Copy number variations (CNVs) have emerged as significant contributors to the elusive genetic causality of inherited eye diseases. In this study, we describe a case with optic atrophy and a brain ...aneurysm, in which a de novo CNV 3q29 deletion was identified.
A 40-year-old female patient was referred to our department after undergoing aneurysm transcatheter arterial embolization for a brain aneurysm. She had no history of systemic diseases, except for unsatisfactory best-corrected visual acuity (BCVA) since elementary school. Electrophysiological tests confirmed the findings in retinal images, indicating optic nerve atrophy. Chromosomal microarray analysis revealed a de novo deletion spanning 960 kb on chromosome 3q29, encompassing OPA1 and six neighboring genes. Unlike previously reported deletions in this region associated with optic atrophy, neuropsychiatric disorders, and obesity, this patient displayed a unique combination of optic atrophy and a brain aneurysm. However, there is no causal relationship between the brain aneurysm and the CNV.
In conclusion, the optic atrophy is conclusively attributed to the OPA1 deletion, and the aneurysm could be a coincidental association. The report emphasizes the likelihood of underestimating OPA1 deletions due to sequencing technology limitations. Recognizing these constraints, healthcare professionals must acknowledge these limitations and consistently search for OPA1 variants/deletions in Autosomal Dominant Optic Atrophy (ADOA) patients with negative sequencing results. This strategic approach ensures a more comprehensive exploration of copy-number variations, ultimately enhancing diagnostic precision in the field of genetic disorders.
In vivo effects of histidine and carnosine against diabetic deterioration in diabetic Balb/cA mice were studied. Histidine and carnosine at 0.5, 1 g/l were added into drinking water. After 4 weeks ...intake of these agents, the content of histidine and carnosine in plasma, heart and liver significantly elevated (
P<0.05). The intake of these agents significantly decreased plasma glucose and fibronectin levels (
P<0.05); however, only 1 g/l histidine and carnosine treatments significantly increased insulin level (
P<0.05) in diabetic mice. Triglyceride level in heart and liver was dose-dependently reduced by histidine or carnosine treatments (
P<0.05); however, only 1 g/l histidine and carnosine treatments significantly reduced cholesterol level in heart and liver (
P<0.05). The administration of histidine or carnosine significantly enhanced catalase activity and decreased lipid oxidation levels in kidney and liver (
P<0.05); however, only 1 g/l histidine and carnosine treatments significantly increased glutathione peroxidase activity (
P<0.05). The increased interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in diabetic mice were significantly suppressed by the intake of histidine or carnosine (
P<0.05). In human low density lipoprotein, histidine or carnosine showed dose-dependently suppressive effect in glucose-induced oxidation and glycation (
P<0.05). These data suggest that histidine and carnosine are potential multiple-protective agents for diabetic complications prevention or therapy.
This study investigated the clinical characteristics of patients with PROM1-related inherited retinal diseases (IRDs).
Patients diagnosed with IRDs who had mutations in PROM1 were identified at ...Linkou Chang Gung Memorial Hospital and Kaohsiung Medical University Hospital in Taiwan. Information on clinical characteristics and best-corrected visual acuity was recorded. Color fundus (CF) images, fundus autofluorescence photography (FAF), spectral-domain optical coherence tomography (SD-OCT), and electroretinograms (ERGs) were analyzed to examine patient phenotypes. PROM1 variants were detected using whole exome sequencing and verified by Sanger sequencing.
Fourteen patients from nine families with PROM1-related IRDs were analyzed. Most patients exhibited chorioretinal atrophy in the macular area, with or without extramacular involvement on CF. Similarly, hypo-autofluorescence confined to the macular area, with or without extramacular involvement, was present for most patients on FAF. Furthermore, SD-OCT revealed outer retinal tubulations and focal or diffuse retinal thinning. ERGs showed variable findings, including maculopathy with normal ERG, subnormal cone response, and extinguished rod and cone responses. We detected five variants of the PROM1 gene, including c.139del, c.794del, c.1238T>A, c.2110C>T, and c.1117C>T.
In this study, we evaluated 14 Taiwanese patients with five PROM1 variants. Additionally, incomplete penetrance of heterozygous PROM1 variants was observed. Furthermore, patients with autosomal dominant PROM1 variants had lesions in the macular area and the peripheral region of the retina. SD-OCT serves as a useful tool for early detection of PROM1-related IRDs, as it captures certain signs of such diseases.
Muscle-invasive urinary bladder urothelial carcinoma (UBUC) is a lethal disease for which effective prognostic markers and potential therapy targets are still lacking. Previous array comparative ...genomic hybridization identified that 3q27 is frequently amplified in muscle-invasive UBUCs, one candidate proto-oncogene,
(
), mapped to this region. We therefore aimed to explore its downstream targets and physiological roles in UBUC progression.
Specimens from UBUC patients, NOD/SCID mice and several UBUC-derived cell lines were used to perform quantitative RT-PCR, fluorescence
hybridization immunohistochemistry, xenograft, gene stable overexpression/knockdown and a series of
experiments.
Amplification of the
gene lead to upregulation of
mRNA and protein levels in a substantial set of advanced UBUCs. High BCL6 protein level significantly predicted poor disease-specific and metastasis-free survivals. Knockdown of the
gene in J82 cells inhibited tumor growth and enhanced apoptosis in the NOD/SCID xenograft model.
experiments demonstrated that BCL6 inhibited cytostasis, induced cell migration, invasion along with alteration of the expression levels of several related regulators. At molecular level, BCL6 inhibited
(
) transcription, subsequent translation and upregulation of phosphorylated/inactive FOXO3 through phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) and/or epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase 1/2 (MAP2K1/2) signaling pathway(s). Two BCL6 binding sites on the proximal promoter region of the
gene were confirmed.
Overexpression of BCL6 served a poor prognostic factor in UBUC patients.
and
studies suggested that BCL6 functions as an oncogene through direct transrepression of the
gene, downregulation and phosphorylation of the FOXO3 protein.
Introduction. Severe sepsis and septic shock are associated with substantial mortality. However, few studies have assessed the risk of septic shock among patients who suffered from urinary tract ...infection (UTI). Materials and Methods. This retrospective study recruited UTI cases from an acute care hospital between January 2006 and October 2012 with prospective data collection. Results. Of the 710 participants admitted for UTI, 80 patients (11.3%) had septic shock. The rate of bacteremia is 27.9%; acute kidney injury is 12.7%, and the mortality rate is 0.28%. Multivariable logistic regression analyses indicated that coronary artery disease (CAD) (OR: 2.521, 95% CI: 1.129–5.628, P=0.024), congestive heart failure (CHF) (OR: 4.638, 95% CI: 1.908–11.273, P=0.001), and acute kidney injury (AKI) (OR: 2.992, 95% CI: 1.610–5.561, P=0.001) were independently associated with septic shock in patients admitted with UTI. In addition, congestive heart failure (female, OR: 4.076, 95% CI: 1.355–12.262, P=0.012; male, OR: 5.676, 95% CI: 1.103–29.220, P=0.038, resp.) and AKI (female, OR: 2.995, 95% CI: 1.355–6.621, P=0.007; male, OR: 3.359, 95% CI: 1.158–9.747, P=0.026, resp.) were significantly associated with risk of septic shock in both gender groups. Conclusion. This study showed that patients with a medical history of CAD or CHF have a higher risk of shock when admitted for UTI treatment. AKI, a complication of UTI, was also associated with septic shock. Therefore, prompt and aggressive management is recommended for those with higher risks to prevent subsequent treatment failure in UTI patients.
In this communication, we report a new type of amphiphilic carboxymethyl-hexanoyl chitosan (CHC)-poly(acrylic acid) (PAA) hybrid macromolecule, which was successfully prepared through polymerization ...of acrylic acid (AA) in the presence of amphiphilic CHC. The chemical structure of the hybrid was characterized by FT-IR and super(1)H NMR, which confirmed a chemical linkage between the amine groups of CHC and hydroxyl groups of AA. This CHC-PAA hybrid exhibited amphiphilic property as the original CHC rendering the self-assembling capability to be tunable in terms of AA concentration. Compared with the existing pristine chitosan-PAA co-polymers, this CHC-PAA hybrid exhibited a relatively high pH-responsive volumetric change by 10-100 times compared with the existing alternatives reported in the literature. The hybrid nanoparticles showed excellent encapsulation efficiency greater than 90% for a hydrophobic anti-cancer substance, (S)-(+)-camptothecin. A pH-responsive drug release behavior was systematically evaluated. Besides, this hybrid also revealed excellent cytocompatibility towards the MCF-7 and BCE cell lines, which, associated with its structural stability, suggests this new type of CHC-PAA hybrid to be a promising biomaterial for oral drug delivery application.
Abstract only
Aberrant activation of phosphatidylinositol 3‐kinase (PI3K)–(protein kinase B) Akt signaling is associated with nasopharyngeal carcinoma (NPC) cells resistance to conventional chemo
/
...radiotherapy. We show that natural active compound 3, 5, 7‐trihydroxyflavone (galangin), a type of bioflavonoid extracted from the galangal root (
Alpinia galangal
), can induce apoptosis and S‐phase arrest of NPC cells through p53‐medulated expression of Bax and p21. Using cell cycle synchronization techniques, we demonstrated that S‐phase synchronized NPC cells were more sensitive to galangin‐induced apoptosis. In ATP‐competitive inhibition assay and thin‐layer chromatography separation of the γ‐
32
P‐labeled phosphatidylinositol 3, 4, 5‐triphosphate product of kinase reaction with purified recombinant p85α and p110α proteins, we found that galangin might be an ATP‐competitive inhibitor by competing ATP binding site on PI3K catalytic subunit p110 alpha with ATP. Our results indicate that galangin induces p53‐mediated cell cycle arrest and apoptosis of NPC cells by interaction with ATP binding site on p110 alpha catalytic domain of PI3K.
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Cervical spondylotic myelopathy (CSM) may seriously affect quality of life. In the literature, there is scarce evidence of the pros and cons of full endoscopic spine surgery in the treatment of CSM. ...The main purpose of this study was to conduct a systematic review to elucidate the efficacy of full endoscopic spine surgery in the management of patients with CSM.
This systematic review was conducted in accordance with the PRISMA guidelines. A systematic search of Web of Science, PubMed MEDLINE, Embase, and Cochrane Library was conducted from the database inception to February 1, 2023.
The study included 183 patients and their age was 56.78 ± 7.87 years. The average surgical time calculated was 96.34 ± 33.58 minutes. Intraoperative blood loss ranged from a minimal amount to 51 mL. The average duration of hospital stay was 3.56 ± 1.6 days. The average span for follow-up was on an interval of 18.7 ± 6.76 months. Significant improvements were noted in all aspects of functional outcomes and image results after full endoscopic cervical spine surgery, with no major complications.
The current study found that both anterior transcorporeal and posterior surgical approaches could be used for the treatment of CSM with a full endoscopic technique. Indications of full endoscopic cervical spine surgery for CSM included cervical disc herniation, central canal stenosis, calcified ligamentum flavum, and ossification of the posterior longitudinal ligament. Improved postoperative outcomes with acceptable surgical complications were noted in this systematic review.
A pH-responsive multifunctional core-shell nanoparticle, named CHC-PY nanoparticle, was successfully synthesized through electrostatic interaction of a thin shell of fluorescent pyranine dye (PY) ...with amphiphilic carboxymethylhexanoyl chitosan (CHC) nanoparticles. Upon encapsulating an anticancer drug, camptothecin (CPT), the CHC-PY nanoparticles exhibited an excellent drug loading efficiency (>95%). The resulting CPT-loaded CHC-PY nanoparticles also exhibited efficient cell internalization and good pH-responsive behavior. After being internalized (via efficient endocytosis pathway), the presence of fluorescent PY shell showed a pH-dependent emission characteristic which allowed the internalized CHC-PY nanoparticles acting as an indicator to distinguish the acidic microenvironment of cancerous cells, compared with normal cells. The pH-sensitive PY shell also acted as a modulator to control the CPT release wherein a higher release rate was detected at lower pH value, which is essentially a potential therapeutic niche for anticancer purposes. This new type of CHC-PY core-shell nanoparticle provides multiple functionality, where a synergistic performance of nanotherapeutics, imaging and even diagnosis at a cellular resolution can be achieved simultaneously.
A series of ruthenium-cymene derivatives subjecting Ru(η6-cymene)Cl22 and substituted bidentate N,O donor precursors have been synthesized and characterized. Reacting Ru(η6-cymene)Cl22 with two ...equivalents the lithium salt of phenyl keto-amine ligands LiL1∼LiL3 resulted in the formation of Ru(η6-cymene)(L)Cl (1–3). Similarly, the reaction between Ru(η6-cymene)Cl22 and two equivalents of LiL4 or NaL5 afforded compounds {Ru(η6-cymene)L4)Cl} (4) and Ru(η6-cymene)(L5)Cl (5). The 1H NMR chemical shifts of aromatic protons of the cymene fragment for compounds 1–5 fell in the range δ 5.54–3.58, showing chemical shifts farther upfield than the corresponding protons of Ru(η6-cymene)Cl22 due to the intramolecular ring current effect. The 2,6-diisopropylphenyl substituted pheny lketo-amine ligand of compound 3 shows a slow C-N bond rotation with the rotation rate constant at ca. 4.62 s−1. The catalytic aminations of benzyl alcohol with benzylamine using compounds 1–3 as catalysts resulted in higher conversion than using compounds 4 and 5. Two products, PhCH = NCH2Ph and HN(CH2Ph)2 were detected, with PhCH = NCH2Ph being the major product. When benzyl alcohol was reacted with phenylamine in the presence of compounds 1–5, the conversions are all greater than 60% and PhCH = NPh was the major product. While sterically hindered 2,6-diisopropylaniline appeared in alcohol amination reactions in the presence of catalysts, no imine or amine products were detected.
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•Ruthenium-cymene derivatives with different N,O-donor precursors were synthesized.•Ruthenium compounds used as catalysts for alcohol amination.•Intramolecular ring-current effect was observed.•Spin saturation transfer appears in the ruthenium systems.
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