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Previous studies show that prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure induces premature testicular aging. However, the evidence is weak, and the underlying mechanisms remain unclear. p38/extracellular signal-regulated kinase (ERK)/c-Jun NH(2)-terminal kinase (JNK) MAPK pathways participate in aging. Leydig cell (LC) senescence results in testicular aging. Whether prenatal DEHP exposure induces premature testicular aging by promoting LC senescence warrants further study. Here, male mice undergo prenatal exposure to 500 mg per kg per day DEHP, and TM3 LCs are treated with 200 µm mono (2-ethylhexyl) phthalate (MEHP). MAPK pathways, testicular toxicity, and senescent phenotypes (ß-gal activity, p21, p16, and cell cycle) of male mice and LCs are explored. Prenatal DEHP exposure induces premature testicular aging in middle-aged mice (poor genital development, reduced testosterone synthesis, poor semen quality, increased ß-gal activity, and upregulated expression of p21 and p16). MEHP induces LCs senescence (cell cycle arrest, increased ß-gal activity, and upregulated expression of p21). p38 and JNK pathways are activated, and the ERK pathway is inactivated. In conclusion, prenatal DEHP exposure induces premature testicular aging by promoting LC senescence through MAPK signaling pathways.
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BACKGROUND: Mass screening and treatment (MSAT) for malaria elimination lacks an ideal diagnostic tool to allow sensitive and affordable test of the target population in the field. This study evaluated whether Capture and Ligation Probe-PCR (CLIP-PCR) could be used in a field MSAT in Laiza City, Myanmar. METHODS: On day 0, two dried blood spots were collected from each participant. On day 1, all samples were screened for Plasmodium in a 20 m2 laboratory with workbench, a biosafety cabinet, a refrigerator, a benchtop shaking incubator and a qPCR machine, by four technicians using CLIP-PCR with sample pooling, at a health clinic of the Chinese bordering town of Nabang. On day 2, all positives were followed up and treated. RESULTS: Of 15,038 persons (65% of the total population) screened, 204 (1.36%) were CLIP-PCR positives. Among them, 188, 14, and 2 were infected with Plasmodium vivax, Plasmodium falciparum, and P. vivax/P. falciparum mix, respectively. The testing capacity was 538 persons/day, with a cost of US$0.92 /person. The proportion of submicroscopic infection was 64.7%. All positive individuals received treatment within 72 h after blood collection. CONCLUSION: Using CLIP-PCR in MSAT in low transmission settings can support the malaria elimination efforts in the China-Myanmar border region.
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Malaria Falciparum , Malaria Vivax , Malaria , Humanos , Mianmar , Malaria/diagnóstico , Malaria/prevención & control , Plasmodium falciparum/genética , Plasmodium vivax/genética , Reacción en Cadena de la Polimerasa/métodos , China/epidemiología , Malaria Vivax/diagnóstico , Malaria Vivax/prevención & control , Malaria Vivax/epidemiología , Malaria Falciparum/epidemiologíaRESUMEN
BACKGROUND: Yin-chen Wu-ling Powder (YWP) has potential therapeutic effects on cholestatic liver disease (CLD), however, its active compounds and conceivable mechanism are as yet indistinct. METHODS: The network pharmacology and gene function annotation examined the multiple active ingredients, potential targets, and possible mechanisms of YWP in CLD treatment. Then the molecular docking reassured the reliability of the core compounds including the key genes and farnesoid X receptor (FXR). Finally, The Mdr2-/- mice were used to test the effect and mechanism of YWP against CLD. RESULTS: The network analysis identified nine main active ingredients, including quercetin, capillarisin, eupalitin, isorhamnetin, skrofulein, genkwanin, cerevisterol, gederagenin, and sitosterol. The PPI network predicted the ten hub genes involved were AKT1, MAPK1, MAPK14, IL6, RXRA, ESR1, IL10, NCOA1, CAV1, and EGFR. The KEGG and GO analysis showed that YWP might contribute to CLD treatment through the PI3K/Akt and MAKP signalings to manage pathological reactions, for instance, inflammatory responses. The molecular docking displayed a functional similarity among the core compounds with ursodeoxycholic acid (UDCA) and Obeticholic acid (OCA) on the effects on AKT1, MAPK1, MAPK14, RXRA, and ESR, and the affinity to FXR. In addition, the YWP could significantly attenuate hepatic injury and improve inflammatory response in Mdr2-/- mice. The mechanism exploration showed that YWP mainly decreased inflammatory response by inhibiting AKT/P38MAPK signaling. CONCLUSION: This study firstly revealed the multiple active ingredients, potential targets, and possible mechanism of YWP to treat CLD based on network pharmacology Analysis and molecular docking. YWP could alleviate cholestasis in Mdr2-/- mice by impairing inflammation via inhibiting AKT/P38MAPK Signaling.
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Colestasis , Medicamentos Herbarios Chinos , Hepatopatías , Proteína Quinasa 14 Activada por Mitógenos , Ratones , Animales , Polvos , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt , Reproducibilidad de los Resultados , Colestasis/tratamiento farmacológico , Colestasis/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Hepatopatías/tratamiento farmacológicoRESUMEN
Objective:To explore the medication safety issues caused by unreasonable sugar-to-fat ratio in clinical practice of parenteral nutrition,providing a basis for the rational use of clinical nutritional drugs.Methods:From the beginning of the database construction until February 28,2023,relevant databases at home and abroad were searched to summarize and analyze the clinical adverse outcomes caused by unreasonable sugar-to-fat ratio prescriptions encountered in the included literature and clinical practice.Results:Eleven articles were included,and 1 case of patient discomfort was improved by adjusting the unreasonable sugar-to-fat ratio.A total of 86 patients were involved,including 51 males and 35 females,with an age range of 18 to 89 years.Among the 86 patients,there were 79 clinical adverse outcomes,including 8 deaths.The incidence rates of clinical adverse outcomes were as follows:abnormal liver function 46.8％(37/79),bile stasis 22.8％(18/79),fat overload syndrome 13.9％(11/79),liver steatosis 11.4％(9/79),platelet reduction 3.8％(3/79),and other 1.3％(1/79).Among the 86 patients,2 cases were clearly recorded to have improved clinical adverse outcomes after adjusting the sugar-to-fat ratio,and the others were not detailed.Conclusions:Inappropriate sugar-to-fat ratio may lead to safety issues related to parenteral nutrition medication and should be given clinical attention.
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To understand how malaria could be eliminated in the original hyperendmic area for malaria along international borders in Yunnan Province, malaria situation and control were described on the basis of seven phases. At last the experiences and lessons of the program that reduced border malaria from hyperendmicity to malaria-free status were summarized. Malaria control and elimination area were particularly difficult in the Yunnan border. The achievement can be attributed to high political commitment, strategic and technical innovations based on the actual locality, effective collaboration and communication with neighbouring countries to carry out cross border interventions. Other border areas might perform their own pilot interventions based on their local context, including malaria burden, governing system, health service structure contextualized based on their socioeconomic development and ecology, and then a local decision could be made according to their own trial results.
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Malaria , China/epidemiología , Ecología , Humanos , Malaria/epidemiología , Malaria/prevención & controlRESUMEN
Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons. Here, we introduced and evaluated a newly modified Mathieu technique, Mathieu combined tunnel (MCT), which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations; we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence. This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China) for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020; sixteen patients underwent surgery using the MCT (MCT group) and ten patients underwent surgery using the tubularized incised plate (TIP) technique (TIP group). The operative time, blood loss, postoperative complications, normal urethral meatus rate, success rate, and Hypospadias Objective Penile Evaluation (HOPE) score were compared between the two groups. The MCT group achieved an overall satisfactory penile appearance and voiding function, with a higher rate of normal urethral meatus (15/16, 93.8%) and a lower rate of glans dehiscence (1/16, 6.2%), compared with the TIP group (70.0% and 30.0%, respectively). However, these differences were not statistically significant, possibly because of the limited number of patients (all P > 0.05). Mean postoperative HOPE scores were similar in the MCT group (mean ± standard deviation: 8.83 ± 0. 89) and TIP group (8.94 ± 0.57) (P > 0.05). No significant differences were found between the two groups in terms of blood loss and success rate, nor in the rates of various complications (e.g., fistula, urethral stricture, and glans dehiscence). In conclusion, the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.
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Niño , Femenino , Humanos , Lactante , Masculino , Hipospadias/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Uretra/cirugía , Procedimientos Quirúrgicos Urológicos Masculinos/métodosRESUMEN
Human adipose-derived stem cells (hASCs) are a promising cell type for bone tissue regeneration. Circular RNAs (circRNAs) have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis. However, how circRNAs regulate hASCs in osteogenesis is still unclear. Herein, we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs. Knockdown of circ_0003204 by siRNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs. We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p. We predicted and confirmed that miR-370-3p had targets in the 3'-UTR of HDAC4 mRNA. The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis. Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model, while overexpression of circ_0003204 inhibited bone defect repair. Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.
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Animales , Humanos , Ratones , Tejido Adiposo/metabolismo , Diferenciación Celular/genética , Células Cultivadas , Histona Desacetilasas/metabolismo , MicroARNs/metabolismo , Osteogénesis/genética , ARN Circular/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal , Células Madre/metabolismoRESUMEN
BACKGROUND: Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised reaching the goal of malaria elimination by 2020. Since 2017, a pilot project on 3 + 1 strategy of joint cross-border malaria prevention and control was carried out for building a malaria buffer in these border areas. Here, 3 were the three preventive lines in China where different focalized approaches of malaria elimination were applied and + 1 was a defined border area in Myanmar where the integrated measures of malaria control were adopted. METHODS: A 5-year retrospective analysis (2015 to 2019) was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence and the parasite prevalence rate in + 1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An. minimus were statistically significant indictors to assess the effectiveness of the 3 + 1 strategy. RESULTS: In + 1 area of Myanmar from 2015 to 2019, the averaged annual parasite incidence was (59.11 ± 40.73)/1000 and Plasmodium vivax accounted for 96.27% of the total confirmed cases. After the pilot project, the annual parasite incidence dropped 89% from 104.77/1000 in 2016 to 12.18/1000 in 2019, the microscopic parasite prevalence rate dropped 100% from 0.34% in 2017 to zero in 2019 and the averaged density of An. Minimus per trap-night dropped 93% from 1.92 in June to 0.13 in September. The submicroscopic parasite prevalence rate increased from 1.15% in 2017 to 1.66% in 2019 without significant difference between the two surveys (P = 0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The averaged annual importation rate from 2015 to 2019 was (0.47 ± 0.15)/1000. After the pilot project, the annual importation rate dropped from 0.59/1000 in 2016 to 0.28/1000 in 2019 with an overall reduction of 53% in the whole county. The reduction was 67% (57.63/1000 to 18.01/1000) in the first preventive line, 52% (0.20/1000 to 0.10/1000) in the second preventive line and 36% (0.32/1000 to 0.22/1000) in the third preventive line. The averaged density of An. Minimus per trap-night in the first preventive line dropped 94% from 2.55 in June to 0.14 in September, without significant difference from that of + 1 area of Myanmar (Z value = - 1.18, P value = 0.24). CONCLUSION: The pilot project on 3 + 1 strategy has been significantly effective in the study areas and a buffer zone of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China.
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Malaria , China/epidemiología , Humanos , Malaria/epidemiología , Malaria/prevención & control , Mianmar/epidemiología , Proyectos Piloto , Estudios RetrospectivosRESUMEN
BACKGROUND: Eliminating malaria and preventing re-establishment of malaria transmission in border areas requires universal coverage of malaria surveillance and a rapid response to any threats (i.e. malaria cues) of re-establishing transmission. MAIN TEXT: Strategy 1: Intensive interventions within 2.5 km-wide perimeter along the border to prevent border-spill malaria. The area within 2.5 km along the international border is the travel radius of anopheline mosquitoes. Comprehensive interventions should include: (1) proactive and passive case detection, (2) intensive vector surveillance, (3) evidence-based vector control, and (4) evidence-based preventative treatment with anti-malarial drugs. Strategy 2: Community-based malaria detection and screening of migrants and travellers in frontier townships. Un-permitted travellers cross borders frequently and present in frontier townships. Maintenance of intensified malaria surveillance should include: (1) passive malaria detection in the township hospitals, (2) seek assistance from villager leaders and health workers to monitor cross border travellers, and refer febrile patients to the township hospitals and (3) the county's Centre for Disease Control and Prevention maintain regular proactive case detection. Strategy 3: Universal coverage of malaria surveillance to detect malaria cues. Passive detection should be consolidated into the normal health service. Health services personnel should remain vigilant to ensure universal coverage of malaria detection and react promptly to any malaria cues. Strategy + 1: Strong collaborative support with neighbouring countries. Based on the agreement between the two countries, integrated control strategies should be carried out to reduce malaria burden for both countries. There should be a clear focus on the border areas between neighbouring countries. CONCLUSION: The 3 + 1 strategy is an experience summary of border malaria control and elimination, and then contributed to malaria elimination in Yunnan's border areas, China. Nevertheless, Yunnan still has remaining challenges of re-establishment of malaria transmission in the border areas, and the 3 + 1 strategy should still be carried out.
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Transmisión de Enfermedad Infecciosa/prevención & control , Malaria/prevención & control , China , Emigración e Inmigración , Humanos , Malaria/diagnóstico , Malaria/transmisiónRESUMEN
BACKGROUND: Eradication of infectious disease is the sanctified public health and sustainable development goal around the world. MAIN BODY: Three antimalarial barriers were developed to control imported malarial cases, and an effective surveillance strategy known as the "1-3-7 approach" was developed to eliminate malaria from the Chinese population. From 2011 to 2019, 5254 confirmed malaria cases were reported and treated in Yunnan Province, China. Among them, 4566 cases were imported from other countries, and 688 cases were indigenous from 2011 to 2016. Since 2017, no new local malarial case has been reported in China. Thus, malaria has been completely eliminated in Yunnan Province. However, malaria is detected in overseas travellers on a regular basis, such as visitors from neighbouring Myanmar. CONCLUSION: Hence, the strategies should be further strengthened to maintain a robust public health infrastructure for disease surveillance and vector control programs in border areas. Such programs should be supported technically and financially by the government to avert the possibility of a malarial resurgence in Yunnan Province.
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Malaria , China/epidemiología , Gobierno , Humanos , Malaria/epidemiología , Malaria/prevención & control , Mianmar , Salud PúblicaRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective treatment strategies. There is an urgent need for the development of new strategies for PDAC therapy. The genetic and phenotypic heterogeneity of PDAC cancer cell populations poses further challenges in the clinical management of PDAC. In this study, we performed single-cell RNA sequencing to characterize PDAC tumors from KPC mice. Functional studies and clinical analysis showed that PDAC cluster 2 cells with highly Hsp90 expression is much more aggressive than the other clusters. Genetic and pharmacologic inhibition of Hsp90 impaired tumor cell growth both in vitro and in vivo. Further mechanistic study revealed that HSP90 inhibition disrupted the interaction between HSP90 and OPA1, leading to a reduction in mitochondrial cristae amount and mitochondrial energy production. Collectively, our study reveals that HSP90 might be a potential therapeutic target for PDAC.
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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies and is known for its high resistance and low response to treatment. Tumor immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Karyopherin alpha 2 (KPNA2), a member of the nuclear transporter family, is elevated in multiple human cancers and accelerates carcinogenesis. However, the specific role of KPNA2 in PDAC remains unclear. In this study, we found that expression of KPNA2 was significantly upregulated in PDAC compared to adjacent nontumor tissue and its high expression was correlated with poor survival outcome by analyzing the GEO datasets. Similar KPNA2 expression pattern was also found in both human patient samples and KPC mouse models through IHC staining. Although KPNA2 knockdown failed to impair the vitality and migration ability of PDAC cells in vitro, the in vivo tumor growth was significantly impeded and the expression of immune checkpoint ligand PD-L1 was reduced by silencing KPNA2. Furthermore, we uncovered that KPNA2 modulated the expression of PD-L1 by mediating nuclear translocation of STAT3. Collectively, our data suggested that KPNA2 has the potential to serve as a promising biomarker for diagnosis in PDAC.
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Antígeno B7-H1/genética , Carcinoma Ductal Pancreático/etiología , Carcinoma Ductal Pancreático/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/metabolismo , Escape del Tumor/inmunología , alfa Carioferinas/genética , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Bases de Datos Genéticas , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pronóstico , Transporte de Proteínas , Factor de Transcripción STAT3/metabolismoRESUMEN
The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechanisms of neutrophils in PDAC liver metastases remain unknown. Here, we show that a subset of P2RX1-negative neutrophils accumulate in clinical and murine PDAC liver metastases. RNA sequencing of murine PDAC liver metastasis-infiltrated neutrophils show that P2RX1-deficient neutrophils express increased levels of immunosuppressive molecules, including PD-L1, and have enhanced mitochondrial metabolism. Mechanistically, the transcription factor Nrf2 is upregulated in P2RX1-deficient neutrophils and associated with PD-L1 expression and metabolic reprogramming. An anti-PD-1 neutralizing antibody is sufficient to compromise the immunosuppressive effects of P2RX1-deficient neutrophils on OVA-activated OT1 CD8+ T cells. Therefore, our study uncovers a mechanism by which metastatic PDAC tumors evade antitumor immunity by accumulating a subset of immunosuppressive P2RX1-negative neutrophils.
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Inmunosupresores/farmacología , Neoplasias Hepáticas/inmunología , Neutrófilos/metabolismo , Neoplasias Pancreáticas/inmunología , Microambiente Tumoral/inmunología , Animales , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos/inmunología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Modelos Animales de Enfermedad , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Noqueados , Mitocondrias/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Páncreas/inmunología , Páncreas/patología , Neoplasias Pancreáticas/patología , Receptores Purinérgicos P2X/genética , Receptores Purinérgicos P2X/inmunología , Receptores Purinérgicos P2X/metabolismoRESUMEN
BACKGROUND: Schisandronic acid (SA), a triterpenoid from fruits of Schisandra sphenanthera, inhibited pan-genotypic HCV entry into human hepatocytes by interfering with virion-cell membrane fusion. It was a promising lead compound for the development of novel HCV entry inhibition agents. OBJECTIVE: The aim of the present study is to search for compounds with more potent anti-HCV and antitumor activities and explore SARs. A series of novel derivatives of SA were designed and synthesized and evaluated for in vitro, their anti-HCV and antitumor activities. METHODS: SA derivatives were synthesized by reduction, condensation, esterification or amidation. The anti-HCV activity of title compounds was tested by inhibition on HCVcc infection of Huh7 cells, and a preliminary MOA study was conducted by determining inhibition on HCVpp entry into Huh7 cells. The antitumor activity in vitro was determined by MTT methods. RESULTS: In total, 24 novel derivatives were synthesized. Most of the compounds inhibited HCVcc infection. Compounds 5h and 6 showed the most potent anti-HCVcc activities and inhibition of HCVpp entry into Huh7 cells without obvious cytotoxicity. Most of the title compounds showed potent in vitro antitumor activities against Bel7404 and SMMC7721 tumor cell lines. Compounds 5j and 6 exhibited more potent antitumor activity than positive control SA and DOX. CONCLUSION: Structural modification of SA could lead to the discovery of potent anti-HCV or antitumor agents. Compounds 5h, 5j and 6 were promising lead compounds for development of novel HCV entry inhibition or antitumor agents.
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Antineoplásicos Fitogénicos/farmacología , Antivirales/síntesis química , Antivirales/farmacología , Hepacivirus/efectos de los fármacos , Triterpenos/química , Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/química , Antivirales/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Hepacivirus/patogenicidad , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Hepatocitos/efectos de los fármacos , Hepatocitos/virología , Humanos , Relación Estructura-Actividad , Internalización del Virus/efectos de los fármacosRESUMEN
BACKGROUND: Licorice is widely used as a hepatoprotective herb for thousands of years in Traditional Chinese Medicine, and its main chemical constituent glycyrrhizin (GL) is used as a treatment for chronic hepatitis in Japan for over 20 years. 18ß-Glycyrrhetinic acid (GA) is the main active metabolite of GL. OBJECTIVE: Series of GA derivatives were designed and synthesized, and their anti-HCV activities were screened to investigate the structure-activity relationship (SAR). Besides, their in-silico ADMET properties were analyzed to search for a promising lead compound for further identification of anti-HCV terpenoid candidates. METHODS: GA derivatives were synthesized via reactions of oxidation, oxime, rearrangement, esterification and acylation. In vitro anti-HCV activity of derivatives was tested on the HCV cell culture (HCVcc) system. In-silico ADMET properties analysis was performed via "pkCSM" and "SwissADME" platforms. RESULTS: Eighteen GA derivatives were synthesized, and their structures were confirmed by MS and NMR spectrums. All compounds exhibited superior HCV inhibitory activity to that of GA. Compound 2 possessed the most potent anti-HCV activity with an IC50 value of 0.79 µM, which is nearly 58 times potent than SA (a previously reported potent anti-HCV terpenoids) and >200 times than GA. SAR revealed that the introduction of 3-oxo, short-chain (C1-C3) aliphatic alcohols or cyclic aliphatic amines is conducive to improving anti-HCV activity. In-silico ADMET prediction demonstrated most of the potent compounds possessed favorable ADMET properties. CONCLUSION: Structural modification of GA at 3-position and 30-position is an effective approach to searching for potent anti-HCV agents. Compound 2, with the most potent anti-HCV activity and favorable in-silico ADMET properties, is a promising lead compound for further identification of anti-HCV terpenoid candidates.
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Ácido Glicirretínico , Triterpenos , Antivirales/farmacología , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacología , Relación Estructura-ActividadRESUMEN
Crohn's disease (CD) is a chronic nonspecific intestinal inflammatory disease with unclear etiology and pathogenesis. At present, it is believed that CD can cause different degrees of metabolic abnormalities, and that the related metabolites also play an important role in the development and progression of the disease. In recent years, metabonomics is becoming more and more well-developed and has provided guidance for clinicians on rational nutritional support. Here is a review on the metabolic changes of multiple systems in CD patients, the application of metabonomics in CD diagnosis and treatment, and the research progress of clinical nutrition intervention.
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Objective:To solve the problem of leg shaking caused by the sudden change of angular acceleration at the joint of periodic motion during circular gait training of lower limb rehabilitation robot. Methods:A kind of quasi-circular gait was proposed, which divided the periodic motion into three phases: start phase, middle phase and end phase. The time was equal in the start phase and the end phase, and could be adjusted with the parameter ratio. The joint trajectories of the two phases were planned by quintic polynomial, and the middle phase was still the circular gait joint trajectory. The trajectory of the proposed quasi-circular gait was simulated. Results:The angular velocity was continuously differentiable and 0, the angular acceleration was continuous and 0, and the end-effector trajectory became flat with the increase of ratio. The results on the physical prototype of the lower limb rehabilitation robot were principally consistent with the simulation, and the machine worked smoothly. Conclusion:The proposed variable quasi-circular gait had smooth angular acceleration at the junction of periodic motions, which effectively solved the jitter problem when using circular gait for lower limb rehabilitation training and avoided secondary injury to the patients.
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OBJECTIVES@#This study aimed to assess the influence of different types of rapid maxillary expansion on root resorption (RR).@*METHODS@#Literature searches were carried out electronically in five English and two Chinese databases. Randomized controlled trials (RCTs), controlled clinical trials (CCTs), cohort studies, and case-control studies were included. The data were extracted by three authors. The risk of bias in the RCTs and nonrandomized studies were assessed in accordance with corresponding scales.@*RESULTS@#Among the 400 articles identified, seven were included for the final analysis. Three studies were graded as high value of evidence, while two and another two studies were graded as moderate value and low value, respectively. According to the available evidence, the tooth-borne maxillary expansion caused more obvious RR of anchorage teeth than the bone-borne one. In addition, the Haas-type palatal acrylic pads could not effectively reduce the degree of RR. The difference in the design of the retainer between the tooth-borne maxillary expansion (the use of a band or wire framework to connect the anchorage tooth) did not cause the difference in the incidence and degree of RR.@*CONCLUSIONS@#Clinical evidence suggested that bone-borne maxillary expansion may decrease the amount of RR, while the amounts of resorption did not significantly differ between Haas and Hyrax and between different retainer types of Hyrax.
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Humanos , Estudios de Casos y Controles , Maxilar , Técnica de Expansión Palatina , Hueso Paladar , Resorción Radicular , DienteRESUMEN
Crohn's disease (CD) is a chronic nonspecific inflammatory bowel disease that can involve the whole digestive tract. At present, the pathogenesis is believed to be mainly related to environment, genetics and intestinal microecology changes. Compared with healthy people, CD patients demonstrate different degrees of flora imbalance in the digestive tract, and the flora composition varies across different regions. In recent years, reconstruction of gastrointestinal microecological balance has become the focus of research. Fecal microbiota transplantation as a new treatment strategy has been gradually applied in clinical practice. Here we reviewed the changes of flora across different regions of digestive tract in patients with CD and the relevant pathogenic mechanism, as well as the progress of fecal microbiota transplantation in the treatment of CD.
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Accumulating evidence has pointed out that metastasis is the leading cause of death in several malignant tumor, including CRC. During CRC, metastatic capacity is closely correlated with reprogrammed energy metabolism. Mitochondrial Pyruvate Carrier 1 (MPC1), as the carrier of transporting pyruvate into mitochondria, linked the glycolysis and TCA cycle, which would affect the energy production. However, the specific role of MPC1 on tumor metastasis in CRC remains unexplored. Here, by data mining of genes involved in pyruvate metabolism using the TCGA dataset, we found that MPC1 was significantly downregulated in CRC compared to nontumor tissues. Similar MPC1 expression pattern was also found in multiple GEO datasets. IHC staining in both human sample and AOM/DSS induced mouse CRC model revealed significant downregulation of MPC1. What is more, we found that MPC1 expression was gradually decreased in normal tissue, primary CRC, and metastasis CRC. Additionally, poor prognosis emerged in the MPC1 low expression patients, especially in patients with metastasis. Following, functional tests showed that MPC1 overexpression inhibited the motility of CRC cells in vitro and MPC1 silencing enhanced liver metastases in vivo. Furthermore, we uncovered that decreased MPC1 activated the Wnt/ß-catenin pathway by promoting nuclear translocation of ß-catenin to mediate the expression of MMP7, E-cadherin, Snail1, and myc. Collectively, our data suggest that MPC1 has the potential to be served as a promising biomarker for diagnosis and a therapeutic target in CRC.