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1.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(7): 990-996, 2024 Jul 10.
Article in Chinese | MEDLINE | ID: mdl-39004972

ABSTRACT

Objective: To analyze the multiple locus variable number tandem repeat analysis (MLVA) genotype polymorphism of Bacillus (B.) anthracis and establish a MLVA genotype database of B. anthracis in China. Methods: B. anthracis strains isolated from different sources in China since 1947 were collected. Genotype identification was carried out using the MLVA15 genotyping protocol based on 15 variable number tandem repeat loci. The genotypes were uniformly numbered and named. The distribution characteristics of the MLVA genotypes of strains were analyzed. Software Bionumerics was used to construct clustering diagrams to analyze the genetic relationships. Results: The MLVA15 clustering analysis subdivided the isolates into 4 major groups and 91 genotypes, 54 of which were unique to China. The genotypes from MLVA15-CHN1 to MLVA15-CHN6 were widely distributed throughout China and in all eras, while other genotypes were restricted to certain regions or eras. Conclusions: This study established a MLVA genotype database of B. anthracis, which provides basis for the understanding of MLVA genetic polymorphisms and the control and molecular source tracing of the anthrax outbreaks in China.


Subject(s)
Bacillus anthracis , Genotype , Minisatellite Repeats , Polymorphism, Genetic , Bacillus anthracis/genetics , China/epidemiology , Phylogeny , Anthrax/microbiology , Anthrax/epidemiology , Multilocus Sequence Typing , Cluster Analysis
2.
Zhonghua Yi Xue Za Zhi ; 104(26): 2424-2430, 2024 Jul 09.
Article in Chinese | MEDLINE | ID: mdl-38978366

ABSTRACT

Objective: To investigate the relationship between maternal exposures to peri-conceptional risk factors and the risk of hypospadias and cryptorchidism in offspring. Methods: Pregnant women who delivered male newborns and participated in the China birth cohort study between February 2018 and December 2020 at the research center of Beijing Obstetrics and Gynecology Hospital, Capital Medical University were selected for the study. All were enrolled at 6-13+6 weeks of their gestation. Baseline risk factor information was collected by questionnaire survey. Information on the outcome of hypospadias and cryptorchidism was obtained by clinical examination at birth and ultrasonography. Logistic regression was used to analyze the Odds Ratio (OR) and 95% Confidence Interval (95%CI) of each factor with respect to the onset of the outcome. Results: A total of 15, 833 pregnant women with an average age of (31.81±3.84) years were included. Among their offsprings, 113 were diagnosed as hypospadias or cryptorchidism (42 hypospadias, 69 cryptorchidism, and 2 both hypospadias and crypterchidism), with an incidence of 7.14‰. The results of multivariate logistic regression analysis showed that mothers with pregnancy history of birth defects (OR=3.01, 95%CI: 1.09-8.35), with preconception Hepatitis B infection (OR=4.74, 95%CI: 1.10-20.42), fetal growth restriction (OR=4.02, 95%CI: 2.10-7.68), multivitamin use since preconception (OR=1.98, 95%CI: 1.12-3.52), and never cook and eat at home (OR=2.17, 95%CI: 1.23-3.82) were risk factors for hypospadias and cryptorchidism (all P<0.05). Conclusions: Obesity in early pregnancy, preconception Hepatitis B infection, pregnancy history of birth defects, fetal growth restriction, multivitamin use before pregnancy, and rarely cook and eat at home were associated with an increased risk of hypospadias or cryptorchidism in their offsprings.


Subject(s)
Cryptorchidism , Hypospadias , Maternal Exposure , Humans , Hypospadias/etiology , Hypospadias/epidemiology , Cryptorchidism/etiology , Cryptorchidism/epidemiology , Female , Male , Pregnancy , Adult , Risk Factors , Maternal Exposure/adverse effects , China/epidemiology , Infant, Newborn , Birth Cohort , Logistic Models , Prenatal Exposure Delayed Effects/etiology , Surveys and Questionnaires
3.
Zhonghua Yi Xue Za Zhi ; 104(26): 2431-2437, 2024 Jul 09.
Article in Chinese | MEDLINE | ID: mdl-38978367

ABSTRACT

Objective: To analyze the association between maternal blood pressure and congenital heart disease (CHD) in offspring. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal and Child Healthcare Hospital and Chengdu Women's and Children's Central Hospital were enrolled in this study. The baseline and follow-up information were collected using an electronic data collection system. Stepwise logistic regression model was used to analyze the association between maternal blood pressure including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure difference (PP) in the first trimester of pregnancy and the risk of CHD in the offspring. A restrictive cubic spline curve was used to draw the dose-response curve between maternal blood pressure and CHD. Results: A total of 55 552 participants were included in this study. Of them, 31 038, 15 375 and 9 139 pregnant women were enrolled in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal & Child Healthcare Hospital and Chendu Women's and Children's Central Hospital, respecitively. The age of pregnant women was (31.3±4.0) and the incidence of CHD in the offspring was 0.78% (435/55 552). Multivariable logistic regression model analysis showed that the increase of SBP (OR=1.01, 95%CI: 1.00-1.02), DBP (OR=1.01, 95%CI: 1.00-1.03) and MAP (OR=1.02, 95%CI: 1.00-1.03) in the first trimester were significantly associated with the risk of CHD in the offspring. The restrictive cubic spline analysis showed a positive linear association of SBP (Ptotal<0.001; Pnon-liear=0.315), DBP (Ptotal<0.001; Pnon-liear=0.928) and MAP (Ptotal<0.001; Pnon-liear=0.929) with the risk of CHD in the offspring. Conclusion: Maternal SBP, DBP and MAP in the first trimester of pregnancy were positively associated with the risk of CHD in the offspring.


Subject(s)
Blood Pressure , Heart Defects, Congenital , Humans , Female , Pregnancy , Adult , China/epidemiology , Risk Factors , Pregnancy Trimester, First , Cohort Studies , Logistic Models
4.
Ecotoxicol Environ Saf ; 283: 116785, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39067075

ABSTRACT

Tea tree is a fluorine (F)-enriched plant, leading to much concern about the safety of drinking tea from tea tree (Camellia sinensis (L.) Kuntze). Tea tree is a perennial leaf-harvested crop, and tea production in China is generally categorized as spring tea, summer tea and autumn tea in its annual growth rounds. However, the seasonally dynamic changes of F content and accumulation in the leaves and its drinking safety are poorly understood. In this study, 85 tea varieties cultivated under the same conditions were investigated to analyze the seasonal variation of F content and it's relationships with F accumulation, aluminum (Al), calcium (Ca) and manganese (Mn) and hazard quotient (HQ) in young leaves (one bud and two leaves, YL) and mature leaves (canopy leaves, ML). The average F contents and accumulations were 350 mg kg-1 and 203 g ha-1 in YL, and they were 2451 mg kg-1 and 2578 g ha-1 in ML, respectively, with F mainly accumulated in ML. As the growing season progresses, the F content showed a gradual increase in YL, while a decrease in ML, inferring that F may be redistributed from mature leaves to young leaves. Additionally, the F content was quite different among tea varieties which are suitable for processing oolong tea, green tea, and black tea, with higher F accumulation in oolong tea varieties than in green and black tea varieties. Moreover, F content and accumulation could be obviously affected by the geographical origin of the tea tree varieties, with significantly higher F content in the varieties from F rich fluorite belts than other regions. Furthermore, F content and accumulation showed a significant positive correlation with the content of Al and Mn (p < 0.05). Based on a daily tea consumption of 8.7 g, the HQ was investigated to show that the proportion of tea leaves with HQ<1 made from spring, summer and autumn tender leaves of 85 varieties was 100 %, 90.6 % and 50.6 %, respectively, indicating that the tea with the best drinking safety comes from spring, followed by summer, and then autumn. This result suggests that it could be necessary to avoid planting tea trees in fluorite mining areas, choose low F tea tree varieties, and control the tenderness of fresh leaves in order to ensure the safety of tea drinking.

5.
World J Clin Cases ; 12(16): 2862-2868, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38899292

ABSTRACT

BACKGROUND: Rectal mucosal melanoma is a rare and highly aggressive disease. Common symptoms include anal pain, an anal mass, or bleeding. As such, the disease is usually detected on rectal examination of patients with other suspected anorectal diseases. However, due to its rarity and nonspecific symptoms, melanoma of the rectal mucosa is easily misdiagnosed. CASE SUMMARY: This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months, without any identifiable cause. During colonoscopy, a bulge of approximately 2.2 cm × 2.0 cm was identified. Subsequently, the patient underwent endoscopic ultrasound (EUS) to characterize the depth of invasion of the lesions. EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes. Following surgical intervention, the excised tissue samples were examined and confirmed to be rectal malignant melanoma. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.

6.
Biodivers Data J ; 12: e123990, 2024.
Article in English | MEDLINE | ID: mdl-38939162

ABSTRACT

Background: The spiny eel genus Sinobdella belongs to the family Mastacembelidae of the order Synbranchiformes. Kottelat and Lim (1994) utilised Rhynchobdellasinensis as the type species to propose the genus. Currently, it contains a single species widespread in eastern and southern China and northern Vietnam. New information: Sinobdellalongitubulus, a new species of spiny eel, is here described from the Xi-Jiang of the Zhu-Jiang Basin in Guangxi Zhuang Autonomous Region, southern China. It differs from the single congeneric species S.sinensis in having a more or less white-brown reticulated pattern on the flank, two tubular anterior nostrils longer than or equal to the rostral appendage, an anal fin heavily mottled with dark brown markings and white spots and bearing a narrow white distal margin; shorter pre-anal length; and fewer abdominal vertebrae. The validity of this new species is corroborated by its monophyly recovered in a COI gene-based phylogenetic analysis and its significant sequence divergence with S.sinensis. A note on the type locality of S.sinensis is also given; its type specimen is possibly from mountain streams of Jiangxi Province, in the lower Chang-Jiang Basin.

7.
Acta Physiol (Oxf) ; 240(8): e14180, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38801063

ABSTRACT

AIM: MicroRNAs (miRNAs) regulate ß-cell function, and ß-cell mitochondria and insulin secretion are perturbed in diabetes. We aimed to identify key miRNAs regulating ß-cell mitochondrial metabolism and novel ß-cell miRNA-mitochondrial pathways. METHODS: TargetScan (http://www.targetscan.org/) was used to predict if 16 miRNAs implicated in ß-cell function target 27 cis-eGenes implicated in mitochondrial activity. The expression of candidate miRNAs and insulin secretion after 24 and 1 h pre-incubation in 2.8, 11.1- and 16.7-mM glucose was measured in clonal INS-1 832/13 ß-cells. MiR-29 silenced INS-1 832/13 cells were assessed for insulin secretion (glucose, pyruvate, and K+), target cis-eGene expression (Ndufv3 and Ndufa10 components of mitochondrial complex I (CI)), OXPHOS (CI-V) protein expression, and mitochondrial OXPHOS respiration/activity. The expression of differentially expressed miR-29 miRNAs was evaluated in Goto-Kakizaki (GK) rat, db/db mouse and type 2 diabetic (T2D) human islets, as well as NMRI mouse islets cultured under glucolipotoxic conditions. RESULTS: MiR-29, miR-15 and miR-124 were predicted to regulate ~20 cis-eGenes, while miR-29 alone was predicted to regulate ≥12 of these in rat and human species. MiR-29 expression and insulin secretion were reduced in INS-1 832/13 cells after 24 h in elevated glucose. MiR-29 knockdown increased all tested insulin secretory responses, Nudfv3, Ndufa10, complex I and II expression, and cellular mitochondrial OXPHOS. MiR-29 expression was reduced in db/db islets but increased in GK rat and T2D human islets. CONCLUSION: We conclude miR-29 is a key miRNA in regulating ß-cell mitochondrial metabolism and insulin secretion via underlying miR-29-OXPHOS complex pathways. Furthermore, we infer reduced miR-29 expression compensatorily enhances insulin secretion under glucotoxicity.


Subject(s)
Insulin Secretion , Insulin-Secreting Cells , MicroRNAs , Mitochondria , MicroRNAs/metabolism , MicroRNAs/genetics , Animals , Insulin-Secreting Cells/metabolism , Mitochondria/metabolism , Rats , Humans , Mice , Insulin/metabolism , Male , Oxidative Phosphorylation , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/genetics
8.
Public Health ; 232: 100-107, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38772197

ABSTRACT

OBJECTIVES: To determine whether gestational cardiovascular health (CVH) during the first trimester is associated with a risk of adverse pregnancy outcomes. STUDY DESIGN: A multicentre prospective cohort; part of the China birth cohort study. METHODS: Pregnant women were recruited at 6-13+6 gestation weeks and followed to delivery to identify pregnancy outcomes. Gestational CVH in the first trimester was assessed using five CVH metrics: body mass index, smoking, blood pressure, glucose, and lipids. Multilevel modified Poisson regression models calculated the relative risks (RRs) and 95% confidence intervals (95% CIs) of gestational CVH for adverse pregnancy outcomes. RESULTS: Among 56,852 pregnant women, the mean score for gestational CVH during the first trimester was 9.1. Adjusting for confounding factors, each 1-point decrease in the total gestational CVH score significantly increased the risk of hypertensive disorders of pregnancy (RR = 1.682, 95% CI: 1.624-1.743), gestational diabetes mellitus (RR = 1.405, 95% CI: 1.384-1.426), preterm birth (RR = 1.184, 95% CI: 1.174-1.195), large for gestational age (RR = 1.224, 95% CI: 1.199-1.250), caesarean delivery (RR = 1.073, 95% CI: 1.049-1.097), and low Apgar score (RR = 1.131, 95% CI: 1.003-1.277) significantly increased. Meanwhile, the risk of small for gestational age decreased (SGA; RR = 0.922, 95% CI: 0.898-0.946). Worsened CVH categories significantly increased the risk of adverse pregnancy outcomes, excluding SGA. CONCLUSIONS: Poor gestational CVH in the first trimester significantly increases the risk of adverse pregnancy outcomes, emphasising the need for early improvement in gestational CVH.


Subject(s)
Pregnancy Outcome , Pregnancy Trimester, First , Humans , Pregnancy , Female , China/epidemiology , Pregnancy Outcome/epidemiology , Adult , Prospective Studies , Diabetes, Gestational/epidemiology , Birth Cohort , Risk Factors , Cardiovascular Diseases/epidemiology , Body Mass Index , Premature Birth/epidemiology , Infant, Newborn , Blood Pressure
9.
Mar Drugs ; 22(3)2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38535466

ABSTRACT

Polymannuronic acid (PM) is an alginate oligosaccharide derived from brown algae with a characterized structure and excellent biological activities. Herein, mice were given different doses of PM through 30-day-long-term intragastric administration, and the contents of the jejunum, ileum, and colon were analyzed by 16S rRNA gene sequencing technology for microbial diversity, and relevant experiments were verified according to the analysis results so as to comprehensively evaluate the effects of PM on the intestinal flora. The PM (400 mg/kg and 100 mg/kg) could regulate the microflora balance at the phylum level and increase the microflora richness in the jejunum, ileum, and colon of the mice. The PM could induce more strains that are negatively correlated with Escherichia, thereby reducing the relative abundance of Escherichia. Analysis of bacterial function showed that high and low doses of PM could promote lipid metabolism in the bacterial communities. Moreover, the PM could reduce serum total cholesterol and cholesterol ester levels in a concentration-dependent manner. High-dose PM could lead to colonic intestinal inflammation by increasing the relative abundance of multiple bacterial groups in the jejunum, ileum, and colon. Moreover, high-dose PM could increase lipopolysaccharide-binding protein and interleukin-1ß levels. Therefore, the dose of PM plays an important role in its efficacy, and its biological activity is dosedifferent.


Subject(s)
Alginic Acid , Gastrointestinal Microbiome , Animals , Mice , RNA, Ribosomal, 16S , Alginates , Ileum
10.
Sci Rep ; 14(1): 411, 2024 01 03.
Article in English | MEDLINE | ID: mdl-38172325

ABSTRACT

Rural children are more at risk for childhood obesity but may have difficulty participating in pediatric weight management clinical trials if in-person visits are required. Remote assessment of height and weight observed via videoconferencing may provide a solution by improving the accuracy of self-reported data. This study aims to validate a low-cost, scalable video-assisted protocol for remote height and weight measurements in children and caregivers. Families were provided with low-cost digital scales and tape measures and a standardized protocol for remote measurements. Thirty-three caregiver and child (6-11 years old) dyads completed remote (at home) height and weight measurements while being observed by research staff via videoconferencing, as well as in-person measurements with research staff. We compared the overall and absolute mean differences in child and caregiver weight, height, body mass index (BMI), and child BMI adjusted Z-score (BMIaz) between remote and in-person measurements using paired samples t-tests and one sample t-tests, respectively. Bland-Altman plots were used to estimate the limits of agreement (LOA) and assess systematic bias. Simple regression models were used to examine associations between measurement discrepancies and sociodemographic factors and number of days between measurements. Overall mean differences in child and caregiver weight, height, BMI, and child BMIaz were not significantly different between remote and in-person measurements. LOAs were - 2.1 and 1.7 kg for child weight, - 5.2 and 4.0 cm for child height, - 1.5 and 1.7 kg/m2 for child BMI, - 0.4 and 0.5 SD for child BMIaz, - 3.0 and 2.8 kg for caregiver weight, - 2.9 and 3.9 cm for caregiver height, and - 2.1 and 1.6 kg/m2 for caregiver BMI. Absolute mean differences were significantly different between the two approaches for all measurements. Child and caregiver age were each significantly associated with differences between remote and in-person caregiver height measurements; there were no significant associations with other measurement discrepancies. Remotely observed weight and height measurements using non-research grade equipment may be a feasible and valid approach for pediatric clinical trials in rural communities. However, researchers should carefully evaluate their measurement precision requirements and intervention effect size to determine whether remote height and weight measurements suit their studies.Trial registration: ClinicalTrials.gov NCT04142034 (29/10/2019).


Subject(s)
Pediatric Obesity , Humans , Child , Body Weight , Pediatric Obesity/diagnosis , Rural Population , Body Height , Body Mass Index , Primary Health Care
11.
J Fish Biol ; 104(2): 410-421, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36740452

ABSTRACT

The tapertail anchovy Coilia brachygnathus, a commercially important species mainly distributed along the mid-lower Chang-Jiang basin, is by far the most dominant species in Lake Honghu. To figure out its success in this semiclosed lake, some basic biological parameters of this anchovy were analysed based on samples seasonally collected from October 2020 to December 2021. The results demonstrated that the age classes of fished individuals varied from 0.5 to 3.5, with the majority (97.36%) being between 0.5 and 3 years old. The size at 50% maturity of 17.2 cm total length (TL) for females and 19.0 cm TL for males corresponded to 1 and 1.6 years, respectively. Coilia brachygnathus has a short life span, early sexual maturity and a relatively fast growth rate. The flourishing of the fish in the lake is mainly attributed to its short life span, early maturity, fast growth rate, closed fishing, pelagic spawners, the availability of plenty of food and low predation effect on it. Age 3.5 year occurs in an extremely small percentage of the total (<3%), indicating that a large number of larger-sized or older fish died after spawning, which is probably one of the major sources of water pollution if the closed fishing measure is adopted in Lake Honghu. Thus, individuals older than 2 years or more than 20.0 cm TL should be harvested. These findings have important management implications for the fish resources in Lake Honghu and beyond.


Subject(s)
Fishes , Lakes , Male , Female , Animals , China
12.
J Fish Biol ; 104(2): 433-449, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36879537

ABSTRACT

Two new species of Leptobotia are here described as L. rotundilobus from the Xin'an-Jiang of the upper Qiantang-Jiang basin in both Anhui and Zhejiang Provinces and the Cao'e-Jiang in Zhejiang Province, and L. paucipinna from the Qing-Jiang of the middle Chang-Jiang basin in Hubei Province, South China. Both have a plain brown body as found in L. bellacauda Bohlen & Slechtová, 2016, L. microphthalma Fu & Ye, 1983, L. posterodorsalis Chen & Lan, 1992 and L. tientainensis (Wu, 1930). The two new species are distinct from these species in vertebral counts, further from L. posterodorsalis in vent placement and further from the other three species in pectoral-fin length. Both differ in caudal-fin coloration and shape, and dorsal-fin location and coloration, and also in internal morphology. Their validity is confirmed by their own monophyly recovered in a phylogenetic analysis based on the mitochondrial cyt b and COI genes.


Subject(s)
Cypriniformes , Animals , Cypriniformes/anatomy & histology , Phylogeny , China , Rivers
13.
J Fish Biol ; 104(2): 345-364, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37927158

ABSTRACT

China harbors a high species diversity of freshwater fishes not shared with any of its neighboring nations. Freshwater fish diversity in the country has been under severe threat from human activities over the past decades, thus conservation freshwater fishes and ecosystems is urgently needed. To accumulate baseline data for guiding protection actions, the third red list assessment of Chinese freshwater fishes was carried out. Among Chinese freshwater fishes assessed, there are 355 at-risk species (22.3% of the total), including 69 ranked as Critically Endangered, 97 as Endangered, and 189 as Vulnerable. Two species are classified as Extinct and one as Regionally Extinct. China's threat level seems to be lower than the known average level found in the IUCN's global assessment of freshwater fishes, but this is an artifact of a high rate of species classified as Data Deficient. Conservation of freshwater fishes is presently facing a grim situation in China. Imperilment of Chinese freshwater fishes is primarily attributed to habitat loss and degradation arising from human perturbations, particularly river damming. Despite the adoption of protected areas setting up, captive breeding and release, and a fishing moratorium, conservation efforts for freshwater fishes are compromised by disproportional attention in China's biodiversity conservation, baseline data deficiency, insufficiently designed protection networks, and inefficient or inadequate implementation of conservation strategies. To achieve the objectives of Chinese freshwater fish conservation, it is proposed to conduct a national-scale survey of fish diversity and reassess their at-risk status, develop systematic conservation planning of freshwater fish diversity and ecosystems, prioritize strategies for protected areas development, perform genetic-based captive breeding for releasing in concert with other protection actions, and implement flexible fishing moratorium strategies in different water bodies.


Subject(s)
Conservation of Natural Resources , Ecosystem , Humans , Animals , Fresh Water , Biodiversity , China , Fishes/genetics
14.
Cell ; 186(26): 5859-5875.e24, 2023 12 21.
Article in English | MEDLINE | ID: mdl-38052213

ABSTRACT

Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-ß, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts. This approach facilitates the co-culture of embryonic and extraembryonic stem cells, revealing a growth inhibition effect exerted by extraembryonic endoderm cells on pluripotent cells, partially through extracellular matrix signaling. Additionally, our cross-species analysis identified both shared and unique transcription factors and pathways regulating FTW-XENs. The embryonic and extraembryonic stem cell co-culture strategy offers promising avenues for developing more faithful embryo models and devising more developmentally pertinent differentiation protocols.


Subject(s)
Embryo, Mammalian , Embryonic Stem Cells , Animals , Coculture Techniques , Macaca fascicularis , Embryonic Stem Cells/metabolism , Cell Differentiation , Endoderm/metabolism , Cell Lineage
15.
Mar Drugs ; 21(12)2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38132944

ABSTRACT

Resistomycin is a natural antibiotic related to quinone that has been shown to exhibit robust antitumor activity. To further characterize the mechanistic basis for such activity, human colorectal cancer (CRC) cells were selected as a model to explore the role of Wnt/ß-catenin signaling in the ability of resistomycin to induce apoptotic cell death. These analyses revealed that resistomycin was able to suppress ß-catenin, TCF4, and GSK-3ß expression, together with that of the downstream targets c-Myc and survivin. This coincided with elevated cleaved caspase-3 and Bax protein levels and a decline in Bcl-2 content. When ß-catenin was silenced, this further enhanced the ability of resistomycin to induce apoptotic CRC cell death, whereas this apoptotic process was partially ablated when cells were treated using lithium chloride to activate Wnt/ß-catenin signaling. Overall, these results support a model wherein resistomycin inhibits Wnt/ß-catenin signaling within CRC cells, thereby inducing apoptotic death. Further research may be warranted to better clarify the potential utility of this compound as a candidate drug for use in the treatment of patients suffering from this form of cancer.


Subject(s)
Colorectal Neoplasms , beta Catenin , Humans , beta Catenin/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Colorectal Neoplasms/pathology , Wnt Signaling Pathway , Apoptosis , Cell Proliferation , Cell Line, Tumor , Gene Expression Regulation, Neoplastic
16.
Cancer Res Commun ; 3(11): 2386-2399, 2023 11 22.
Article in English | MEDLINE | ID: mdl-37874199

ABSTRACT

XIAP, the most potent mammalian inhibitor of apoptosis protein (IAP), critically restricts developmental culling of sympathetic neuronal progenitors, and is correspondingly overexpressed in most MYCN-amplified neuroblastoma tumors. Because apoptosis-related protein in the TGFß signaling pathway (ARTS) is the only XIAP antagonist that directly binds and degrades XIAP, we evaluated the preclinical effectiveness and tolerability of XIAP antagonism as a novel targeting strategy for neuroblastoma. We found that antagonism of XIAP, but not other IAPs, triggered apoptotic death in neuroblastoma cells. XIAP silencing induced apoptosis while overexpression conferred protection from drug-induced apoptosis. From a screen of IAP inhibitors, first-in-class ARTS mimetic A4 was most effective against high-risk and high XIAP-expressing neuroblastoma cells, and least toxic toward normal liver- and bone marrow-derived cells, compared with pan-IAP antagonists. On target engagement assays and nuclear magnetic resonance spectroscopy, A4 was observed to degrade rather than inhibit XIAP, catalyzing rapid degradation of XIAP through the ubiquitin-proteasome pathway. In MYCN-amplified neuroblastoma patient-derived xenografts, A4 significantly prolonged survival as a single agent, and demonstrated synergism with standard-of-care agents to reduce their effective required doses 3- to 6-fold. Engagement and degradation of XIAP by ARTS mimetics is a novel targeting strategy for neuroblastoma that may be especially effective against MYCN-amplified disease with intrinsically high XIAP expression. First-in-class ARTS mimetic A4 demonstrates preclinical efficacy and warrants further development and study. SIGNIFICANCE: XIAP degradation is sufficient to kill MYCN-amplified neuroblastoma which overexpresses and relies on XIAP as a brake against cell death, without affecting normal cells.


Subject(s)
Neuroblastoma , X-Linked Inhibitor of Apoptosis Protein , Animals , Humans , N-Myc Proto-Oncogene Protein/genetics , X-Linked Inhibitor of Apoptosis Protein/genetics , Apoptosis , Neuroblastoma/drug therapy , Inhibitor of Apoptosis Proteins/metabolism , Mammals/metabolism
17.
Carbohydr Polym ; 321: 121334, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37739547

ABSTRACT

Polyguluronic acid (PG), a polysaccharide from alginate, possesses excellent bioactivities. We prepared high-purity PG with 10.41 kDa molecular weight (Mw) and a 59 average degree of polymerization (DP) by acid hydrolysis, three pH grades, Q-Sepharose column elution, and Sephadex G-25 column desalination. Then, we evaluated the PG protective effects on doxorubicin-induced cardiotoxicity (DIC) in vitro and in vivo. The nontoxic PG enhanced cellular viability, reduced cell pyroptosis morphology, diminished the LDH and IL-1ß release, and downregulated expressions of ASC oligomerization, NLRP3, cl-CASP1, and GSDMD, by which PG protected the cardiomyocytes from NLRP3 inflammasome-mediated pyroptosis in doxorubicin-stimulated HL-1 cells and C57BL/6J mice. The probable underlying mechanism may be that PG downregulated doxorubicin -induced Peli1, the deficiency of which could inhibit doxorubicin-induced NLRP3 inflammasome-mediated pyroptosis. These results suggested that polysaccharide PG from alginate could prevent DIC and may be a potential therapeutic agent or bioactive material for preventing DIC.


Subject(s)
Inflammasomes , Pyroptosis , Mice , Animals , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein , Cardiotoxicity/drug therapy , Alginates/pharmacology , Doxorubicin/toxicity , Nuclear Proteins , Ubiquitin-Protein Ligases
18.
Pharm Biol ; 61(1): 1401-1412, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37667488

ABSTRACT

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects. OBJECTIVE: We evaluated the neuroprotective effects of SPJ on aging rats. MATERIALS AND METHODS: Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro. RESULTS: SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p < 0.05 or p < 0.01 vs. 22 M). The in vitro studies also demonstrated that SPJ attenuated d-Gal-induced cell senescence concomitant with the improvement in mitochondrial function; SPJ, also up-regulated the Mfn2 and Opa1 protein levels, whereas the Drp1 protein level (p < 0.05 or p < 0.01 vs. d-Gal group) was down-regulated. DISCUSSION AND CONCLUSIONS: Further research on the elderly population will contribute to the development and utilization of SPJ for the treatment of neurodegenerative disorders.


Subject(s)
Neuroblastoma , Panax , Aged , Humans , Rats , Animals , Rats, Sprague-Dawley , Aging , Galactose , Mitochondria
19.
Zootaxa ; 5306(2): 232-242, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37518526

ABSTRACT

The generic diagnostic characters of Paracercopis (Hemiptera: Cercopoidea: Cercopidae) are redefined and the autapomorphies are proposed to support the monophyly of the genus. Scanning electron micrographs of antennal sensilla and sensilla on rostral apex of P. seminigra (Melichar, 1902) are provided for the first time. A checklist together with new distribution records and key to the species of the genus are provided. Host plant associations of Paracercopis species are reported for the first time. Paracercopis unicolor Liang, Zhang & Xiao, sp. nov., representing the seventh and largest species of the genus is described from Hubei Province in south central China.


Subject(s)
Hemiptera , Animals , China , Microscopy , Sensilla
20.
Sensors (Basel) ; 23(14)2023 Jul 11.
Article in English | MEDLINE | ID: mdl-37514610

ABSTRACT

Compared to wide-field telescopes, small-field detection systems have higher spatial resolution, resulting in stronger detection capabilities and higher positioning accuracy. When detecting by small fields in synchronous orbit, both space debris and fixed stars are imaged as point targets, making it difficult to distinguish them. In addition, with the improvement in detection capabilities, the number of stars in the background rapidly increases, which puts higher requirements on recognition algorithms. Therefore, star detection is indispensable for identifying and locating space debris in complex backgrounds. To address these difficulties, this paper proposes a real-time star extraction method based on adaptive filtering and multi-frame projection. We use bad point repair and background suppression algorithms to preprocess star images. Afterwards, we analyze and enhance the target signal-to-noise ratio (SNR). Then, we use multi-frame projection to fuse information. Subsequently, adaptive filtering, adaptive morphology, and adaptive median filtering algorithms are proposed to detect trajectories. Finally, the projection is released to locate the target. Our recognition algorithm has been verified by real star images, and the images were captured using small-field telescopes. The experimental results demonstrate the effectiveness of the algorithm proposed in this paper. We successfully extracted hip-27066 star, which has a magnitude of about 12 and an SNR of about 1.5. Compared with existing methods, our algorithm has advantages in both recognition rate and false-alarm rate, and can be used as a real-time target recognition algorithm for space-based synchronous orbit detection payloads.

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