[Effect of UCP2-siRNA on inflammatory response of cardiomyocytes induced by septic serum].

OBJECTIVE: To study the effect of uncoupling protein 2 (UCP2)-siRNA on the inflammatory response of rat cardiomyocytes (H9C2) induced by septic serum and to investigate the possible role of UCP2 in the development of septic cardiomyopathy. METHODS: Serum samples were separately collected from normal rats and septic rats. Cultured rat cardiac cells (H9C2) were randomly divided into blank control, normal serum, 10% septic serum, UCP2-siRNA+10% septic serum and negative siRNA+10% septic serum groups. Stimulation with 10% septic serum was performed for 12 hours in relevant groups. The mRNA expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) was measured by RT-PCR. The expression of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor-kappa B (NF-κB) was measured by Western blot. RESULTS: The expression levels of p-p38 and NF-κB in the UCP2-siRNA+10% septic serum group were significantly higher than in the 10% septic serum group (P<0.05). The UCP2-siRNA+10% septic serum group had a significantly higher TNF-α mRNA expression than the 10% septic serum group (P<0.01), but IL-1ß mRNA expression showed no significant difference between the two groups. CONCLUSIONS: UCP2 plays a regulatory role in the activation of p38 MAPK and NF-κB and the expression of downstream inflammatory mediators in H9C2 cells stimulated with septic serum.

Advances in fluorescent probe development for bioimaging of potential Parkinson's biomarkers.

Parkinson's disease (PD) is a common neurodegenerative disease. The clinical symptoms of PD are usually related to motor symptoms, including postural instability, rigidity, bradykinesia, and resting tremors. At present, the pathology of PD is not yet clear. Therefore, revealing the underlying pathological mechanism of PD is of great significance. A variety of bioactive molecules are produced during the onset of Parkinson's, and these bioactive molecules may be a key factor in the development of Parkinson's. The emerging fluorescence imaging technology has good sensitivity and high signal-to-noise ratio, making it possible to deeply understand the pathogenesis of PD through these bioactive molecules. Currently, fluorescent probes targeting PD biomarkers are widely developed and applied. This article categorizes and summarizes fluorescent probes based on different PD biomarkers, systematically introduces their applications in the pathological process of PD, and finally briefly elaborates on the challenges and prospects of these probes. We hope that this review will provide in-depth reference insights for designing fluorescent probes, and contribute to study of the pathogenesis and clinical treatment of PD.

Functional variant in methionine synthase reductase decreases the risk of Down syndrome in China.

AIM: Down syndrome (DS) is the most common genetic cause of human mental retardation and the genes involved in homocysteine/folate metabolism may play important roles in this condition. Methionine synthase reductase (MTRR) is one of the key regulatory enzymes involved in the metabolic pathway of homocysteine. We investigated whether the polymorphism C524T of the MTRR gene is associated with DS. METHOD: A total of 104 mothers of children born with DS and 184 healthy mothers were included. The polymorphisms were detected by polymerase chain reaction and restriction fragment length polymorphism analysis. Plasma folate and total plasma homocysteine (t-Hcy) concentrations were also measured. RESULTS: Significant differences in the distributions of C524T alleles were observed between case and control mothers; a decreased risk of DS was associated with the 524TT genotype (OR=0.34), CT+TT genotype (OR=0.60). The mean t-Hcy value in the case group was higher than the mean value in the control group. t-Hcy concentrations were lower in TT homozygote than CC homozygote among the cases but not among the controls. CONCLUSION: MTRR C524T polymorphism decreases the risk of DS in the Chinese population.

Polymorphisms in genes RFC-1/CBS as maternal risk factors for Down syndrome in China.

PURPOSE: To explore the relationship between genetic polymorphisms in reduced folate carrier 1 (RFC-1), cystathionine b-synthase (CBS), two key genes in folate metabolism, and the risk of Down syndrome in China. METHODS: Genomic DNA was isolated from the peripheral lymphocytes of 104 mothers born children with Down syndrome and 184 age-matched control mothers. Polymerase chain reaction and restriction-fragment length polymorphism were used to examine the polymorphisms of RFC-1 A80G, CBS T833C and the relationship between these genotypes and the risk of Down syndrome was analyzed. RESULTS: We found that there were significant differences between RFC-1 G80G, CBS C833C polymorphisms among mothers of children with Down syndrome than among control mothers, with odds ratio of 1.51 (95 % CI 1.05-2.18), 1.53 (95 % CI 1.07-2.18) respectively. The combined presence of RFC1 mutant alleles and the CBS homozygous mutant allele (15/104) was associated with a 4.81-fold increased risk of having a child with Down syndrome (95 % CI 1.82-12.68, P = 0.0007). CONCLUSIONS: We concluded that RFC-1 and CBS gene mutation alleles are related to Down syndrome, and women with mutation RFC-1 G80G, CBS C833C OR combined with RFC-1 A80G and CBS 833TT genotype increase the risk of Down syndrome in China.

Investigating Doxorubicin's mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives.

Introduction: Cervical cancer remains a significant global health burden, and Doxorubicin is a crucial therapeutic agent against this disease. However, the precise molecular mechanisms responsible for its therapeutic effects are not fully understood. Methods: In this study, we employed a multi-omics approach that combined transcriptomic and metabolomic analyses with cellular and in vivo experiments. The goal was to comprehensively investigate the molecular landscape associated with Doxorubicin treatment in cervical cancer. Results: Our unbiased differential gene expression analysis revealed distinct alterations in gene expression patterns following Doxorubicin treatment. Notably, the ANKRD18B gene exhibited a prominent role in the response to Doxorubicin. Simultaneously, our metabolomic analysis demonstrated significant perturbations in metabolite profiles, with a particular focus on L-Ornithine. The correlation between ANKRD18B gene expression and L-Ornithine levels indicated a tightly controlled gene-metabolite network. These results were further confirmed through rigorous cellular and in vivo experiments, which showed reductions in subcutaneous tumor size and significant changes in ANKRD18B, L-Ornithine, and Doxorubicin concentration. Discussion: The findings of this study underscore the intricate interplay between transcriptomic and metabolomic changes in response to Doxorubicin treatment. These insights could have implications for the development of more effective therapeutic strategies for cervical cancer. The identification of ANKRD18B and L-Ornithine as key components in this process lays the groundwork for future research aiming to unravel the complex molecular networks that underlie Doxorubicin's therapeutic mechanism. While this study provides a solid foundation, it also highlights the necessity for further investigation to fully grasp these interactions and their potential implications for cervical cancer treatment.

Intracranial germinoma combined with parathyroid adenoma in a male pediatric patient: A case report.

Cases of young patients combined with intracranial germinoma and parathyroid adenoma are extremely rare. A 6.25-year-old boy was diagnosed with growth hormone deficiency at his first visit and was then treated with growth hormone substitution. Later, he was clinically diagnosed with central diabetes insipidus (CDI) and primary hyperparathyroidism, whereas no abnormal imaging evidence was identified, except for a thickened pituitary stalk. Due to persistent follow-up, parathyroid adenoma and intracranial germinoma were verified in succession. The patient had derived benefits from parathyroidectomy and chemotherapy plus radiotherapy. We concluded that children and adolescents who present with CDI and pituitary stalk thickening should undergo repeated screenings for underlying intracranial germinoma. Multiple lesions involving the parathyroid gland and pituitary should alert physicians to the possibility of multiple endocrine neoplasia or other inherited diseases; therefore, genetic screening is recommended.

Clinical characteristics and gene mutation analysis of methylmalonic aciduria.

Methylmalonic aciduria (MMA) is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase (MCM, mut complementation group) or in the synthesis of the MCM cofactor adenosylcobalamin (cbl complementation groups). The defects in the mut complementation group accounts for the largest number of patients with isolated MMA. At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now. This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients. Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry (GC-MS), and from some of their parents as well. Amplification and direct sequencing of the MUT coding regions (exon 2-13) and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations. In this group, six novel mutations in the MUT gene, c.424A>G (p.T142A), c.786T>G (p.S262R), c.808G>C (p.G270R), c.1323_1324insA, c.1445-1G>A and c.1676+77A>C were identified. p.T142A and p.G270R were respectively detected at a heterozygous level in one patient. Two previously reported mutations, c.682C>T (p.R228X) and c.323G>A (p.R108H) were also found in this study. In addition, six previously described single nucleotide polymorphism (SNP), c.636A>G (p.K212K), c.1495G>A (p.A499T), c.1595A>G (p.H532R), c.1992G>A (p.A664A), c.2011G>A (p.V671I) and c.1677-53A>G were identified. In this study, we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.

Regulating effect of heterojunctions on electrocatalytic oxidation of methanol for Pt/WO3-NaTaO3 catalysts.

Pt/WO3-NaTaO3 composite catalysts for different W/Ta molar ratios were obtained via a facile hydrothermal method. The WO3-NaTaO3 heterojunction was constituted and could be regulated by the adjustment of the W : Ta ratio, as confirmed by multiple characterizations. Due to the favorable CO anti-poisoning characteristics ascribed to the sufficient surface -OHad provided by both WO3 and NaTaO3, excellent stability of the WO3-NaTaO3 composite in acidic and alkaline environments, and charge transfer from metal oxide to Pt, the as-obtained Pt/WO3-NaTaO3 composite catalyst could exhibit desirably high electrocatalytic performances. As a result, the as-prepared Pt/WO3-NaTaO3 (W : Ta = 3 : 1) and Pt/WO3-NaTaO3 (W : Ta = 0.2 : 1) products exhibited optimal performances in the methanol oxidation reaction (MOR) process in acids and alkalis, respectively, as compared to those of commercial Pt/C, Pt/NaTaO3, and Pt/WO3 catalysts. In particular, in acidic and alkaline environments, the highest electrocatalytic activity of Pt/WO3-NaTaO3 catalyst could reach three times that of commercial Pt/C and its stability could reach more than five times that of commercial Pt/C. Density functional theory calculations further proved the enhancement of WO3 with regard to methanol electrooxidation.

Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China.

OBJECTIVE: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA methylation and synthesis, and the risk of Down syndrome in China. METHODS: Genomic DNA was isolated from the peripheral lymphocytes of 64 mothers of children with Down syndrome and 70 age matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C-->T, MTRR 66A-->G and the relationship between these genotypes and the risk of Down syndrome was analyzed. RESULTS: The results show that the MTHFR 677C-->T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 3.78 (95% confidence interval (CI), 1.78 approximately 8.47). In addition, the homozygous MTRR 66A-->G polymorphism was independently associated with a 5.2-fold increase in estimated risk (95% CI, 1.90 approximately 14.22). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than the presence of either alone, with an odds ratio of 6.0 (95% CI, 2.058 approximately 17.496). The two polymorphisms appear to act without a multiplicative interaction. CONCLUSION: MTHFR and MTRR gene mutation alleles are related to Down syndrome, and CT, TT and GG gene mutation types increase the risk of Down syndrome.

Coupled Heterojunction Sn2Ta2O7@SnO2: Cooperative Promotion of Effective Electron-Hole Separation and Superior Visible-light Absorption.

In this work, a novel heterostructure integrated by two wide-band gap semiconductors, SnO2 and Sn2Ta2O7, is successfully prepared via a hydrothermal approach. Hollow Sn2Ta2O7 spheres were first formed, and small SnO2 particles were then well-dispersed onto the outside surface of the spheres, forming a p-n heterostructure. This heterostructure exhibits a higher potential edge that yielded enhanced photoredox ability. Further, the heterostructure is of Z-type with a consistent internal electric field direction, which effectively separates the photogenerated electron-hole pairs. Although both component semiconductors do not absorb visible light, the resulted p-n heterostructure is surprisingly observed to show an outstanding photocatalytic performance under visible light illumination. Such a visible light response is concluded to be the consequence of the impurity band formed by Sn(2+) doped in SnO2 and Sn(4+) in Sn2Ta2O7 via in situ redox. The existence of coupled Sn(2+) and Sn(4+) ions in p-n heterostructure is responsible for the absence of defects and the regenerated catalytic activities. The findings reported here may provide an approach to fabricate the new types of photocatalysts with a synergetic promotion for visible light absorption and sustained photocatalytic activities by coupling different wide-band semiconductors.

Clinical Characteristics and Gene Mutation Analysis of Methylmalonic Aciduria / 华中科技大学学报（医学）（英德文版）

Methylmalonic aciduria (MMA) is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase (MCM,mut complementation group) or in the synthesis of the MCM cofactor adenosylcobalamin (cbl complementation groups).The defects in the mut complementation group accounts for the largest number of patients with isolated MMA.At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now.This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients.Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry (GC-MS),and from some of their parents as well.Amplification and direct sequencing of the MUT coding regions (exon 2-13) and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations.In this group,six novel mutations in the MUT gene,c.424A＞G (p.T142A),c.786T＞G (p.S262R),c.808G＞C(p.G270R),c.1323_1324insA,c.1445-1G＞A and c.1676+77A＞C were identified.p.T142A and p.G270R were respectively detected at a heterozygous level in one patient.Two previously reported mutations,c.682C＞T (p.R228X) and c.323G＞A (p.R108H) were also found in this study.In addition,six previously described single nucleotide polymorphism (SNP),c.636A＞G (p.K212K),c.1495G＞A(p.A499T),c.1595A＞G (p.H532R),c.1992G＞A (p.A664A),c.2011G＞A (p.V671I) and c.1677-53A＞Gwere identified.In this study,we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.