Amiodarone Advances the Apoptosis of Cardiomyocytes by Repressing Sigmar1 Expression and Blocking KCNH2-related Potassium Channels.

BACKGROUND: Heart failure (HF) is the ultimate transformation result of various cardiovascular diseases. Mitochondria-mediated cardiomyocyte apoptosis has been uncovered to be associated with this disorder. OBJECTIVE: This study mainly delves into the mechanism of the anti-arrhythmic drug amiodarone on mitochondrial toxicity of cardiomyocytes. METHODS: The viability of H9c2 cells treated with amiodarone at 0.5, 1, 2, 3, and 4 µM was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and Sigmar1 expression was examined by quantitative real-time PCR (qRTPCR). After transfection, the viability, apoptosis, reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), and potassium voltage-gated channel subfamily H member 2 (KCNH2) expression in H9c2 cells were assessed by MTT, flow cytometry, ROS assay kit, mitochondria staining kit, and Western blot. RESULTS: Amiodarone at 1-4 µM notably weakened H9c2 cell viability with IC50 value of 2.62 ± 0.43 µM. Amiodarone at 0.5-4 µM also evidently suppressed the Sigmar1 level in H9c2 cells. Amiodarone repressed H9c2 cell viability and KCNH2 level and triggered apoptosis, ROS production and mitochondrial depolarization, while Sigmar1 upregulation reversed its effects. Moreover, KCNH2 silencing neutralized the combined modulation of amiodarone and Sigmar1 up-regulation on H9c2 cell viability, apoptosis, and ROS production. CONCLUSION: Amiodarone facilitates the apoptosis of H9c2 cells by restraining Sigmar1 expression and blocking KCNH2-related potassium channels.

The effect of dapagliflozin on anemia in elderly patients with heart failure by bioinformatics analysis.

BACKGROUND: Anemia associated with heart failure is frequent and can exacerbate the symptoms of heart failure. Dapagliflozin is the first SGLT-2 inhibitor with significant cardiovascular protection. However, the effect of dapagliflozin on anemia in elderly patients with heart failure is unknown. OBJECTIVE: We aimed to study the effect of dapagliflozin on anemia in elderly patients with heart failure by bioinformatics analysis. METHODS: The target genes were determined, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network and modules were constructed. The dapagliflozin-targets network in anemia and heart failure was constructed. Molecular docking experiments between dapagliflozin and its key target AKT1 were performed. RESULTS: We found 1 dapagliflozin related target gene and 2 disease related genes. Totally, 134 target genes of dapagliflozin on anemia in elderly patients with heart failure were determined. The pathways may involve lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, hepatitis B, insulin signaling pathway, fluid shear stress and atherosclerosis, neurotrophin signaling pathway, insulin resistance, toxoplasmosis, colorectal cancer, and EGFR tyrosine kinase inhibitor resistance. The hub genes in network were AKT1, TP53, GAPDH, TNF, CASP3, EGFR, and MAPK3. The structure of dapagliflozin and AKT1 molecular docking was exhibited. CONCLUSIONS: The hub genes in network were AKT1, TP53, GAPDH, TNF, CASP3, EGFR, and MAPK3. The structure of dapagliflozin and AKT1 molecular docking was exhibited.

A study on the correlation between MTHFR and folic acid combined with trace elements for the prevention of fetal malformations in the first trimester of pregnancy.

This study aims to elucidate and examine the intricate interrelation between 5,10-methylenetetrahydrofolate reductase (MTHFR), combined folic acid (FA), and trace element supplementation as a preventive strategy against fetal malformations during the inaugural trimester of pregnancy. Eighty pregnant women selected from our hospital's early obstetrics department from May 2021 to August 2021. Pregnant women are divided into the MTHFR combined group, FA, and trace element group. Comparing the basic data of patients, analyzing adverse reactions in pregnant women, and total birth risk situation, detecting MTHFR gene polymorphisms, and analyzing the correlation between MTHFR and FA in the prevention of fetal malformations in early pregnancy. Compared with the north, the southern region is more prone to FA deficiency. MTHFR degree of the MTHFR combined group was positively correlated with fetal malformations. The deformity rate was negatively correlated with FA and trace elements. Pregnant women in the first trimester may have fetal malformations, and the malformation rate is negatively correlated with FA and positively correlated with MTHFR level. Importantly, the inverse relationship between FA supplementation and malformation incidence underscores its significance as a preventive measure.

Concurrent OPA1 mutation and chromosome 3q deletion leading to Behr syndrome: a case report.

BACKGROUND: Optic atrophy 1 (OPA1) gene mutations are associated with dominantly inherited optic neuropathy resulting in a progressive loss of visual acuity. Compound heterozygous or homozygous variants that lead to severe phenotypes, including Behr syndrome, have been reported rarely. CASE PRESENTATION: Here, we present a 14-month-old boy with early onset optic atrophy, congenital cataracts, neuromuscular disorders, mental retardation, and developmental delay. Combined genetic testing, including whole exome sequencing (WES) and chromosomal microarray analysis, revealed a concurrent OPA1 variant (c.2189 T > C p.Leu730Ser) and de novo chromosome 3q deletion as pathogenic variants leading to the severe phenotype. CONCLUSIONS: Our case is the first reporting a novel missense OPA1 variant co-occurring with a chromosomal microdeletion leading to a severe phenotype reminiscent of Behr syndrome. This expands the mutation spectrum of OPA1 and inheritance patterns of this disease.

Time-Resolved Detection of Fingermarks on Non-Porous and Semi-Porous Substrates Using Sr2MgSi2O7:Eu2+, Dy3+ Phosphors.

Eu(2+), Dy(3+) co-doped strontium-magnesium silicate phosphors, Sr2MgSi2O7:Eu(2+), Dy(3+) (SMSEDs), have shown great potential in optoelectronic device due to their unique luminescent property. However, their potential applications in forensic science, latent fingermark detection in particular, are still being investigated. In this contribution, SMSEDs were successfully employed to latent fingermarks on a variety of non-porous and semi-porous surfaces, including aluminum foil, porcelain, glass, painted wood, colored paper, and leather. All the results illustrated that this luminescent powder, as a long-lasting phosphorescence material (LLP), was an ideal time-resolved detection reagent of fingermark for elimination of background interferences from various difficult substrates, and offered a good contrast to allow their identification without the need to enhance the results compared to nanosized organic fluorescent powder.

A purple acid phosphatase plays a role in nodule formation and nitrogen fixation in Astragalus sinicus.

The AsPPD1 gene from Astragalus sinicus encodes a purple acid phosphatase. To address the functions of AsPPD1 in legume-rhizobium symbiosis, its expression patterns, enzyme activity, subcellular localization, and phenotypes associated with its over-expression and RNA interference (RNAi) were investigated. The expression of AsPPD1 was up-regulated in roots and nodules after inoculation with rhizobia. Phosphate starvation reduced the levels of AsPPD1 transcripts in roots while increased those levels in nodules. We confirmed the acid phosphatase and phosphodiesterase activities of recombinant AsPPD1 purified from Pichia pastoris, and demonstrated its ability to hydrolyze ADP and ATP in vitro. Subcellular localization showed that AsPPD1 located on the plasma membranes in hairy roots and on the symbiosomes membranes in root nodules. Over-expression of AsPPD1 in hairy roots inhibited nodulation, while its silencing resulted in nodules early senescence and significantly decreased nitrogenase activity. Furthermore, HPLC measurement showed that AsPPD1 overexpression affects the ADP levels in the infected roots and nodules, AsPPD1 silencing affects the ratio of ATP/ADP and the energy charge in nodules, and quantitative observation demonstrated the changes of AsPPD1 transcripts level affected nodule primordia formation. Taken together, it is speculated that AsPPD1 contributes to symbiotic ADP levels and energy charge control, and this is required for effective nodule organogenesis and nitrogen fixation.

[Construction of Astragalus sinicus AD-cDNA library and identification of proteins interact with the leghemoglobin].

OBJECTIVE: The objectives of this work were (i) to construct a yeast two-hybrid AD-cDNA library of Astragalus sinicus and provide a fundamental system to screen target proteins involved symbiotic nitrogen fixation, and (ii) to isolate the target proteins interacting with the leghemoglobin. METHODS: By using the Matchmaker Library Construction & Screening Kit (Clontech), we constructed a yeast AD-cDNA library basing on the total RNA, which was isolated from the root and nodule tissues of A. sinicus at different developmental stages infected by Mesorhizobium huakuii 7653R. RESULTS: The quality examination of the AD-cDNA library showed that the transformation efficiency was 1.0 x 10(6) transformants/3 microg pGADT7-Rec DNA, and the average length of cDNA inserts was around 1.0 kb. The library was then screened with the leghemoglobin AsB2510 as bait by yeast two-hybrid system, and 26 positive clones was obtained on SD/-Leu/-Trp/-His/-Ade containing X-gal. 10 of them were individually further confirmed by resuing the plasmid, amplifying the cDNA insert and retesting the protein-interacting phenotype. CONCLUSIONS: The cDNA inserts of positive clones were sequenced and undertaken a blast analysis in NCBI database, it was found that clone LY-53 contained a tify domain and divergent CCT motif, which was an important transcription factor needs in-depth investigation.