Association between skeletal muscle and left ventricular mass in patients with hyperthyroidism.

Objective: This study aims to investigate the relationship between skeletal muscle and left ventricular mass (LVM) in patients with hyperthyroidism, providing theoretical and data-based foundations for further research on the interaction between secondary muscle atrophy and cardiac remodeling. Methods: A retrospective data collection was conducted, including 136 patients with hyperthyroidism (Study group) and 50 healthy participants (control group). The Study group was further divided into Group A (high LVM) and Group B (low LVM) based on LVM size. Multiple linear regression analysis was performed to examine the correlation between skeletal muscle and LVM, with model evaluation. Based on the results, further nonlinear regression analysis was conducted to explore the detailed relationship between skeletal muscle and LVM. Results: Compared to the control group, the Study group exhibited significantly lower LVM, skeletal muscle mass index (SMI), and skeletal muscle mass (SMM) (P<0.05). Within the subgroups, Group A had significantly higher SMI, SMM, and hand grip strength compared to Group B (P<0.05). The results of the multiple linear regression showed a certain correlation between SMI (ß=0.60, P=0.042, 95% CI=0.02~1.17) and hand grip strength (ß=0.34, P=0.045, 95% CI=0.01~0.67) with LVM. However, the residuals of the multiple regression did not follow a normal distribution (K-S=2.50, P<0.01). Further results from a generalized linear model and structural equation modeling regression also demonstrated a correlation between SMI (ß=0.60, P=0.040, 95% CI=0.03~1.17) (ß=0.60, P=0.042, 95% CI=0.02~1.17) and hand grip strength (ß=0.34, P=0.043, 95% CI=0.01~0.67) (ß=0.34, P=0.045, 95% CI=0.01~0.67) with LVM. Conclusion: Patients with hyperthyroidism may exhibit simultaneous decreases in LVM, SMM, and SMI. The LVM in patients is correlated with SMM and hand grip strength, highlighting the need for further exploration of the causal relationship and underlying mechanisms. These findings provide a basis for the prevention and treatment of secondary sarcopenia and cardiac pathology in patients with hyperthyroidism.

Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis.

Monofluoromethyl (CH2F) motifs exhibit unique bioactivities and are considered privileged units in drug discovery. The radical monofluoromethylative difunctionalization of alkenes stands out as an appealing approach to access CH2F-containing compounds. However, this strategy remains largely underdeveloped, particularly under metal-free conditions. In this study, we report on visible light-mediated three-component monofluoromethylation/acylation of styrene derivatives employing NHC and organic photocatalyst dual catalysis. A diverse array of α-aryl-ß-monofluoromethyl ketones was successfully synthesized with excellent functional group tolerance and selectivity. The mild and metal-free CH2F radical generation strategy from NaSO2CFH2 holds potential for further applications in fluoroalkyl radical chemistry.

Catalyst-Free Trans-Selective Oxyiodination and Oxychlorination of Alkynes Employing N-X (Halogen) Reagents.

ß-halogenated enol esters and ethers are versatile building blocks in organic synthesis, which has attracted increasing attention. In this study, we report the facile trans-oxyiodination and oxychlorination of alkynes, leading to the direct construction of versatile halogenated enol esters and ethers. This transformation features an easy operation, optimal atomic economy, a strong functional group tolerance, broad substrate scope, and excellent trans-selectivity. Employing highly electrophilic bifunctional N-X (halogen) reagents was the key to achieving broad reaction generality. To our knowledge, this transformation represents the first oxyhalogenation system employing N-X (halogen) reagents as both oxylation and halogenation sources.

The neuroprotective effects of peracetylated chitosan oligosaccharides against ß-amyloid-induced cognitive deficits in rats.

Chitosan oligosaccharides (COSs) have been reported to possess a broad range of activities such as antitumor, antioxidant and neuroprotective activities. In this study, the protective effects and mechanisms of peracetylated chitosan oligosaccharides (PACOs) against Aß-induced cognitive deficits were investigated in Sprague-Dawley (SD) rats. PACOs treatment significantly improved the learning and memory function of Alzheimer's disease (AD) rats and attenuated the neuron cell damage caused by Aß. PACOs also markedly reduced the levels of lactate dehydrogenase (LDH) and Malondialdehyde (MDA) and decreased the phosphorylation of Tau protein to inhibit oxidative injury and inflammatory responses in AD rats. Further studies indicated that PACOs may promote the repair of Aß induced nerve damage and inhibit neuronal apoptosis mainly through regulating PI3K/Akt/GSK3ß signaling pathway. Consistently, the transcriptome analysis verified that the differentially expressed genes (DEGs) were mainly involved in neuron development and the PI3K-Akt signaling pathway. Taken together, peracetylated chitosan oligosaccharides (PACOs) have the potential to be developed into novel anti-AD agents targeting the cellular PI3K/Akt/GSK3ß signaling pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00172-3.

Brain-targeted lycopene-loaded microemulsion modulates neuroinflammation, oxidative stress, apoptosis and synaptic plasticity in ß-amyloid-induced Alzheimer's disease mice.

OBJECTIVES: ß-Amyloid protein (Aß) plays pivotal roles in pathogenesis of Alzheimer's disease (AD) and triggers various pathophysiological events. Lycopene is a promising neuroprotector with multiple bioactivities, while its bioavailability is limited. Lycopene-loaded microemulsion (LME) possessing superior bioavailability and brain-targeting efficiency was developed in our previous study. In this investigation, we aimed to comprehensively evaluate its neuroprotective effects and underlying mechanisms using intracerebroventricular (ICV) Aß1-42 injection mice. METHODS: Mice were assigned to the Sham, Aß, Aß + LME and Aß + lycopene dissolved in olive oil (LOO) groups. ICV Aß1-42 administration was performed, followed by oral gavage of brain-targeted LME or conventional LOO formulation for 3 weeks. Brain samples were harvested for immunohistochemistry, biochemical assays and western blotting analyses. RESULTS: Our findings verified Aß-induced neurotoxicity on neuroinflammation, oxidative stress, apoptosis, Aß metabolisms and synaptic plasticity. LME supplementation dramatically attenuated astrocytosis and microgliosis, decreased malondialdehyde production and rescued antioxidant capacities, normalized apoptotic parameters and alleviated neuronal loss, inhibited amyloidogenic processing and activated non-amyloidogenic pathway, together with upregulating synaptic protein expressions and restoring synaptic plasticity. Nevertheless, most of these phenomena were not observed for mice treated with LOO, implying that LME showed significantly higher therapeutic efficacy against Aß injury. DISCUSSION: In summary, brain-targeted LME could exert neuroprotective function via suppressing a series of cascades triggered by Aß aggregates, thus ameliorating Aß neurotoxicity and associated abnormalities. Given this, LME may serve as an attractive candidate for AD prevention and treatment, and superiority of brain-targeting delivery is highlighted.

Neuroprotective effects of neural stem cells pretreated with neuregulin1ß on PC12 cells exposed to oxygen-glucose deprivation/reoxygenation.

Studies on ischemia/reperfusion (I/R) injury suggest that exogenous neural stem cells (NSCs) are ideal candidates for stem cell therapy reperfusion injury. However, NSCs are difficult to obtain owing to ethical limitations. In addition, the survival, differentiation, and proliferation rates of transplanted exogenous NSCs are low, which limit their clinical application. Our previous study showed that neuregulin1ß (NRG1ß) alleviated cerebral I/R injury in rats. In this study, we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1ß on PC12 cells injured by oxygen-glucose deprivation/reoxygenation (OGD/R). Our results found that 5 and 10 nM NRG1ß promoted the generation and proliferation of NSCs. Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1ß improved the level of reactive oxygen species, malondialdehyde, glutathione, superoxide dismutase, nicotinamide adenine dinucleotide phosphate, and nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial damage in injured PC12 cells; these indexes are related to ferroptosis. Research has reported that p53 and solute carrier family 7 member 11 (SLC7A11) play vital roles in ferroptosis caused by cerebral I/R injury. Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4 (GPX4) was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells, but this change was alleviated after co-culturing NSCs with damaged PC12 cells. These findings suggest that NSCs pretreated with NRG1ß exhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.

MicroRNA-29b Suppresses Inflammation and Protects Blood-Brain Barrier Integrity in Ischemic Stroke.

Objectives: Following cerebral ischemia, microRNA- (miR-) 29b in circulating blood is downregulated. This study investigates the underlying mechanism and implications of miR-29b in leukocyte induction. Methods: miR-29b from stroke patients and rats with middle cerebral artery occlusion (MCAO) were assessed using real-time polymerase chain reaction (PCR). miR-29b agomir was used to increase miR-29b expression in leukocytes via intravenous injection. C1q and tumor necrosis factor (C1QTNF) 6, interleukin- (IL-) 1ß, zonula occludens- (ZO-) 1, occludin, and ischemic outcomes were assessed in MCAO rats. Additionally, hCMEC/D3 cells were subjected to oxygen-glucose deprivation (OGD) and cocultured with HL-60 cells. Results: miR-29b levels in neutrophils were found to be significantly lower in stroke patients compared with healthy controls, which may indicate its high diagnostic sensitivity and specificity for stroke. Moreover, miR-29b levels in leukocytes showed a negative correlation with National Institute of Health Stroke Scale (NIHSS) scores and C1QTNF6 levels. In MCAO rats, miR-29b overexpression reduced brain infarct volume and brain edema, decreasing IL-1ß levels in leukocytes and in the brain 24 hours poststroke. miR-29b attenuated IL-1ß expression via C1QTNF6 inhibition, leading to decreased blood-brain barrier (BBB) disruption and leukocyte infiltration. Moreover, miR-29b overexpression in HL-60 cells downregulated OGD-induced hCMEC/D3 cell apoptosis and increased ZO-1 and occludin levels in vitro. Conclusion: Leukocytic miR-29b attenuates inflammatory response by augmenting BBB integrity through C1QTNF6, suggesting a novel miR-29b-based therapeutic therapy for ischemic stroke.

Insidious Attentional Deficits in Patients With Cerebral Small Vessel Disease Revealed by Attention Network Test.

Background: Several reports have indicated potential cognitive decline for cerebral small vessel disease (CSVD), especially in attention domain, whereas the attentional function at network level is still elusive. In this study, we used the attention network test (ANT) paradigm to characterize the efficiency of the alerting, orienting, and executive control networks in patients with CSVD and explore possible correlations between attention network efficiencies and obtained CSVD total score. Methods: A total of 31 patients with CSVD and 30 healthy controls matched for age, gender, and education level were recruited. After neuropsychological and anxiety/depression/somatization assessments, an original version of ANT containing different cue conditions and target stimuli was used to investigate independent attentional components, and then, behavioral performance (accuracy and reaction time) and network efficacy were recorded and analyzed. Results: Assessed by traditional neuropsychological scale (MoCA), we did not find difference between groups on general cognition. Nevertheless, the overall reaction time to targets of ANT was markedly prolonged in patients with CSVD, and similar phenomenon was observed for overall accuracy on ANT. Moreover, patients showed significantly lower orienting and executive control network efficiencies compared with controls, while not for alerting network. These impairments were correlated with total CSVD burdens, but not with anxiety, depression, or somatization. Conclusions: Although general and almost all individual cognitive function evaluated by MoCA seemed to remain intact, the orienting and executive control function was impaired in individuals with CSVD, which was modulated by lesion grades. Our observations implied insidious attentional deficits regarding CSVD. Given this, considering its simplicity and sensitivity, ANT could serve as an attractive tool for early diagnosis of cognitive dysfunction. Further investigations on the availability of ANT detection for CSVD are warranted.

Transplantation of Human Umbilical Cord Mesenchymal Stem Cells-Derived Neural Stem Cells Pretreated with Neuregulin1ß Ameliorate Cerebral Ischemic Reperfusion Injury in Rats.

Ischemic stroke is a common cerebrovascular disease and recovering blood flow as early as possible is essential to reduce ischemic damage and maintain neuronal viability, but the reperfusion process usually causes additional damage to the brain tissue in the ischemic area, namely ischemia reperfusion injury. The accumulated studies have revealed that transplantation of exogenous neural stem cells (NSCs) is an ideal choice for the treatment of ischemia reperfusion injury. At present, the source and efficacy of exogenous NSCs after transplantation is still one of the key issues that need to be resolved. In this study, human umbilical cord mesenchymal stem cells (hUC-MSCs) were obtained and induced into NSCs byadding growth factor and neuregulin1ß (NRG1ß) was introduced during the differentiation process of NSCs. Then, the rat middle cerebral artery occlusion/reperfusion (MCAO/R) models were established, and the therapeutic effects were evaluated among groups treated by NRG1ß, NSCs and NSCs pretreated with 10 nM NRG1ß (NSCs-10 nM NRG1ß) achieved through intra-arterial injection. Our data show that the NSCs-10 nM NRG1ß group significantly improves neurobehavioral function and infarct volume after MCAO/R, as well as cerebral cortical neuron injury, ferroptosis-related indexes and mitochondrial injury. Additionally, NSCs-10 nM NRG1ß intervention may function through regulating the p53/GPX4/SLC7A11 pathway, and reducing the level of ferroptosis in cells, further enhance the neuroprotective effect on injured cells.

Long non-coding RNA H19 promotes leukocyte inflammation in ischemic stroke by targeting the miR-29b/C1QTNF6 axis.

AIMS: Inflammatory processes induced by leukocytes are crucially involved in the pathophysiology of acute ischemic stroke. This study aimed to elucidate the inflammatory mechanism of long non-coding RNA (lncRNA) H19-mediated regulation of C1q and tumor necrosis factor 6 (C1QTNF6) by sponging miR-29b in leukocytes during ischemic stroke. METHODS: H19 and miR-29b expression in leukocytes of patients with ischemic stroke and rats with middle cerebral artery occlusion were measured by real-time polymerase chain reaction. H19 siRNA and miR-29b antagomir were used to knock down H19 and miR-29b, respectively. We performed in vivo and in vitro experiments to determine the impact of H19 and miR-29b on C1QTNF6 expression in leukocytes after ischemic injury. RESULTS: H19 and C1QTNF6 upregulation, as well as miR-29b downregulation, was detected in leukocytes of patients with stroke. Moreover, miR-29b could bind C1QTNF6 mRNA and repress its expression, while H19 could sponge miR-29b to maintain C1QTNF6 expression. C1QTNF6 overexpression promoted the release of IL-1ß and TNF-α in leukocytes, further exacerbated blood-brain barrier disruption, and aggravated the cerebral ischemic injury. CONCLUSIONS: Our findings confirm that H19 promotes leukocyte inflammation by targeting the miR-29b/C1QTNF6 axis in cerebral ischemic injury.

Evodiamine induces ROS-Dependent cytotoxicity in human gastric cancer cells via TRPV1/Ca2+ pathway.

Evodiamine (EVO), a key active ingredient of the fruit of Evodiae fructus, is provided with antitumor effects (mainly cytotoxic effect) including proliferation inhibition, cell cycle arrest, apoptosis, and metastasis inhibition. Our study aims to explain the underlying role of TRPV1/Ca2+ in EVO-induced cytotoxicity in human gastric cancer cells. Human gastric cancer line BGC-823 was used to study EVO-induced cytotoxicity. Cell viability was examined using CCK-8 assay. Apoptosis was examined using Annexin V-FITC/PI staining assay. Intracellular ROS ([ROS]i) levels were examined using DCFH-DA assay. Mitochondrial morphology was examined using Mitotracker Green staining. Mitochondrial membrane potential (Δψm) were examined using JC-1 assay. Intracellular Ca2+ levels ([Ca2+]i) were examined using Fluo-4 AM assay. Mitochondrial ROS ([ROS]m)levels were examined using Mitotracker Green/MitoSOX Red staining. Mitochondrial Ca2+ ([Ca2+]m)levels were examined using Mitotracker Green/Rhod-2 Red staining. The protein levels was detected by Western blot. EVO exposure causes significant ROS generation and apoptotic cell death. Pretreatment of EUK134 significantly ameliorated EVO-induced apoptotic cell death. Furthermore, EVO exposure induced [ROS]i generation and mitochondrial dysfunction, including [ROS]m generation and Δψm dissipation, which can be significantly attenuated by pre-incubation of rotenone indicating that [ROS]m is the main source of EVO-induced intracellular ROS generation. Importantly, EVO-induced cytotoxicity was significantly ameliorated by intracellular Ca2+ chelation, confirming that EVO induces cell death through Ca2+ overload. Pharmacological and genetic inhibition of TRPV1 could significantly attenuate Ca2+ influx, ROS generation and apoptotic cell death induced by EVO exposure, while exogenous TRPV1 overexpression could augment the EVO-induced cytotoxicity. Moreover, genetic inhibition of mitochondrial calcium uniporter (MCU) attenuated EVO-induced cell death and mitochondrial dysfunction. EVO exposure induced endoplasmic reticulum (ER) stress demonstrated by the activation of PERK/CHOP in cells exposed to EVO, and PERK/CHOP activation was depleted by EUK134 pre-treatment. Our results support the concept that EVO induces ROS-dependent cytotoxicity via TRPV1/Ca2+ Pathway.

Effect of evodiamine on cell death pathways in human gastric cancer cells.

Evodiamine (EVO) exerts anti-cancer effect in a majority of cancer cells. BGC-823 and SGC-7901 cells were used to study EVO-induced cytotoxicity in human gastric cancer cell. Our results demonstrated that EVO exposure elicited cell vialibility decrease and G2/M arrest caused by induction of cdc2/cyclin B1 complex activation. EVO also induced caspase-dependent apoptosis and necroptosis caused by induction of actication of RIP, RIP3 and MLKL. Moreover, increase of reactive oxygen species (ROS) levels and cytotoxicity induced by EVO were significantly attenuated by co-treatment with a ROS scavenger, EUK134. In conclusion, EVO induced ROS-dependent cytotoxicity, which may involve apoptosis and necroptosis, in human gastric cancer cells.

Selective Impairment of Processing Task-Irrelevant Emotional Faces in Cerebral Small Vessel Disease Patients.

BACKGROUND: Few reports have implied electrophysiological alterations and neurocognitive abnormalities in patients with cerebral small vessel disease (CSVD), while no investigation is available regarding emotional processing. In the present study, pre-attentive processing of facial expressions was compared between CSVD sufferers and healthy controls using expression-related visual mismatch negativity (EMMN) as the indicator. METHODS: A total of 22 CSVD patients (12 males) and 21 age-matched healthy controls (12 males) were recruited for neuropsychological and emotional assessments, as well as electroencephalogram recording and analysis. We employed an expression-related oddball paradigm to investigate automatic emotional processing, and a series of schematic emotional faces (neutral, happy, sad) unrelated to subject's task were present in the test to avoid low-level processing of facial features. RESULTS: Although the distinctions of neuropsychological (MoCA and MMSE), emotional (GAD-7 and PHQ-9) and behavioral parameters (reaction time to target stimuli and response accuracy) did not reach significant levels, mean amplitudes of sad EMMN in time intervals of 150-250 ms and 250-350 ms were remarkably reduced in CSVD patients compared with healthy controls, but not for happy EMMN. Furthermore, in the control group, sad EMMN was demonstrated to be larger (more negative) than happy EMMN, while this interesting phenomenon disappeared in the CSVD group. CONCLUSION: Our findings confirmed selective impairment of processing expressions which were task-irrelevant in CSVD patients, without the existence of negative bias (sad superiority) effect. The efficacy of EMMN as an electrophysiological evaluation marker of CSVD should be taken into account in future investigations.

Preliminary Findings on Visual Event-Related Potential P3 in Asymptomatic Patients with Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease is the primary cause of cognitive impairment. Therefore, early recognition is of great significance. Some studies have shown that asymptomatic cerebral small vessel disease (aCSVD) patients have abnormal neurocognitive function, but this is not readily apparent at the initial stage. The objective of this paper was to assess visual spatial attention by event-related potential (ERP) examination and to analyze the relationship between ERP data and clinical characteristics in patients with aCSVD. METHODS: We selected 25 aCSVD patients and enrolled 23 age-matched normal subjects as the control group. We measured the latency and amplitude of original/corresponding differential ERP components using the modified visual oddball paradigm, which included a standard stimulus, target stimulus, and new stimulus. Additionally, we selected aberrant ERP components to study the correlations between the ERP data and clinical characteristics of the patients with aCSVD. RESULTS: We found not only lower amplitude but also significantly longer P3 latency in the aCSVD patients. The above results were further verified by analyzing the different components (target minus standard and novel minus standard) of P3. Furthermore, abnormal ERPs in the aCSVD patients were closely related to the changes observed with imaging. CONCLUSION: It was demonstrated that the speed and capability of processing visual spatial information was impaired in aCSVD patients compared with healthy controls. Thus, ERP examination could detect the presence of attentional deficits and might become a rapid and sensitive method for the early diagnosis of aCSVD. However, its availability needs further investigation.

Lycopene-Loaded Microemulsion Regulates Neurogenesis in Rats with Aß-Induced Alzheimer's Disease Rats Based on the Wnt/ß-catenin Pathway.

Objective: To investigate the effects of lycopene-loaded microemulsion (LME) on the cognitive function and neurogenesis in the dentate gyrus (DG) of the hippocampus and subventricular (SVZ) region of rats with amyloid ß- (Aß-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/ß-catenin pathway. Methods: Healthy Wistar rats were divided into four groups: the blank control (CON), AD control, traditional lycopene (LOO), and LME groups. The CON and AD groups were fed with normal saline, while the LOO group was fed with traditional lycopene, and the LME group was fed with lycopene-loaded microemulsion. Behavioral tests were performed after three weeks of gastric administration. Immunofluorescence-labeled cells were used to observe the differentiation and maturation of new nerve cells in the DG of the hippocampus and SVZ region. qRT-PCR and Western blotting detected the expression of neurogenesis genes and Wnt/ß-catenin pathway-related proteins, respectively. Results: On the Morris water maze test, LME rats had significantly shortened movement trajectory on the searching platform, reduced escape latency time, and increased residence time on the original platform quadrant. In addition, more LME rats crossed the platform when it was removed. Thus, LME can improve the spatial learning and memory of Aß-induced AD rats. On qRT-PCR, LME significantly increased Reelin, Nestin, and Pax6 gene expressions, which regulate neurogenesis. Immunofluorescence showed that LME could significantly increase BrdU+, Dcx+, BrdU+/Neun+, BrdU+/Dcx+ cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1+ and Iba1+/BrdU+ cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/ß-catenin pathway by upregulating Wnt3a, ß-catenin, Disheveled (Dvl), and p-GSK3ß and downregulating p-ß-catenin and GSK3ß. Conclusion: LME attenuates cognitive impairment in Aß-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/ß-catenin pathway.

Neuroprotective effects of salidroside on ageing hippocampal neurons and naturally ageing mice via the PI3K/Akt/TERT pathway.

Studies have found that salidroside, isolated from Rhodiola rosea L, has various pharmacological activities, but there have been no studies on the effects of salidroside on brain hippocampal senescence. The purpose of this study was to investigate the mechanistic role of salidroside in hippocampal neuron senescence and injury. In this study, long-term cultured primary rat hippocampal neurons and naturally aged C57 mice were treated with salidroside. The results showed that salidroside increased the viability and MAP2 expression, reduced ß-galactosidase (ß-gal) levels of rat primary hippocampal neurons. Salidroside also improved cognition dysfunction in ageing mice and alleviated neuronal degeneration in the ageing mice CA1 region. Moreover, salidroside decreased the levels of oxidative stress and p21, p16 protein expressions of hippocampal neurons and ageing mice. Salidroside promoted telomerase reverse transcriptase (TERT) protein expression via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. In conclusion, our findings suggest that salidroside has the potential to be used as a therapeutic strategy for anti-ageing and ageing-related disease treatment.

Cerebroprotein hydrolysate-I protects senescence-induced by D-galactose in PC12 cells and mice.

Cerebroprotein hydrolysate-I (CH-I)，a mixture of peptides extracted from porcine brain tissue，has shown a neuroprotective effect, but its role in brain senescence is unclear. In the present study, we established a senescence model of PC12 cells and mice to investigate the effect of CH-I on brain senescence via JAK2/STAT3 pathway. The results showed that CH-I could improve cell viability, inhibit the apoptosis of cells, and reduce the senescence-positive cells induced by D-galactose. In vivo, CH-I improved the learning ability and memory of aging mice, reduced neuronal damage in mice hippocampus. Mechanism studies showed that CH-I could adjust BDNF protein expressions, activate JAK2/STAT3 pathway, and finally enhance telomerase activity. All these findings indicated that CH-I showed a neuroprotective effect against brain senescence. These results might provide further reference and support for the application of CH-I in delaying aging.

Risk factors associated with recurrence of ischemic stroke after intracranial stenting in china: a case-control study.

Objectives: To investigate the factors affecting the risk of recurrent stroke after intracranial artery stenting.Methods: This is a subgroup analysis of a prospective single-arm registry study with 20 participating sites. Patients aged 18-85 years old with symptomatic intracranial atherosclerotic stenosis caused by 70-99% stenosis combined with poor collaterals were included in this study. The median follow-up in this study was 26.4 months.Results: A total of 260 patients were recruited in this study. Ischemic stroke related to target vessel occurred in 11 patients (4.2%) from 30 days to the last follow-up. The multivariate analysis revealed age ≥60 years old (OR: 11.991, 95% CI: 1.400-102.716; p = 0.023), no smoking (OR: 0.087, 95% CI: 0.010-0.787; p = 0.030), and Mori C type (OR: 5.129, 95% CI: 1.242-21.178; p = 0.024) retained significance in the model. There was no significant difference in the ischemic stroke based on medical history of hypertension, diabetes, dyslipidemia, baseline percent stenosis, length of stenosis, residual stenosis, and different stent types.Conclusions: Recurrence of ischemic stroke after intracranial stenting may be associated with elderly age, non-smoking, and Mori C type lesion. These factors will need to be monitored in future trials of intracranial stenting.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01968122.

The Correlation Between COVID-19 Activities and Climate Factors in Different Climate Types Areas.

OBJECTIVE: To investigate the epidemiological characteristics of human infection with corona virus disease 2019 (COVID-19) in Moscow, Lima, Kuwait, and Singapore to analyze the effects of climate factors on the incidence of COVID-19. METHODS: Collect the daily incidence of COVID-19 and related climate data in four areas, construct a negative binomial regression model, and analyze the correlation between the incidence of COVID-19 and meteorological factors. RESULTS: AH was the climate factor affecting the incidence of COVID-19 in Moscow, Lima, and Singapore; Ta and RH were the climate factors affecting the incidence of COVID-19 in Kuwait. CONCLUSIONS: The incidence of COVID-19 in four areas were all associated with the humidity, and climate factors should be taken into consideration when epidemic prevention measures are taken, and environment humidification may be a feasible approach to decrease COVID-19 virus transmission.

Endoplasmic reticulum stress and autophagy are involved in adipocyte-induced fibrosis in hepatic stellate cells.

Liver fibrosis, with the characterization of progressive accumulation of extracellular matrix (ECM), is the common pathologic feature in the process of chronic liver disease. Hepatic stellate cells (HSCs) which are activated and differentiate into proliferative and contractile myofibroblasts are recognized as the main drivers of fibrosis. Obesity-related adipocytokine dysregulation is known to accelerate liver fibrosis progression, but the direct fibrogenic effect of mature adipocytes on HSCs has been rarely reported. Therefore, the purpose of this study was to explore the fibrogenic effect of adipocyte 3T3-L1 cells on hepatic stellate LX-2 cells. The results showed that incubating LX-2 cells with the supernatant of 3T3-L1 adipocytes triggered the expression of ECM related proteins, such as α-smooth muscle actin (α-SMA), type I collagen (CO-I), and activated TGF ß/Smad2/3 signaling pathway in LX-2 cells. In addition, 3T3-L1 cells inhibited insulin sensitivity, activated endoplasmic reticulum stress and autophagy to promote the development of fibrosis. These results supported the notion that mature adipocytes can directly activate hepatic stellate cells, and the establishment of an in vitro model of adipocytes on HSCs provides an insight into screening of drugs for liver diseases, such as nonalcoholic fatty liver disease.