Correlative study on retinal microvascular changes and sex hormones in male patients with central serous chorioretinopathy

Central serous chorioretinopathy (CSC) is a disease in which the outer retinal barrier is damaged with high incidence in young adult males. We aimed to analyze the correlations between retinal microvascular changes and sex hormone levels. The vascular density of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP), foveal avascular zone (FAZ) area, choriocapillary blood flow area, and the subfoveal choroidal thickness (SCT) were investigated by optical coherence tomography angiography (OCTA). We also determined the levels of sex hormones (adrenaline (AD), norepinephrine (NE), dopamine (DA), corticosteroids (Cor), aldosterone (ALD), estradiol (E2) and total testosterone (TT)). The relationship between sex hormone levels and OCTA parameters was then determined. We detected significantly higher levels of NE, Cor and TT in serum from the observation group than in the control group (p < 0.05). Significant correlations were identified between SCT and choriocapillary blood flow area in the affected eyes, contralateral eyes and healthy eyes in the control group (p < 0.05). SCT levels of both eyes in the observation group were higher and the choriocapillary blood flow area was smaller than in the control group. The SCT in affected eyes from the observation group were higher than the contralateral eyes (p < 0.05). The choriocapillary blood flow area was significantly smaller than in the contralateral eyes (p < 0.05). Correlation analysis unveiled that NE, Cor and TT levels were positively correlated with SCT in CSC patients and negatively correlated with choriocapillary blood flow area (p < 0.05). The serum levels of sex hormone levels in male CSC patients were different from those in healthy men of the same age. Our findings suggest that the serum levels of NE, Cor and TT levels may influence the pathogenesis of CSC by affecting SCT thickness and choriocapillary blood flow

Effects of Active Components of Fuzi and Gancao Compatibility on Bax, Bcl-2, and Caspase-3 in Chronic Heart Failure Rats

Hypaconitine (HA) and glycyrrhetinic acid (GA) are active components of Fuzi (Aconitum carmichaelii) and Gancao (Glycyrrhiza uralensis Fisch); they have been used in compatibility for chronic heart failure (CHF) from ancient times. The purpose of the present research was to explore whether apoptosis pathways were related with the protective effects of HA + GA against CHF rats or not. The rats were progressed with transverse-aortic constriction (TAC) operation for 4 weeks to build the CHF state, and then the Digoxin (1 mg/kg), HA (2.07 mg/kg), GA (25 mg/kg), and HA (2.07 mg/kg) + GA (25 mg/kg) were orally administrated to rats for 1 week. The levels of BNP and cTnI in the plasma were decreased in the HA + GA group, and the heart/body weight ratio (H/B) and left ventricular (LV) parameters of transthoracic echocardiography were also declined; moreover, the expressions of Bax, Bcl-2, and caspase-3 were all improved in the HA + GA group than other groups in the immunohistochemistry and western blot methods. In general, the data suggested that Fuzi and Gancao compatibility could protect the CHF rats from apoptosis, which provided a strong evidence for further searching for mechanisms of them

Functional and structural analysis of a novel splice site HMBS variant in a Chinese AIP patient

Background: Acute intermittent porphyria (AIP) is a rare metabolic disorder that results from mutations in the gene encoding hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP follows an autosomal dominant inheritance pattern, but most carriers are asymptomatic. The clinical manifestations of AIP include acute attacks of abdominal pain and neuropsychiatric disturbances. The pathogenicity of novel HMBS variants identified in Chinese patients has not been well established.Objective: The article aims to identify the pathogenic mutation in an AIP patient and prove its pathogenicity through in vitro experiments.Methods: A 22-year-old female diagnosed with AIP participated in the study. Variant screening of her HMBS gene was carried out through Sanger sequencing. To ascertain the consequences of the newly discovered variant, we conducted in vitro experimentation targeting HMBS gene expression and enzymatic function. Additionally, protein structure analysis was performed. Cycloheximide treatment and UPF1-specific siRNA knockdown were employed to assess the impact of the mutation on the mechanism of non-sense-mediated mRNA decay (NMD).Results: A novel splice site variant in the HMBS gene (c.648_651+1delCCAGG) was detected in the patient, which caused aberrant mRNA splicing. In vitro experiments demonstrated that this variant significantly decreased the expression of HMBS. Further investigation confirmed that this decrease was due to NMD. Additionally, structural analysis indicated that this variant would destabilize the HMBS protein and impair its catalytic activity. To gain a comprehensive understanding of HMBS mutations in the context of AIP, we conducted a literature search on PubMed using the keywords ‘HMBS’ and ‘Acute intermittent porphyria’ from 2013 to 2023. This search yielded 19 clinical case reports written in English, which collectively described 220 HMBS gene mutations worldwide.Conclusion: The study identified and proved the pathogenicity of a novel splice site HMBS variant for the first time. Our results elucidated the pathological mechanism by which this mutation causes AIP through reducing HMBS expression and activity. These findings provide theoretical guidance for the diagnosis, treatment and genetic counseling of AIP patients

Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population

<p>Abstract</p> <p>Background</p> <p>The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed <it>TP53 </it>72Arg>Pro and <it>MDM2 </it>309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored.</p> <p>Methods</p> <p>In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP.</p> <p>Results</p> <p>We found an increased NPC risk associated with the <it>MDM2 </it>GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the <it>TP53 </it>Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of <it>MDM2 </it>and <it>TP53 </it>polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both <it>MDM2 </it>GG and <it>TP53 </it>Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58).</p> <p>Conclusion</p> <p>The findings suggest that polymorphisms of <it>MDM2 </it>and <it>TP53 </it>genes may be genetic modifier for developing NPC.</p

Single nucleus genome sequencing reveals high similarity among nuclei of an endomycorrhizal fungus

Nuclei of arbuscular endomycorrhizal fungi have been described as highly diverse due to their asexual nature and absence of a single cell stage with only one nucleus. This has raised fundamental questions concerning speciation, selection and transmission of the genetic make-up to next generations. Although this concept has become textbook knowledge, it is only based on studying a few loci, including 45S rDNA. To provide a more comprehensive insight into the genetic makeup of arbuscular endomycorrhizal fungi, we applied de novo genome sequencing of individual nuclei of Rhizophagus irregularis. This revealed a surprisingly low level of polymorphism between nuclei. In contrast, within a nucleus, the 45S rDNA repeat unit turned out to be highly diverged. This finding demystifies a long-lasting hypothesis on the complex genetic makeup of arbuscular endomycorrhizal fungi. Subsequent genome assembly resulted in the first draft reference genome sequence of an arbuscular endomycorrhizal fungus. Its length is 141 Mbps, representing over 27,000 protein-coding gene models. We used the genomic sequence to reinvestigate the phylogenetic relationships of Rhizophagus irregularis with other fungal phyla. This unambiguously demonstrated that Glomeromycota are more closely related to Mucoromycotina than to its postulated sister Dikarya

Loading and Light Degradation Characteristics of Bt Toxin on Nanogoethite: A Potential Material for Controlling the Environmental Risk of Bt Toxin

Transgenic Bt-modified crops release toxins into soil through root exudates and upon decomposition of residues. The fate of these toxins in soil has not been yet clearly elucidated. Nanogoethite was found to have a different influence on the lifetime and insecticidal activity of Bt toxin. The aim of this study was to elucidate the adsorption characteristics of Bt toxin on nanogoethite and its activity changes before and after adsorption. The adsorption of toxin on nanogoethite reached equilibrium within 5 h, and the adsorption isotherm of Bt toxin on nanogoethite conformed to the Langmuir equation (R2>0.9690). In the range of pH from 6.0 to 8.0, larger adsorption occurred at lower pH value. The toxin adsorption decreased with the temperature between 10 and 50°C. The results of FTIR, XRD, and SEM indicated that toxin did not influence the structure of nanogoethite and the adsorption of toxin only on the surface of nanogoethite. The LC50 value for bound toxin was higher than that of free toxin, and the nanogoethite greatly accelerated the degradation of toxin by ultraviolet irradiation. The above results suggested that nanogoethite is a potential material for controlling the environmental risk of toxin released by Bt transgenic plants

Sensitive Detection of KRAS Mutations by Clustered Regularly Interspaced Short Palindromic Repeats

Kirsten rat sarcoma viral oncogene (KRAS) is the isoform most frequently mutated in human tumors. Testing for activating KRAS mutations has important implications for diagnosis and the personalized medicine of cancers. The current techniques for detecting KRAS mutations have moderate sensitivity. The emerging clustered regularly interspaced short palindromic repeats (CRISPR) system shows great promise in the detection of nucleic acids and is revolutionizing medical diagnostics. This study aimed to develop CRISPR–Cas12a as a sensitive test to detect KRAS mutations. Serially diluted DNA samples containing KRAS mutations are subjected to CRISPR–Cas12a and polymerase chain reaction (PCR). CRISPR–Cas12a and PCR can specifically detect 0.01% and 0.1% mutant KRAS DNA in the presence of wild-type KRAS DNA, respectively. Twenty pairs of lung tumor and noncancerous lung tissues are tested by CRISPR–Cas12a, PCR, and direct sequencing. CRISPR–Cas12a could identify the G12C mutation in five of 20 tumor tissues, while both PCR and direct sequencing discovered the KRAS mutation in three of the five tumor tissues. Furthermore, the results of CRISPR–Cas12a for testing the mutation could be directly and immediately visualized by a UV light illuminator. Altogether, CRISPR–Cas12a has a higher sensitivity for the detection of KRAS mutations compared with PCR and sequencing analysis, and thus has diagnostic and therapeutic implications. Nevertheless, the technique needs to be validated for its clinical significance in a large and prospective study