Novel insights into the activating transcription factor 4 in Alzheimer's disease and associated aging-related diseases: Mechanisms and therapeutic implications.

Ageing is inherent to all human beings, most mechanistic explanations of ageing results from the combined effects of various physiological and pathological processes. Additionally, aging pivotally contributes to several chronic diseases. Activating transcription factor 4 (ATF4), a member of the ATF/cAMP response element-binding protein family, has recently emerged as a pivotal player owing to its indispensable role in the pathophysiological processes of Alzheimer's disease and aging-related diseases. Moreover, ATF4 is integral to numerous biological processes. Therefore, this article aims to comprehensively review relevant research on the role of ATF4 in the onset and progression of aging-related diseases, elucidating its potential mechanisms and therapeutic approaches. Our objective is to furnish scientific evidence for the early identification of risk factors in aging-related diseases and pave the way for new research directions for their treatment. By elucidating the signaling pathway network of ATF4 in aging-related diseases, we aspire to gain a profound understanding of the molecular and cellular mechanisms, offering novel strategies for addressing aging and developing related therapeutics.

Nesfatin-1: A Biomarker and Potential Therapeutic Target in Neurological Disorders.

Nesfatin-1 is a novel adipocytokine consisting of 82 amino acids with anorexic and anti-hyperglycemic properties. Further studies of nesfatin-1 have shown it to be closely associated with neurological disorders. Changes in nesfatin-1 levels are closely linked to the onset, progression and severity of neurological disorders. Nesfatin-1 may affect the development of neurological disorders and can indicate disease evolution and prognosis, thus informing the choice of treatment options. In addition, regulation of the expression or level of nesfatin-1 can improve the level of neuroinflammation, apoptosis, oxidative damage and other indicators. It is demonstrated that nesfatin-1 is involved in neuroprotection and may be a therapeutic target for neurological disorders. In this paper, we will also discuss the role of nesfatin-1 as a biomarker in neurological diseases and its potential mechanism of action in neurological diseases, providing new ideas for the diagnosis and treatment of neurological diseases.

Atypical neuroimaging findings in patients with acquired hepatocerebral degeneration.

BACKGROUND: Acquired hepatocerebral degeneration (AHD) is now widely recognized by physicians. Although hyperintensity in the bilateral globus pallidus in T1-weighted magnetic resonance images (MRIs) are characteristic neuroimaging findings, accumulating reports indicate that atypical neuroimaging findings are not rare. This study aimed to describe the spectrum of atypical neuroimaging findings and related factors in patients with AHD. METHODS: From February 2017 to January 2019, a retrospective study was conducted of 28 patients with AHD in the Shengjing Hospital of China Medical University. The neurological manifestations, clinical parameters, and biochemical and neuroimaging findings were analyzed. RESULTS: Among 28 patients, 14 patients were diagnosed with viral hepatitis-caused hepatocirrhosis, which was the most common cause of AHD. Resting tremor, cognitive impairment, and parkinsonian gait were the most common neurologic symptoms. Bilateral globus pallidus T1-weighted hyperintensity was detected in 26 patients (26/28, 92.9%). Ten patients (10/28, 35.7%) were determined to have an atypical neuroimaging finding. Binary logistic regression analysis indicated that age at onset of neurologic symptoms (odds ratio = 1.29, 95% confidence interval [CI] 1.03-1.61; p = 0.030) and Child-Pugh scores (odds ratio = 2.52, 95% CI, 1.01-6.31; p = 0.048) were independently associated with atypical neuroimaging findings in AHD. CONCLUSION: The clinical manifestations of AHD are diverse; resting tremor, cognitive impairment, and parkinsonian gait were the most common. More than one third of patients had atypical neuroimaging findings. Age at onset of neurologic symptoms and Child-Pugh scores may be important predictors of atypical neuroimaging findings in patients with AHD.

Serum cystatin C is associated with carotid atherosclerosis in patients with acute ischemic stroke.

BACKGROUND: Accumulating studies have shown that cystatin C may play important roles in the pathogenesis of arteriosclerosis. However, the association between serum cystatin C and the characteristics of carotid plaques has not been elucidated. Furthermore, the diagnostic value of serum cystatin C in carotid stenosis has not been studied. METHODS: Serum cystatin C in 156 patients with acute ischemic stroke (AIS) in the carotid artery was measured by ELISA. Intima-media thickness (IMT), stenosis of the symptomatic common carotid artery (CCA), extra/intracranial internal carotid artery (ICA) stenosis, and plaque characteristics were measured and recorded. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of serum cystatin C in carotid stenosis. RESULTS: One hundred fifty-six patients were divided into two groups based on their cystatin C levels. The degree of arteriosclerosis, the severity of plaques, and stenosis of the symptomatic CCA were significantly higher in the patients with high cystatin C levels. In addition, the rate of unstable plaques was significantly higher in those with high cystatin C. Serum cystatin C levels of 1.075 and 1.125 mg/L had diagnostic value in distinguishing stenosis of CCA and extracranial ICA, respectively. CONCLUSIONS: Higher cystatin C levels were strongly correlated with symptomatic CCA stenosis and the rate of unstable plaques. Analysis of cystatin C levels may be useful for the identification of CCA stenosis and extracranial ICA in patients with AIS.

Neurological manifestations and neuroimaging presentations in patients with severe preeclampsia: predisposing factors and clinical implications.

BACKGROUND AND PURPOSE: Neurological manifestations and neuroimaging abnormalities are common in patients with severe preeclampsia; however, the differences between these abnormal features occurring during early- and late-onset severe preeclampsia are unclear, and the factors associated with abnormal imaging changes in patients with neurological manifestations have not yet been fully elucidated. MATERIALS AND METHODS: A retrospective study was conducted on 172 patients with severe preeclampsia from January 2017 to June 2018 in the Department of Neurology and Obstetrics, Shengjing Hospital of China Medical University. The neurological manifestations, clinical parameters, laboratory, and neuroimaging findings were analyzed. RESULTS: Early- and late-onset preeclampsia were diagnosed in 83 and 89 patients, respectively. Headache and dizziness were more common in patients with early-onset preeclampsia than in patients with late-onset preeclampsia (p = 0.013, p = 0.004, respectively). Serum uric acid, creatinine, and urea nitrogen were significantly elevated in the patients with early-onset preeclampsia (p < 0.001, p = 0.004, and p = 0.005, respectively). Neuroimaging was performed in 81 patients, of which 57 were positive. Findings indicating cerebral edema were the most common neuroimaging abnormality. Gestational weeks (p = 0.014), headache (p < 0.001), and blood urea nitrogen level (p = 0.027) may be associated with positive imaging findings. By multiple logistic regression, headache (OR = 10.2, 95% CI, 2.4-42.7; p = 0.002) proved to be an independent factor associated with neuroimaging abnormality. CONCLUSIONS: Neurological symptoms such as headache and dizziness were more common in patients with early-onset preeclampsia. Renal dysfunction may also associate with early-onset severe preeclampsia. Cerebral edema was the most common neuroimaging abnormality, and headache might be independently associated with abnormal imagine changes.

Influential factors and clinical significance of an atypical presentation of posterior reversible encephalopathy syndrome in patients with eclampsia.

BACKGROUND AND PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiologic entity for which eclampsia is one of the most common predisposing conditions. Despite the imaging changes typically reported, the predisposing factors and clinical implications of atypical presentations have yet to be fully clarified. METHODS: A total of 56 patients with PRES were selected for study. Demographic, clinical, and laboratory data were analyzed, focusing on atypical presentations of PRES. Multiple logistic regression was applied to identify factors impacting such atypical presentations, and functional outcomes were assessed upon patient discharge. RESULTS: Overall, 22 of the 56 patients (39.3%) displayed features of atypical PRES. By multiple logistic regression, headache (OR = 5.39; 95% CI, 1.24-23.51; p = 0.025) and frequent convulsions (OR = 4.41; 95% CI, 1.09-17.91; p = 0.038) proved to be independent factors associated with atypical PRES. Ultimately, outcomes of 18 patients were gauged as poor, based on the modified Rankin Scale (mRS). Logistic regression indicated that visual disturbances (OR = 9.02; 95% CI, 1.37-59.35; p = 0.02), frequent convulsions (OR = 9.47; 95% CI, 1.67-53.63; p = 0.01), and restricted diffusion on imaging (OR = 11.96; 95% CI, 1.76-81.11; p = 0.01) were independently associated with poor outcomes in patients with eclampsia-related PRES. CONCLUSION: Headache and frequent convulsions are independently associated with atypical presentations of PRES. If present, restricted diffusion may help in predicting poor outcomes of such patients upon discharge.

Fluid-attenuated inversion recovery vascular hyperintensities in anterior circulation acute ischemic stroke: associations with cortical brain infarct volume and 90-day prognosis.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is often observed in conjunction with acute ischemic stroke (AIS) of the carotid system. However, the significance of FVH in patients with AIS has not been fully elucidated. The purpose of this study is to investigate the effects of FVH on the final infarct volume (including cortical and deep brain infarct volume) and on 90-day prognosis in AIS patients. MATERIAL AND METHODS: We analyzed data of 160 patients who had AIS of anterior circulation. FVH was identified and the cortical brain infarct volume (CBIV) and deep brain infarct volume (DBIV) were calculated. We assessed 90-day clinical outcome using the modified Rankin Scale (mRS). RESULTS: FVH was identified in 83 of the 160 patients (51.88%). Patients with FVH showed larger CBIV (13.94 ± 25.55 vs. 6.56 ± 13.49 ml; p = 0.025), more frequent intracranial-large artery disease (74.70 vs. 27.27%; p < 0.001), and more severe clinical impairment on admission (NIHSS 7.22 ± 4.01 vs. 5.42 ± 4.52; p = 0.009). Considering the factors influencing prognosis, FVH positivity (OR = 2.12, 95% CI 1.13-3.99; p = 0.02) and NIHSS (at discharge) (OR = 2.14, 95% CI 1.64-2.78; p < 0.001) were independently associated with 90-day clinical outcome of AIS patients. CONCLUSION: FVH is a more common finding associated with larger CBIV, intracranial-large artery disease, and more severe strokes on admission. In the presence of good collateral circulation, FVH may be a predictor of better outcome in anterior circulation AIS patients at 90 days.

Clinical characteristics and factors associated with short-term prognosis in adult patients with autoimmune encephalitis of non-neoplastic etiology.

BACKGROUND: Reports that autoimmune encephalitis (AE) is associated with antibodies have increased; however, little is known about the distribution of clinical symptoms, imaging changes, and prognostic factors in patients with AE of non-neoplastic etiology. Accordingly, we evaluated the clinical characteristics and factors associated with short-term prognosis. METHODS: From January 2016 to June 2018, 31 adult patients were diagnosed with AE of non-neoplastic etiology at Shengjing Hospital of China Medical University and their demographic and clinical characteristics were abstracted. Factors affecting disease severity and predictors of prognosis were analyzed. RESULTS: Among 31 patients, 19 had anti-NMDAR, 5 had anti-GABABR, and 7 had anti-LGI1 antibody encephalitis. Status epilepticus, ataxia, and cognitive dysfunction were the most common neurological symptoms. Deep white matter (DWM) abnormalities were the most common changes observed on MRI. Logistic regression analysis indicated that conscious disturbance (odds ratio = 11.67, 95%, confidence interval 2.13-64.04; p = 0.005) is an independent factor associated with poor prognosis in AE. CONCLUSION: The clinical manifestations of AE are diverse; status epilepticus, ataxia, and cognitive dysfunction are most common. The DWM of the brain, rather than the limbic lobe system, was most prone to MR signal abnormalities. Conscious disturbance may be an important predictor of poor short-term prognosis in patients with AE of non-neoplastic etiology.

Association of serum growth differentiation factor 15 level with acute ischemic stroke in a Chinese population.

Background: Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-ß family. Elevated GDF-15 concentrations are associated with increased risks of cardiovascular diseases, diabetes mellitus and cerebrovascular disease. Objective: This study aimed to determine the clinical significance of serum GDF-15 level after acute ischemic stroke (AIS) in a Chinese population. Methods: We compared serum GDF-15 levels between 83 AIS patients and 124 controls. At admission and on day 7, we recorded the National Institutes of Health Stroke Scale score and measured serum GDF-15 levels for AIS patients and for control patients at admission. Stroke volumes were calculated using diffusion-weighted magnetic resonance imaging performed at admission. Clinical outcomes were evaluated 90 days later using the modified Rankin Scale. Results: Serum GDF-15 level at admission was significantly higher in AIS patients than in controls (p < .01). GDF-15 level on day 7 was significantly higher in the poor outcomes group than in the good outcomes group (p < .05). Higher GDF-15 levels at admission and on day 7 were related to larger stroke volumes (p < .01). Binary logistic regression indicated that serum GDF-15 level at admission may be independently related with AIS (p < .01). Serum GDF-15 level on day 7 may independently associated with poor outcomes after AIS (p < .05). Conclusions: GDF-15 level at admission may independently related to AIS, and GDF-15 level on day 7 could independently predict outcomes at 90 days after AIS. GDF-15 may provide prognostic information after AIS in a Chinese population.

Cystatin C as an index of acute cerebral infraction recurrence: one-year follow-up study.

BACKGROUND AND PURPOSE: Cystatin C is associated with acute cerebral infarction (ACI). However, the correlation of serum cystatin C level with recurrence of ACI and different subtypes of ACI had not been fully clarified. The aim of this study was to detect the relationship between serum cystatin C level and recurrent ACI in one-year follow-up and different subtypes of ACI. METHODS: A total of 532 consecutive patients with ACI and 339 healthy controls were included. All ACI patients were followed up for one year, the clinical and biochemical characteristics of ACI and ACI recurrent patients were documented and analyzed. RESULTS: A total of 477 (89.7%) patients completed one-year follow-up study, 64 (13.4%) patients suffered ACI recurrence. The results showed serum cystatin C was 1.04 ± 0.19 mg/L and 1.14 ± 0.49 mg/L in control and ACI, respectively (p< .001). The significant risk factors for ACI recurrence were presence of hypertension (p = .009, OR =3.32), diabetes (p =.03, OR =1.87), coronary heart disease (p = .01, OR =2.46), and cystatin C (p = .003, OR =2.87). The risk of ACI recurrence increased with serum cystatin C level. Additionally, cystatin C level was associated with different subtypes of ACI; large-artery atherosclerosis (LAA) subtype had the highest level of cystatin C in ACI and recurrent ACI group. CONCLUSIONS: Serum cystatin C level is an independent prediction biomarker for ACI recurrence. LAA subtype of ACI and ACI recurrence was more closely related to elevated cystatin C level.

Posterior reversible encephalopathy syndrome with spinal cord involvement (PRES-SCI) as a rare complication of severe diabetic ketoacidosis: a case report and review of the literature.

INTRODUCTION: In addition to diffuse brain oedema, diabetic ketoacidosis (DKA) can lead to ischaemic or haemorrhagic stroke, extrapontine myelinolysis, and sinovenous thrombosis. However, posterior reversible encephalopathy syndrome (PRES) and spinal cord oedema are rarely reported in patients with DKA. METHODS: We present a case of a 17-year-old-girl who developed headache, blurred vision, and paraplegia after her DKA was controlled. Sequential magnetic resonance (MR) scans of the brain and spinal cord were performed. RESULTS: Brain MR showed large patchy lesions in the bilateral white matter of the parieto-occipital lobes, which had high T2 signal intensity and low T1 signal intensity. MR scanning of the spinal cord showed longitudinal confluent central spinal cord T2 hyperintensity spanning seven thoracic spinal segments. With symptomatic treatment, the patient's headache and vision disturbance subsided within 1 week. Subsequent MR scans demonstrated that the lesion in the spinal cord had decreased significantly in 10 days, and the large patchy lesions in the brain disappeared completely in 2 months. Her paraplegia improved gradually without obvious sequela 3 months later. The evolution of the disease and radiological findings supported the diagnosis of PRES with spinal cord involvement. CONCLUSION: To the best of our knowledge, this is the first case report describing PRES with spinal cord involvement as a complication of DKA. PRES is a rare complication that should be considered along with other neurological complications of DKA when focal deficits appear.

Influential factors and clinical significance of fluid-attenuated inversion recovery vascular hyperintensities in transient ischemic attacks of carotid arterial system.

PURPOSE: Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is often observed in conjunction with acute ischemic stroke (AIS) of the carotid system. Despite its bearing on patient care outcomes, factors influencing FVH and its clinical significance in patients with transient ischemic attacks (TIAs) of the carotid arterial system have yet to be evaluated. METHODS: Consecutive inpatients (N = 154) diagnosed with TIAs of the carotid system in a 2-year period (2012-2014) were enrolled in our study. Each had undergone magnetic resonance imaging (MRI) within 72 h of symptom onset, followed by intracranial and extracranial vascular imaging. We investigated the frequency and nature of factors associated with FVH, also examining its clinical significance in the 30-day prognosis of TIA. RESULTS: Of the 154 patients enrolled (male, 92; mean age 63.0 ± 11.9), FVH was confirmed in 61 patients (39.6%). In logistic regression analysis, intracranial large-artery disease (LAD) (OR = 2.39, 95% CI 1.16-4.92; p = 0.018) and prior stroke (OR = 3.33, 95% CI 1.48-7.51; p = 0.004) emerged as factors independently associated with FVH positivity. Ultimately, 25 patients (16.2%) progressed to AIS within a 30-day follow-up period. Logistic regression analysis indicated that contralateral FVH positivity (OR = 5.98, 95% CI 1.81-19.76; p = 0.003), atrial fibrillation (OR = 7.05, 95% CI 1.33-37.40; p = 0.022), and extracranial LAD (OR = 4.12, 95% CI 1.26-13.41; p = 0.019) were independently associated with AIS during the 30-day follow-up of TIAs in these patients. CONCLUSION: Intracranial LAD and previous stroke are independently associated with FVH in patients experiencing carotid system TIAs. If present, FVH may predict an oncoming AIS in the 30 days following a TIA.

20(s)-ginsenoside Rg3 promotes apoptosis in human ovarian cancer HO-8910 cells through PI3K/Akt and XIAP pathways.

Ovarian cancer is a serious tumor which represents a great threat to women's health. Recently, researchers had found that 20(s)-ginsenoside Rg3 could inhibit growth of several cancer cell lines; however, the mechanism is not fully understood so far. In the present study, we found that 20(s)-ginsenoside Rg3 reduced cell viability and induced apoptosis in a dose- and time-dependent manner in the human ovarian cancer cells HO-8910. The induction of apoptosis was accompanied by downregulation of phosphatidylinositol 3-kinase (PI3K)/Akt family proteins and inhibitor of apoptosis protein (IAP) family proteins. 20(s)-ginsenoside Rg3 treatment resulted in activation of caspase-3 and -9, which may partly explain the anti-cancer activity of 20(s)-ginsenoside Rg3. Taken together, our study for the first time suggests that 20(s)-ginsenoside Rg3 is able to enhance apoptosis of HO-8910 cells, at least in part, through downregulation of PI3K/Akt and IAP family proteins. Moreover, the triggering of caspase-3 and -9 activation mediated apoptotic induction. Our data indicate that 20(s)-ginsenoside Rg3 is an effective apoptosis-inducing natural compound in ovarian cancer cells and may have a role in future therapies for ovarian cancer.

Relationship between the therapeutic potential of various plant-derived bioactive compounds and their related microRNAs in neurological disorders.

BACKGROUND: Neurological disorders, such as ischemic stroke, spinal cord injury, neurodegenerative diseases, and glioblastoma often lead to long-term disability and death. MicroRNAs (miRNAs) are small single-stranded non-coding RNAs of approximately 22 nucleotides, known to participate in both normal and pathological development, making them ideal therapeutic targets for clinical intervention. Several recent studies have suggested that plant-derived bioactive compounds (PDBCs) can have anti-atherosclerosis, antioxidant, and anti-inflammatory effects by regulating miRNAs. Thus, miRNAs are novel targets for the action of PDBCs. PURPOSE: The aim of this review was to evaluate the current status of PDBCs targeted miRNAs by dissecting their development status through a literature review. METHODS: A manual and electronic search was performed for English articles available from inception up to June 2022 reporting PDBCs and their regulating relationship with miRNAs for the therapeutic potential of neurological disorders. Information was retrieved from scientific databases including PubMed, ScienceDirect, Web of Science, Google Scholar and Chemical Abstracts Services. Keywords used for the search engines were "miRNAs" AND "Plant-derived bioactive compounds" in conjunction with "(native weeds OR alien invasive)" AND "traditional herbal medicine". RESULTS: A total of 37 articles were retrieved on PDBCs and their related miRNAs in neurological disorders. These PDBCs from traditional herbal medicine may play a therapeutic role in neurological disorders in a variety of mechanisms by regulating the corresponding miRNAs. These mechanisms mainly include inhibiting oxidative stress, anti-neuroinflammation, anti-autophagy, and anti-apoptosis. PDBC are a group of chemically distinct compounds derived from medicinal plants, some of which have therapeutic effects on neurological disorders. CONCLUSION: The emergence of miRNAs as pathological regulatory factors provides a new direction for the study of bioactive compounds in Traditional Chinese medicine and the elucidating of their epigenetic effects. Elucidating the regulatory relationship between bioactive compounds and miRNAs may help to identify new therapeutic targets and promoting the application of these compounds in precision medicine through their targeted molecular activity.

Focus on Alzheimer's Disease: The Role of Fibroblast Growth Factor 21 and Autophagy.

Alzheimer's disease (AD) is a disorder of the central nervous system that is typically marked by progressive cognitive impairment and memory loss. Amyloid ß plaque deposition and neurofibrillary tangles with hyperphosphorylated tau are the two hallmark pathologies of AD. In mammalian cells, autophagy clears aberrant protein aggregates, thus maintaining proteostasis as well as neuronal health. Autophagy affects production and metabolism of amyloid ß and accumulation of phosphorylated tau proteins, whose malfunction can lead to the progression of AD. On the other hand, defective autophagy has been found to induce the production of the neuroprotective factor fibroblast growth factor 21 (FGF21), although the underlying mechanism is unclear. In this review, we highlight the significance of aberrant autophagy in the pathogenesis of AD, discuss the possible mechanisms by which defective autophagy induces FGF21 production, and analyze the potential of FGF21 in the treatment of AD. The findings provide some insights into the potential role of FGF21 and autophagy in the pathogenesis of AD.

Ferroptosis: a potential therapeutic target for Alzheimer's disease.

The most prevalent dementia-causing neurodegenerative condition is Alzheimer's disease (AD). The aberrant buildup of amyloid ß and tau hyperphosphorylation are the two most well-known theories about the mechanisms underlying AD development. However, a significant number of pharmacological clinical studies conducted around the world based on the two aforementioned theories have not shown promising outcomes, and AD is still not effectively treated. Ferroptosis, a non-apoptotic programmed cell death defined by the buildup of deadly amounts of iron-dependent lipid peroxides, has received more attention in recent years. A wealth of data is emerging to support the role of iron in the pathophysiology of AD. Cell line and animal studies applying ferroptosis modulators to the treatment of AD have shown encouraging results. Based on these studies, we describe in this review the underlying mechanisms of ferroptosis; the role that ferroptosis plays in AD pathology; and summarise some of the research advances in the treatment of AD with ferroptosis modulators. We hope to contribute to the clinical management of AD.

Neuroprotective Mechanisms of Salidroside in Alzheimer's Disease: A Systematic Review and Meta-analysis of Preclinical Studies.

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that occurs in old age and pre-aging, characterized by progressive cognitive dysfunction and behavioral impairment. Salidroside (Sal) is a phenylpropanoid mainly isolated from Rhodiola species with various pharmacological effects. However, the exact anti-AD mechanism of Sal has not been clearly elucidated. This meta-analysis aims to investigate the possible mechanisms by which Sal exerts its anti-AD effects by evaluating behavioral indicators and biochemical characteristics. A total of 20 studies were included, and the results showed that the Sal treatment significantly improved behavior abnormalities in AD animal models. With regard to neurobiochemical indicators, Sal treatment could effectively increase the antioxidant enzyme superoxide dismutase, decrease the oxidative stress indicator malondialdehyde, and decrease the inflammatory indicators interleukin 1ß, interleukin 6, and tumor necrosis factor α. Sal treatment was effective in reducing neuropathological indicators, such as amyloid-ß levels and the number of apoptotic cells. When the relevant literature on the treatment of rodent AD models is combined with Sal, the therapeutic potential of Sal through multiple mechanisms was confirmed. However, further confirmation by higher quality studies, larger sample sizes, and more comprehensive outcome evaluations in clinical trials is needed in the future.

The Therapeutic Potential of Hydroxycinnamic Acid Derivatives in Parkinson's Disease: Focus on In Vivo Research Advancements.

Hydroxycinnamic acid derivatives (HCDs) are polyphenols that are abundant in cereals, coffee, tea, wine, fruits, vegetables, and other plant-based foods. To aid in the clinical prevention and treatment of Parkinson's disease (PD), we evaluated in vivo investigations of the pharmacological properties of HCDs relevant to PD, and their pharmacokinetic and safety aspects. An extensive search of published journals was conducted using several literature databases, including PubMed, Google Scholar, and the Web of Science. The search terms included "hydroxycinnamic acid derivatives," "ferulic acid," "caffeic acid," "sinapic acid," "p-coumaric acid," "Parkinson's disease," and combinations of these keywords. As of April 2023, 455 preclinical studies were retrieved, of which 364 were in vivo studies; we included 17 of these articles on the pharmaceutics of HCDs in PD. Available evidence supports the protective effects of HCDs in PD due to their anti-inflammatory, antioxidant, as well as antiapoptotic physiological activities. Studies have identified possible molecular targets and pathways for the protective actions of HCDs in PD. However, the paucity of studies on these compounds in PD, and the risk of toxicity induced with high-dose applications, limits their use. Thus, multifaceted studies of HCDs in vitro and in vivo are needed.

Kaempferol as a therapeutic agent in Alzheimer's disease: Evidence from preclinical studies.

BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia and seriously affects human life and health. Kaempferol (KMP) is a common flavonoid, that is mainly derived from the rhizomes of Kaempferol galanga L. and is widely found in various fruits and vegetables. Previous studies have suggested that KMP has multiple pharmacological activities. However, the anti-AD mechanism of KMP has not been elucidated. METHODS: This systematic review aims to summarize the existing preclinical experiments on KMP, further confirm the therapeutic effect of KMP in an AD model, and summarize the possible mechanism by which KMP exerts anti-AD effects. Electronic databases, including PubMed, China National Knowledge Infrastructure (CNKI), Baidu Academic, and Wanfang, were searched using the keywords of 'Kaempferol,' 'KMP,' 'pharmacology,' and 'Alzheimer's disease'. RESULTS: We evaluated the reliability of the 12 included studies, and the results showed that the anti-AD mechanism of KMP was reliable and that the prospect of KMP in the treatment of cognitive impairment was promising. We comprehensively assessed the neuroprotective effects of KMP in in vivo and in vitro models of AD. These studies shown that KMP ameliorated AD through several mechanisms, including its antioxidant, anti-inflammatory, anti-apoptotic, and anti-acetylcholinesterase effects. CONCLUSION: KMP may exert anti-AD effects through various mechanisms and is a potential drug with broad prospects for the treatment of AD.

Study on the association between pregnancy-associated plasma protein-A and acute cerebral infarction.

Objective: We aimed to study the correlation between pregnancy-associated plasma protein-A (PAPP-A) and acute cerebral infarction (ACI). Methods: Patients who had the symptoms of paralysis, aphasia, or sudden neurological impairment from June 2020 to October 2021 were chosen. There were 159 patients diagnosed with ACI as the experimental group and 102 patients without ACI as the control group. We collected clinical data and observed whether they have a certain impact on plasma PAPP-A levels. The ACI group was divided into two groups: mild neurological deficit group (NIHSS score < 3) and moderate and severe neurological deficit group (NIHSS score > 3). The ACI group was divided into the atherosclerotic-type group and the arteriolar occlusion-type group according to the TOAST classification. The ACI group was divided into a good prognosis group (mRS ≤ 2 points) and a poor prognosis group (mRS > 2 points) using the Modified Rankin Scale (mRS) for 90 days of follow-up. Plasma PAPP-A levels were compared between those groups. Results: (1) The plasma PAPP-A level in patients with ACI (1.840 ± 0.281) was significantly higher than that in the control group (1.690 ± 0.260). Smoking history, leukocyte count, cystatin C, homocysteine, and plasma PAPP-A levels were independently correlated with ACI. (2) The level of PAPP-A in patients with moderate and severe neurological impairment was lower than that in patients with mild neurological impairment. (3) The level of PAPP-A in patients in the arteriolar occlusion-type group was higher than that in patients in the atherosclerosis-type group. (4) The PAPP-A levels in the group with elevated low-density lipoprotein are higher than those in the group with normal low-density lipoprotein. (5) Plasma PAPP-A level was not correlated with infarction location, infarction volume, or prognosis at the 90-day follow-up. Conclusion: (1) The level of plasma PAPP-A could be the independent risk factor of ACI. It is positively correlated with triglyceride and cholesterol content. (2) PAPP-A level is positively correlated with low-density lipoprotein. (3) PAPP-A levels between different disease severities have a significant difference. (4) The level of plasma PAPP-A in the arteriolar occlusion-type group was higher than that in the atherosclerotic-type group.