Prevalence and risk factors for dementia and mild cognitive impairment among older people in Southeast China: a community-based study.

BACKGROUND: With the aging population, the number of individuals with dementia in China is increasing rapidly. This community-based study aimed to investigate the prevalence and risk factors for dementia and mild cognitive impairment (MCI) among older adults in China. METHODS: In this study, 20,070 individuals aged ≥ 65 were recruited between January 1, 2022, and February 1, 2023, from ten communities in Xiamen City, China. We collected data on age, sex, level of education, and medical history, as well as global cognition and functional status. The prevalence of dementia and MCI was examined, and the risk factors for different groups were assessed. RESULTS: The overall prevalence of dementia and MCI was approximately 5.4% (95% confidence interval [CI], 5.1-5.7) and 7.7% (95% CI, 7.4-8.1), respectively. The results also indicated that dementia and MCI share similar risk factors, including older age, female sex, hypertension, and diabetes mellitus. Compared with individuals with no formal education, those with > 6 years of education had an odds ratio for MCI of 1.83 (95% CI, 1.49-2.25). We also found that only 5.5% of the positive participants chose to be referred to the hospital for further diagnosis and treatment during follow-up visits. CONCLUSIONS: This study estimated the prevalence and risk factors for dementia and MCI among individuals aged ≥ 65 years in Southeast China. These findings are crucial for preventing and managing dementia and MCI in China.

Inhibitory role of remifentanil in hepatic ischemia-reperfusion injury through activation of Fmol/Parkin signaling pathway: A study based on network pharmacology analysis and high-throughput sequencing.

BACKGROUND: This study was conducted to elucidate the critical molecular pathways underlying the protective effects of remifentanil against hepatic ischemia-reperfusion injury in rats. Our approach integrated network pharmacology analysis with high-throughput sequencing to achieve a comprehensive understanding of the mechanisms involved. STUDY DESIGN/METHODS: The study utilized GSE24430 gene expression data from GEO to investigate remifentanil's impact on Hepatic Ischemia-Reperfusion Injury in rats. Weighted Correlation Network Analysis (WGCNA) was employed to pinpoint crucial genes and identify modules of co-expressed genes. Differential analysis with the "Limma" package revealed genes differentially expressed in IRI vs. control groups. PubChem and PharmMapper provided target genes affected by remifentanil. Protein-protein interaction networks were constructed via GeneCards and STRING. Functional analysis pinpointed core genes involved in remifentanil's IRI alleviation. IRI rat models were established, and hepatic injury indicators, liver structure via H&E staining, autophagosome counts via electron microscopy, and gene/protein expression via RT-qPCR and Western blot were assessed. High-throughput sequencing analyzed molecular pathways affected by varying remifentanil doses in IRI rats. RESULTS: In the study, we discovered four primary co-expression modules associated with hepatic IRI, and the grey module exhibited the highest correlation with hepatic IRI.A total of sixty-eight genes that were differentially expressed were found to have a connection with hepatic IRI.Network pharmacology analysis found that remifentanil may alleviate hepatic IRI through Fmol.found that the Fmol/Parkin signaling pathway may alleviate hepatic IRI via Additionally, the database autophagy. The established hepatic IRI rat models further confirmed the above findings. CONCLUSION: Our study established that remifentanil triggers the Fmol/Parkin signaling cascade, amplifying the expression levels of Fmol and Parkin. This process culminates in the activation of autophagy within hepatic cells, ultimately alleviating hepatic ischemia-reperfusion injury (IRI).

Amorfrutins Relieve Neuropathic Pain through the PPARγ/CCL2 Axis in CCI Rats.

Neuropathic pain is a public health problem. Although many pharmaceuticals are used to treat neuropathic pain, effective and safe drugs do not yet exist. In this study, we tested nociceptive responses in CCI rats, and ELISA assay was performed to examine the expression of proinflammatory cytokines. We found that amorfrutins significantly reduce the pain behaviors in CCI rats and suppress the expression of proinflammatory cytokines (TNFα, IL-6, and IL-1ß) and chemokines (CCL2/CCR2) in the spinal cord. However, concurrent administration of a PPARγ antagonist, GW9662, reversed the antihyperalgesic effect induced by amorfrutins. The results indicate that amorfrutins inhibit the inflammation and chemokine expression by activating PPARγ, thus relieving neuropathic pain in CCI rats. Therefore, PPARγ-CCL2/CCR2 pathway might represent a new treatment option for neuropathic pain.

MiR-122-5p suppresses neuropathic pain development by targeting PDK4.

The complex pathogenesis and limited efficacy of available treatment make neuropathic pain difficult for long periods of time. Several findings suggested the regulatory role of microRNA in the development of neuropathic pain. This study aims to investigate the functional role of miR-122-5p in the development of neuropathic pain. Down-regulation of miR-122-5p was observed in spinal cords of rats with neuropathic pain. We also found that overexpressing miR-122-5p by intrathecal injection of miR-122-5p lentivirus in a mouse model of chronic sciatic nerve injury (CCI) prevented neuropathic pain behavior. In HEK-293 T cells, luciferase activity was significantly decreased in the transfection group with mimic-miR-122-5p in wild-type PDK4 reporter, compared with mutant PDK4 reporter. Increased PDK4 expression was also observed during the progression of neuropathic pain. Intrathecal injection of both mimic-miR-122-5p and shPDK4 in CCI mice downregulated PDK4 expression to a lower level when compared with injected with shPDK4. In CCI mice, transfection of shPDK4 suppressed mechanical allodynia and thermal hyperalgesia, while co-transfection of shPDK4 and LV-miR-122-5p resulted in stronger levels of mechanical allodynia and thermal hyperalgesia inhibition. Taken together, the data suggest that miR-122-5p inhibits PDK4 expression, attenuating neuropathic pain. This result suggests the potential role of miR-122-5p acting as a target for the treatment of neuropathic pain.

Dexmedetomidine Attenuates Neuroinflammatory-Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway.

OBJECTIVE: Dexmedetomidine (DEX) exhibits neuroprotective effects as a multifunctional neuroprotective agent in numerous neurological disorders. However, in traumatic brain injury (TBI), the molecular mechanisms of these neuroprotective effects remain unclear. The present study investigated whether DEX, which has been reported to exert protective effects against TBI, could attenuate neuroinflammatory-induced apoptosis and clarified the underlying mechanisms. METHODS: A weight-drop model was established, and DEX was intraperitoneally injected 30 min after inducing TBI in rats. The water content in the brain tissue was measured. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays were performed on histopathological tissue sections to evaluate neuronal apoptosis. Enzyme-linked immunosorbent assay and PCR were applied to detect the levels of the inflammatory factors, TNF-α, IL-1ß, IL-6, and NF-κB. RESULTS: TBI-challenged rats exhibited significant neuronal apoptosis, which was characterized via the wet-to-dry weight ratio, neurobehavioral functions, TUNEL assay results and the levels of cleaved caspase-3, Bax upregulation and Bcl-2, which were attenuated by DEX. Western blot, immunohistochemistry, and PCR results revealed that DEX promoted Nrf2 expression and upregulated expression of the Nrf2 downstream factors, HO-1 and NQO-1. Furthermore, DEX treatment markedly prevented the downregulation of inflammatory response factors, TNF-α, IL-1ß and NF-κB, and IL-6. INTERPRETATION: Administering DEX attenuated inflammation-induced brain injury in a TBI model, potentially via the Nrf2 signaling pathway.

Breviscapine provides a neuroprotective effect after traumatic brain injury by modulating the Nrf2 signaling pathway.

Breviscapine (BVP) has been widely used in the treatment of several systemic diseases, including those of the cardiovascular and cerebrovascular systems. But, few studies have looked at the neuroprotective effects of BVP and its potential effect in treating traumatic brain injury (TBI). The present study investigated the neuroprotective effect of BVP following TBI and illuminated the underlying mechanism. The weight drop-induced closed diffuse traumatic brain injury method was used to induce TBI in rats. BVP was injected intraperitoneally 30 minutes after TBI. Neurologic scores were performed to measure behavioral outcomes. Nissl staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays were performed on histopathologic tissue sections to evaluate neuronal apoptosis. The nuclear factor erythroid 2-related factor 2 (Nrf2) and its related downstream proteins, including heme oxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO1) were detected with Western blots. BVP treatment alleviated or attenuated TBI-induced neuron cell apoptosis and improved neurobehavioral functions through the upregulated expression of Nrf2 and its related downstream proteins. This study, using the drug, BVP, we present new mechanisms responsible for neuronal apoptosis in TBI with possible involvement of the Nrf2 pathway.

Dexmedetomidine reduces oxidative stress and provides neuroprotection in a model of traumatic brain injury via the PGC-1α signaling pathway.

The protective effects of dexmedetomidine (DEX) mediated by reductions of oxidative stress, mitochondrial damage and disintegration have been demonstrated in many injury models. However, whether DEX has a beneficial effect on traumatic brain injury (TBI) remains unknown. In this study, the neuroprotective effect of DEX and its potential mechanism were assessed in a model of TBI. DEX treatment relieved encephala edema and neuron cell apoptosis and increased behavioral function. These protective effects were accompanied by upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α) expression. These findings imply that DEX protects neurons following TBI, possibly by activating the PGC-1α pathway. The data will help clarify the mechanisms responsible for the anti-apoptosis effect of DEX with possible involvement of the PGC-1α pathway.

The miR-31-SOX10 axis regulates tumor growth and chemotherapy resistance of melanoma via PI3K/AKT pathway.

MicroRNAs were thought to play a regulatory role through complementarity to target messenger RNA (mRNA). Our previous study revealed a miR-31-SOX10 axis that regulated tumor growth and resistance to chemotherapy of melanoma. Up-regulation of SOX10 and down-regulation of miR-31 were found in melanoma tissues. SOX10 was further identified as a target of miR-31. Overexpression of SOX10 dramatically promoted melanoma cell proliferation and chemotherapy resistance both in vitro and in vivo. While enforced miR-31 expression suppressed cell growth and enhanced the chemosensitivity of melanoma cells, the re-expression of SOX10 rescued these effects by activating PI3K/AKT signaling pathway. In conclusion, our results demonstrated that SOX10 acted as an oncogene and was negatively regulated by miR-31, which supports the potential therapeutic strategy against melanoma by targeting the miR-31-SOX10 axis.

PPARγ activation ameliorates postoperative cognitive decline probably through suppressing hippocampal neuroinflammation in aged mice.

Neuroinflammation plays a key role in many neurodegenerative disorders, including postoperative cognitive decline (POCD). Growing evidence has demonstrated that activation of the peroxisome proliferator-activated receptor-γ (PPARγ) attenuates the inflammatory response and improves cognitive dysfunction associated with many neuropsychiatric disorders. We hypothesize that down-regulation of PPARγ is linked to neuroinflammation and the subsequent cognitive deficits observed in an animal model of POCD. In the present study, the POCD animal model was established by performing an exploratory laparotomy under isoflurane anesthesia in 20-month-old male C57BL/6 mice. Behavioral tests, inflammatory biomarkers, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß, ionized calcium-binding adaptor molecule-1 (IBA1)-positive cells, as well as glial fibrillary acidic protein (GFAP)-positive cells and brain-derived neurotrophic factor (BDNF), were measured. Herein, we showed that surgery induced profound impairment in cognition that was associated with significant decreases in PPARγ and BDNF expression, and significant increases in IL-1ß, IBA1-positive cells, and GFAP-positive cells in the hippocampus. As expected, the PPARγ agonist pioglitazone attenuated the surgery-induced inflammatory changes and rescued the associated cognitive impairment. However, these beneficial effects were abolished by the PPARγ specific antagonist GW9662, suggesting a pivotal role of the PPARγ pathway in the pathogenesis of POCD. Taken together, our results provide evidence that down-regulation of PPARγ may be involved in neuroinflammation and subsequent POCD, and suggest that activation of PPARγ by pioglitazone may represent a new way to prevent or treat POCD.

Rutin Acid Ameliorates Neural Apoptosis Induced by Traumatic Brain Injury via Mitochondrial Pathways in Mice.

Rutin reportedly conveys many beneficial effects, including neuroprotection in brain injury. However, the mechanisms underlying these effects are still not well understood. This study investigates the effect of rutin on potential mechanisms for neuroprotective effects, using the weight-drop model of traumatic brain injury (TBI) in male mice treated either with rutin or a vehicle via intraperitoneal injection 30 min after TBI. After euthanasia and 24 h after TBI, all mice were examined by tests, including neurologic scores, blood-brain barrier permeability, brain water content and neuronal cell death in the cerebral cortex. Results indicate that the levels of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD) were restored by rutin treatment. Rutin treatment resulted in the downregulation of caspase-3 expression in a reduced number of positive cells under terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and also the improved survival of neurons. Furthermore, pretreatment levels of MDA were restored, while Bcl-2-associated X protein translocation to mitochondria and cytochrome c release into cytosol were reduced by rutin treatment. Our results demonstrate that rutin improves neurological outcome by protecting neural cells against apoptosis via mechanisms that involve the mitochondria following TBI.

Berberine alleviates postoperative cognitive dysfunction by suppressing neuroinflammation in aged mice.

Postoperative cognitive dysfunction (POCD) is a significant cause of morbidity after surgery, especially for the elderly. Accumulating evidence has demonstrated that neuroinflammation plays a key role in the pathogenesis of POCD. Thus, we hypothesized that berberine, an isoquinoline alkaloid with anti-inflammatory effects, could improve surgery-induced cognitive impairment. Twenty-month-old male C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to mimic the clinical human abdominal surgery. For the interventional studies, mice received berberine (10mg/kg) or vehicle intraperitoneally. For the in vitro study, we examined the effects of berberine on lipopolysaccharide (LPS)-induced inflammatory mediators by cultured BV2 cells. Behavioral tests, expressions of IBA1, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were performed at the indicated time points. In the present study, we showed that surgery impaired the contextual fear memory, as evidenced by the significantly decreased freezing time to the context. This behavioral change coincided with marked increases in IBA1, TNF-α, IL-1ß, and IL-6 in the prefrontal cortex and hippocampus only at 24h but not 7 d after surgery. In BV2 cells, LPS induced significantly increased TNF-α and IL-1ß expressions. Notably, berberine treatment rescued surgery-induced cognitive impairment and inhibited the release of IBA1, IL-1ß, and IL-6 in the hippocampus. In line with the in vivo study, berberine treatment suppressed LPS-stimulated production of TNF-α and IL-1ß in BV2 cells. In conclusion, our study suggests that berberine could alleviate POCD by suppressing neuroinflammation in aged mice.

Open Set face recognition using transduction.

This paper motivates and describes a novel realization of transductive inference that can address the Open Set face recognition task. Open Set operates under the assumption that not all the test probes have mates in the gallery. It either detects the presence of some biometric signature within the gallery and finds its identity or rejects it, i.e., it provides for the "none of the above" answer. The main contribution of the paper is Open Set TCM-kNN (Transduction Confidence Machine-k Nearest Neighbors), which is suitable for multiclass authentication operational scenarios that have to include a rejection option for classes never enrolled in the gallery. Open Set TCM-kNN, driven by the relation between transduction and Kolmogorov complexity, provides a local estimation of the likelihood ratio needed for detection tasks. We provide extensive experimental data to show the feasibility, robustness, and comparative advantages of Open Set TCM-kNN on Open Set identification and watch list (surveillance) tasks using challenging FERET data. Last, we analyze the error structure driven by the fact that most of the errors in identification are due to a relatively small number of face patterns. Open Set TCM-kNN is shown to be suitable for PSEI (pattern specific error inhomogeneities) error analysis in order to identify difficult to recognize faces. PSEI analysis improves biometric performance by removing a small number of those difficult to recognize faces responsible for much of the original error in performance and/or by using data fusion.

Motion estimation using Statistical Learning Theory.

This paper describes a novel application of Statistical Learning Theory (SLT) to single motion estimation and tracking. The problem of motion estimation can be related to statistical model selection, where the goal is to select one (correct) motion model from several possible motion models, given finite noisy samples. SLT, also known as Vapnik-Chervonenkis (VC), theory provides analytic generalization bounds for model selection, which have been used successfully for practical model selection. This paper describes a successful application of an SLT-based model selection approach to the challenging problem of estimating optimal motion models from small data sets of image measurements (flow). We present results of experiments on both synthetic and real image sequences for motion interpolation and extrapolation; these results demonstrate the feasibility and strength of our approach. Our experimental results show that for motion estimation applications, SLT-based model selection compares favorably against alternative model selection methods, such as the Akaike's fpe, Schwartz' criterion (sc), Generalized Cross-Validation (gcv), and Shibata's Model Selector (sms). The paper also shows how to address the aperture problem using SLT-based model selection for penalized linear (ridge regression) formulation.