Predictive modeling of perioperative blood transfusion in lumbar posterior interbody fusion using machine learning.

Background: Accurate estimation of perioperative blood transfusion risk in lumbar posterior interbody fusion is essential to reduce the number, cost, and complications associated with blood transfusions. Machine learning algorithms have the potential to outperform traditional prediction methods in predicting perioperative blood transfusion. This study aimed to construct a machine learning-based perioperative transfusion risk prediction model for lumbar posterior interbody fusion in order to improve the efficacy of surgical decision-making. Methods: We retrospectively collected clinical data on 1905 patients who underwent lumbar posterior interbody fusion surgery at the Second Hospital of Shanxi Medical University between January 2021 and March 2023. All the data was randomly divided into a training set and a validation set, and the "feature_importances" method provided by eXtreme Gradient Boosting (XGBoost) algorithm was applied to select statistically significant features on the training set to establish five machine learning prediction models. The optimal model was identified by utilizing the area under the curve (AUC) and the probability calibration curve on the validation set. Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME) were employed for interpretable analysis of the optimal model. Results: In the postoperative outcomes of patients, the number of hospital days in the transfusion group was longer than that in the non-transfusion group. Additionally, the transfusion group experienced higher total hospital costs, 90-day readmission rates, and complication rates within 90 days after surgery than the non-transfusion group. A total of 9 features were selected for the models. The XGBoost model performed best with an AUC value of 0.958. The SHAP values showed that intraoperative blood loss, intraoperative fluid infusion, and number of fused segments were the top 3 most important features affecting perioperative blood transfusion in lumbar posterior interbody fusion. The LIME algorithm was used to interpret the individualized prediction. Conclusion: Surgery, ASA class, levels fused, total intraoperative blood loss, operative time, and preoperative Hb are viable predictors of perioperative blood transfusion in lumbar posterior interbody fusion. The XGBoost model has demonstrated superior predictive efficacy compared to the traditional logistic regression model, making it a more effective decision-making tool for perioperative blood transfusion.

Rhizospheric pore-water content predicts the biochar-attenuated accumulation, translocation, and toxicity of cadmium to lettuce.

Metal bioavailability controls its behaviors in soil-plant system, especially involved in biochar amendment. This study compared a rhizospheric pore-water extraction against a BCR sequential extraction method to understand cadmium (Cd) bioavailability in two typical Chinese soils. Soils were spiked with five levels of Cd (CdCl2) and remediated with 3% corn-straw derived biochar. After 60 days of lettuce growth, Cd accumulation and enzyme activities in tissues were analyzed. Results showed that biochar increased soil properties (pH, CEC and SOM) compared to un-amended soils, but decreased contents of bioavailable Cd in soil pore-water (Cdpore-water) and BCR extracted Cd (CdFi+Fii). Contents of Cdpore-water were lower in yellow-brown soils than that in red soils. Pearson analysis showed that bioavailable Cd is negatively correlated with soil pH and CEC (p < 0.05). Cd accumulation in lettuce roots and leaves both were decreased by biochar addition, and the established linear equations proved that soil Cdpore-water is the best predictor for Cd accumulation in lettuce roots (r2 = 0.964) and in leaves (r2 = 0.953), followed by CdFi+Fii. Transfer factor (TF) values of Cd from roots to leaves were lower than 1, and slightly better correlated with soil Cdpore-water (r = -0.674, p < 0.01) than CdFi+Fii (r = -0.615, p < 0.01). Aggregated boosted tree (ABT) analyses indicated that soil properties together with Cdpore-water contribute more than 50% to root enzyme activities. Collectively, soil Cdpore-water is a promising predictor of Cd bioavailability, accumulation and toxicity in soil-plant system with biochar addition.

Tumor suppressor miR-424-5p abrogates ferroptosis in ovarian cancer through targeting ACSL4.

Ovarian cancer is the most lethal gynecological cancer. In spite of recent advances, clinical outcomes remain poor, urgently needing novel therapeutic approaches. Growing evidence indicates that microRNAs play crucial roles in ovarian carcinogenesis and progression and that ferroptosis serves as a novel tumor suppressor. However, the molecular mechanisms of miRNA-mediated ferroptosis regulation in ovarian cancer are still largely unknown. In the present study, we show that miR-424-5p negatively regulates ferroptosis by directly targeting ACSL4 in ovarian cancer cells. Upregulation of miR-424-5p suppressed ACSL4 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. Meanwhile, knockdown of miR-424-5p increased the sensitivity of ovarian cancer cells to erastin and RSL3. Furthermore, ACSL4 was upregulated in ovarian cancer tissues, and high ACSL4 expression predicted worse prognosis and sensitized ovarian cancer cells to erastin- and RSL3-induced ferroptosis. Importantly, decreases in lipid peroxides and ferroptotic cell death mediated by miR-424-5p could be abrogated by ACSL4 overexpression. Taken together, our findings demonstrate that miR-424-5p regulates ferroptosis by targeting ACSL4 in ovarian cancer cells and suggest a potential therapeutic approach for ovarian cancer.

Efficacy and safety of massage therapy for chronic atrophic gastritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic atrophic gastritis (CAG) is an established precursor of gastric carcinoma with high prevalence worldwide. It is a typical complex gastro-intestinal disease with multiple influence factors, of which exact mechanisms remain unelucidated. Therefore, an ideal strategy to relieve CAG is urgently needed. In recent years, massage therapy has been increasingly accepted by CAG patients due to its lower costs, fewer unwanted side effects and safety for clinical use. In this systematic review, we aim to evaluate the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating chronic atrophic gastritis: Wanfang and Pubmed Database, China National Knowledge Infrastructure Database, Cochrane Central register of controlled trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to September 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. RESULT: This proposed study will evaluate the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. The outcomes will include changes in CAG relief and adverse effect. CONCLUSION: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.

Fruitless Wolfberry-Sprout Extract Rescued Cognitive Deficits and Attenuated Neuropathology in Alzheimer's Disease Transgenic Mice.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease featured by memory loss, neuroinflammation and oxidative stress. Overproduction or insufficient clearance of Aß leads to its pathological aggregation and deposition, which is considered the predominant neuropathological hallmark of AD. Therefore, reducing Aß levels and inhibiting Aß-induced neurotoxicity are feasible therapeutic strategies for AD treatment. Wolfberry has been traditionally used as a natural antioxidant and anti-aging product. However, whether wolfberry species has therapeutic potential on AD remains unknown. METHOD: The effects of fruitless wolfberry-sprout extract (FWE) on Aß fibrillation and fibril disaggregation was measured by thioflavin T fluorescence and transmission electron microscope imaging; Aß oligomer level was determined by dot-blot; Cell viability and apoptosis was assessed by MTT and TUNEL assay. The levels of Aß40/42, oxidative stress biomarkers and inflammatory cytokines were detected by corresponding kits. 8-month-old male APP/PS1 mice and their age-matched WT littermates were treated with FWE or vehicle by oral administration (gavage) once a day for 4 weeks. Then the cognitive performance was determined using object recognition test and Y-maze test. The Aß burden and gliosis was evaluated by immunostaining and immunoblotting, respectively. RESULTS: FWE significantly inhibited Aß fibrillation and disaggregated the formed Aß fibrils, lowered Aß oligomer level and Aß-induced neuro-cytotoxicity, and attenuated oxidative stress in vitro. Oral administration of FWE remarkably improved cognitive function, reduced Aß burden, decreased gliosis and inflammatory cytokines release, and ameliorated oxidative stress in the brains of APP/PS1 mice. CONCLUSION: These findings indicate that FWE is a promising natural agent for AD treatment.

An indoleamine 2, 3-dioxygenase siRNA nanoparticle-coated and Trp2-displayed recombinant yeast vaccine inhibits melanoma tumor growth in mice.

Therapeutic vaccine is a promising approach in cancer therapy. But tumor-associated antigen peptides have weak immunogenicity and cancer patients are often characterized by immunosuppression and tolerance, leading to less efficiency of immunotherapy. We here successfully developed indoleamine 2, 3-dioxygenase (IDO) siRNA nanoparticle-coated and tyrosinase-related protein 2 (Trp2)-displayed recombinant Saccharomyces cerevisiae (YCP). YCPs had positive charges with a diameter of approximately 5µm, resulting in selective phagocytosis by APC cells. YCP-delivered siRNA and Trp2 successfully escaped from phagosomes, efficiently inhibited IDO expression in DCs, promoted the immune reaction of T cell against Trp2, increased the secretion of proinflammatory cytokines such as IFN-γ,TNF-α, and IL-6, and decreased the generation of regulatory T cells. Moreover, YCPs significantly inhibited melanoma tumor growth by alleviating immune tolerance and promoting Trp2-specific CD8+ T cell immune response. These results suggest that Saccharomyces cerevisiae as a combined immunotherapeutic platform to simultaneously delivery IDO-siRNA and Trp2 epitope peptide is a promising vaccine system for melanoma treatment.

MgAl-layered double hydroxide nanoparticles co-delivering siIDO and Trp2 peptide effectively reduce IDO expression and induce cytotoxic T-lymphocyte responses against melanoma tumor in mice.

Active immunotherapy has shown promising potential for cancer treatment. However, there still remain major challenges including induction of a potent and specific T-cell response against the endogenous antigen and retention of tumor immunity. To address these problems, we used layered double hydroxide (LDH) nanoparticles (NPs) to co-deliver tyrosinase-related protein 2 (Trp2) and indoleamine 2,3-dioxygenase siRNA (siIDO) to dendritic cells (DCs). These LDH NPs were readily taken in by DCs, and escaped from endosomes into the cytoplasm. Compared with free Trp2 peptide or siIDO, the vaccination with the LDH NPs co-delivering Trp2 and siIDO significantly inhibited tumor growth in melanoma mouse models by relieving IDO-mediated immune suppression and increasing naïve and specific T cell activation process in vivo. Thus, these LDH NPs, which have a high loading capacity for peptide or siRNA effectively protect and deliver Trp2 and siIDO, overcome the immune tolerance and strengthen T cell immunity, are potential therapeutics to enhance cancer treatment.

Role of Cervical Cerclage and Vaginal Progesterone in the Treatment of Cervical Incompetence with/without Preterm Birth History.

BACKGROUND: Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important health-care priority. The cervical incompetence is a well-known risk factor for PTB and its incidence is about 0.1-2.0%, while there is no ideal optimum treatment recommended currently. The cervical incompetence causes about 15% of habitual abortion in 16-28 weeks. This study aimed to evaluate the effectiveness and safety of cervical cerclage and vaginal progesterone in the treatment of cervical incompetence with/without PTB history. METHODS: We retrospectively observed the pregnancy outcome of 198 patients diagnosed with cervical incompetence from January 2010 to October 2015 in Beijing Hospital. Among the 198 women involved, women who had at least one PTB before 32 weeks (including abortion in the second trimester attributed to the cervical competence) were assigned to the PTB history cohort, and others were assigned to the non-PTB history cohort. All women underwent cerclage placement (cervical cerclage group) or administrated with vaginal progesterone (vaginal progesterone group) until delivery. The outcomes of interest were the differences in gestational age at delivery, the rate of premature delivery, neonatal outcome, complications, and route of delivery between the two treatment groups. RESULTS: Among the 198 patients with cervical incompetence, 116 patients in PTB history cohort and 80 patients in non-PTB history cohort were included in the final analysis. In the PTB history cohort, cervical cerclage group had significantly longer cervical length at 2 weeks after the start of treatment (23.1 ± 4.6 mm vs. 12.4 ± 9.1 mm, P = 0.002), higher proportion of delivery ≥37 weeks' gestation (63.4% vs. 33.3%, P = 0.008), bigger median birth weight (2860 g vs. 2250 g, P = 0.031), and lower proportion of neonates whose 1-min Apgar score <7 (5.9% vs. 33.3%, P = 0.005), compared with vaginal progesterone group. No significant differences were found in other outcome measures between the two treatment groups. In the non-PTB history cohort, there were no significant differences in the maternal outcomes between cervical cerclage and vaginal progesterone groups, such as median gestational age at delivery (37.4 weeks vs. 37.3 weeks, P = 0.346) and proportion of delivery ≥37 weeks' gestation (55.9% vs. 60.9%, P = 0.569). There were also no significant differences in the neonatal outcomes between the cervical cerclage and vaginal progesterone groups including the median birth weight (2750 g vs. 2810 g, P = 0.145), perinatal mortality (5.9% vs. 6.5%, P = 0.908), and 1-min Apgar scores (8.8% vs. 8.7%, P = 0.984). CONCLUSIONS: Cervical cerclage showed more benefits in the maternal and neonatal outcomes than vaginal progesterone therapy for women with an asymptomatic short cervix and prior PTB history, while cervical cerclage and vaginal progesterone therapies showed similar effectiveness for women with an asymptomatic short cervix but without a history of PTB.

Naturally occurring autoantibodies against Aß oligomers exhibited more beneficial effects in the treatment of mouse model of Alzheimer's disease than intravenous immunoglobulin.

Alzheimer's disease (AD) is characterized by memory loss, intracellular neurofibrillary tangles, and extracellular plaque deposits composed of ß-amyloid (Aß). Previous reports showed that naturally occurring autoantibodies, such as intravenous immunoglobulin (IVIG), benefited patients with moderate-stage AD who carried an APOE-ε4 allele. However, the mechanism underlying the role of IVIG remains unclear. In this study, we identified naturally occurring autoantibodies against Aß oligomers (NAbs-Aßo), which were purified by Aß42 oligomer or Cibacron Blue affinity chromatography from IVIG and termed as Oli-NAbs and Blue-NAbs, respectively. Oli-NAbs and Blue-NAbs recognized Aß42 oligomers or both Aß40 and 42 oligomers, differently. Both antibodies inhibited Aß42 aggregation and attenuated Aß42-induced cytotoxicity. Compared with vehicles, Oli-NAbs, Blue-NAbs and IVIG significantly improved the memory and cognition, and reduced the soluble and oligomeric Aß levels in APPswe/PS1dE9 transgenic mice. Further investigation showed that Blue-NAbs at increased doses effectively decreased plaque burden and insoluble Aß levels, whereas Oli-NAbs significantly declined the microgliosis and astrogliosis, as well as the production of proinflammatory cytokines in vivo. Therefore, high levels of these antibodies against oligomeric Aß40 or Aß42 were required, correspondingly, to achieve the optimal effect. NAbs-Aßo could be condensed to a high concentration by affinity chromatography and its isolation from IVIG may not interfere with the normal function of conventional IVIG as its concentration is very low. Thus, the isolated NAbs-Aßo as an extra product of plasma required low cost and the enriched NAbs-Aßo may be more feasible than IVIG for the treatment of AD.

Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress.

Recent evidence showed that amylin deposition is not only found in the pancreas in type 2 diabetes mellitus (T2DM) patients, but also in other peripheral organs, such as kidneys, heart and brain. Circulating amylin oligomers that cross the blood-brain barrier and accumulate in the brain may be an important contributor to diabetic cerebral injury and neurodegeneration. Moreover, increasing epidemiological studies indicate that there is a significant association between T2DM and Alzheimer's disease (AD). Amylin and ß-amyloid (Aß) may share common pathophysiology and show strikingly similar neurotoxicity profiles in the brain. To explore the potential effects of rutin on AD, we here investigated the effect of rutin on amylin aggregation by thioflavin T dyeing, evaluated the effect of rutin on amylin-induced neurocytotoxicity by the MTT assay, and assessed oxidative stress, as well as the generation of nitric oxide (NO) and pro-inflammatory cytokines in neuronal cells. Our results showed that the flavonoid antioxidant rutin inhibited amylin-induced neurocytotoxicity, decreased the production of reactive oxygen species (ROS), NO, glutathione disulfide (GSSG), malondialdehyde (MDA) and pro-inflammatory cytokines TNF-α and IL-1ß, attenuated mitochondrial damage and increased the GSH/GSSG ratio. These protective effects of rutin may have resulted from its ability to inhibit amylin aggregation, enhance the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and reduce inducible nitric oxide synthase (iNOS) activity. These in vitro results indicate that rutin is a promising natural product for protecting neuronal cells from amylin-induced neurotoxicity and oxidative stress, and rutin administration could be a feasible therapeutic strategy for preventing AD development and protecting the aging brain or slowing neurodegenerative processes.

Decreasing oxidative stress and neuroinflammation with a multifunctional peptide rescues memory deficits in mice with Alzheimer disease.

Alzheimer disease (AD) is characterized by extracellular senile plaques, intracellular neurofibrillary tangles, and memory loss. Aggregated amyloid-ß (Aß), oxidative stress, and inflammation have pivotal roles in the pathogenesis of AD. Therefore, the inhibition of Aß-induced neurotoxicity, oxidative stress, and inflammation is a potential therapeutic strategy for the treatment of AD. In this study, a heptapeptide, isolated from a Ph.D.-C7C library by phage display, attenuated Aß42-induced cytotoxicity in SH-SY5Y neuroblastoma cells and reduced Aß42-induced oxidative stress by decreasing the production of reactive oxygen species and glutathione disulfide. As a result, glutathione level increased and superoxide dismutase and glutathione peroxidase activities were enhanced in vitro and in vivo. This peptide also suppressed the inflammatory response by decreasing the release of proinflammatory cytokines, such as tumor necrosis factor α and interleukin 1ß, in microglia and by reducing microgliosis and astrogliosis in AD transgenic mice. This peptide was intracerebroventricularly administered to APPswe/PS1dE9 transgenic mice. We found that this peptide significantly improved spatial memory and reduced the amyloid plaque burden and soluble and insoluble Aß levels. Our findings suggest that this multifunctional peptide has therapeutic potential for an Aß-targeted treatment of AD.

Activated scavenger receptor A promotes glial internalization of aß.

Beta-amyloid (Aß) aggregates have a pivotal role in pathological processing of Alzheimer's disease (AD). The clearance of Aß monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aß at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide XD4 activates the class A scavenger receptor (SR-A) on the glia by increasing the binding of Aß to SR-A, thereby promoting glial phagocytosis of Aß oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, XD4 enhances the internalization of Aß monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits Aß oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-α and IL-1ß, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.

Rutin improves spatial memory in Alzheimer's disease transgenic mice by reducing Aß oligomer level and attenuating oxidative stress and neuroinflammation.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular ß-amyloid (Aß) plaques and intracellular neurofibrillary tangles in the brain. Aß aggregation is closely associated with neurotoxicity, oxidative stress, and neuronal inflammation. The soluble Aß oligomers are believed to be the most neurotoxic form among all forms of Aß aggregates. We have previously reported a polyphenol compound rutin that could inhibit Aß aggregation and cytotoxicity, attenuate oxidative stress, and decrease the production of nitric oxide and proinflammatory cytokines in vitro. In the current study, we investigated the effect of rutin on APPswe/PS1dE9 transgenic mice. Results demonstrated that orally administered rutin significantly attenuated memory deficits in AD transgenic mice, decreased oligomeric Aß level, increased super oxide dismutase (SOD) activity and glutathione (GSH)/glutathione disulfide (GSSG) ratio, reduced GSSG and malondialdehyde (MDA) levels, downregulated microgliosis and astrocytosis, and decreased interleukin (IL)-1ß and IL-6 levels in the brain. These results indicated that rutin is a promising agent for AD treatment because of its antioxidant, anti-inflammatory, and reducing Aß oligomer activities.

Pan-amyloid oligomer specific scFv antibody attenuates memory deficits and brain amyloid burden in mice with Alzheimer's disease.

Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer's disease (AD), Parkinson disease (PD), Huntington's disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligomer-specific single-chain variable fragment (scFv) antibody, W20, isolated from a naïve human scFv library, can recognize oligomers assembled from α-synuclein, amylin, insulin, Aß40/42, prion peptide 106-126, and lysozyme, inhibit the aggregation of various amyloid, and attenuate amyloid oligomer-induced cytotoxicity In vitro. Furthermore, W20 recognized the amyloid oligomers in all types of plaques, Lewy bodies, and amylin deposits in the brain tissues of AD and PD patients and in the pancreas of type 2 diabetes patients. In the current study, we showed that W20 blocked the binding of Aß oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with Aß levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.

A peptide binding to the ß-site of APP improves spatial memory and attenuates Aß burden in Alzheimer's disease transgenic mice.

Amyloid precursor protein cleaving enzyme 1 (BACE1), an aspartyl protease, initiates processing of the amyloid precursor protein (APP) into ß-amyloid (Aß); the peptide likely contributes to development of Alzheimer's disease (AD). BACE1 is an attractive therapeutic target for AD treatment, but it exhibits other physiological activities and has many other substrates besides APP. Thus, inhibition of BACE1 function may cause adverse side effects. Here, we present a peptide, S1, isolated from a peptide library that selectively inhibits BACE1 hydrolytic activity by binding to the ß-proteolytic site on APP and Aß N-terminal. The S1 peptide significantly reduced Aß levels in vitro and in vivo and inhibited Aß cytotoxicity in SH-SY5Y cells. When applied to APPswe/PS1dE9 double transgenic mice by intracerebroventricular injection, S1 significantly improved the spatial memory as determined by the Morris Water Maze, and also attenuated their Aß burden. These results indicate that the dual-functional peptide S1 may have therapeutic potential for AD by both reducing Aß generation and inhibiting Aß cytotoxicity.

Rutin inhibits ß-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines.

Alzheimer's disease (AD) is a complex, multi-factorial neurodegenerative disease. The aggregation of soluble ß-amyloid (Aß) into fibrillar deposits is a pathological hallmark of AD. The Aß aggregate-induced neurotoxicity, inflammatory reactions, oxidative stress, and nitric oxide (NO) generation are strongly linked to the etiology of AD. Here, we show that the common dietary flavonoid, rutin, can dose-dependently inhibit Aß42 fibrillization and attenuate Aß42-induced cytotoxicity in SH-SY5Y neuroblastoma cells. Moreover, rutin decreases the formation of reactive oxygen species (ROS), NO, glutathione disulfide (GSSG), and malondialdehyde (MDA), reduces inducible nitric oxide synthase (iNOS) activity, attenuates mitochondrial damage, increases the glutathione (GSH)/GSSG ratio, enhances the activities of super oxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and modulates the production of proinflammatory cytokines by decreasing TNF-α and IL-1ß generation in microglia. Taken together, the actions of rutin on multiple pathogenic factors deserves further investigation for the prevention and treatment of AD.

A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aß42-induced cytotoxicity and increasing microglial phagocytosis.

Alzheimer's disease (AD) is characterized by progressive memory loss due to extracellular senile plaques and intracellular neurofibrillary tangles. The toxic ß-amyloid (Aß) aggregates that form in AD can induce the overproduction of reactive oxygen species (ROS), nitric oxide (NO), and proinflammatory cytokines. These Aß aggregates likely play a pivotal role in the onset and progression of AD. Reducing Aß generation, inhibiting Aß toxicity, and improving Aß clearance are promising therapeutic strategies for AD. The present paper is the first to reveal a heptapeptide (XD4) isolated from a Ph.D.-C7C library through phage display that significantly inhibited Aß cytotoxicity, increased the microglial phagocytosis of Aß, decreased the Aß-induced generation of ROS and NO, and attenuated the disequilibrium of calcium homeostasis in vitro. Remarkably, XD4 also attenuated memory deficits in ß-amyloid precursor protein/presenilin 1 (APPswe/PS1dE9) transgenic mice, and reduced amyloid plaque burden and Aß40/42 levels. The results of the present study indicate that this peptide, which specifically targets Aß, may be a promising new therapy for patients exhibiting cognitive impairment and increased Aß burden.