Frequency-dependent alterations in functional connectivity in patients with Alzheimer's Disease spectrum disorders.

Background: In the spectrum of Alzheimer's Disease (AD) and related disorders, the resting-state functional magnetic resonance imaging (rs-fMRI) signals within the cerebral cortex may exhibit distinct characteristics across various frequency ranges. Nevertheless, this hypothesis has not yet been substantiated within the broader context of whole-brain functional connectivity. This study aims to explore potential modifications in degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) among individuals with amnestic mild cognitive impairment (aMCI) and AD, while assessing whether these alterations differ across distinct frequency bands. Methods: This investigation encompassed a total of 53 AD patients, 40 aMCI patients, and 40 healthy controls (HCs). DC and VMHC values were computed within three distinct frequency bands: classical (0.01-0.08 Hz), slow-4 (0.027-0.073 Hz), and slow-5 (0.01-0.027 Hz) for the three respective groups. To discern differences among these groups, ANOVA and subsequent post hoc two-sample t-tests were employed. Cognitive function assessment utilized the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA). Pearson correlation analysis was applied to investigate the associations between MMSE and MoCA scores with DC and VMHC. Results: Significant variations in degree centrality (DC) were observed among different groups across diverse frequency bands. The most notable differences were identified in the bilateral caudate nucleus (CN), bilateral medial superior frontal gyrus (mSFG), bilateral Lobule VIII of the cerebellar hemisphere (Lobule VIII), left precuneus (PCu), right Lobule VI of the cerebellar hemisphere (Lobule VI), and right Lobule IV and V of the cerebellar hemisphere (Lobule IV, V). Likewise, disparities in voxel-mirrored homotopic connectivity (VMHC) among groups were predominantly localized to the posterior cingulate gyrus (PCG) and Crus II of the cerebellar hemisphere (Crus II). Across the three frequency bands, the brain regions exhibiting significant differences in various parameters were most abundant in the slow-5 frequency band. Conclusion: This study enhances our understanding of the pathological and physiological mechanisms associated with AD continuum. Moreover, it underscores the importance of researchers considering various frequency bands in their investigations of brain function.

Functionalized 3D Hydroxyapatite Scaffold by Fusion Peptides-Mediated Small Extracellular Vesicles of Stem Cells for Bone Tissue Regeneration.

3D printing technology offers extensive applications in tissue engineering and regenerative medicine (TERM) because it can create a three-dimensional porous structure with acceptable porosity and fine mechanical qualities that can mimic natural bone. Hydroxyapatite (HA) is commonly used as a bone repair material due to its excellent biocompatibility and osteoconductivity. Small extracellular vesicles (sEVs) derived from bone marrow mesenchymal stem cells (BMSCs) can regulate bone metabolism and stimulate the osteogenic differentiation of stem cells. This study has designed a functionalized bone regeneration scaffold (3D H-P-sEVs) by combining the biological activity of BMSCs-sEVs and the 3D-HA scaffold to improve bone regeneration. The scaffold utilizes the targeting of fusion peptides to increase the loading efficiency of sEVs. The composition, structure, mechanical properties, and in vitro degradation performance of the 3D H-P-sEVs scaffolds were examined. The composite scaffold demonstrated good biocompatibility, substantially increased the expression of osteogenic-related genes and proteins, and had a satisfactory bone integration effect in the critical skull defect model of rats. In conclusion, the combination of EVs and 3D-HA scaffold via fusion peptide provides an innovative composite scaffold for bone regeneration and repair, improving osteogenic performance.

A Case of Pyoderma Gangrenosum after Partial Small Bowel Resection.

ABSTRACT: Pyoderma gangrenosum (PG) is a rare, noninfectious inflammatory disease of unknown etiology that affects the skin and mucous membranes. The development of PG after partial small bowel resection is very rare and can initially resemble an infectious complication, although it is an inflammatory disease.This report presents the case of a 55-year-old man who underwent partial small bowel resection for incomplete intestinal obstruction and developed postoperative infection-like manifestations, including redness and swelling of the incision, severe pain, and yellow-green turbid fluid from the drainage tube. After completing a skin biopsy that suggested massive neutrophil infiltration, multiple secretion cultures for Pseudomonas aeruginosa (+), and systemic screening without other comorbidities, a diagnosis of postoperative PG and P aeruginosa infection was determined.Early detection of this complication is essential for patient recovery because primary surgical treatment, which is contraindicated in such cases, can worsen PG. Therefore, PG should be treated conservatively with corticosteroids.

Total removal of a large esophageal schwannoma by submucosal tunneling endoscopic resection: A case report and review of literature.

BACKGROUND: Primary schwannoma is a rare submucosal tumor of the esophagus, which is most often benign, and surgery is the only effective treatment. So far, only a few cases have been reported. Herein, we reported a single case diagnosed with primary esophageal schwannoma that was totally removed by submucosal tunneling endoscopic resection (STER). CASE SUMMARY: A 62-year-old man presented to the hospital with a history of resection of a malignant gastric tumor and mild dysphagia. Endoscopic examination revealed a large submucosal elevated lesion in the esophagus 25-30 cm from the incisors. Endoscopic ultrasonography detected a 45 mm × 35 mm × 31 mm hypoechoic lesion; chest computed tomography showed a mass of approximately 55 mm × 35 mm × 29 mm. A preliminary examination showed features suggestive of a stromal tumor. Pathological findings indicated esophageal schwannoma. Next, STER alone was performed to completely resect the mass, and the patient recovered well post-surgery. Afterward, the patient was discharged and showed no tumor recurrence at 33 mo of follow-up. CONCLUSION: Endoscopic resection is still an effective treatment for large esophageal schwannomas (> 30 mm) under meticulous morphological evaluation.

Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study.

Biological aging biomarkers, such as leukocyte telomere length (LTL) and epigenetic clocks, have been associated with the risk of cerebral small vessel disease (CSVD) in several observational studies. However, it is unclear whether LTL or epigenetic clocks play causal roles as prognostic biomarkers in the development of CSVD. We performed a Mendelian randomization (MR) study of LTL and four epigenetic clocks on ten subclinical and clinical CSVD measures. We obtained genome-wide association (GWAS) data for LTL from the UK Biobank (N = 472,174). Data on epigenetic clocks were derived from a meta-analysis (N = 34,710), and CSVD data (N cases =1293-18,381; N controls = 25,806-105,974) were extracted from the Cerebrovascular Disease Knowledge Portal. We found that genetically determined LTL and epigenetic clocks were not individually associated with ten measures of CSVD (IVW p > 0.05), and this result was consistent across sensitivity analyses. Our findings imply that LTL and epigenetic clocks may not help in predicting CSVD development as causal prognostic biomarkers. Further studies are needed to illustrate the potential of reverse biological aging in serving as an effective form of preventive therapy for CSVD.

Modification of the small intestinal submucosa membrane with oligopeptides screened from intrinsically disordered regions to promote angiogenesis and accelerate wound healing.

A slow vascularization rate is considered one of the major disadvantages of biomaterials used for accelerating wound healing. Several efforts, including cellular and acellular technologies, have been made to facilitate biomaterial-induced angiogenesis. However, no well-established techniques for promoting angiogenesis have been reported. In this study, a small intestinal submucosa (SIS) membrane modified by an angiogenesis-promoting oligopeptide (QSHGPS) screened from intrinsically disordered regions (IDRs) of MHC class II was used to promote angiogenesis and accelerate wound healing. Because the main component of SIS membranes is collagen, the collagen-binding peptide sequence TKKTLRT and the pro-angiogenic oligopeptide sequence QSHGPS were used to construct chimeric peptides to obtain specific oligopeptide-loaded SIS membranes. The resulting chimeric peptide-modified SIS membranes (SIS-L-CP) significantly promoted the expression of angiogenesis-related factors in umbilical vein endothelial cells. Furthermore, SIS-L-CP exhibited excellent angiogenic and wound-healing abilities in a mouse hindlimb ischaemia model and a rat dorsal skin defect model. The high biocompatibility and angiogenic capacity of the SIS-L-CP membrane make it promising in angiogenesis- and wound healing-related regenerative medicine.

SIS membrane modification to improve antimicrobial and osteogenic properties for guide bone regeneration.

The guided bone regeneration (GBR) technique is the most common and durable approach to repairing bone defects in periodontal surgery. However, membrane exposure causes bacterial infiltration, which lowers the functional integrity of the barrier membrane and destroys bone repair. Here, an antibacterial peptide-modified small intestinal submucosa (SIS) membrane is used as a new GBR membrane for effective bone regeneration. The peptide JH8194 was placed into chitosan microspheres to preserve its stability and allow for sustained release, which realizes rapid and efficient functional modification of the SIS membrane. Biocompatibility and certain antibacterial activities were found in the modified SIS membrane (SIS@CS-JH8194). Additionally, in vitro experiments showed that SIS@CS-JH8194 promoted the expression of osteogenic-related factors and decreased the secretion of inflammatory factors in rat bone mesenchymal stem cells. In vivo experiments showed that SIS@CS-JH8194 could effectively promote bone regeneration in rat skull defects. In this work, we created a new antibacterial GBR membrane to help avoid postoperative infection and improve bone tissue regeneration.

Guided bone regeneration with extracellular matrix scaffold of small intestinal submucosa membrane.

Guided bone regeneration (GBR) is a promising strategy for repairing bone defects using bioactive membranes. In this study, a new type of GBR membrane based on the small intestinal submucosa (SIS) was created, and its surface structure, cytological characteristics, and bone defect repair ability were compared with commonly used membranes. Our results show that compared to the Heal-all and Dentium membranes, the SIS membrane has an asymmetric structure that does not affect the proliferation of bone marrow mesenchymal stem cells (BMSCs). Instead, it increased their formation of calcium nodules and expression of bone morphogenetic protein-2 (BMP-2), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteopontin (OPN). Six weeks after their insertion into a rat calvarial defect model, increased bone growth was observed in the SIS membrane group. Our results indicate that the SIS membrane has good biocompatibility and is more effective in promoting early bone formation than existing membranes. Given the wide range of source materials and simple preparation processes available, SIS membrane is a promising candidate for guided bone regeneration.

Novel fusion peptides deliver exosomes to modify injectable thermo-sensitive hydrogels for bone regeneration.

Injectable thermo-sensitive hydrogels composed of small intestinal submucosa (SIS) with exosomes derived from bone marrow mesenchymal stem cells (BMSCs) are desired for bone regeneration. However, poor mechanical properties limit the clinical application of SIS hydrogels. Herein, the mechanical properties of SIS hydrogels incorporated with 3-(3,4-dihydroxyphenyl) propionic acid (CA) are assessed. The results show that the mechanical properties of SIS hydrogels are improved. In addition, the retention and stability of exosomes over time at the defect site are also challenges. Fusion peptides are designed by connecting collagen-binding domines (CBDs) of collagen type I/III with exosomal capture peptides CP05 (CRHSQMTVTSRL) directly or via rigid linkers (EAAAK). In vitro experiments demonstrate that fusion peptides are contribute to promoting the positive effect of exosomes on osteogenic differentiation of BMSCs. Meanwhile, the results of hydrogels combining exosomes and fusion peptides in the treatment of rat skull defect models reveal that fusion peptides could enhance the retention and stability of exosomes, thereby strengthen the therapeutic effect for skull defects. Therefore, SIS hydrogels with CA modified by fusion peptides and exosomes appear to be a promising strategy in bone regenerative medicine.

Small Intestinal Submucosa Membrane Modified by Fusion Peptide-Mediated Extracellular Vesicles to Promote Tissue Regeneration.

Tissue injury, which often occurs in daily life, remains challenging in clinical medicine. Developing a novel biomaterial with the capability to provide an ideal microenvironment and homeostasis around the wound is highly desirable for effective tissue regenerative medicine. The small intestinal submucosa (SIS) membrane possesses a precise spatial structure with excellent biocompatibility. Extracellular vesicles (EVs) derived from umbilical cord mesenchymal stem cells can achieve rapid cell proliferation and migration with little immune response by creating a satisfactory microenvironment. In this study, fusion peptide-mediated EVs are able to modify the surface of the SIS membrane via specific combination. In vitro studies prove that modified SIS membranes can promote cell migration and spreading. This phenomenon may be because of the activation of TEADs, which regulate cell behavior. By constructing a rat abdominal wall defect model, it is further demonstrated that the modified SIS membrane is more conducive to tissue regeneration. Collectively, these results suggest that SIS membranes modified by fusion peptide-mediated EVs achieve excellent biofunction and provide promising prospects for tissue regeneration.

Amplitude of low-frequency fluctuations on Alzheimer's disease with depression: evidence from resting-state fMRI.

BACKGROUND: The prevalence of Alzheimer's disease (AD) comorbid with depression is common. However, the mechanisms of AD with depression remain unclear. AIMS: To investigate the regional alterations of brain activity of AD with depression in resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: 154 patients with AD who met the inclusion criteria were recruited from the Zhejiang Provincial People's Hospital from October 2014 to October 2016. According to whether the core symptoms of depression were present, patients were divided into two groups, 22 patients with AD with depression (AD-D) and 52 patients with AD without depression (AD-nD). The amplitude of low frequency fluctuations (ALFF) was compared between two groups by performing independent-samples t-test. RESULTS: Compared with the AD-D group, increased ALFF values in the bilateral superior frontal gyrus, left middle frontal gyrus and left inferior frontal gyrus were observed in the AD-nD group. The brain activity in the AD-nD group in the bilateral superior frontal gyrus, left middle frontal gyrus and the left inferior frontal gyrus was higher than the AD-D group. CONCLUSIONS: Resting-state brain functional alterations may be closely bound up with the pathophysiologic features of patients with AD with depressive symptoms.

The interaction between serum amyloid A and Toll-like receptor 2 pathway regulates inflammatory cytokine secretion in human gingival fibroblasts.

BACKGROUND: Serum amyloid A (SAA) has been identified to trigger inflammation response, and play a crucial role in chronic inflammatory diseases. However, the regulatory mechanism of SAA still remains unclear during the development of periodontitis METHODS: SAA mRNA and protein expression were detected in healthy and inflammatory gingival tissues using real-time polymerase chain reaction (PCR) and immunohistochemistry. Human recombinant SAA (Apo-SAA), Pam3CSK4 (a Toll-like receptor (TLR) 2 ligand), siRNA-SAA, or TLR2 neutralizing antibody was applied to treat human gingival fibroblasts, respectively, or combined. SAA, TLRs, and inflammatory cytokines interleukin (IL)-6 and IL-8 were analyzed by real-time PCR, western blotting, or enzyme-linked immunosorbent assay. RESULTS: SAA expression increased in human inflammatory gingival tissues from patients with periodontitis (P <0.05). Apo-SAA could increase not only the mRNA expression of TLR2 (P <0.05), but also IL-6 and IL-8 mRNA and protein levels (P <0.05) which was suppressed by TLR2 antibody in human gingival fibroblasts. Pam3CSK4 increased SAA, IL-6, and IL-8 levels (P <0.05). However, the expression of SAA, IL-6, and IL-8 decreased after transfection of siRNA-SAA (P <0.05). CONCLUSION: SAA not only increases in inflammatory gingiva, but also triggers inflammatory cytokine secretion via interacting with TLR2 pathway in human gingival fibroblasts, which indicates that SAA is involved in periodontal inflammation.