The role of Foxo3a in neuron-mediated cognitive impairment.

Cognitive impairment (COI) is a prevalent complication across a spectrum of brain disorders, underpinned by intricate mechanisms yet to be fully elucidated. Neurons, the principal cell population of the nervous system, orchestrate cognitive processes and govern cognitive balance. Extensive inquiry has spotlighted the involvement of Foxo3a in COI. The regulatory cascade of Foxo3a transactivation implicates multiple downstream signaling pathways encompassing mitochondrial function, oxidative stress, autophagy, and apoptosis, collectively affecting neuronal activity. Notably, the expression and activity profile of neuronal Foxo3a are subject to modulation via various modalities, including methylation of promoter, phosphorylation and acetylation of protein. Furthermore, upstream pathways such as PI3K/AKT, the SIRT family, and diverse micro-RNAs intricately interface with Foxo3a, engendering alterations in neuronal function. Through several downstream routes, Foxo3a regulates neuronal dynamics, thereby modulating the onset or amelioration of COI in Alzheimer's disease, stroke, ischemic brain injury, Parkinson's disease, and traumatic brain injury. Foxo3a is a potential therapeutic cognitive target, and clinical drugs or multiple small molecules have been preliminarily shown to have cognitive-enhancing effects that indirectly affect Foxo3a. Particularly noteworthy are multiple randomized, controlled, placebo clinical trials illustrating the significant cognitive enhancement achievable through autophagy modulation. Here, we discussed the role of Foxo3a in neuron-mediated COI and common cognitively impaired diseases.

Does a hyperechogenic endometrial mass in the uterus during controlled ovarian stimulation affect assisted reproductive technology cycle outcomes?

OBJECTIVES: Healthy embryos and endometrial receptivity are keys to the success of in-vitro fertilization and embryo transfer (IVF-ET). Abnormal transvaginal ultrasonography (TVU) findings in the endometrium are a concern during assisted reproductive technology (ART) treatments. Observation of a hyperechogenic endometrial mass (HEM) during controlled ovarian stimulation (COS) in an IVF or intracytoplasmic sperm injection (ICSI) cycle is a dilemma. Here we investigated whether an HEM would affect ART cycle outcomes. STUDY DESIGN: We analyzed all data from patients who underwent IVF or ICSI treatment cycles from January 1, 2009 to December 31, 2016 at our institution. Patients diagnosed with an HEM were included. Each woman was matched with two control subjects of similar age (± 1 year), in terms of the number of cycles, type of infertility (primary or secondary), protocol used for COS, but with no HEM identified by TVU. Baseline characteristics, COS response, and pregnancy outcomes after ET were compared. RESULTS: In all, 1088 patients were diagnosed with an HEM. Of these, 426 met the inclusion criteria and were matched with 852 controls. Baseline characteristics showed no significant differences between the groups. The peak endometrial thickness was significantly greater in the experimental group than in the control group (1.15 ± 0.18 cm vs. 1.08 ± 0.21 cm, p < 0.001). The live birth rates were 43.7% vs 46.2% in the experimental and control groups, respectively. There were no significant between-group differences in the rates of biochemical or clinical pregnancy or abortions at any stage. CONCLUSIONS: Newly diagnosed HEMs < 18 mm in diameter monitored by TVU did not impair the outcomes of ART following COS in this study. If other conditions are suitable, completion of ART cycles should be the appropriate approach in such cases. KEY MESSAGE: Newly diagnosed hyperechogenic endometrial masses measuring <18 mm in diameter monitored by TVU during COS did not adversely affect the outcomes of these IVF/ICSI-ET cycles.

[Abnormal processing characteristics to basic emotional faces in the early phase in children with autism spectrum disorder].

OBJECTIVE: To explore the recognition ability and abnormal processing characteristics to basic emotional faces in the early phase in children with autism spectrum disorders (ASD). METHODS: Photos of Chinese static faces with four basic emotions (fearful, happy, angry and sad) were used as stimulus. Twenty-five ASD children and twenty-two age- and gender-matched typical developed children (normal controls) were asked to match the emotional faces with words. Event-related potential (ERP) data were recorded concurrently. RESULTS: N170 latencies for total emotion and fearful face in the left temporal region were faster than in the right one in normal controls (P<0.05), but the results were not noted in ASD children. Further, N170 latencies in the left temporal region of ASD children were slower than normal controls for total emotion, fearful and happy faces (P<0.05), and their N170 latencies in the right temporal region were prone to slower than normal controls for angry and fearful faces. CONCLUSIONS: The holistic perception speed of emotional faces in the early cognitive processing phase in ASD children is slower than normal controls. The lateralized response in the early phase of recognizing emotional faces may be aberrant in children with ASD.

[Association between intelligence development and facial expression recognition ability in children with autism spectrum disorder].

OBJECTIVE: To investigate the features of intelligence development, facial expression recognition ability, and the association between them in children with autism spectrum disorder (ASD). METHODS: A total of 27 ASD children aged 6-16 years (ASD group, full intelligence quotient >70) and age- and gender-matched normally developed children (control group) were enrolled. Wechsler Intelligence Scale for Children Fourth Edition and Chinese Static Facial Expression Photos were used for intelligence evaluation and facial expression recognition test. RESULTS: Compared with the control group, the ASD group had significantly lower scores of full intelligence quotient, verbal comprehension index, perceptual reasoning index (PRI), processing speed index（PSI), and working memory index (WMI) (P<0.05). The ASD group also had a significantly lower overall accuracy rate of facial expression recognition and significantly lower accuracy rates of the recognition of happy, angry, sad, and frightened expressions than the control group (P<0.05). In the ASD group, the overall accuracy rate of facial expression recognition and the accuracy rates of the recognition of happy and frightened expressions were positively correlated with PRI (r=0.415, 0.455, and 0.393 respectively; P<0.05). The accuracy rate of the recognition of angry expression was positively correlated with WMI (r=0.397; P<0.05). CONCLUSIONS: ASD children have delayed intelligence development compared with normally developed children and impaired expression recognition ability. Perceptual reasoning and working memory abilities are positively correlated with expression recognition ability, which suggests that insufficient perceptual reasoning and working memory abilities may be important factors affecting facial expression recognition ability in ASD children.

[On "the moxibustion shouldn't be applied at Shimen (CV 5) on female"].

The TCM theory "moxibustion shouldn't be applied at Shimen (CV 5) on female" is discussed in this article, which provides theoretical instruction on proper clinical application of Shimen (CV 5). Based on literature study, ancient classics concerning contraindication of "moxibustion shouldn't be applied at Shimen (CV 5) on female" were studied. TCM theory "moxibustion shouldn't be applied at Shimen (CV 5) on female" was explored profoundly through ancient record, physiological relations between Shimen (CV 5) and pregnancy, the relation between the anatomic structure of Shimen (CV 5) and the extra acupoint Jueyun Xue. And the result indicated that as an acupoint with contraindications, Shimen (CV 5) should be attached with great importance in its clinical practice on female patients. Reinforcing manipulation should be given instead of reducing. Moxibustion should be applied with cautiousness on the point, especially during pregnancy.

The effect of leptin on the osteoinductive activity of recombinant human bone morphogenetic protein-2 in nude mice.

OBJECTIVE: To investigate the effect of leptin in the model of ectopic bone formation that utilizes subcutaneously implanted recombinant human bone morphogenetic protein-2 (rhBMP-2)-containing type I collagen discs. METHODS: This study was performed in the Clinical Research Center, Southern Medical University, Guangzhou, China from November 2008 to June 2009. A single dose of 20 ul saline (group A), 20 ug leptin (group B), 2 ug rhBMP-2 (group C), 2 ug rhBMP-2 + 20 ug leptin (group D), and type I collagen disks as a carrier were mixed, and subcutaneously implanted into the back of nude mice (n=12). The effect of ectopic bone formation was evaluated by radiography, dual-energy X absorptiometry, biochemical examination of alkaline phosphatase (ALP) activity, histological observation, and semi-quantitative evaluation 4 and 8 weeks after surgery. RESULTS: At 4 and 8 weeks after operation the radiographs, bone mass density, ALP, and histology values showed significant intragroup and intergroup differences, with those at 8 weeks being higher than those at 4 weeks. CONCLUSION: Our results indicated that the sustainedly released material with collagen as a carrier combined treatment with leptin and rhBMP-2 has a very good osteoinductive activity. Leptin is a positive modulator for the osteoinductive efficacy of BMPs, they have synergistic effect. Its mechanisms are probably related to promote the formation of new-vessels and proliferation/ differentiation of many kinds of cells.

Leptin expression by heterotopic ossification-isolated tissue in rats with Achilles' tenotomy.

OBJECTIVE: To set up heterotopic ossification (HO) models according to McClure and determine whether leptin messenger ribonucleic acid (mRNA) and protein are expressed in HO-isolated tissue. METHODS: This study was performed in the Department of Spine and Orthopedics, Southern Medical University, Guangzhou, China from November 2007 to June 2008. Thirty-six male rats were randomly divided into sham, partial achilles' tenotomy (PAT), and achilles' tenotomy (AT) groups, with 12 rats in each group. X-ray and histological examination were carried out to ensure the formation of HO at 5 and 10 weeks after operation. Specimens from achilles tendons and surrounding tissue were taken and processed. Meanwhile, the expression of leptin mRNA (5 and 10 weeks) and protein (10 weeks) in achilles tendons and the surrounding tissue were examined respectively using reverse transcription-polymerase chain reaction assay and immunohistochemical methods. RESULTS: There were no leptin mRNA and protein expression in the sham and a weak expression in the PAT of Achilles tendons and surrounding tissue, whereas there was strong expression in the AT group. CONCLUSION: Leptin is involved in the formation of HO, its mechanisms is related to induction of bone formation and maturation through a series of cellular events, including: proliferation/differentiation of many kinds of cells, collagen synthesis, mineralization, and vascularization of the extracellular matrix.