalence of E. bieneusi infection was 54.2% (645/1,190), with differences in prevalence observed among geographical areas, ages, and pig breeds. Moreover, 10 E. bieneusi genotypes were identified based on internal transcribed spacer region genotyping, including eight known genotypes (EbpC, EbpA, CHG19, CHC5, Henan-III, I, D, and H) and two novel genotypes (XZP-I and XZP-II). Multilocus sequence typing revealed 18, 7, 17, and 13 genotypes at minisatellite/microsatellite loci MS1, MS3, MS4, and MS7, respectively. Strong linkage disequilibrium (LD) and few numbers of recombination events, suggest a clonal structure of the E. bieneusi population examined in this study. The low pairwise genetic distance (FST ) and gene flow (Nm) values indicated limited gene flow in the E. bieneusi population from different hosts, with phylogenetic, structure, and median-joining network analyses all indicating the existence of host and geographical isolation. The identification of isolates belonging to nine human-pathogenic genotypes indicates that pigs play an important role in the dissemination of E. bieneusi, improving our present understanding of E. bieneusi epidemiology in the studied region.
Asunto(s)
Enterocytozoon/aislamiento & purificación , Microsporidiosis/veterinaria , Enfermedades de los Porcinos/microbiología , Adaptación Fisiológica , Animales , China/epidemiología , Enterocytozoon/clasificación , Enterocytozoon/genética , Enterocytozoon/fisiología , Genotipo , Humanos , Microsporidiosis/microbiología , Tipificación de Secuencias Multilocus/métodos , Técnicas de Tipificación Micológica/métodos , Filogenia , Porcinos , Enfermedades de los Porcinos/epidemiología , Zoonosis/microbiología , Zoonosis/transmisiónRESUMEN
BACKGROUND: Cryptosporidium spp. are important zoonotic pathogens infecting a wide range of vertebrate hosts, and causing moderate to severe diarrhea in humans. Cryptosporidium infections are frequently reported in humans and animals worldwide, but little research has been done on local pig breeds such as Tibetan pigs and Yunan Black pigs and imported pig breeds such as Landrace pigs in China. Therefore, a total of 1089 pig fecal samples from four intensive farms in four areas of China, including Tibetan pigs from Gongbujiangda County (n = 180) and Mainling County (n = 434), Tibet, Yunan Black pigs from Sanmenxia, Henan Province (n = 246), and Landrace pigs from Kaifeng, Henan Province (n = 229), and were screened for the presence of Cryptosporidium with microscopy and nested PCR amplification of the small subunit rRNA gene. RESULTS: The total infection rate of Cryptosporidium in 1089 fecal samples of three different pig breeds was 2.11% (23/1089), and the infection rates of Tibetan pigs, Yunan Black pigs, and Landrace pigs were 0.49% (3/614), 0.41% (1/246), and 8.30% (19/229), respectively. The prevalence of Cryptosporidium infection was significantly higher in weaned piglets (1-2 months) (4.36%, 21/482) than in younger and older age groups (p < 0.01). Sequence analysis of positive samples revealed that there was no mixed infection in our study population, which included 12 cases of C. suis mono-infections (52.17%, 12/23) and 11 cases of C. scrofarum mono-infections (47.83%, 11/23). C. suis was identified in one pre-weaned piglet (< 1 month) and 11 weaned piglets (1-2 months), while C. scrofarum was only detected in 10 weaned piglets (1-2 months) and one finished pig (> 2 months). CONCLUSIONS: This is the first report on the identification of Cryptosporidium spp. in Tibetan pigs, and our findings also elucidate the occurrence and distribution of Cryptosporidium in three different pig breeds in Tibet and Henan, China. More molecular epidemiological studies are required to better clarify the prevalence and public health significance of Cryptosporidium in different pigs.
Asunto(s)
Criptosporidiosis/epidemiología , Cryptosporidium/genética , Enfermedades de los Porcinos/parasitología , Factores de Edad , Animales , China/epidemiología , Criptosporidiosis/parasitología , Reacción en Cadena de la Polimerasa/veterinaria , Prevalencia , ARN Protozoario/genética , ARN Ribosómico/genética , Análisis de Secuencia de ADN , Especificidad de la Especie , Porcinos , Enfermedades de los Porcinos/epidemiologíaRESUMEN
The application of classic formulas from Shanghan Zabing Lun has a long history in treatment of dysmenorrhea. However, the understanding on how to use classic formula in treatment of dysmenorrhea is still insufficient in the traditional Chinese medicine (TCM), mainly limited to syndrome differentiation and the formula-syndrome correlation. The treatment method of syndrome differentiation is flexible and changeable, but the process is tedious and difficult to copy. In addition, its experience is not easy to summarize and pass on, and it is difficult for beginners to comprehend the essence. Formula-syndrome correlation method is accurate, quick acting, but subjective, too mechanical, and will have obvious side effects in case of prescription mistakes. For complex diseases or when suffering from a variety of diseases, the efficacy of formula-syndrome correlation method is not so obvious. By analyzing the advantages and limitations of these two methods, the author has created a four-dimensional therapy which combines the advantages of these two, from four dimensions including disease differentiation, syndromes differentiation, time differentiation, and constitution differentiation in clinical application for dysmenorrheal. Its clinical curative effect is satisfactory. Four-dimensional therapy is a way of thinking, to guide clinicians for accurate diagnosis and precisely choosing drugs; meanwhile, the personalized health guidance is given according to different constitutions and different seasons, which also has certain significance to treat the undiseased.
Asunto(s)
Medicamentos Herbarios Chinos , Dismenorrea , Femenino , Humanos , Medicina Tradicional China , SíndromeRESUMEN
"Mistreatment by warming therapy" refers to various symptoms/syndromes caused by improper use of fire methods mentioned in Treatise on Febrile Diseases, which are similar to damaged yin induced fire-heat syndrome (injury of yin, consumption of qi, loss of yin, consumption of body fluid) manifested after radiotherapy and/or chemotherapy in modern clinics. Better efficacy was obtained in treating various symptoms/syndromes by using nourishing yin purging fire method. In this paper authors focuses on exploring guiding significance of using "Mistreatment by warming therapy" in treating non-small cell lung cancer (NSCLC).
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Medicina Tradicional China , Guías de Práctica Clínica como Asunto , Humanos , SíndromeRESUMEN
BACKGROUND: Oxidative stress and inflammation exert central roles in burn-induced intestinal injury. Crocetin, a natural carotenoid compound from gardenia fruits and saffron, has been shown to inhibit oxidative stress and inflammatory response. However, the possibility of crocetin to be used in the treatment of intestinal injury after burn injury has not been investigated. The purpose of the present study was to investigate the effects and potential mechanisms of crocetin in burn-induced intestinal injury. MATERIALS AND METHODS: Several free radical-generating and lipid peroxidation models were used to systematically assess the antioxidant activities of crocetin in vitro. A common burn model was used to induce the intestinal injury in rats. Changes in the levels of malondialdehyde, superoxidase dismutase, catalase, glutathione peroxidase, tumor necrosis factor α, interleukin 6, polymorphonuclear neutrophil accumulation, intestinal permeability, and intestinal histology were examined. RESULTS: In several models of antioxidant activity, crocetin exhibited marked inhibitory action against free radicals and lipid peroxidation. Crocetin increased levels of antioxidant enzymes and reduced intestinal oxidative injury in burn models. In addition, crocetin inhibited polymorphonuclear neutrophil accumulation, ameliorated tumor necrosis factor α and interleukin 6 levels, intestinal permeability, and histological changes. CONCLUSIONS: Crocetin treatment may protect against burn-induced small intestinal injury, possibly by inhibiting burn-induced oxidative stress and inflammatory response.
Asunto(s)
Quemaduras/tratamiento farmacológico , Carotenoides/uso terapéutico , Intestinos/lesiones , Animales , Antioxidantes/análisis , Relación Dosis-Respuesta a Droga , Peroxidación de Lípido , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Vitamina A/análogos & derivadosRESUMEN
OBJECTIVE: To observe the effect of Angong Niuhuang Pill (ANP) on Thl/Th2 in cerebral infarction patients and to explore the mechanism of phlegm-heat obstructing orifices. METHODS: Re- cruited were 30 cerebral infarction patients of phlegm-heat obstructing orifices syndrome (PHOOS) both in China and Indonesia. They were assigned to 4 groups according to the use of ANP, the Chinese treatment group, the Indonesia treatment group, the Chinese control group, and the Indonesia control group. Patients in the two control groups received conventional treatment, while those in the two treatment group additionally took ANP for 30 successive days. Their adverse reactions were observe, and levels of INF-γ and IL-4 were detected. RESULTS: The INF-γ level and the INF-γ/IL-4 ratio significantly decreased, and the IL-4 level increased after treatment in the four groups with statistical difference (P < 0.05). Compared with the control group after treatment in the same country, the INF-γ level and the INF-γ/IL-4 ratio were lower, and the IL-4 level was higher in the two treatment groups (P < 0.05). Compared with the two Chinese groups, the INF-γ level and the INF-γ/IL-4 ratio were higher, and the IL-4 level was lower in the two Indonesian groups (P < 0.05). There was no statistical difference in the post-treatment indices between the two treatment groups. CONCLUSIONS: ANP had moderating effect on Th1/Th2 in cerebral infarction pa- tients. Cerebral infarction patients of PHOOS might exist certain relation with Th1/Th2.
Asunto(s)
Infarto Cerebral/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Productos Biológicos , China , Medicamentos Herbarios Chinos/farmacología , Calor , Humanos , Indonesia , Interferón gamma/metabolismo , Interleucina-4/metabolismoRESUMEN
OBJECTIVE: To explore the analgesic effect of Zhixin Formula (ZF) and its effects on spinal glial fibrillary acidic protein (glial fibillary acidic protein, GFAP, a marker of astrocyte) , CD11b (a maker of microglia), Toll like receptors (TLR2 and TLR4) and nuclear factor κB (NF-κB) in bone cancer pain model rats. METHODS: Totally 20 male SD rats were randomly divided into the blank control group and the bone cancer pain group, 10 in each group. The bone cancer pain model was induced by injecting ascites tumor fluid containing 3 x 10(3) Walker256 cell line from the left tibia. Ethological tests, X-ray test, and HE staining were performed to confirm a successful modeling. After model was successfully established, 70 male SD rats were randomly divided into seven groups, 10 in each group: the blank control group, the bone cancer pain group (as the model group), the Western medicine (WM) group (Tramadol Hydrochloride), the high dose ZF group, the middle dose ZF group, the low dose ZF group, and the Chinese medicine (CM) group (Wulin Zhitong Capsule). Fourteen days after modeling, rats in the high, middle, and low dose ZF groups were administrated by gastrogavage with 9, 4.5, and 2.25 g/kg ZF water condensed preparation respectively, once a day for seven consecutive days. On day 21 MS typical protein expressions including GFAP, CD11b, TLR (2,4) and NF-κB from cornu dorsal medullae spindis L4-L5 were detected by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: Compare with the blank control group, increased weight in the model group was slow and showed a decreasing trend (P < 0.01), spontaneous ambulatory pain score (SAPS) obviously increased (P < 0.01), paw withdrawal threshold (PWT) obviously decreased in the model group (P < 0.05, P < 0.01). Results of lateral tibial X-ray and HE staining showed obvious changes and damage occurred in bone structures of rats in the model group. Immunohistochemistry showed that GFAP expression significantly increased in the model group (P < 0.05). Protein levels of NF-κB also significantly increased in the model group (P < 0.05). Compared with the model group, CD11b expressions obviously decreased in the middle and high dose ZF groups (P < 0.01). Meanwhile, protein expressions of TLR2 and TLR4, as well as NF-κB also obviously decreased (P < 0.05). CONCLUSION: ZF had analgesic effect, which might be probably related to inhibiting proliferation and activation of gliocytes, as well as activation of TLRs and NF-κB.
Asunto(s)
Neoplasias Óseas/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , FN-kappa B/metabolismo , Animales , Astrocitos , Neoplasias Óseas/tratamiento farmacológico , Proteína Ácida Fibrilar de la Glía , Masculino , Microglía , Osteosarcoma , Dolor , Ratas , Ratas Sprague-DawleyRESUMEN
Background: The CD1A gene, a key component of the human immune system and part of the CD1 family, plays a crucial role in presenting lipid antigens to T cells. Abnormal CD1A expression is associated with various immune-related diseases and tumors. However, the biological function of CD1A in COAD is unclear. Methods: Multiple databases were systematically employed to conduct an analysis of CD1A expression in pan-cancer and COAD, along with its clinical-pathological features. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of CD1A were performed using the 'clusterProfiler' package. The Protein-protein interaction (PPI) analysis of CD1A was used the STRING database. Additionally, TIMER and ssGSEA tools were used to explore the relationship between CD1A expression in COAD and immune cell infiltration. The study also investigated the association between CD1A expression and N6-methyladenosine (m6A) modification genes in the TCGA COAD cohort and constructed a CD1A-centric competing endogenous RNA (ceRNA) regulatory network. Results: CD1A displays varying expression levels in various tumors, including COAD, and is closely linked to clinical-pathological characteristics. GO analysis suggests that CD1A plays a role in important processes like antigen processing and presentation, leukocyte-mediated immunity, and lymphocyte-mediated immunity. KEGG analysis identifies CD1A's involvement in key pathways such as the Chemokine signaling pathway and Cytokine-cytokine receptor interaction. PPI analysis highlights CD1A's interactions with CD207, CD1C, CD1E, FOXP3, and ITGB2. ssGSEA analysis indicates a significant relationship between CD1A expression and the infiltration of various immune cells in COAD. Significant associations were found between CD1A and m6A modification genes in COAD. Furthermore, a CD1A-centered ceRNA regulatory network has been constructed. Conclusion: CD1A emerges as a potential biomarker for the diagnosis and treatment of COAD, showing a strong association with tumor immune infiltration, m6A modification, and the ceRNA network.
RESUMEN
Background: An increasing corpus of evidence has identified the involvement of N-acetyltransferase 1 (NAT1), a member of the NAT family, in the progression of various cancers. However, the specific function of NAT1 in colon cancer (COAD) remains elusive. This study aims to decip her the role of NAT1 in COAD and its associated mechanisms. Methods: The Tumor Immunity Evaluation Resource (TIMER), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases were employed to assess the NAT1 expression level in COAD. The differential expression between COAD and normal colon tissue was further validated using quantitative real-time reverse-transcription PCR (RT-qPCR) and Western blot (WB) analyses. Additionally, survival analysis of NAT1 in COAD was carried out using the PrognoScan database and TCGA dataset. The functions of NAT1 were explored through gene set enrichment analysis (GSEA) and immuno-infiltration analysis. Results: There was a significant reduction in NAT1 expression in COAD samples compared to normal tissue. Notably, low NAT1 expression in COAD correlated significantly with various clinical parameters such as tumor stage (T stage, N stage, M stage, pathologic stage), primary therapy outcome, carcinoembryonic antigen (CEA) level, and lymphatic invasion. The downregulation of NAT1 was also strongly linked with poor outcomes in overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS). Cox regression analysis highlighted NAT1 as an independent prognostic indicator for overall survival in COAD patients. GSEA results revealed NAT1's involvement in multiple pathways, including the neuroactive ligand-receptor interaction, olfactory transduction, olfactory signaling, extracellular matrix receptor interaction, calcium signaling, and focal adhesion pathways. Furthermore, NAT1 expression was found to significantly correlate with infiltration levels of various immune cells. Conclusion: The findings reveal NAT1's potential as a valuable prognostic biomarker for COAD. Moreover, its associated mechanisms offer insights that might pave the way for therapeutic interventions for COAD patients.
RESUMEN
With high prevalence and substantial mortality, metabolic dysfunction-associated steatotic liver disease and chronic obstructive pulmonary disease (COPD) are significant public health concerns. Utilizing a large, population-based dataset from the National Health and Nutrition Examination Survey, our study probes the relationship between COPD prevalence and hepatic steatosis and fibrosis, as measured by Vibration-Controlled Transient Elastography. We analyzed data from 693 individuals with COPD and 7229 without. Through weighted multivariate logistic regression analysis, a restricted cubic spline curve, and threshold effect analysis, we investigated the correlation between the severity of hepatic steatosis and fibrosis and the presence of COPD. Our findings revealed a positive correlation between the controlled attenuation parameter (CAP) and COPD prevalence [OR = 1.03 (95% CI 1.01, 1.05)], even after multivariate adjustment. Furthermore, we observed a U-shaped association between CAP and COPD, where the inflection point, CAP value of 264.85 dB/m, corresponded to the lowest COPD prevalence. Our study emphasizes a substantial and complex link between hepatic steatosis and COPD. These findings urge healthcare professionals to factor liver health into COPD management and prompt further exploration into the underlying mechanisms. This could pave the way for the development of improved prevention and treatment strategies.
Asunto(s)
Hígado Graso , Cirrosis Hepática , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/patología , Masculino , Femenino , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Persona de Mediana Edad , Hígado Graso/complicaciones , Hígado Graso/epidemiología , Hígado Graso/patología , Prevalencia , Anciano , Encuestas Nutricionales , Diagnóstico por Imagen de Elasticidad , AdultoRESUMEN
PURPOSE: Accurate identification of primary breast cancer and axillary positive-node response to neoadjuvant chemotherapy (NAC) is important for determining appropriate surgery strategies. We aimed to develop combining models based on breast multi-parametric magnetic resonance imaging and clinicopathologic characteristics for predicting therapeutic response of primary tumor and axillary positive-node prior to treatment. MATERIALS AND METHODS: A total of 268 breast cancer patients who completed NAC and underwent surgery were enrolled. Radiomics features and clinicopathologic characteristics were analyzed through the analysis of variance and the least absolute shrinkage and selection operator algorithm. Finally, 24 and 28 optimal features were selected to construct machine learning models based on 6 algorithms for predicting each clinical outcome, respectively. The diagnostic performances of models were evaluated in the testing set by the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: Of the 268 patients, 94 (35.1 %) achieved breast cancer pathological complete response (bpCR) and of the 240 patients with clinical positive-node, 120 (50.0 %) achieved axillary lymph node pathological complete response (apCR). The multi-layer perception (MLP) algorithm yielded the best diagnostic performances in predicting apCR with an AUC of 0.825 (95 % CI, 0.764-0.886) and an accuracy of 77.1 %. And MLP also outperformed other models in predicting bpCR with an AUC of 0.852 (95 % CI, 0.798-0.906) and an accuracy of 81.3 %. CONCLUSIONS: Our study established non-invasive combining models to predict the therapeutic response of primary breast cancer and axillary positive-node prior to NAC, which may help to modify preoperative treatment and determine post-NAC surgery strategy.
Asunto(s)
Axila , Neoplasias de la Mama , Ganglios Linfáticos , Terapia Neoadyuvante , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Adulto , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Quimioterapia Adyuvante , Aprendizaje Automático , Metástasis Linfática/diagnóstico por imagen , Algoritmos , Anciano , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Sensibilidad y Especificidad , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Área Bajo la Curva , RadiómicaRESUMEN
Bone development and lung function are integral to child and adolescent health. Both influence an individual's overall well-being and potentially affect long-term health. Utilizing a comprehensive dataset from the National Health and Nutrition Examination Survey, this study aims to elucidate the relationship between lung function and bone mineral density (BMD) in a representative sample of children and adolescents. The analysis covered 3410 participants aged 8 to 19 years. We employed weighted multivariate linear regression and restricted cubic spline curve visualizations to explore the intricate association between lung function metrics, particularly first-second expiratory volume 1 second/forced vital capacity ratio, and lumbar BMD. Our data indicated a positive association between lung function and lumbar BMD in children and adolescents. Specifically, higher lung function metrics were linked with increased lumbar BMD. This association was more pronounced in younger participants or those with a lower body mass index. A significant positive relationship exists between lung function and BMD in the pediatric population. Recognizing this association is crucial for holistic health strategies for children and adolescents. This study underscores the need for integrated health monitoring during formative years, which can influence health trajectories as these individuals transition to adulthood.