ABSTRACT
Increasing evidence underscores the pivotal role of ferroptosis in Parkinson's Disease (PD) pathogenesis. Acteoside (ACT) has been reported to possess neuroprotective properties. However, the effects of ACT on ferroptosis and its molecular mechanisms remain unknown. This study aimed to explore whether ACT can regulate ferroptosis in dopaminergic (DA) neurons within both in vitro and in vivo PD models and to elucidate the underlying regulatory mechanisms. PD models were established and treated with various concentrations of ACT. Cell viability assays, Western blot, lipid peroxidation assessments, immunohistochemistry, and transmission electron microscopy were employed to confirm ACT's inhibition of ferroptosis and its protective effect on DA neurons across PD models. Immunofluorescence staining, MitoSOX staining, and confocal laser scanning microscopy further validated ACT's regulation regulatory effects on ferroptosis via the Nrf2-mitophagy pathway. Four animal behavioral tests were used to assess behavioral improvements in PD animals. ACT inhibited ferroptosis in PD models in vitro, as evidenced by increased cell viability, the upregulation of GPX4 and SLC7A11, reduced lipid peroxides, and attenuation of mitochondrial morphological alterations typical of ferroptosis. By activating the Nrf2-mitophagy axis, ACT enhanced mitochondrial integrity and reduced lipid peroxidation, mitigating ferroptosis. These in vitro results were consistent with in vivo findings, where ACT treatment significantly preserved DA neurons, curbed ferroptosis in these cells, and alleviated cognitive and behavioral deficits. This study is the first demonstration of ACT's capability to inhibit neuronal ferroptosis and protect DA neurons, thus alleviating behavioral and cognitive impairments in both in vitro and in vivo PD models. Furthermore, The suppression of ferroptosis by ACT is achieved through the activation of the Nrf2-mitophagy signaling pathway. Our results show that ACT is beneficial for both treating and preventing PD. They also offer novel therapeutic options for treating PD and molecular targets for regulating ferroptosis.
ABSTRACT
The pathogenesis of glioma has remained unclear. In this study, it was found that high expression of the outer dense fibers of sperm tail 3B (ODF3B) in gliomas was positively correlated with the grade of glioma. The higher the grade, the worse the prognosis. ODF3B is closely related to the growth and apoptosis of glioma. In terms of mechanism, ODF3B was found to affect the proliferation and apoptosis of glioma through the JAK1 and JAK2/STAT3 pathways. ODF3B was also found to affect the growth and apoptosis of glioma in vivo. We conclude that ODF3B affects glioma proliferation and apoptosis via the JAK/STAT pathway and is a potential therapeutic target.
ABSTRACT
OBJECTIVES: To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants. METHODS: A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared. RESULTS: The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively. CONCLUSIONS: SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.
Subject(s)
Infant, Premature , Infant, Small for Gestational Age , Infant, Newborn , Child , Infant , Female , Humans , Child, Preschool , Gestational Age , Longitudinal Studies , Retrospective StudiesABSTRACT
Most mammals tolerate exposure to hypobaric hypoxia poorly as it may affect multiple regulatory mechanisms and inhibit cell proliferation, promote apoptosis, limit tissue vascularization, and disrupt the acid-base equilibrium. Here, we quantified the functional state of germ cell development and demonstrated the interaction between the germ and somatic cells via single-cell RNA sequencing (scRNA-seq). The present study elucidated the regulatory effects of hypobaric hypoxia exposure on germ cell formation and sperm differentiation by applying enrichment analysis to genomic regions. Hypobaric hypoxia downregulates the genes controlling granule secretion and organic matter biosynthesis, upregulates tektin 1 (TEKT1) and kinesin family member 2C (KIF2C), and downregulates 60S ribosomal protein 11 (RPL11) and cilia- and flagella-associated protein 206 (CFAP206). Our research indicated that prosaposin-G protein-coupled receptor 37 (PSAP-GPR37) ligands mediate the damage to supporting cells caused by hypobaric hypoxic exposure. The present work revealed that hypoxia injures peritubular myoid (PTM) cells and spermatocytes in the S phase. It also showed that elongating spermatids promote maturation toward the G2 phase and increase their functional reserve for sperm-egg binding. The results of this study provide a theoretical basis for future investigations on prophylactic and therapeutic approaches toward protecting the reproductive system against the harmful effects of hypobaric hypoxic exposure.
ABSTRACT
BACKGROUND: Rattus norvegicus and Suncus murinus are important reservoirs of zoonotic bacterial diseases. An understanding of the composition of gut and oropharynx bacteria in these animals is important for monitoring and preventing such diseases. We therefore examined gut and oropharynx bacterial composition in these animals in China. RESULTS: Proteobacteria, Firmicutes and Bacteroidetes were the most abundant phyla in faecal and throat swab samples of both animals. However, the composition of the bacterial community differed significantly between sample types and animal species. Firmicutes exhibited the highest relative abundance in throat swab samples of R. norvegicus, followed by Proteobacteria and Bacteroidetes. In throat swab specimens of S. murinus, Proteobacteria was the predominant phylum, followed by Firmicutes and Bacteroidetes. Firmicutes showed the highest relative abundance in faecal specimens of R. norvegicus, followed by Bacteroidetes and Proteobacteria. Firmicutes and Proteobacteria had almost equal abundance in faecal specimens of S. murinus, with Bacteroidetes accounting for only 3.07%. The family Streptococcaceae was most common in throat swab samples of R. norvegicus, while Prevotellaceae was most common in its faecal samples. Pseudomonadaceae was the predominant family in throat swab samples of S. murinus, while Enterobacteriaceae was most common in faecal samples. We annotated 33.28% sequences from faecal samples of S. murinus as potential human pathogenic bacteria, approximately 3.06-fold those in R. norvegicus. Potential pathogenic bacteria annotated in throat swab samples of S. murinus were 1.35-fold those in R. norvegicus. CONCLUSIONS: Bacterial composition of throat swabs and faecal samples from R. norvegicus differed from those of S. murinus. Both species carried various pathogenic bacteria, therefore both should be closely monitored in the future, especially for S. murinus.
Subject(s)
Bacteria/classification , RNA, Ribosomal, 16S/analysis , Rats/microbiology , Shrews/microbiology , Animals , Bacteria/genetics , China , Feces/microbiology , Microbiota , Oropharynx/microbiologyABSTRACT
BACKGROUND: The comparisons of molecular characterization and antibiotic resistance of Klebsiella pneumoniae (KP) isolates from humans and other animal hosts are not well studied. Our goal was to compare the molecular epidemiology of KP strains that were isolated from urban rodents, shrews, and healthy people. RESULTS: K. pneumoniae (KP) isolates were isolated from fecal samples of rodents, shrews and healthy adults in 2015 in southern China. In total, 465 fecal samples were collected, of which 85 from rodents, 105 from shrews, and 275 from healthy adults. Antimicrobial susceptibility and production of extended-spectrum ß-lactamases (ESBL) of the isolates were tested. PCR-based methods were used to detect specific genes, including ESBL genes (blaTEM, blaSHV, and blaCTX-M) in ESBL-producing isolates, capsular serotypes (K1, K2, K5, K20, K54, and K57) in hypervirulent KPs (hvKPs), and virulence genes (magA, wcaG, rmpA, uge, kfu, and aerobactin) in hvKP isolates. Multilocus sequence type (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to exclude the homology of these isolates. The carriage rate of KP in urban rodents and shrews (78.42%) was higher than that in healthy adults (66.18%) (χ2 = 8.206, P = 0.004). The prevalence rates of ESBL-producing isolates among rodents, shrews, and humans were 7.94, 12.79, and 17.03%, respectively. The positive rates of CTX-M, TEM and SHV types in ESBL-producing isolates were 29.79, 27.66, and 17.02%, respectively. Serotype K1, K5, K20, and K57 were detected in both small mammals and humans. PFGE typing revealed thirty-six clusters. PFGE cluster A was clustered by samples of shrews and healthy adult, with a similarity of 88.4%. MLST typing revealed thirty-eight types. ST23 and ST35 were detected in samples of shrews and healthy adults. ST37 was detected in samples of 2 rodents and a healthy adult. CONCLUSIONS: Overlapping serotypes of hvKP were observed in both the animals and humans. The same PFGE or MLST types were also found in isolates derived humans, rodents and shrews. Therefore, urban rodents and shrews might play a certain role in the transmission of drug-resistant and hypervirulent KP.
Subject(s)
Anti-Bacterial Agents/pharmacology , Klebsiella pneumoniae/classification , Shrews/microbiology , Virulence Factors/genetics , Animals , Drug Resistance, Bacterial , Electrophoresis, Gel, Pulsed-Field , Feces/microbiology , Healthy Volunteers , Humans , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/pathogenicity , Mice , Microbial Sensitivity Tests , Multilocus Sequence Typing , Phylogeny , RatsABSTRACT
In recent years, hepatitis B virus (HBV) has been detected in some species of animals. In this study, we found HBV-like nucleotide sequences in murine rodents and Asian house shrews (Suncus murinus) collected in China. A total of 801 animals were trapped. We found that 0.48% (3/624) of the murine rodents and 1.69% (3/177) of Asian house shrews were positive for HBV-like DNA. Detection of HBV-like DNA in brown rats (Rattus norvegicus), rice-field rat (Rattus losea), and Asian house shrews indicated that these species of animals might be hosts for HBV. However, none of the HBV-like DNA-positive animals was additionally positive for anti-HBV antibodies or hepatitis B surface antigen. A 585 bp nucleic acid sequence, mapping to a hepadnavirus, was extracted from rice-field rat, and bores strong resemblance to human HBV genotype B sequences. Further research is required to investigate the hepadnaviruses within the murine rodent and Asian house shrew populations to uncover the origin and zoonotic potential of HBV.
Subject(s)
Hepatitis B virus/genetics , Hepatitis B/veterinary , Rodent Diseases/virology , Animals , China , DNA, Viral , Hepatitis B/epidemiology , Hepatitis B virus/classification , Liver/virology , Phylogeny , Rats , Rodent Diseases/epidemiology , Sequence Analysis, DNA , Shrews/virology , ZoonosesABSTRACT
Bocaparvovirus infections of humans and both wild and domestic animals have been widely reported around the world. In this study, we detected and genetically characterized porcine bocavirus (PBoV) carried by murine rodents (Rattus norvegicus, Rattus tanezumi, and Rattus losea) and house shrews (Suncus murinus) in China. Between May 2015 and May 2017, 496 murine rodents and 23 house shrews were captured in four Chinese provinces. Nested polymerase chain reaction was used to investigate the prevalence of PBoV in throat swab, faecal and serum samples. A total of 7.5% (39/519) throat swab samples, 60.5% (309/511) faecal samples, and 22.9% (52/227) serum samples were PBoV-positive. The prevalence among R. norvegicus and R. tanezumi was higher than that among R. losea and house shrews. PBoV-positive samples were found in all four provinces. Phylogenetic analysis based on partial viral capsid protein 1/2 (VP1/VP2) showed that sequences obtained in this study formed a novel group (PBoV G4). In addition, five near full-length PBoV genomes (4,715-4,798 nt) were acquired. These genomes encoded two non-structural proteins, NS1 (1,908 nt in four genomes and 1,923 nt in the remaining genome) and NP1 (600 nt), and the structural proteins, VP1/VP2 (1,851 nt). Phylogenetic analysis showed that PBoV G4 is distinct from rodent, human, and other bocaviruses. In conclusion, PBoV G4 prevalence was high among two common murine rodents in China, and the pathogenecity of PBoV G4 need to be further clarified.
Subject(s)
Bocavirus/isolation & purification , Parvoviridae Infections/veterinary , Rats , Rodent Diseases/epidemiology , Shrews , Animals , China/epidemiology , Feces/virology , Parvoviridae Infections/blood , Parvoviridae Infections/epidemiology , Parvoviridae Infections/virology , Pharynx/virology , Phylogeny , Polymerase Chain Reaction/veterinary , Prevalence , Rodent Diseases/blood , Rodent Diseases/virologyABSTRACT
OBJECTIVE: To investigate the prevalence of the adeno-associated virus (AAV) in murine rodents and house shrews in 4 provinces of China. METHODS: A total of 469 murine rodents and 19 house shrews were captured between May 2015 and May 2017. Cap gene of AAV sequences was obtained to evaluate the genetic characteristics of rat AAV. RESULTS: Rat AAVs were found in 54.7% (267/488) of throat swabs, 14.3% (70/488) of fecal samples, and 18.4% (41/223) of serum samples. Rat AAVs were detected in 3 species of murine rodents including Rattus norvegicus (34.8%), R. tanezumi (43.0%), and R. losea (2.3%), and house shrews (Suncus murinus) (26.1%) from the selected sampling sites. Fourteen near-full-length Cap gene sequences, ranging in length from 2,156 to 2,169 nt, were isolated from the fecal samples of R. norvegicus and R. tanezumi. These 14 sequences shared a high identity of 97.4% at the nucleotide level and 99.1% at the amino acid level. Phylogenetic analysis showed that the rat AAV formed a distinct clade, distinguishable from the AAV discovered in humans and in other animals. CONCLUSIONS: A high prevalence of rat AAV that was highly conserved within the Cap gene was found in 3 common murine rodents and house shrews in China.
Subject(s)
Carrier State/veterinary , Carrier State/virology , Dependovirus , Parvoviridae Infections/veterinary , Rats/virology , Shrews/virology , Animals , China/epidemiology , DNA, Viral/genetics , Feces/virology , Parvoviridae Infections/blood , Pharynx/virology , Phylogeny , Prevalence , Rodentia/virologyABSTRACT
OBJECTIVE: To explore the role of bromodomain and extra terminal (BET) bromodomain in hematopoietic differentiation from human enbryonic stem cells (hESC). METHODS: The effect of BET hematopoietic inhibitor I-BET151 on hematopoietic differentiation from hESC was detected by using a monolayer hematopoietic defferentiation model, immunofluorescence, flow cytometry and real-time PCR; moreover the role of I-BET151 in process of hematopoietic differentiation was explored by adding I-BET151 in different differentiation stages. RESULTS: The analysis results of immunofluorescence, flow cytometry and real-time PCR showed that I-BET 151 significantly inhibited the generation of CD43 positive hematopoietic stem and progenitor cells (HSPCs). It was found that the addition of I-BET 151 in different stages, including APLNR+ lateral plate mesoderm production, CD34+CD31+ hemogenic endothelium (HEP) generation and endothelial-to-hematopoietic transition, significantly suppressed the generation of CD43 positive hematopoietic progenitor cells. CONCLUSION: I-BET 151 inhibites hematopoietic differentiation from hESCs at several stages, suggesting that the BET bromodomain plays important roles in multiple stages of hematopoietic differentiation from hESCs.
Subject(s)
Human Embryonic Stem Cells , Apelin Receptors , Cell Differentiation , Flow Cytometry , Hemangioblasts , Hematopoietic Stem Cells , HumansABSTRACT
Optical coherence tomography (OCT) is an emergent imaging tool used for noninvasive diagnosis of skin diseases. The present meta-analysis was carried out to assess the accuracy of OCT for the diagnosis of skin cancer. We conducted a systematic literature search though EMBASE, Medline, PubMed, the Cochrane Library, and Web of Science database for relevant articles published up to June 6, 2017. The quality of the included studies was assessed using the QUADAS-2 tool and the Oxford Levels of Evidence Scale. Statistical analyses were conducted using the software Meta-Disc version 1.4 and STATA version 12.0. A total of 14 studies involving more than 813 patients with a total of 1958 lesions were included in our analyses. The pooled sensitivity and specificity of OCT for skin cancer diagnoses were 91.8% and 86.7%, respectively. Subgroup analysis showed that the pooled sensitivities of OCT for detecting basal cell carcinoma (BCC), squamous cell carcinoma (SCC), actinic keratosis, and malignant melanoma were 92.4%, 92.3%, 73.8%, and 81.0%, respectively. The pooled specificities were 86.9%, 99.5%, 91.5%, and 93.8%, respectively. OCT appears to be useful for the detection of BCC and SCC. It is a valuable diagnostic method when screening for early skin cancers.
Subject(s)
Image Interpretation, Computer-Assisted , Melanoma/diagnostic imaging , Skin Neoplasms/diagnostic imaging , Tomography, Optical Coherence , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle AgedABSTRACT
PURPOSE: Dermoscopy and reflectance confocal microscopy (RCM) are non-invasive methods for diagnosis of malignant skin tumours. The aim of this study was to compare the accuracy of dermoscopy and RCM for the diagnosis of malignant skin tumours. METHODS: Systematic electronic literature searches were conducted to include PubMed, Medline, Embase, the Cochrane Library database, and Web of Science, up to 26 April 2016. Pooled additional detection rate (ADR), diagnostic accuracy, and 95% confidence intervals (CIs) were calculated using STATA and Meta-Disc analysis. RESULTS: Eight published studies were included in the analysis, involving 1141 skin lesions, which reported a per-lesion analysis of dermoscopy and RCM. Within the same patient group and at the per-lesion level, RCM significantly increased the detection rate of malignant skin tumours by 7.7% (95% CI 0.01-0.14). The pooled sensitivity of dermoscopy was similar to RCM [88.1% (95% CI 0.85-0.91) vs. 93.5% (95% CI 0.91-0.96)]. The specificity of dermoscopy was significantly lower than that of RCM [52.9% (95% CI 0.49-0.57) vs. 80.3% (95% CI 0.77-0.83)]. The pooled ADR of RCM for melanoma detection was 4.3% (95% CI 0.002-0.08). Pooled sensitivity and specificity of dermoscopy for melanoma detection were 88.4% (95% CI 0.84-0.92) and 49.1% (95% CI 0.45-0.53), respectively. The pooled sensitivity and specificity of RCM were 93.5% (95% CI 0.90-0.96) and 78.8% (95% CI 0.75-0.82), respectively. CONCLUSIONS: When compared with dermoscopy, RCM has a significantly greater diagnostic specificity for malignant skin tumours and so could improve their detection rate.