scholarly journals Combining viscosity-restricted intramolecular motion and mitochondrial targeting leads to selective tumor visualization

2020 ◽  
Vol 56 (49) ◽  
pp. 6684-6687 ◽  
Author(s):  
Le Yu ◽  
Jun Feng Zhang ◽  
Mingle Li ◽  
Dewei Jiang ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Mitochondrial Targeting ◽  
Tumor Visualization ◽  
Tumor Tissues ◽  
Intramolecular Motion ◽  
Molecular Conjugate

We report a novel fluorescent molecular conjugate, V-M1, enabling an accurate visualization of tumor tissues.

Crystal structures of plant inorganic pyrophosphatase, an enzyme with a moonlighting autoproteolytic activity

2019 ◽  
Vol 476 (16) ◽  
pp. 2297-2319 ◽  
Author(s):  
Marta Grzechowiak ◽  
Milosz Ruszkowski ◽  
Joanna Sliwiak ◽  
Kamil Szpotkowski ◽  
Michal Sikorski ◽  
...  
Keyword(s):  
Site Directed Mutagenesis ◽  
Size Exclusion ◽  
Inorganic Pyrophosphatase ◽  
Prolonged Storage ◽  
Mitochondrial Targeting ◽  
Cleavage Rate ◽  
Inorganic Pyrophosphate ◽  
Putative Signal Peptide ◽  
Targeting Peptide

Abstract Inorganic pyrophosphatases (PPases, EC 3.6.1.1), which hydrolyze inorganic pyrophosphate to phosphate in the presence of divalent metal cations, play a key role in maintaining phosphorus homeostasis in cells. DNA coding inorganic pyrophosphatases from Arabidopsis thaliana (AtPPA1) and Medicago truncatula (MtPPA1) were cloned into a bacterial expression vector and the proteins were produced in Escherichia coli cells and crystallized. In terms of their subunit fold, AtPPA1 and MtPPA1 are reminiscent of other members of Family I soluble pyrophosphatases from bacteria and yeast. Like their bacterial orthologs, both plant PPases form hexamers, as confirmed in solution by multi-angle light scattering and size-exclusion chromatography. This is in contrast with the fungal counterparts, which are dimeric. Unexpectedly, the crystallized AtPPA1 and MtPPA1 proteins lack ∼30 amino acid residues at their N-termini, as independently confirmed by chemical sequencing. In vitro, self-cleavage of the recombinant proteins is observed after prolonged storage or during crystallization. The cleaved fragment corresponds to a putative signal peptide of mitochondrial targeting, with a predicted cleavage site at Val31–Ala32. Site-directed mutagenesis shows that mutations of the key active site Asp residues dramatically reduce the cleavage rate, which suggests a moonlighting proteolytic activity. Moreover, the discovery of autoproteolytic cleavage of a mitochondrial targeting peptide would change our perception of this signaling process.

Spreading of the vestibular schwannoma into porus acusticus internus. Endoscopic removal possibilities

2018 ◽  
pp. 40-44
Author(s):  
Orest Palamar ◽  
Andriy Huk ◽  
Dmytro Okonskyi ◽  
Ruslan Aksyonov ◽  
Dmytro Teslenko
Keyword(s):  
Vestibular Schwannoma ◽  
Internal Auditory Canal ◽  
Residual Tumor ◽  
Endoscopic Technique ◽  
Vestibular Schwannomas ◽  
Endoscopic Removal ◽  
Tumor Removal ◽  
Tumor Spread ◽  
Microsurgical Technique ◽  
Tumor Visualization

Aim: To investigate the features of the vestibular schwannoma spread into the internal auditory canal and the possibilities of endoscopic removal. Objectives: To improve tumor visualization in the internal auditory canal; to create a sufficient view angle for tumor removal during endoscopic opening of the internal auditory canal. Materials and methods: The results of surgical treatment of 20 patients with vestibular schwannomas in which the tumor spread to the internal auditory canal were analyzed. Microsurgical tumor removal was performed in 14 cases; Fully endoscopic removal of vestibular schwannomas was performed in 6 cases. The internal auditory canal opening was performed in 14 cases using microsurgical technique and in 6 cases with fully the endoscopic technique. Results: Gross total removal was achieved in 18 cases, subtotal removal in 2 cases. The tumor spread into the internal auditory canal was removed in all cases (100%). Opening the internal auditory canal using the endoscopic technique allows to increase the view angle (up to 20%) and to visualize along the axis of canal. Conclusions: 1) Endoscopic assistance technique allows to improve residual tumor visualization much more better then microsurgical technique; 2) Internal auditory canal opening using endoscopic technique is much more effective than the microsurgical technique (trepanning depth is larger); 3) Endoscopic methods for the internal auditory canal opening allows to increase canal angle view up to 20% (comparing to the microsurgical view).

THE CONTRIBUTION OF LACTATE AND PHOSPHATE ANIONS TO THE BUFFER PROPERTIES OF TISSUE HOMOGENATES OF BREAST ADENOCARCINOMA

2019 ◽  
Vol 65 (5) ◽  
pp. 684-690
Author(s):  
Margarita Barsukova ◽  
Yekaterina Khomutova ◽  
Yevgeniy Khomutov
Keyword(s):  
Mammary Gland ◽  
Buffer Capacity ◽  
Tumor Tissue ◽  
Mammary Adenocarcinoma ◽  
Breast Adenocarcinoma ◽  
Acid Base ◽  
Adjacent Tissue ◽  
Tumor Tissues ◽  
Tissue Homogenates ◽  
Phosphate Anions

The article discusses the role of conjugated lactic acid/ lactate anion (LacH/Lac-) and dihydrogenphosphate anion/ hydrogenphosphate anion (H2PO4-/HPO42-) pairs in the formation of the buffer properties of tissue as a factor determining pH. The buffer properties of homogenates of the tissue of adenocarcinoma of the mammary gland and the adjacent tissue were quantitatively characterized by the buffer capacity which was determined by potentiometric titration. The concentrations of acid anions were determined spectrophotometrically. The material was biopsy specimens of mammary gland adenocarcinoma (T1-4, N0-1, M0) and adjacent tissue of 22 patients aged from 33 to 75 years. It was found that the buffer capacity of tumors is in 2.5 times higher than in normal tissue. It was established that for the tumor tissue, the buffer capacity of the LacH/Lac- system is in 3 times higher, and the buffer capacity of the H2PO4-/HPO42-system is in 2.5 times greater than for normal untransformed tissue. Concentrations of lactate anions (1,93 ± 0,50 vs 0,57 ± 0,22; p <0.001) and phosphate anions (2,54 ± 0,39 vs 0,70 ± 0,19; p <0,001) in homogenates of the tumor tissue were significantly higher in tumor tissue in comparison with the adjacent tissue. A strong correlation was found between the concentration of phosphate anions and the buffer capacity for tumor tissue (r = 0,857; p = 0,002) and for adjacent tissue (r = 0,917; p <0,001). The correlation between the concentration of lactate anions and the buffer capacity for tumor tissues can be estimated as average (r = 0,626; p = 0,053), while it is absent for the adjacent tissue (r = 0,494; p = 0,147). The results suggest that the acid-base properties of homogenates of mammary adenocarcinoma tissues are determined by two buffer systems: LacH/Lac- and H2PO4-/HPO42-, while the intracellular acid-base homeostasis of non-transformed tissues is mainly determined by the H2PO4-/HPO42- system.

The Mitochondrion-targeted Antioxidants in Kidney Disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Xinrui Li ◽  
Liang Ma ◽  
Ping Fu
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Clinical Characteristics ◽  
Kidney Diseases ◽  
Oxygen Species ◽  
Mitochondrial Targeting ◽  
Mitochondria Dysfunction ◽  
Cellular Reactive Oxygen Species ◽  
Novel Strategy ◽  
The Relationship

: Mitochondria are potent source of cellular reactive oxygen species (ROS) and are vulnerable to oxidative damage. Mitochondria dysfunction could result in adenosine triphosphate (ATP) decrease and cell death. The kidney is an ATPconsuming organ, and the relationship between mitochondrial dysfunction and renal disease has been long noted. Mitochondrial targeting is a novel strategy for kidney diseases. At present, there are several ways to target mitochondria such as the addition of a triphenylphosphonium cation, mitochondria-targeted peptides, and nanocarrier. There are also a variety of choices for the payload, such as nitroxides, quinone derivates, vitamins and so on. This review summarized chemical and also clinical characteristics of various mitochondria-targeted antioxidants and focused on their application and perspectives in kidney diseases.

Role of Exosomes in Photodynamic Anticancer Therapy

2020 ◽  
Vol 27 (40) ◽  
pp. 6815-6824 ◽  
Author(s):  
Yuan Jiang ◽  
Chuanshan Xu ◽  
Wingnang Leung ◽  
Mei Lin ◽  
Xiaowen Cai ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Basic Principle ◽  
Photochemical Reaction ◽  
Cell Communication ◽  
Anticancer Therapy ◽  
Bioactive Molecules ◽  
Promising Alternative ◽  
Tumor Tissues ◽  
Significant Attention

Photodynamic Therapy (PDT) is a promising alternative treatment for malignancies based on photochemical reaction induced by Photosensitizers (PS) under light irradiation. Recent studies show that PDT caused the abundant release of exosomes from tumor tissues. It is well-known that exosomes as carriers play an important role in cell-cell communication through transporting many kinds of bioactive molecules (e.g. lipids, proteins, mRNA, miRNA and lncRNA). Therefore, to explore the role of exosomes in photodynamic anticancer therapy has been attracting significant attention. In the present paper, we will briefly introduce the basic principle of PDT and exosomes, and focus on discussing the role of exosomes in photodynamic anticancer therapy, to further enrich and boost the development of PDT.

Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4605-4610 ◽  
Author(s):  
Atena Soleimani ◽  
Farzad Rahmani ◽  
Gordon A. Ferns ◽  
Mikhail Ryzhikov ◽  
Amir Avan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Current Knowledge ◽  
Akt Signaling ◽  
Tumor Tissues ◽  
Radio Therapy ◽  
Signaling Axis ◽  
Cancer Tumor ◽  
Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

Recombinant adeno-associated virus 9-mediated expression of Kallistatin suppresses lung tumor growth in mice

2020 ◽  
Vol 20 ◽  
Author(s):  
Weihong Qu ◽  
Jianguo Zhao ◽  
Yaqing Wu ◽  
Ruian Xu ◽  
Shaowu Liu
Keyword(s):  
Lung Cancer ◽  
Gene Therapy ◽  
Tumor Growth ◽  
Lung Tumor ◽  
Control Group ◽  
High Dose ◽  
Blank Control Group ◽  
Adeno Associated Virus ◽  
Tumor Tissues ◽  
Subcutaneous Xenograft

Background:: Lung cancer remains the most common cause of cancer-related deaths in China and worldwide. Traditional surgery and chemotherapy do not offer an effective cure although gene therapy may be a promising future alter-native. Kallistatin (Kal) is an endogenous inhibitor of angiogenesis and tumorigenesis. Recombinant adeno-associated virus (rAAV) is considered the most promising vector for gene therapy of many diseases due to persistent and long-term transgen-ic expression. Objective:: The aim of this study was to investigate whether rAAV9-Kal inhibited NCI-H446 subcutaneous xenograft tumor growth in mice. Method:: The subcutaneous xenograft mode were induced by subcutaneous injection of 2×106 H446 cells into the dorsal skin of BALB/c nude mice. The mice were administered with ssrAAV9-Kal (single-stranded rAAV9) or dsrAAV9-Kal (double-stranded rAAV9）by intraperitoneal injection (I.P.). Tumor microvessel density (MVD) was examined by anti-CD34 stain-ing to evaluate tumor angiogenesis. Results:: Compared with the PBS (blank control) group, tumor growth in the high-dose ssrAAV9-Kal group was inhibited by 40% by day 49, and the MVD of tumor tissues was significantly decreased. Conclusion:: The results indicate that this therapeutic strategy is a promising approach for clinical cancer therapy and impli-cate rAAV9-Kal as a candidate for gene therapy of lung cancer.

Calreticulin is Differentially Expressed in Invasive Ductal Carcinoma: A Comparative Study

2019 ◽  
Vol 16 (2) ◽  
pp. 148-155
Author(s):  
Asma Tariq ◽  
Rana Muhammad Mateen ◽  
Iram Fatima ◽  
Muhammad Waheed Akhtar
Keyword(s):  
Invasive Ductal Carcinoma ◽  
Tumor Tissue ◽  
Ductal Carcinoma ◽  
Tissue Level ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Two Dimensional Gel Electrophoresis ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Grade Ii

Objective: The aim of the present study was to build protein profiles of untreated breast cancer patients of invasive ductal carcinoma grade II at tissue level in Pakistani population and to compare 2-D profiles of breast tumor tissues with matched normal tissues in order to evaluate for variations of proteins among them. Materials & Methods: Breast tissue profiles were made after polytron tissue lysis and rehydrated proteins were further characterized by using two-dimensional gel electrophoresis. On the basis of isoelectric point (pI) and molecular weight, proteins were identified by online tool named Siena 2-D database and their identification was further confirmed by using MALDI-TOF. Results: Among identified spots, 10 proteins were found to be differentially expressed i.e.; COX5A, THIO, TCTP, HPT, SODC, PPIA, calreticulin (CRT), HBB, albumin and serotransferrin. For further investigation, CRT was selected. The level of CRT in tumors was found to be significantly higher than in normal group (p < 0.05). The increased expression of CRT level in tumor was statistically significant (p = 0.010) at a 95% confidence level (p < 0.05) as analyzed by Mann-Whitney. CRT was found distinctly expressed in high amount in tumor tissue as compared to their matched normal tissues. Conclusion: It has been concluded that CRT expression could discriminate between normal tissue and tumor tissue so it might serve as a possible candidate for future studies in cancer diagnostic markers.

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