Panacea seed “Nigella”: A review focusing on regenerative effects for gastric ailments

Nigella sativa (NS) or black cumin is a dark, thin, and crescent-shaped, seeded shrub belonging to the Ranunculaceae family commonly growing on Mediterranean coasts in Saudi Arabia, northern Africa and Asia. They have amazing curative and therapeutic features that make them one of the most popular, safe, non-detrimental, and cytoprotective medicinal plant that can be used for prevention and treatment of many complicated diseases. Originally, N. sativa was used to treat migraines and allergy, and researches have shown its effectiveness in destroying cancer cells as well. The gastro protective effect of NS oil and its constituents has also been reported earlier; however, the complete perception on etiology and pathogenesis of gastric ulcer is not yet clear. Herein, we attempt to unveil some of the potential mechanisms exhibited by NS in preventing problems related to gastric ulcers. Gastric ailments like ulcers and tumors are the most common disorders of the gastro-intestinal tract in the present day life of the industrialized world. Gastric ulcer being a multifaceted problem exhibits complex etiology and is the fourth most common cause of cancer mortality. Drug interactions and toxicity are the main hindrances in chemotherapy. The existing merits and demerits of modern-day drugs make us turn toward the plant kingdom which may provide a valuable resource of novel potent natural compounds for pharmaceuticals or alternately, as dietary supplements. In this context, the revered phytotherapeutic N. sativa comes as a promising savior in today’s times. This review aims to summarize, both the functional and disease-related effects in the area of gastroenterology.     

In vivo determination of aluminum,cobalt, chromium,copper, nickel,titanium and vanadium in oral mucosa cells from orthodontic patients with mini-implants by Inductively coupled plasma-mass spectrometry (ICP-MS)

Miniscrews are used as orthodontic anchorage devices in the dentistry clinical practice but the in vivo metallic release from these structures has been not previously investigated. The aim of this study was to determine the content of Al, Co, Cr, Cu, Ni, Ti and V in oral mucosa cells of control subjects, patients under orthodontic treatment and with both, orthodontic treatment and miniscrew, in order to know the contribution of these mini-implants to the total metallic content. ICP-MS measurements revealed the following ascending order: Cr < Ni < Ti < Cu < Al, and Co and V were practically undetected. Significant differences in comparison to the control group were found for Cu in the orthodontic group, and for Ni in both, orthodontic and orthodontic + miniscrew groups. Potential correlations among metallic elements and with some clinical factors were also explored. These findings suggest that miniscrews do not increase significantly the metal release.     

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

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Connexin32 inhibits gastric carcinogenesis through cell cycle arrest and altered expression of p21Cip1 and p27Kip1

Gap junctions and their structural proteins, connexins (Cxs), have been implicated in carcinogenesis. To explore the involvement of Cx32 in gastric carcinogenesis, immunochemical analysis of Cx32 and proliferation marker Ki67 using tissue-microarrayed human gastric cancer and normal tissues was performed. In addition, after Cx32 overexpression in the human gastric cancer cell line AGS, cell proliferation, cell cycle analyses, and p21^Cip1 and p27^Kip1 expression levels were examined by bromodeoxyuridine assay, flow cytometry, real-time RT-PCR, and western blotting. Immunohistochemical study noted a strong inverse correlation between Cx32 and Ki67 expression pattern as well as their location. In vitro, overexpression of Cx32 in AGS cells inhibited cell proliferation significantly. G₁ arrest, up-regulation of cell cycle-regulatory proteins p21^Cip1 and p27^Kip1 was also found at both mRNA and protein levels. Taken together, Cx32 plays some roles in gastric cancer development by inhibiting gastric cancer cell proliferation through cell cycle arrest and cell cycle regulatory proteins. [BMB Reports 2013; 46(1): 25-30]     

Ultrastructural studies of endocrine-like cells in the fundic gastric mucosa of the bullfrog,Rana catesbeiana

Summary This study is concerned with electron-microscopic observations on endocrine or paracrine cells in the fundic gastric mucosa of the bullfrog. Also, an attempt was made to identify the histamine-releasing cells involved in the secretagogue response. At least three distinct endocrine-like cell types were found. The classification is based on the appearance of secretory granules and other organelles, and the relationship of endocrine-like cells with other cells in the tissue. The amphibian endocrine-like cells resemble the ECL, D and EC cells of mammals. Type-I (ECL) cells showed degranulation after repeated stimulation with tetragastrin (TG), acetylcholine (ACh) and K⁺ depolarizing solution, all of which release histamine.     

Phospho-regulated ACAP4-Ezrin Interaction Is Essential for Histamine-stimulated Parietal Cell Secretion

The ezrin-radixin-moesin proteins provide a regulated linkage between membrane proteins and the cortical cytoskeleton and also participate in signal transduction pathways. Ezrin is localized to the apical membrane of parietal cells and couples the protein kinase A activation cascade to the regulated HCl secretion. Our recent proteomic study revealed a protein complex of ezrin-ACAP4-ARF6 essential for volatile membrane remodeling (Fang, Z., Miao, Y., Ding, X., Deng, H., Liu, S., Wang, F., Zhou, R., Watson, C., Fu, C., Hu, Q., Lillard, J. W., Jr., Powell, M., Chen, Y., Forte, J. G., and Yao, X. (2006) Mol. Cell Proteomics 5, 1437–1449). However, knowledge of whether ACAP4 physically interacts with ezrin and how their interaction is integrated into membrane-cytoskeletal remodeling has remained elusive. Here we provide the first evidence that ezrin interacts with ACAP4 in a protein kinase A-mediated phosphorylation-dependent manner through the N-terminal 400 amino acids of ACAP4. ACAP4 locates in the cytoplasmic membrane in resting parietal cells but translocates to the apical plasma membrane upon histamine stimulation. ACAP4 was precipitated with ezrin from secreting but not resting parietal cell lysates, suggesting a phospho-regulated interaction. Indeed, this interaction is abolished by phosphatase treatment and validated by an in vitro reconstitution assay using phospho-mimicking ezrin^S66D. Importantly, ezrin specifies the apical distribution of ACAP4 in secreting parietal cells because either suppression of ezrin or overexpression of non-phosphorylatable ezrin prevents the apical localization of ACAP4. In addition, overexpressing GTPase-activating protein-deficient ACAP4 results in an inhibition of apical membrane-cytoskeletal remodeling and gastric acid secretion. Taken together, these results define a novel molecular mechanism linking ACAP4-ezrin interaction to polarized epithelial secretion.     

Role of NF-κB transcriptional factor activation during chronic fluoride intoxication in development of oxidative-nitrosative stress in rat’s gastric mucosa

Fluoride compounds are known as hazardous environmental pollutants that can enter the body with drinking water. Chronic exposure to fluoride leads to development of oxidative stress and can lead to activation of nuclear factor κB (NF-κB). The aim of this work is to clarify the role of NF-kB activation in production of reactive nitrogen and oxygen species, activity of antioxidant enzymes and intensity of lipid peroxidation (LPO) in gastric mucosa of rats during chronic fluoride intoxication.Materials and methodsWe carried out the study on 18 mature male rats of the Wistar line. The animals were divided into 3 groups: control animals (6), group of chronic fluoride intoxication (6), and animals (6), which received the NF-κB inhibitor, namely ammonium pyrrolidine dithiocarbamate (PDTC) in a dose of 76 mg / kg (iNF-κB group) during modeling of chronic fluoride intoxication. To assess the development of oxidative stress we studied superoxide production (O₂^-), activity of superoxide dismutase (SOD), catalase (CAT) and concentration of free malondialdehyde (MDA). We also assessed NO production and concentration of its metabolites (peroxynitrite, nitrosilated thiol groups, nitrites).ResultsChronic fluoride intoxication leads to NO hyperproduction with subsequent increase in concentration of its later metabolites (peroxynitrite, nitrosilated thiol groups, nitrites). Production of O₂^- increases, SOD activity decreases, CAT activity increases and MDA concentration also increases. Inhibition of NF-kB activation by PDTC normalizes the parameters studied.ConclusionsActivation of NF-κB during chronic fluoride intoxication leads to the development of hyperproduction of NO and development of oxidative-nitrosative stress.     

MMP-2 and TIMP-2 expression,quantitative analysis and biomechanical changes in scar hypertrophy after autologous free transplantation of rabbit oral mucosa and scrotal skin

This study aimed to investigate the long-term scar hypertrophy in the rabbit transplanted oral mucosa and scrotal skin with changed matrix environment, as well as the scar location expression, quantitative analysis of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) and biomechanical changes in the transplanted tissues. The split-thickness skin grafts were collected from the oral mucosas and scrotal skins of 30 male rabbits, and prepared into reelpipes for autologous transplantation into the rabbit back muscular tissues. Samples were collected to carry out elastic tensile mechanical detection and histological observation. The maximum longitudinal tensile displacement of scrotal skin before 8 weeks of transplantation was greater than that after 8 weeks of transplantation (P < 0.05). The expression intensities of MMP-2 and TIMP-2 in the oral mucosa and in scrotal skin at 2 W time point were higher than those at T_o time point (P < 0.05). The expression quantities of TIMP-2 in oral mucosa and scrotal skin during 8–24 W were higher than those of MMP-2 (P < 0.05). At 8 W time point, the TIMP-2/MMP-2 ratio in scrotal skin was higher than that in oral mucosa (P < 0.05). MMP-2 and TIMP-2 expression in normal oral mucosa and scrotal skin is weak, but their expression is remarkably up-regulated after 2 weeks of transplantation, revealing that scar formation was related to the high expression of MMP-2 and TIMP-2. At the 8th–24th weeks, the AOD values of TIMP-2 in oral mucosa and scrotal skin are apparently higher than those of MMP-2; moreover, the TIMP-2/MMP-2 ratio in scrotal skin at the 8th week was higher than that in oral mucosa, which can well explain the earlier scar formation in scrotal skin than in oral mucosa, and it also suggests that the different expression levels between TIMP-2 and MMP-2 may account for the important cause of scar formation.     

Proximal fluid proteomics for the discovery of digestive cancer biomarkers

Most digestive malignancies have asymptomatic course, often progressing to poor outcome stages. Surgical resection usually represents the only potentially curative option but a prior assumption of the malignant nature of the lesion is mandatory to avoid exposing patients to unnecessary risks. Unfortunately, currently available diagnostic tools lack accuracy in many cases, consequently more reliable markers are needed to improve detection of malignant lesions. In this challenging context, fluids surrounding digestive malignancies represent a valuable source for the search of new potential biomarkers and proteomic tools offer the opportunity to achieve this goal. The new field of proximal fluid proteomics is thus emerging in the arena of digestive cancer biomarker discovery.