Hepatoma-derived growth factor (HDGF) has proliferative, angiogenic, and neurotrophic activity. It plays a putative role in the development and progression of cancer. When expressed in cells, the mitogenic activity of HDGF depends on its nuclear localization, but it also stimulates proliferation when added to the cell culture medium. A cell surface receptor for HDGF has not been identified so far. We investigated the interaction of various purified recombinant HDGF fusion proteins with the cell surface of NIH 3T3 fibroblasts. We showed that binding of a HDGF--galactosidase fusion protein to the cell surface of NIH 3T3 fibroblasts was saturable, occurred with high affinity (K D ؍ 14 nM), and had a proliferative effect. We identified a peptide comprising amino acid residues 81-100 within the amino-terminal part of HDGF that bound to the cell surface of NIH 3T3 cells with saturation and affinity values similar to those of HDGF. When added to primary human fibroblasts, this peptide stimulated proliferation. Substitution of a single amino acid (K96A) within this peptide was sufficient to abolish its binding to the cell surface and its proliferative activity. In contrast, when expressed transiently in NIH 3T3 cells, a HDGF--galactosidase fusion protein in which amino acid residues 81-100 were deleted still had proliferative activity, whereas a fusion protein containing only the 81-100 peptide did not. Our results suggest the existence of a plasma membrane-located HDGF receptor for which signaling depends on amino acid residues 81-100 of HDGF. This region differs from the one that has been recently identified to be essential for mitogenic activity depending on the nuclear localization of HDGF. Thus, HDGF exerts its proliferative activity via two different pathways.
BackgroundThe liver performs diverse functions that are essential for life. In the absence of reliable liver protective drugs, a large number of natural medicinal preparations are used for the treatment of liver diseases. Therefore the present study aims to investigate the hepatoprotective effects of Salix subserrata Willd flower ethanolic extract (SFEE) against carbon tetrachloride (CCl4)-induced liver damage.MethodsRats were divided into 4 groups of 10 animals each. Group I served as the normal healthy control, groups II rats were intoxicated with CCl4 i.p. (0.8 ml/kg body weight CCl4/olive oil, twice weekly for 9 weeks), group III rats received CCl4 i.p. and SFEE orally (150 mg/kg daily) and group IV rats received CCl4 i.p. and Silymarin orally (100 mg/kg, daily). The hepatoprotective potential of SFEE in rats was evaluated by measuring the protein levels of two inflammatory biomarkers; tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa-B (NF-kB) in addition to other liver biomarkers. Histopathological changes in the liver were assessed using hematoxylin and eosin staining (HE).ResultsThe administration of SFEE showed hepatic protection at an oral dose of 150 mg/kg. SFEE significantly reduced the elevated serum levels of intracellular liver enzymes as well as liver biomarkers in comparison to CCl4− intoxicated group. Notably, SFEE significantly reduced the expression levels of TNF-α and NFkB proteins compared to their levels in CCl4 intoxicated group. These findings were confirmed with the histopathological observations, where SFEE was capable of reversing the toxic effects of CCl4 on liver cells compared to that observed in CCl4-intoxicated animals.ConclusionOur results show that SFEE has potential hepatoprotective effects at 150 mg/kg. These effects can be regarded to the antioxidant and anti-inflammatory properties of the extract.
The present study aims to investigate the potential antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate (BS) gum resin against carbon tetrachloride (CCl 4 )-induced liver damage. Four groups consisting of eight rats each were designated: Group I, normal healthy control; group II, CCl 4 -induced liver fibrosis; group III, CCl 4 -induced liver fibrosis followed by BS treatment daily for two weeks; and group IV, CCl 4 -induced liver fibrosis followed by silymarin treatment daily for two weeks. Expression of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB), interleukin-6 (IL-6), transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) were assessed, in addition to histopathological and fibrotic changes in liver tissues isolated from the rats. BS significantly ameliorated CCl 4 -induced increases in serum aspartate (AST) and alanine transaminase (ALT) levels, reduced lactate dehydrogenase (LDH) activities in addition to restoring total bilirubin, triglyceride and albumin levels. BS treatment also alleviated oxidative stress and improved total antioxidant capacity in the liver, and reduced the expression of TNF-α, NF-κB, TGF-β, IL-6 and COX-2. On a histopathological level, BS treatment also exhibited antifibrotic activity. In conclusion, these findings suggest that BS contains potentially hepatoprotective effects against CCl 4-induced liver injury via its antioxidant, anti-inflammatory and antifibrotic characteristics.
Hepatoma-derived growth factor-related proteins (HRP) comprise a family of 6 members, which the biological functions are still largely unclear. Here we show that during embryogenesis HRP-3 is strongly expressed in the developing nervous system. At early stages of development HRP-3 is located in the cytoplasm and neurites of cortical neurons. Upon maturation HRP-3 relocalizes continuously to the nuclei and in the majority of neurons of adult mice it is located exclusively in the nucleus. This redistribution from neurites to nuclei is also found in embryonic cortical neurons maturing in cell culture. We show that HRP-3 is necessary for proper neurite outgrowth in primary cortical neurons. To identify possible mechanisms of how HRP-3 modulate neuritogenesis we isolated HRP-3 interaction partners and demonstrate that it binds tubulin through the N-terminal so called HATH region, which is strongly conserved among members of the HRP family. It promotes tubulin polymerization, stabilizes and bundles microtubules. This activity depends on the extranuclear localization of HRP-3. HRP-3 thus could play an important role during neuronal development by its modulation of the neuronal cytoskeleton.Neuritogenesis is a key step in nervous system development in which neurons extend dendrites and axons and connect to different targets in and outside the nervous system. The proper regulation of this process is controlled by a number of extraand intracellular molecules expressed by neurons themselves or non-neuronal cells in their surroundings. Multiple studies indicate that rearrangement of the neuronal cytoskeleton in response to extracellular signals is an important mechanism during neurite extension and pathfinding (1-3). Manipulation of the polymerization and depolymerization of microtubules has shown that regulation of microtubule assembly and maintenance is important for neuritogenesis (4). Microtubule dynamics are regulated by a huge number of regulatory proteins like tau or other microtubule-associated proteins (MAPs) 4 (5). In addition, proteins like CRMP-2 that interact with tubulin dimers and accelerate the assembly of tubulin into microtubles have been shown to be involved in the regulation of neuronal polarity and neuritogenesis (6 -10). Despite all advances, however, made in the understanding of the role of the cytoskeleton and its regulatory proteins during neuritic growth there are still many open questions regarding the regulation of these processes. Therefore identifying new molecules binding to and modulating the turnover of microtubules is of high interest for the understanding of how neurite outgrowth is regulated. Hepatoma-derived growth factor (HDGF) is a protein that was purified from secretions of hepatoma cells by virtue of its growth factor activity. Subsequently 5 additional proteins were identified in which the 97 N-terminal amino acid residues show strong similarity to HDGF. Accordingly this family of proteins has been termed HDGF-related proteins (HRP) (11-13). HDGF has neurotrophic activity for hippo...
The transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur through an airborne route, in addition to contaminated surfaces and objects. In hospitals, it has been confirmed by several studies that SARS-CoV-2 can contaminate surfaces and medical equipment especially in hospitals dedicated to coronavirus disease 2019 (COVID-19) patients. The aim of this study was to detect the contamination of hands, objects, and surfaces in isolation rooms and also in outpatients' clinics in hospitals and polyclinics. Environmental contamination of public high-touch surfaces in public facilities was also investigated during an active COVID-19 pandemic. Random swabs were also taken from public shops, pharmacies, bakeries, groceries, banknotes, and automated teller machines (ATMs). Samples were analyzed for SARS-CoV-2 positivity using real-time polymerase chain reaction.In the COVID-19 regional reference hospital, only 3 out of 20 samples were positive for SARS-CoV-2 RNA. Hand swabs from SARS-CoV-2-positive patients in isolation rooms were occasionally positive for viral RNA. In outpatients' clinics, door handles were the most contaminated surfaces. Dental chairs, sinks, keyboards, ophthalmoscopes, and laboratory equipment were also contaminated. Although no positive swabs were found in shops and public facilities, random ATM swabs returned a positive result for SARS-CoV-2. Although there is no longer a focus on COVID-19 wards and isolation hospitals, more attention is required to decontaminate frequently touched surfaces in health-care facilities used by patients not diagnosed with COVID-19. Additionally, high-touch public surfaces such as ATMs require further disinfection procedures to limit the transmission of the infection.
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