Constructing a Non-Negative Low Rank and Sparse Graph with Data-Adaptive Features

This paper aims at constructing a good graph for discovering intrinsic data structures in a semi-supervised learning setting. Firstly, we propose to build a non-negative low-rank and sparse (referred to as NNLRS) graph for the given data representation. Specifically, the weights of edges in the graph are obtained by seeking a nonnegative low-rank and sparse matrix that represents each data sample as a linear combination of others. The so-obtained NNLRS-graph can capture both the global mixture of subspaces structure (by the low rankness) and the locally linear structure (by the sparseness) of the data, hence is both generative and discriminative. Secondly, as good features are extremely important for constructing a good graph, we propose to learn the data embedding matrix and construct the graph jointly within one framework, which is termed as NNLRS with embedded features (referred to as NNLRS-EF). Extensive experiments on three publicly available datasets demonstrate that the proposed method outperforms the state-of-the-art graph construction method by a large margin for both semi-supervised classification and discriminative analysis, which verifies the effectiveness of our proposed method

Lipopolysaccharide preconditioning enhances the efficacy of mesenchymal stem cells transplantation in a rat model of acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Mesenchymal stem cells (MSCs)-based regenerative therapy is currently regarded as an alternative approach to salvage the acute myocardial infarcted hearts. However, the efficiency of MSCs transplantation is limited by lower survival rate of engrafted MSCs. In previous study, we found that 1.0 μg/ml Lipopolysaccharide (LPS) could protect MSCs against apoptosis induced by oxidative stress and meanwhile enhance the proliferation of MSCs. Therefore, in the present study, we firstly preconditioned MSCs with 1.0 μg/ml LPS, then transplanted MSCs into ischemic myocardium, and observed the survival and cardiac protective capacity of MSCs in a rat model of acute myocardial infarction. Furthermore, we tried to explore the underlying mechanisms and the role of Toll-like receptor-4 (TLR4) in the signal pathway of LPS-induced cardiac protection.</p> <p>Methods and results</p> <p>Acute myocardial infarction model was developed by left anterior descending coronary artery ligation. 60 rats were divided into 4 groups randomly and given an intramyocardial injection of one of the following treatments: 30 μl PBS (control group), 3 × 10⁶wild MSCs/30 μl (wMSCs group), 3 × 10⁶LPS-preconditioned wild MSCs/30 μl (LPS-wMSCs group), or 3 × 10⁶LPS-preconditioned TLR4 gene deleted MSCs/30 μl (LPS-tMSCs group). After 3 weeks, LPS-preconditioned wild MSCs transplantation ameliorated cardiac function and reduced fibrosis of infarcted myocardium. Vascular density was markedly increased in LPS-wMSCs group compared with other three groups. Survival rate of engrafted MSCs was elevated and apoptosis of myocardium was reduced in infarcted heart. Expression of vascular endothelial growth factor (VEGF) and phospho-Akt was increased in the infarcted myocardium after transplantation of LPS-preconditioned MSCs.</p> <p>Conclusion</p> <p>LPS preconditioning enhanced survival of engrafted MSCs, stimulated expression of VEGF and activated PI3K/Akt pathway. LPS preconditioning before MSCs transplantation resulted in superior therapeutic neovascularization and recovery of cardiac function. LPS preconditioning provided a novel strategy in maximizing biologic and functional properties of MSCs.</p

Anti-HER-2 engineering antibody ChA21 inhibits growth and induces apoptosis of SK-OV-3 cells

<p>Abstract</p> <p>Background and Aims</p> <p>Anti-HER-2 antibodies targeting distinct epitopes have different biological functions on cancer cells. In a previous study, we demonstrated that anti-HER-2 engineering antibody ChA21 was able to bind to subdomain I of HER-2 extracellular domain. In this study, The effects of ChA21 on growth and apoptosis against ovarian carcinoma cell SK-OV-3 over-expressing HER-2 <it>in vitro </it>and <it>in vivo </it>were investigated.</p> <p>Methods</p> <p>Cell growth inhibition was evaluated by MTT assay. Apoptosis was detected by TUNEL stain, transmission electron microscopy and flow cytometry on cultured cells and tissue sections from nude mice xenografts. The apoptosis-related proteins Bax and Bcl-2 were assessed by immunohistochemistry.</p> <p>Results</p> <p>We found that treatment of ChA21 caused a dose-dependent decrease of cell proliferation <it>in vitro </it>and a significant inhibition of tumor growth <it>in vivo</it>. ChA21 therapy led to a significant increase in the induction of apoptosis, and up-regulated the expression of Bax, while the expression of Bcl-2 was down-regulated.</p> <p>Conclusion</p> <p>These data suggest that ChA21 inhibits the growth and induces apoptosis of SK-OV-3 via regulating the balance between Bax and Bcl-2.</p

Natrium Benzoate Alleviates Neuronal Apoptosis via the DJ-1-Related Anti-oxidative Stress Pathway Involving Akt Phosphorylation in a Rat Model of Traumatic Spinal Cord Injury

This study aimed to explore the neuroprotective effects and mechanisms of natrium benzoate (NaB) and DJ-1 in attenuating reactive oxygen species (ROS)-induced neuronal apoptosis in traumatic spinal cord injury (t-SCI) in rats. T-SCI was induced by clip compression. The protein expression and neuronal apoptosis was evaluated by Western blotting, double immunofluorescence staining and transmission electron microscope (TEM). ROS level, spinal cord water content (SCWC) and Evans blue (EB) extravasation was also examined. Locomotor function was evaluated by Basso, Beattie, and Bresnahan (BBB) and inclined plane test (IPT) scores. We found that DJ-1 is expressed in spinal cord neurons and increased after t-SCI. At 24 h post-injury, the levels of DJ-1, p-Akt, SOD2, ROS, p-p38 MAPK/p38 MAPK ratio, and CC-3 increased, while the Bcl-2/Bax ratio decreased. NaB upregulated DJ-1, p-Akt, and SOD2, decreased ROS, p-p38 MAPK/p38 MAPK ratio, and CC-3, and increased the Bcl-2/Bax ratio, which were reversed by DJ-1 siRNA. The proportion of CC-3- and TUNEL-positive neurons also increased after t-SCI and was reduced by NaB. These effects were reversed by MK2206. Moreover, the level of oxDJ-1 increased after t-SCI, which was decreased by DJ-1 siRNA, NaB or the combination of them. NaB also reduced mitochondrial vacuolization, SCWC and EB extravasation, and improved locomotor function assessed by the BBB and IPT scores. In conclusion, NaB increased DJ-1, and thus reduced ROS and ROS-induced neuronal apoptosis by promoting Akt phosphorylation in t-SCI rats. NaB shows potential as a therapeutic agent for t-SCI, with DJ-1 as its main target

Sodium Benzoate Attenuates Secondary Brain Injury by Inhibiting Neuronal Apoptosis and Reducing Mitochondria-Mediated Oxidative Stress in a Rat Model of Intracerebral Hemorrhage: Possible Involvement of DJ-1/Akt/IKK/NFκB Pathway

Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. The aim of this study was to explore whether Sodium Benzoate (NaB) could reduce neural cell apoptosis and alleviate neurological deficits after ICH. To assess the therapeutic effects of NaB, first, we measured brain water content, neurobehavior, and blood-brain barrier (BBB) integrity at 24 h after ICH in different groups. Then western blot and immunofluorescence staining (IF) were applied to test the levels of different proteins. Transmission electron microscope (TEM) was used to observe ultra-structures within the cells in different groups. The results showed that levels of DJ-1, p-Akt and p-IκB kinase (IKK) increased after ICH and peaked at 24 h. Besides, NaB significantly upregulated DJ-1 in both cytoplasm and mitochondria, and also increased the levels of p-Akt, p-IKK and Bcl-2/Bax ratio, but decreased the levels of caspase-3 and caspase-9. Additionally, NaB decreased reactive oxygen species (ROS) while increased adenosine triphosphate (ATP), which then improving the neurological functions at 24 h and long-term (21 days) memory and spatial learning ability after ICH. However, the results mentioned above could be greatly reversed by MK2206 and rotenone. Therefore, we concluded that NaB could attenuate secondary brain injury via inhibiting neuronal apoptosis and reducing mitochondria-mediated oxidative stress via DJ-1/Akt/IKK/NFκB pathway

Sirt3 Ameliorates Oxidative Stress and Mitochondrial Dysfunction After Intracerebral Hemorrhage in Diabetic Rats

Aim: Sirtuin3 (sirt3) plays a pivotal role in improving oxidative stress and mitochondrial dysfunction which directly induced neuronal apoptosis after intracerebral hemorrhage (ICH). Reactive oxygen species (ROS) is also a critical activator in triggering NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasomes activation which can regulate inflammatory responses in brain. Moreover, hyperglycemia can aggravate the ICH-induced damage. Hence, this study was designed to investigate the mechanisms of neuroprotection of sirt3 in hyperglycemic ICH.Methods: ICH model was established by autologous blood injection. Hyperglycemia was induced by intraperitoneal injection with streptozotocin. Honokiol (HKL, a pharmacological agonist of sirt3) was injected intraperitoneally at doses of 2.5, 5, or 10 mg/kg. Sirt3 small interfering RNA transfection was implemented through intracerebroventricular injection. The expression of sirt3 and its downstream signaling molecules were detected using Western blotting or immunofluorescence staining. Morphological changes of mitochondria were detected by electron microscopy. SH-SY5Y cells were incubated with 10 μM oxyhemoglobin for 48 h to establish an in vitro ICH model, and then JC-1 staining was used to determine mitochondrial membrane potential (Δψm).Results: Hyperglycemia could suppress sirt3 expression after ICH when compared with non-diabetic rats. Sirt3 protein expression was decreased to the minimum at 24 h in perihematoma tissues. Electron microscope analysis indicated that hyperglycemic ICH induced extensive mitochondrial vacuolization. HKL attenuated ROS accumulation, adenosine triphosphate reduction, and Δψm through Sirt3–superoxide dismutase 2 (SOD2) and Sirt3–NRF1–TFAM pathway. Sirt3 knockdown could exacerbate the neuronal apoptosis and reverse the positive effects of HKL. Sirt3 activation could decrease NLRP3 and interleukin-1β levels through deacetylating SOD2 and scavenging ROS.Conclusion: HKL protects against hyperglycemic ICH-induced neuronal injury via a sirt3-dependent manner

Melatonin Protects Against Neuronal Apoptosis via Suppression of the ATF6/CHOP Pathway in a Rat Model of Intracerebral Hemorrhage

Neuronal apoptosis is an important factor accounting for the poor outcomes of intracerebral hemorrhage (ICH). This study first showed that inhibition of activating transcription factor 6 (ATF6) could alleviate secondary brain injury through anti-apoptosis after ICH in rats. Melatonin, ATF6 and CCAAT/enhancer-binding protein homologous protein (CHOP) siRNAs were applied in this study. Brain edema, neurological functions, blood-brain barrier (BBB) integrity were evaluated at 24 h after ICH. Western blot analysis was used to evaluate the protein level of target proteins (ATF6, CHOP, Bip, Bcl-2, Bax, and cleaved caspase-3). Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the mRNA level of ATF6, CHOP and cleaved caspase-3. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and caspase-3 immunofluorescence staining were applied to evaluate the neuronal cell death. The results suggested that the levels of ATF6 and its downstream protein, CHOP, were upregulated and reached the peak at 24 h after ICH. ATF6 was highly expressed in neurons. The administration of melatonin significantly decreased the mRNA and protein levels of ATF6, and its downstream targets, CHOP and cleaved caspase-3, but increased the Bcl-2/Bax ratio, which ameliorated the neurological functions. The CHOP siRNA significantly reversed the pro-apoptotic effect induced by the increased ATF6 level after ICH. Melatonin could protect against neuronal apoptosis via suppression of ATF6/CHOP arm of ER-stress-response pathway

Expert Consensus on Microtransplant for Acute Myeloid Leukemia in Elderly Patients -Report From the International Microtransplant Interest Group

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4). Others included donor screening, infusion of donor cells, laboratory examinations, and complications of treatment

A Case of Congenital Syringocystadenoma Papilliferum

ABSTRACT: Syringocystadenoma papilliferum (SCAP) is a rare benign skin tumor that develops from the apocrine or eccrine glands. Here, we report the case of a 2-year-old girl who presented with an asymptomatic, slowly growing lesion on her scalp. On physical examination, a 2 cm × 1 cm red papillary plaque with a crusted surface was noted on her scalp. Histopathological examination revealed papillomatous expansion of the epidermis and cystic invaginations extending from the epidermis down to the deep dermis. The cystic structures were lined by papillae with two layers of columnar epithelium, which showed decapitation secretion. Based on the above clinicopathological findings, a diagnosis of congenital scalp SCAP was made