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2022 ◽  
Vol 12 (3) ◽  
pp. 653-658
Xin Yang ◽  
Shandan Wang

This study intends to promote bone marrow mesenchymal stem cells (BMSCs) differentiation into neural stem cells by down-regulating p38 MAPK/NF-κB to heal neurodegeneration. 26 patients with neurodegenerative diseases were enrolled from the Department of Neurology along with recruitment of 26 other healthy controls followed by analysis of p38 MAPK/NF-κB signaling pathway expression by ELISA. BMSCs were cultured and characterized by flow cytometry. Western blot and qRTPCR measured the p38 MAPK/NF-κB expression in the absence or presence of p38 MAPK/NF-κB inhibitors. p38 MAPK/NF-κB expression in 26 neurodegenerative patients was significantly higher than that of 26 healthy controls. The qRT-PCR and western blot results showed that the neural stem cell-specific proteins expression was increased as days went; after addition of p38 MAPK/NF-κB inhibitor, the expression of related specific genes were significantly decreased. In conclusion, inhibition of the expression of p38 MAPK/NF-κB signaling pathway can heal neurodegeneration by promoting the differentiation of BMSCs into neural stem cells.

2022 ◽  
Vol 12 (5) ◽  
pp. 1065-1070
Jin Song ◽  
Jiahan Chang ◽  
Xue Lin ◽  
Cibo Fan ◽  
Lili Han ◽  

Triple-negative breast cancer (TNBC) remains a threat to women’s life with a lack of targeted therapy. This study aimed to explore the role of PTEN derived from BMSCs in TNBC. We carried out a retrospective analysis of 65 TNBC patients and 30 healthy subjects from October 2016 to January 2021 with a 10-year follow up. PTEN expression in TNBC tissues and cells was determined by RTqPCR. Functional experiments were conducted to evaluate PTEN’s effect on TNBC cell biological behaviors using MTT assay and Transwell assay, as well as on PI3K-Akt-HIF-1α-VEGF signaling transduction. PTEN was up-regulated in TNBC tissues relative to healthy controls and it was negatively associated with the survival rate. In in vitro experiments, PTEN overexpression increased cell viability and invasion and knocking down of PTEN exerted opposite effect. The expression of PI3K was directly regulated by PTEN. Up-regulation of PTEN resulted in a decline in HIF-1α, Akt and VEGF expressions, which were elevated after knocking down of PTEN. In conclusion, PTEN derived from BMSCs promotes TNBC cell development through blocking PI3K-Akt-HIF-1α-VEGF signaling pathway, providing a new theoretical basis for targeted therapy of TNBC.

2022 ◽  
Charalampos Papadopoulos ◽  
Eleftheria Spourita ◽  
Konstantinos Mimidis ◽  
George Kolios ◽  
Ioannis Tentes ◽  

Non-alcoholic steatohepatitis (NASH) constitutes a significant cause of deaths, liver transplantations and economic costs worldwide. Despite extended research, investigations on the role of erythrocytes are scarce. Red blood cells from experimental animals and human patients with NASH, present phosphatidylserine exposure which is then recognized by Kupffer cells. This event leads to erythrophagocytosis, and amplification of inflammation through iron disposition. In addition, it has been shown that erythrocytes from NASH patients release the chemokine MCP1, leading to increased TNF-α release from macrophages RAW 264.7. However, erythrophagocytosis can also be caused by reduced CD47 levels. In addition, increased MCP1 release could be either signal-induced, or caused by higher MCP1 levels on the erythrocyte membrane. Finally, erythrocyte efferocytosis could provide additional inflammatory metabolites. In this study, we measured the erythrocyte membrane levels of CD47 and MCP1 by ELISA, and cholesterol and sphingosine with thin-layer chromatography. 18 patients (8 men, 10 women aged 56.7+/-11.5 years) and 14 healthy controls (7 men, 7 women aged 39.3+/-15.5 years) participated in our study. The erythrocyte CD47 levels were decreased in the erythrocyte membranes of NASH patients (844+/-409 pg/ml) compared to healthy controls (2969+/-1936 pg/ml) with P(Healthy>NAFLD)=99.1%, while the levels of MCP1 were increased in NASH patients (389+/-255 pg/ml), compared to healthy controls (230+/-117 pg/ml) with P(Healthy<NAFLD)=88.9%. Moreover, in erythrocyte membranes there was a statistically significant accumulation of sphingosine and cholesterol in NASH patients, compared to healthy controls. Our results imply that erythrocytes release chemotactic (find me signals) MCP1, while containing reduced (do not eat me signals) CD47. These molecules can lead to erythrophagocytosis. Next, increased (goodbye signals) sphingosine and cholesterol could augment inflammation by metabolic reprogramming.

2022 ◽  
Vol 23 (1) ◽  
Jing Ren ◽  
Qun Yao ◽  
Minjie Tian ◽  
Feng Li ◽  
Yueqiu Chen ◽  

Abstract Background Migraine is a common and disabling primary headache, which is associated with a wide range of psychiatric comorbidities. However, the mechanisms of emotion processing in migraine are not fully understood yet. The present study aimed to investigate the neural network during neutral, positive, and negative emotional stimuli in the migraine patients. Methods A total of 24 migraine patients and 24 age- and sex-matching healthy controls were enrolled in this study. Neuromagnetic brain activity was recorded using a whole-head magnetoencephalography (MEG) system upon exposure to human facial expression stimuli. MEG data were analyzed in multi-frequency ranges from 1 to 100 Hz. Results The migraine patients exhibited a significant enhancement in the effective connectivity from the prefrontal lobe to the temporal cortex during the negative emotional stimuli in the gamma frequency (30–90 Hz). Graph theory analysis revealed that the migraine patients had an increased degree and clustering coefficient of connectivity in the delta frequency range (1–4 Hz) upon exposure to positive emotional stimuli and an increased degree of connectivity in the delta frequency range (1–4 Hz) upon exposure to negative emotional stimuli. Clinical correlation analysis showed that the history, attack frequency, duration, and neuropsychological scales of the migraine patients had a negative correlation with the network parameters in certain frequency ranges. Conclusions The results suggested that the individuals with migraine showed deviant effective connectivity in viewing the human facial expressions in multi-frequencies. The prefrontal-temporal pathway might be related to the altered negative emotional modulation in migraine. These findings suggested that migraine might be characterized by more universal altered cerebral processing of negative stimuli. Since the significant result in this study was frequency-specific, more independent replicative studies are needed to confirm these results, and to elucidate the neurocircuitry underlying the association between migraine and emotional conditions.

2022 ◽  
Vol 7 (4) ◽  
pp. 311-314
Ambu Pandey ◽  
Kamal Narayan Kalita ◽  
Aprajeeta Baruah

Bipolar Disorder is a major mental illness characterized by episodic occurrence of mood symptoms which can be of mania, depression or a mixed episode. The role of Uric Acid in the etiopathogenesis of episodic mental illnesses might be considered recognized long back in 19th century. Lithium was used as treatment for gouty arthritis and that in some cases helped to control mental illnesses. Multiple role of uric acid in the Central Nervous System have been recognized now. In the present study 30 patients in manic episodes were included and their serum Uric Acid level was compared to age and sex matched healthy controls twice at the interval of three weeks. It was found that Uric Acid level of cases was significantly higher than in controls before the initiation of treatment. Uric Acid level of manic group showed a significant decline after three weeks of treatment initiation. There was no significant change in Uric Acid level of control group after three weeks Serum Uric Acid levels are elevated during manic phase of Bipolar Disorder and decreases after initiation of treatment. There may be more research to find whether uric acid can be considered a biomarker for Bipolar illnesses and also an indicator for treatment response.

2022 ◽  
Vol 14 (1) ◽  
Xin Wang ◽  
Ya-li Wu ◽  
Yuan-yuan Zhang ◽  
Jing Ke ◽  
Zong-wei Wang ◽  

Abstract Background AK098656 may be an adverse factor for coronary heart disease (CHD), especially in patients with hypertension. This study aimed to analyze the effect of AK098656 on CHD and CHD with various complications. Methods A total of 117 CHD patients and 27 healthy control subjects were enrolled in the study. Plasma AK098656 expression was determined using the quantitative real-time polymerase chain reaction. Student’s t-test was used to compare AK098656 expression levels in different groups. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to quantify the discrimination ability between CHD patients and health controls and between CHD and CHD + complications patients. The relationship between AK098656 and coronary stenosis was analyzed using Spearman’s correlation. Results AK098656 expression was remarkably higher in CHD patients than in healthy controls (P = 0.03). The ROC curve revealed an effective predictive AK098656 expression value for CHD risk, with an AUC of 0.656 (95% CI 0.501–0.809). Moreover, AK098656 expression was increased in CHD + complications patients compared to CHD patients alone (P = 0.005), especially in patients with hypertension (CHD + hHTN, P = 0.030). The ROC curve revealed a predictive AK098656 prognostic value for discriminating between CHD and CHD + hHTN patients, with an AUC of 0.666 (95% CI 0.528–0.805). There was no significant difference in AK098656 expression in CHD patients with diabetes mellitus compared to CHD patients alone. In addition, AK098656 expression in CHD patients was positively correlated with stenosis severity (R = 0.261, P = 0.006). Conclusion AK098656 expression was significantly increased in patients with CHD, especially those with hypertension, and its expression level was positively correlated with the degree of coronary stenosis. This implied that AK098656 may be a risk factor for CHD and can potentially be applied in clinical diagnosis or provide a novel target for treatment.

2022 ◽  
Vol 23 (1) ◽  
Tiffani J. Mungoven ◽  
Kasia K. Marciszewski ◽  
Vaughan G. Macefield ◽  
Paul M. Macey ◽  
Luke A. Henderson ◽  

Abstract Background The precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. The aim of this investigation is to extend our previous investigation to determine if higher brain centers display altered activation patterns and connectivity in migraineurs during acute orofacial noxious stimuli. Methods Functional magnetic resonance imaging was performed in 29 healthy controls and 25 migraineurs during the interictal and immediately (within 24-h) prior to migraine phases. We assessed activation of higher cortical areas during noxious orofacial heat stimulation using a thermode device and assessed whole scan and pain-related changes in connectivity. Results Despite similar overall pain intensity ratings between all three groups, migraineurs in the group immediately prior to migraine displayed greater activation of the ipsilateral nucleus accumbens, the contralateral ventrolateral prefrontal cortex and two clusters in the dorsolateral prefrontal cortex (dlPFC). Reduced whole scan dlPFC [Z + 44] connectivity with cortical/subcortical and brainstem regions involved in pain modulation such as the putamen and primary motor cortex was demonstrated in migraineurs. Pain-related changes in connectivity of the dlPFC and the hypothalamus immediately prior to migraine was also found to be reduced with brainstem pain modulatory areas such as the rostral ventromedial medulla and dorsolateral pons. Conclusions These data reveal that the modulation of brainstem pain modulatory areas by higher cortical regions may be aberrant during pain and these alterations in this descending pain modulatory pathway manifests exclusively prior to the development of a migraine attack.

2022 ◽  
Vol 8 (4) ◽  
pp. 304-307
Jayshri Sadashiv Jankar

Serum ferritin, an acute phase reactant, is an indicator of the body's iron reserves. Increased body iron reserves and subclinical hemochromatosis have been linked to the development of hyperglycaemia, type 2 diabetes, metabolic syndrome, and potentially diabetic retinopathy, nephropathy, and vascular dysfunction, according to recent research. The objective of this study was to see if there was a link between Serum Ferritin and Type 2 diabetes and metabolic syndrome, as well as to see if there was a link between S. ferritin and HbA1c.The present study included 50 diagnosed cases of type 2 diabetes mellitus (males: 32, females: 18) and 50 healthy controls of same age (males: 28, females: 22). Serum ferritin levels, glycated hemoglobin were measured and compared. : When diabetic patients were compared to controls, serum ferritin was considerably greater, and serum ferritin had a positive correlation with the duration of diabetes and glycated hemoglobin. Positive correlation was found between serum ferritin levels and glycated hemoglobin and duration of disease.

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262600
Rodrigo B. Aires ◽  
Alexandre A. de S. M. Soares ◽  
Ana Paula M. Gomides ◽  
André M. Nicola ◽  
Andréa Teixeira-Carvalho ◽  

In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.

2022 ◽  
pp. 1-11
Kasumi Yasuda ◽  
Shinichi Yamada ◽  
Shinya Uenishi ◽  
Natsuko Ikeda ◽  
Atsushi Tamaki ◽  

<b><i>Introduction:</i></b> The hippocampus is relevant to cognitive function in schizophrenia (SCZ) and mood disorder patients. Although not anatomically uniform, it is clearly divided into subfields. This study aimed to elucidate the relationship between hippocampal subfield volume and cognitive function in patients with SCZ, bipolar disorder (BP), and major depressive disorder (MDD). <b><i>Methods:</i></b> The study included 21 patients with SCZ, 22 with BP, and 21 with MDD and 25 healthy controls (HCs). Neurocognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. We obtained hippocampal subfield volumes using FreeSurfer 6.0. We compared the volumes of the hippocampal subfield between the 4 groups and ascertained correlation between the cognitive composite score and hippocampal subfield volume in each group. <b><i>Results:</i></b> The SCZ group had significantly lower cognitive composite score than the BP, MDD, and HC groups. In the SCZ group, the left and right hippocampus-amygdala transition area and right subiculum and right presubiculum volumes were significantly reduced compared to those in the HC group. The left presubiculum volumes in the SCZ group were significantly reduced compared to those in the MDD group. Subfield volumes did not significantly differ between the BP, MDD, and HC groups. Interestingly, in the SCZ group, volumes of the right CA1, right molecular layer of the hippocampus, and right granule cell and molecular layer of the dentate gyrus were significantly correlated with the cognitive composite score. <b><i>Conclusion:</i></b> Patients with SCZ had poorer cognitive function, which is related to their hippocampal pathology, than those with mood disorders.

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