Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior.

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region-specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway and the ventral tegmental area-nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Synaptic cell adhesion molecules contribute to the pathogenesis and progression of fragile X syndrome.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a monogenic cause of autism spectrum disorders. Deficiencies in the fragile X messenger ribonucleoprotein, encoded by the FMR1 gene, lead to various anatomical and pathophysiological abnormalities and behavioral deficits, such as spine dysmorphogenesis and learning and memory impairments. Synaptic cell adhesion molecules (CAMs) play crucial roles in synapse formation and neural signal transmission by promoting the formation of new synaptic contacts, accurately organizing presynaptic and postsynaptic protein complexes, and ensuring the accuracy of signal transmission. Recent studies have implicated synaptic CAMs such as the immunoglobulin superfamily, N-cadherin, leucine-rich repeat proteins, and neuroligin-1 in the pathogenesis of FXS and found that they contribute to defects in dendritic spines and synaptic plasticity in FXS animal models. This review systematically summarizes the biological associations between nine representative synaptic CAMs and FMRP, as well as the functional consequences of the interaction, to provide new insights into the mechanisms of abnormal synaptic development in FXS.

Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Effect of angiogenesis inhibitors on wound healing in patients with ovarian cancer: A meta-analysis.

Angiogenic inhibitors have been demonstrated to inhibit tumour cells in ovarian carcinoma, but the initial data are not accurate enough to indicate the influence of these drugs on the post-therapy wound healing. In order to assess the effect of angiogenic inhibitors on the treatment of wound healing in ovarian carcinoma, we performed a meta-analysis of related literature. For this meta-analysis, we looked up the data from 4 databases: PubMed, EMBASE, Web of Science and the Cochrane Library. All literature searches were performed up to October 2023. The ROBINS-I tool was applied to evaluate the risk of bias in the inclusion trials, and statistical analysis was performed with RevMan 5.3. In this research, 971 related research were chosen, and 9 of them were selected. These studies were published between 2013 and 2023. In all 9 trials, a total of 3902 patients were enrolled. There was a significant reduction in the risk of wound infection in the control group than in those who received angiogenesis inhibitors (OR, 0.66; 95% CI, 0.49-0.89 p = 0.007). The risk of developing an abscess was not significantly different from that of those who received angiogenesis inhibitors (OR, 0.80; 95% CI, 0.20-3.12 p = 0.74). The risk of perforation in the control group was smaller than that in those receiving angiogenic inhibitors (OR, 0.25; 95% CI, 0.11-0.56 p = 0.0006). There was a significant increase in the risk of injury and GI perforation in women who received angiogenic inhibitors than in the control group. But the incidence of abscess did not differ significantly among the two groups.

Single-Point Mutation Near Active Center Increases Substrate Affinity of Alginate Lyase AlgL-CD.

Alginate lyases have been widely used for the preparation of bioactive alginate oligosaccharides. An alginate lyase AlgL-CD was rationally designed by introducing alkaline amino acid residues near active center to increase activity. One of its mutants E226K presented much higher activity than wild-type AlgL-CD. Substrate affinity of E226K increased 10 folds as the Km values indicated. The spectra of intrinsic emission fluorescence and circular dichroism of E226K suggested the whole enzyme turned to be more flexible. The 8-anilino-1-naphthalenesulfonate (ANS)-binding assay showed that the hydrophobic active center of E226K was more available to ligand. Molecular dynamic analysis of the enzyme-substrate complex showed that lid loops of the active center in E226K turned to be more opened up, which might contribute to the increase of substrate-binding affinity. Meanwhile, the catalytic residue of E226K was closer to the hydrogen donor C5 atom of the substrate to increase catalysis rate. The final degradation products of alginate by E226K were determined to be identical with that of AlgL-CD. This study provides guidance for improving enzymatic preparation efficiency of bioactive alginate oligosaccharides.

Truncation of κ­carrageenase for higher κ­carrageenan oligosaccharides yield with improved enzymatic characteristics.

Carrageenase is useful for preparation of carrageenan oligosaccharides, which have significant bioactivity. We expressed a κ­carrageenase gene from Zobellia sp. ZL-4 in full-length (κ-ZL-4) or after truncation of the carbohydrate binding module and the Type-IX secretion module (κ-ZL-4-GH16). κ-ZL-4-GH16 showed a specific activity (134.22 U/mg) 1.93 times higher than that of κ-ZL-4, and its thermal and pH stability also increased. The best activity of κ-ZL-4-GH16 was presented at pH 3.0-6.0, which was lower than the optimal pH of reported κ-carrageenases. The enzyme-substrate affinity of κ-ZL-4-GH16 was higher than that of κ-ZL-4, demonstrated by its lower Michaelis-Menten constant (0.704 mg/mL at pH 6.0). Importantly, κ-ZL-4-GH16 released 10-fold more κ-carrageenan disaccharides than κ-ZL-4. The κ-carrageenan tetrose and hexose produced by the two enzymes were purified and structurally identified. Molecular docking with κ-carrageenan hexose suggested that the efficiency improvement after truncation might be attributed to the conformation differences of the two enzymes.