Risk of Excess Maternal Folic Acid Supplementation in Offspring.

Folate, also known as vitamin B9, facilitates the transfer of methyl groups among molecules, which is crucial for amino acid metabolism and nucleotide synthesis. Adequate maternal folate supplementation has been widely acknowledged for its pivotal role in promoting cell proliferation and preventing neural tube defects. However, in the post-fortification era, there has been a rising concern regarding an excess maternal intake of folic acid (FA), the synthetic form of folate. In this review, we focused on recent advancements in understanding the influence of excess maternal FA intake on offspring. For human studies, we summarized findings from clinical trials investigating the effects of periconceptional FA intake on neurodevelopment and molecular-level changes in offspring. For studies using mouse models, we compiled the impact of high maternal FA supplementation on gene expression and behavioral changes in offspring. In summary, excessive maternal folate intake could potentially have adverse effects on offspring. Overall, we highlighted concerns regarding elevated maternal folate status in the population, providing a comprehensive perspective on the potential adverse effects of excessive maternal FA supplementation on offspring.

EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity.

Life experience can leave lasting marks, such as epigenetic changes, in the brain. How life experience is translated into storable epigenetic information remains largely unknown. With unbiased data-driven approaches, we predicted that Egr1, a transcription factor important for memory formation, plays an essential role in brain epigenetic programming. We performed EGR1 ChIP-seq and validated thousands of EGR1 binding sites with methylation patterns established during postnatal brain development. More specifically, these EGR1 binding sites become hypomethylated in mature neurons but remain heavily methylated in glia. We further demonstrated that EGR1 recruits a DNA demethylase TET1 to remove the methylation marks and activate downstream genes. The frontal cortices from the knockout mice lacking Egr1 or Tet1 share strikingly similar profiles in both gene expression and DNA methylation. In summary, our study reveals EGR1 programs the brain methylome together with TET1 providing new insight into how life experience may shape the brain methylome.

Short-term curative effect and safety of propranolol combined with laser in the treatment of infantile hemangiomas.

Short-term curative effect and safety of propranolol combined with laser in the treatment of infantile hemangiomas was studied, so as to provide reference for clinical treatment. A total of 100 cases of infantile hemangiomas admitted to the Affiliated Hospital of Jining Medical University from October 2014 to June 2016 were selected into this study. According to the random number table method, they were divided into the control group and the observation group, with 50 cases in each group. The infant patients in the control group were treated with laser alone, and the infant patients in the observation group were treated with propranolol combined with laser. The healing time, the number of times of laser therapy, the short-term curative effect, the changes in serum inflammatory factors before and after treatment and the incidence of adverse reactions were compared between the two groups of infant patients. The healing time and the times of laser therapy of the infant patients in the observation group were less than those of the infant patients in the control group, and the differences were statistically significant (p<0.05). The short-term curative effect of the observation group (98%) was higher than that of the control group (82%), and the difference was statistically significant (p<0.05). The levels of serum inflammatory factors interleukin (IL)-2, IL-6 and IL-10 in the two groups of infant patients after treatment were lower than those before treatment, and the levels in the observation group were lower than those in the control group, and the differences were statistically significant (p<0.05). Propranolol combined with laser in the treatment of infantile hemangiomas has remarkable short-term curative effects. It can effectively reduce the levels of inflammatory factors, shorten the healing time and reduce the number of times of laser therapy. It is safe and worthy of clinical promotion.

Ulcerative colitis in an adult patient mimicking Henoch-Schönlein purpura: A case report.

RATIONALE: Ulcerative colitis (UC) is one of the chronic inflammatory diseases of the intestinal tract. UC being misdiagnosed as Henoch-Schönlein purpura (HSP) in the elderly has seldom been reported about. PATIENT CONCERNS: A 64-year-old man was admitted to the hospital with petechiae and palpable purpura in lower limbs and abdominal pain for about 1 month. DIAGNOSES: Colonoscopy demonstrated severe inflammation in the colon, mucosal congestion, and edema, and multiple hemorrhages and ulcerations, with purulent adhesions. A histopathologic examination of the colon biopsies revealed extensive infiltration of immune cells and mucosal ulcerations in the intestine. UC was diagnosed. INTERVENTIONS: The patient was treated with prednisone (1.0 mg/kg/d) with progressive dose reduction. OUTCOMES: The skin lesions were healed within 4 weeks, and his abdominal pain was alleviated remarkably. He is currently under follow-up. LESSONS: As the treatment used for patients with HSP was not effective, it was advised that UC should be taken into consideration.

Alteration of lysosome fusion and low-grade inflammation mediated by super-low-dose endotoxin.

Subclinical super-low-dose endotoxin LPS is a risk factor for the establishment of low-grade inflammation during the pathogenesis and progression of chronic diseases. However, the underlying mechanisms are not well understood. At the cellular level, a disruption of lysosome fusion with endosomes or autophagosomes may contribute to the potentiation of low-grade inflammation. In this study, we identified that subclinical super-low-dose endotoxin LPS can potently inhibit the process of endosome acidification and lysosome fusion with endosomes or autophagosomes in primary macrophages. Super-low-dose LPS induced the inhibitory phosphorylation of VPS34, thus leading to the disruption of endosome-lysosome fusion. This effect may depend upon the clearance and relocation of Tollip in macrophages by super-low-dose LPS. Consistent with this notion, Tollip-deficient macrophages had constitutively elevated levels of VPS34 inhibitory phosphorylation and constitutive disruption of endosome-lysosome fusion. By employing a skin excision wound-healing model, we observed that Tollip-deficient mice had significantly elevated levels of cell stress and reduced wound repair. This study reveals a novel mechanism responsible for the modulation of endosome-lysosome fusion and low-grade inflammation in innate macrophages.

Development of a clinical chemiluminescent immunoassay for serum GPC3 and simultaneous measurements alone with AFP and CK19 in diagnosis of hepatocellular carcinoma.

BACKGROUND: Glypican-3 (GPC3) is an oncofetal antigen that shows great promise as a biomarker for diagnosis of hepatocellular carcinoma (HCC), but there is no reliable kit that can be used to detect it in clinics. The aim of this study is to develop a stable performance kit for GPC3 detection in clinics. DESIGN AND METHODS: The paired antibodies were identified through cycle-screening methods based on our previous research. Then, a double antibodies sandwich chemiluminescent immunoassay for detecting serum GPC3 was developed. The performance of the developed GPC3 diagnostic kit was evaluated by detecting the concentration of serum GPC3 and assessing its single or combined use with alpha fetoprotein (AFP) and cytokeratin 19 fragment (CK19) for HCC diagnosis. RESULTS: The assay demonstrated a linear range of 10-800 ng/ml, the cross-reactivity rate at 0.018% (AFP), 0.020% (carcino-embryonic antigen), and 0.021% (CK19), respectively. The minimum detectable concentration was 0.05 ng/ml; the intraassay coefficient of variation (CV) and interassay CV were both less than 10%, with good stability and reproducibility. GPC3 has a high sensitivity (54.2%) and specificity (99.4%) in diagnosing HCC. The level of GPC3 in HCC was robust higher than that in healthy or other liver diseases' sera (108.67 ± 230.04 ng/ml vs. 3.99 ± 7.68 ng/ml). The diagnostic sensitivity of GPC3 single or combined with CK19 and AFP for HCC was evaluated, and the rates were 54.2 and 90.6%, respectively. CONCLUSIONS: An applicable chemiluminescent immunoassay with stable performance against GPC3 in diagnosing HCC has been established and the combination of GPC3 with CK19 and AFP could improve the diagnostic sensitivity for HCC.

Clinical application of specific antibody against glypican-3 for hepatocellular carcinoma diagnosis.

Glypican-3 (GPC3) is a promising tumor marker for hepatocellular carcinoma (HCC) diagnosis with high sensitivity and specificity. The aim of this study was to establish an immunohistochemical detection method for GPC3 using the 7D11 monoclonal antibody (7D11 mAb) and evaluate its application for HCC diagnosis. The feasibility of the 7D11 mAb was evaluated by immunohistochemistry performed on adjacent normal liver and intrahepatic cholangiocarcinoma (ICC) samples, Furthermore, the serum GPC3 levels were evaluated in 40 HCC patients, 7 ICC patients and 50 healthy donors. The results showed that GPC3 was expressed in 85% of HCC tissues (34/40), but was undetectable in ICC tissues and adjacent normal tissues.GPC3 was significantly increased in the serum of HCC patients (17/40, 42.5%) but was undetectable in the serum of ICC patients (0/7, 0%) and healthy donors(0/50, 0%). This prospective study evaluated the clinical usefulness of 7D11 mAb for GPC3 detection in HCC patients. In conclusion, the use of 7D11 mAb might be good for GPC3 large-scale applications for clinical diagnosis of HCC.