BACKGROUND: Yes-associated protein 1 (YAP1) is highly expressed in liver cancer and has been used as an independent prognostic marker for hepatocellular carcinoma (HCC), while inhibition of YAP1 slows down the progressio...BACKGROUND: Yes-associated protein 1 (YAP1) is highly expressed in liver cancer and has been used as an independent prognostic marker for hepatocellular carcinoma (HCC), while inhibition of YAP1 slows down the progression of HCC. Interleukin-18 (IL-18) also tends to be highly expressed in liver cancer. Previous research has proved that dihydroartemisinin (DHA) plays an important role in HCC treatment by reducing YAP1 expression. However, the relationship between YAP1 and IL-18 has not been reported in HCC, especially during DHA therapy. OBJECTIVE: The purpose of this study was to clarify the relationship between YAP1 and IL-18 in HCC cells, and to explicit the role of IL-18 in the treatment of HCC by DHA. METHODS AND RESULTS: We found that YAP1 and IL-18 were highly expressed in patients with hepatocellular carcinoma by bioinformatics analysis. Moreover, YAP1 was positively correlated with IL18 in liver cancer. YAP1 and IL18 correlated with immune cell infiltration, notably T cell exhaustion. YAP1 knockdown decreased IL-18 expression, while YAP1 overexpression increased the IL-18 expression in HCC cells. DHA reduced IL-18 expression through YAP1 in HCC cells. Further, DHA reduced the growth of Hepa1-6 cells subcutaneous xenograft tumors by inhibiting the expression of YAP1 and IL-18. However, DHA improved IL-18 in serum and adjacent tissues from DEN/TCPOBOP-induced liver tumor model in C57BL/6 mice. CONCLUSION: YAP1 was positively correlated with IL-18 in HCC. DHA reduced the expression of IL-18 by inhibiting YAP1 and plays a role in the treatment of HCC. Our study suggested that IL-18 is a potential target for the treatment of HCC, and DHA is a promising drug for HCC therapy. DATA AVAILABILITY: The dataset that supports the findings of this study is available from the corresponding author upon reasonable request.
The migratory process is a highly organized, differentiated, and polarized stage by which many signaling pathways are regulated to control cell migration. Since the significant evidence of migrating cells is the reorgani...The migratory process is a highly organized, differentiated, and polarized stage by which many signaling pathways are regulated to control cell migration. Since the significant evidence of migrating cells is the reorganization of the cytoskeleton. In the recent study, the cell migration model was assessed on the fact that any disruption obtained in the cellular monolayer confluent, may cause stimulation for surrounding cells to migrate. We attempt to demonstrate the morphological alterations associated with these migrating cells. In this case, sterilized 1 N NaOH (1 µl) was used as alkaline burnt. It leads to scratching the monolayer of hepatocellular carcinoma (HLF cell line) allowing cells to lose their connection. Scanning electron microscopy (SEM), fluorescence microscopy, light inverted microscopy, and dark field were used for discovering the morphological alterations associated with migrating cancer cells. The findings show that cells exhibited distinctive alterations including a polarizing stage, accumulation of the actin nodules in front of the nucleus, and protrusions. Nuclei appeared as lobulated shapes during migration. Lamellipodia and uropod were extended as well. Additionally, TGFβ1 proved its expression in HLF and SNU449 after their stimulation. It is demonstrated that hepatocellular carcinoma cells can migrate after their stimulation and there is a caution against the indiscriminate application of alkalinizing drug therapy.
Superoxide dismutase (SOD) is an antioxidant enzyme with multiple metal cofactors that can specifically clear reactive oxygen species (ROS), which plays an important role in a variety of ultraviolet-induced lesions. Ther...Superoxide dismutase (SOD) is an antioxidant enzyme with multiple metal cofactors that can specifically clear reactive oxygen species (ROS), which plays an important role in a variety of ultraviolet-induced lesions. Therefore, SOD has the anti-ultraviolet radiation effect. The objective of this study was to compare the differences in the anti-ultraviolet radiation effect of SOD with distinct metal cofactors: Cu/Zn-SOD and Mn-SOD. SOD was first purified using hydrophobic interaction chromatography and ion-exchange chromatography. Second, the Methylthiazolyldiphenyl-tetrazolium bromide method and cell senescence kits were used to study the protective effect of SOD on ultraviolet-induced cell damage. Finally, the protective effect of SOD on ultraviolet -induced skin damage was histopathologically evaluated, and the expression levels of malondialdehyde (MDA) and matrix metalloproteinases (MMPs) in tissues were detected. The results showed that Cu/Zn-SOD was superior to Mn-SOD in promoting cell proliferation, alleviating cell damage, protecting skin structure, and regulating the expression levels of MDA and MMPs, and it has no side effects. In conclusion, Cu/Zn-SOD had a better anti-ultraviolet radiation effect than Mn-SOD, and it can be used in anti-aging and anti-ultraviolet skin-care products.
Toll-like receptors (TLRs) are essential for identifying and detecting pathogen-associated molecular patterns (PAMPs) produced by a variety of pathogens, including viruses and bacteria. Since TLR2 is the only TLR capable...Toll-like receptors (TLRs) are essential for identifying and detecting pathogen-associated molecular patterns (PAMPs) produced by a variety of pathogens, including viruses and bacteria. Since TLR2 is the only TLR capable of creating functional heterodimers with more than two other TLR types, it is very important for vertebrate immunity. TLR2 not only broadens the variety of PAMPs that it can recognize but has also the potential to diversify the subsequent signaling cascades. TLR2 is ubiquitous, which is consistent with the wide variety of tasks and functions it serves. Immune cells, endothelial cells, and epithelial cells have all been found to express TLR2. This review aims to gather currently available information about the preservation of this intriguing immunological molecule in the phylum of vertebrates.
Alesci A, Pergolizzi S, Mokhtar DM
… +10 more, Fumia A, Aragona M, Lombardo GP, Messina E, D'Angelo R, Lo Cascio P, Sayed RKA, Albano M, Capillo G, Lauriano ER
The integument acts as a barrier to protect the body from harmful pathogenic infectious agents, parasites, UV rays, trauma, and germs. The integument of invertebrates and vertebrates are structurally different: while inv...The integument acts as a barrier to protect the body from harmful pathogenic infectious agents, parasites, UV rays, trauma, and germs. The integument of invertebrates and vertebrates are structurally different: while invertebrates usually have a simple monolayer epidermis frequently covered by mucus, cuticles, or mineralized structures, vertebrates possess a multilayered epidermis with several specialized cells. This study aims to describe by morphological, histological, and immunohistochemical analyses, the morpho-structural adaptations throughout evolution of the integument of gastropod Aplysia depilans (Gmelin, 1791), ascidian Styela plicata (Lesuer, 1823), myxine hagfish Eptatretus cirrhatus (Forster, 1801) and teleost Heteropneustes fossilis (Bloch, 1794) for the first time, with special reference to sensory epidermal cells. Different types of cells could be identified that varied according to the species; including mucous cells, serous glandular cells, clavate cells, club cells, thread cells, and support cells. In all integuments of the specimens analyzed, sensory solitary cells were identified in the epidermis, immunoreactive to serotonin and calbindin. Our study provided an essential comparison of integuments, adding new information about sensory epidermal cells phylogenetic conservation and on the structural changes that invertebrates and vertebrates have undergone during evolution.
Maximising the number of cells arrested at metaphase and their resolution is fundamentally important for molecular cytogenetic investigations, particularly in fish, which typically yield low mitotic index and have highly...Maximising the number of cells arrested at metaphase and their resolution is fundamentally important for molecular cytogenetic investigations, particularly in fish, which typically yield low mitotic index and have highly condensed chromosomes. To overcome these limitations, fish were injected with a mitotic stimulator (the yeast, Saccharomyces cerevisiae) to improve the mitotic index, and the intercalating agent ethidium bromide to produce elongated chromosomes. Specifically, adults were injected with activated yeast and then Colcemid (0.025 µg/µl solution, 10 µl per 1 g of body weight) at 24-96 h post yeast injections, followed by chromosome preparations from multiple tissues. Results showed that gill tissue had the highest number of dividing cells at 72 h post yeast exposure with no significant (p > 0.05) differences between the sexes. Nonetheless, sex-specific differences in the mitotic index were observed in spleen, kidney, and liver, which may be attributed to sex-specific differences in immune responses. For elongation of mitotic chromosomes, individuals (both sexes) were first injected with activated yeast and after 48 h with ethidium bromide (2 or 4 µg/ml) and Colcemid (0.05 µg/µl solution, 10 µl per 1 g of body weight). Following which, animals were sampled at three time points (1, 4 and 8 h) for chromosome preparations. The results show that the optimum elongation of metaphase chromosomes of males and females was achieved by using 2 µg/ml and 4 µg/ml, respectively, for 1 h. Interestingly, the average mitotic chromosome length (μm) of males and females post-ethidium bromide exposure was significantly different (p < 0.05) for both concentrations, except at 1 h exposure for 2 µg/ml EtBr. Such differences can be attributed to overall chromosomal condensation differences between sexes. Regardless, the increased mitotic index and chromosome resolution could benefit cytogenetic studies in other fish species.
Several strategies have been proposed to enhance wound healing results. Along with other forms of wound dressing, the human amniotic membrane (HAM) has long been regarded as a biological wound dressing that decreases inf...Several strategies have been proposed to enhance wound healing results. Along with other forms of wound dressing, the human amniotic membrane (HAM) has long been regarded as a biological wound dressing that decreases infection and enhances healing. This study investigates the feasibility and effectiveness of wound healing using decellularized HAM (dAM) and stromal HAM (sAM) in combination with adipose-derived human mesenchymal stem cells (AdMSCs). The dAM and sAM sides of HAM were employed as wound dressing scaffolds, and AdMSCs were seeded on top of either dAM or sAM. Sixty healthy Wistar rats were randomly divided into three groups: untreated wound, dAM/AdMSCs group, and sAM/AdMSCs group. The gene expression of VEGF and COL-I was measured in vitro. Wound healing was examined after wounding on days 3, 7, 14, and 21. The expression level of VEGF was significantly higher in sAM/AdMSCs than dAM/AdMSCs (P ≤ 0.05), but there was no significant difference in COL-I expression (P ≥ 0.05). In vivo research revealed that on day 14, wounds treated with sAM/AdMSCs had more vascularization than wounds treated with dAM/AdMSCs (P ≤ 0.01) and untreated wound groups on days 7 (P ≤ 0.05) and 14 (P ≤ 0.0001), respectively. On days 14 (P < 0.05 for sAM/AdMSCs, P < 0.01 for dAM/AdMSCs), and 21 (P < 0.05 for sAM/AdMSCs, P < 0.01 for dAM/AdMSCs), the collagen deposition in the wound bed was significantly thicker in the sAM/AdMSCs and dAM/AdMSCs groups compared to untreated wounds. The study demonstrated that the combination of sAM and AdMSCs promotes wound healing by enhancing angiogenesis and collagen remodeling.
Decidual immunological mediators modulate placental formation, decidualization and fetal development. However, the effect of maternal hyperthyroidism on decidual immunology needs further research. The aim of this study w...Decidual immunological mediators modulate placental formation, decidualization and fetal development. However, the effect of maternal hyperthyroidism on decidual immunology needs further research. The aim of this study was to evaluate the population of uterine natural killer cells (uNKs) and the expression of immunological mediators in the decidua of female rats throughout pregnancy. Wistar rats were used and hyperthyroidism was induced by daily administration of L-thyroxine (T4) throughout pregnancy. The population of uNK cells in decidua was evaluated by immunostaining Lectin DBA, as well as the expression of interferon γ (INFγ), macrophage migration inhibitory factor (MIF), interleukin 15 (IL-15) and inducible nitric oxide synthase (iNOS) at 7, 10, 12, 14 and 19 days of gestation (DG). Maternal hyperthyroidism reduced the DBA+ uNK cell population in the decidua at 7 (P < 0.05) and 10 (P < 0.01) DGs compared to that in the control group, while it increased in the basal decidua (P < 0.05) and metrial gland (P < 0.0001) at the 12th DG. Hyperthyroidism also increased immunostaining of IL-15 (P < 0.0001), INFγ (P < 0.05), and MIF (P < 0.05) in the 7th DG, and increased immunostaining of IL-15 (P < 0.0001) and MIF (P < 0.01) in e 10th DG. However, excess thyroxine reduced IL-15 expression in the metrial gland and/or basal decidua in the 12th (P < 0.05), 14th (P < 0.01), and 19th (P < 0.001) DGs, as was also observed for INFγ in the basal decidua (P<0.001) and metrial gland (P < 0.0001) in the 12th DG. Regarding iNOS, an antiinflammatory cytokine, lower expression was observed in the basal decidua of hyperthyroid animals at 7 and 12 DGs (P < 0.05), whereas an increase occurred in the 10th DG (P < 0.05). These data demonstrate that maternal hyperthyroidism in female rats, particularly between 7 and 10 DGs, reduces the population of DBA+ uNKs in the decidua and increases the expression of inflammatory cytokines, suggesting a more proinflammatory environment in early pregnancy caused by this gestational disease.
Regarding their reversible damage of insulin-producing cells (IPCs) and the inefficiency of treatment methods for type 1 diabetes mellitus (T1DM), scientists decided to produce IPCs from an unlimited source of cells. But...Regarding their reversible damage of insulin-producing cells (IPCs) and the inefficiency of treatment methods for type 1 diabetes mellitus (T1DM), scientists decided to produce IPCs from an unlimited source of cells. But the production of these cells is constantly faced with problems such as low differentiation efficiency in cell therapy and regenerative medicine. This study provided an ideal differentiation medium enriched with plasma-rich platelet (PRP) delivery to produce IPCs from menstrual blood-derived stem cells (MenSCs). We compared them with and without PRP differentiation medium. MenSCs were then cultured in two experimental groups: with/without PRP differentiation medium and a control group (undifferentiated MenSCs). After 18 days, differentiated cells were analyzed for expression of pancreatic gene markers by real-time PCR. Immunocytochemical staining was used to detect the presence of insulin and Pdx-1 in the differentiated cells, and insulin and C-peptide secretion response to glucose were tested by ELISA. Finally, the morphology of differentiated cells was examined by an inverted microscope. In vitro studies showed that MenSCs differentiated in the PRP differentiation medium had strong properties of IPCs such as pancreatic islet-like structure. The expression of pancreatic markers at both RNA and protein levels showed that the differentiation efficiency was higher in the PRP differentiation medium. In both experimental groups, the differentiated cells were functional and secreted C-peptide and insulin on glucose stimulation, but the secretion of C-peptide and insulin in the PRP group was higher than those cultured in the without PRP differentiation medium. Our findings showed that using of PRP enriched differentiation medium can promote the differentiation of MenSCs into IPCs compared to the without PRP culture group. Therefore, the use of PRP into differentiation media can be proposed as a new approach to producing IPCs from MenSCs and used in cell-based therapies for T1DM.
PURPOSE: This study aims to investigate whether the bone marrow mesenchymal stem cells (BMSCs) of rat and mice can spontaneously express troponin T (cTnT) in vitro. METHODS: The BMSCs of rats and mice were cultured in vi...PURPOSE: This study aims to investigate whether the bone marrow mesenchymal stem cells (BMSCs) of rat and mice can spontaneously express troponin T (cTnT) in vitro. METHODS: The BMSCs of rats and mice were cultured in vitro. The expression of cTnT in the BMSCs of rats and mice was detected by immunofluorescence, immunohistochemistry, and Western blot. The detection of cTnT and α-sarcomeric actin coexpression on the surface of BMSCs was determined using immunofluorescence and qRT-PCR. RESULTS: In rats and mice, cTnT expression was detected in a portion of BMSCs. The positive rates of cTnT in rats and mice were approximately 10-52 % and 27-60 %, respectively. According to the results of the Western blot analysis, the gray values of cTnT in rats and mice were 0.64 ± 0.02 and 1.08 ± 0.03, respectively. Additionally, the surface of BMSCs can express cTnT and α-sarcomeric actin, which is a marker for striated muscle. CONCLUSION: The BMSCs of rats and mice can spontaneously express cTnT and automatically differentiate striated muscles in vitro.
Pulmonary fibrosis is a severe condition in interstitial lung diseases (ILD) such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-ILD, where the underlying mechanism is not well defined and with no curative...Pulmonary fibrosis is a severe condition in interstitial lung diseases (ILD) such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-ILD, where the underlying mechanism is not well defined and with no curative treatments available. Serotonin (5-HT) signaling via the 5-HT receptor has been recognized as a promising preclinical target for fibrosis. Despite this, the involvement of the 5-HT receptor in fibrotic ILD is widely unexplored. This work highlights the spatial pulmonary distribution of the 5-HT receptor in patients with IPF and systemic sclerosis-ILD. We show that the 5-HT receptor is located in typical pathological structures e.g. honeycomb cysts and weakly in fibroblast foci. Together with immunohistochemistry and immunofluorescence stainings of patient derived distal lung tissues, we identified cell targets for 5-HT receptor interference in type II alveolar epithelial cells, endothelial cells and M2 macrophages. Our results emphasize the role of 5-HT receptor as a target in lung fibrosis, warranting further consideration in targeting fibrotic ILDs.
Approaches to the design and construction of biomimetic scaffolds for osteochondral tissue, show increasing advances. Considering the limitations of this tissue in terms of repair and regeneration, there is a need to dev...Approaches to the design and construction of biomimetic scaffolds for osteochondral tissue, show increasing advances. Considering the limitations of this tissue in terms of repair and regeneration, there is a need to develop appropriately designed scaffolds. A combination of biodegradable polymers especially natural polymers and bioactive ceramics, shows promise in this field. Due to the complicated architecture of this tissue, biphasic and multiphasic scaffolds containing two or more different layers, could mimic the physiology and function of this tissue with a higher degree of similarity. The purpose of this review article is to discuss the approaches focused on the application of biphasic scaffolds for osteochondral tissue engineering, common methods of combining layers and the ultimate consequences of their use in patients were discussed.
Fluoride compounds are abundant and widely distributed in the environment at various concentrations, which can seriously injure the human body. In this study, we aim to evaluate the effects of excessive fluoride exposure...Fluoride compounds are abundant and widely distributed in the environment at various concentrations, which can seriously injure the human body. In this study, we aim to evaluate the effects of excessive fluoride exposure on the liver, kidney, and heart tissues of healthy female Xenopus laevis by administering NaF (0, 100, and 200 mg/L) in drinking water for 90 days. The expression level of procaspase-8, cleaved-caspase-8, and procaspase-3 proteins were determined by Western blot. Compared with the control group, the group exposed to NaF exhibited expression levels of procaspase-8, cleaved-caspase-8, and procaspase-3 proteins that were considerably upregulated at a concentration of 200 mg/L in the liver and kidney. The cleaved-caspase-8 protein expression in the group exposed to a high concentration of NaF was lower than that in the control group in heart. Histopathological results by hematoxylin and eosin staining showed that excessive NaF exposure caused necrosis of hepatocytes and vacuolization degeneration. Granular degeneration and necrosis in renal tubular epithelial cells were also observed. Moreover, hypertrophy of myocardial cells, atrophy of myocardial fibers and disorder of myocardial fibers were detected. These results demonstrated that NaF-induced apoptosis and the mediated death receptor pathway activation ultimately damaged the liver and kidney tissues. This finding offers a fresh perspective on the effects of F-induced apoptosis in X. laevis.
Marrow adipose tissue (MAT) adversely affects bone metabolism under certain conditions. Although mechanical stress is an important factor in regulating MAT and bone mass, how stress from different rehabilitation protocol...Marrow adipose tissue (MAT) adversely affects bone metabolism under certain conditions. Although mechanical stress is an important factor in regulating MAT and bone mass, how stress from different rehabilitation protocols after anterior cruciate ligament (ACL) reconstruction affects trabecular bone and MAT is unclear. We aimed to examine the effects of joint immobilization and treadmill exercise on trabecular bone and MAT after ACL reconstruction. Rats received unilateral knee ACL transection and reconstruction surgery. After surgery, rats were reared without intervention, with joint immobilization, or with treadmill exercise (12 m/min, 60 min/day, six days/week), with untreated rats as controls. At two or four weeks after starting experiments, we examined histological changes in trabecular bone and MAT in the proximal tibial epiphysis. After ACL reconstruction, there were no significant changes in trabecular bone area and MAT area at both time points. Joint immobilization after ACL reconstruction resulted in reduced trabecular bone area and MAT accumulation due to adipocyte hyperplasia and hypertrophy within four weeks. Treadmill exercise after ACL reconstruction did not affect any parameters in trabecular bone and MAT. We detected a moderate negative correlation between trabecular bone area and MAT area. Therefore, MAT accumulation induced by joint immobilization may contribute, at least in part, to reducing trabecular bone area. To minimize trabecular bone loss and MAT accumulation, joint immobilization after ACL reconstruction should be minimized. Exercise after ACL reconstruction did not alter trabecular bone and MAT.
Vohwinkel syndrome (VS) is a very rare autosomal dominant disorder that can cause disability and deformity in severe cases. Mutations of the LOR (loricrin) and GJB2 (Cx26) genes have been found in VS so far. Many studies...Vohwinkel syndrome (VS) is a very rare autosomal dominant disorder that can cause disability and deformity in severe cases. Mutations of the LOR (loricrin) and GJB2 (Cx26) genes have been found in VS so far. Many studies have indicated that the differentiation and growth of epidermal keratinocytes are regulated by mutant Cx26, and it may explain the pathogenesis of VS. It has been found that transforming growth factor β1 (TGF-β1) expression was lower in G130V (OE1) and D66H (OE2) mutant keratinocytes in the VS model with GJB2 mutation as compared to normal keratinocytes (NC). TGF-β is a cytokine involved in the regulation of processes like cell proliferation and differentiation in different types of cells. At present, many in vitro studies focus on TGF- β 1 inhibition of keratinocyte growth.However, the relationship between TGF-β1 and VS remains unknown. This study aimed at elucidating the role and potential pathogenic mechanism of TGF-β in VS. The results indicated that the down-regulation expression of TGF-β1 in VS was linked to cell proliferation inhibition through p-Smad3/c-myc. In contrast, low-dose TGF-β1 treatment of VS keratinocytes can improve their proliferation inhibition and up-regulate the expression Cyclin D1. This suggests that low doses of TGF-β1 can improve the proliferation of VS and provide new insights into its treatment.
Extracellular vesicles (EVs) are heterogeneous membrane-bound complexes of cell-derived and nanosized structures originating from the endosomal system and subsequently released from the plasma membrane. EVs contribute si...Extracellular vesicles (EVs) are heterogeneous membrane-bound complexes of cell-derived and nanosized structures originating from the endosomal system and subsequently released from the plasma membrane. EVs contribute significantly to intercellular communication and are involved in pigmentation processes that rely on tight communication between keratinocytes and melanocytes in the epidermis. Microphthalmia-associated transcription factor (MITF) induces melanogenesis and modulates the expression factors involved in melanosome biogenesis, maturation and dispersal in melanocytes. Here, we evaluated the effects of MITF on the fate of multivesicular bodies and the biogenesis of extracellular vesicles of melanocytes. It was found that MITF increased the expression of subunits of the endosomal sorting complex, required for transport (ESCRT), including VPS37, VPS36B, and tetraspanin CD81, which are key mediators of multivesicular body biogenesis. Over 110 miRNAs, including miR-211-5p, miR-335-5p, let-7g-5p and miR-28a-3p, were differentially expressed in melanocyte-derived EVs after overexpression of MITF in melanocytes. These miRNAs have been reported to be key regulators of plasma protein binding, changes in the cell membrane system and transferase activity. These results suggest that while enhancing melanogenesis, melanocytes may mediate intercellular communication with surrounding cells by serving as EV delivery vehicles.
OBJECTIVES: Peroxisomal trans-2-enoyl-CoA reductase (PECR) encodes proteins related to fatty acid metabolism and synthesis. It has been confirmed that PECR has decreased expression in colon cancer and breast cancer, whil...OBJECTIVES: Peroxisomal trans-2-enoyl-CoA reductase (PECR) encodes proteins related to fatty acid metabolism and synthesis. It has been confirmed that PECR has decreased expression in colon cancer and breast cancer, while the role of PECR in liver cancer is unknown. We aimed to study the role and mechanism of PECR in the genesis and development of liver cancer. METHODS: In this study, the expression of PECR was queried in the Cancer Genome Atlas Database and Western Blotting and RT-PCR experiments were carried out in paired liver cancer tissues to detect the expression of PECR. Functional tests were evaluated by cell count kit-8 (CCK-8), Flow cytometry, wound healing assay, Transwell, migration. In vivo study, we constructed a nude mouse tumorigenic model to observe the effect of PECR on the proliferation of liver cancer. And the tumor body of the mouse was taken out for histochemistry (IHC). Multiple Cox regression was used to analyze the correlation between PECR and Clinicopathology. RESULTS: We confirmed that the overexpression of PECR inhibited the proliferation, migration and invasion of hepatocellular carcinoma and promoted the apoptosis of hepatocellular carcinoma. The low expression group of PECR promoted the proliferation and metastasis of liver cancer. In vivo, overexpression of PECR inhibits the proliferation of mouse tumors. In addition, the mechanism study shows that PECR may indirectly affect the proliferation of hepatocellular carcinoma cells through ERK pathway. CONCLUSION: In general, PECR may be a new diagnostic marker and a potential therapeutic target for hepatocellular carcinoma.
Articular cartilage and subchondral bones were used to be the samples for studying effects of drugs in the joint degenerative diseases such as osteoarthritis. Because of the deposition of mineral salts, articular cartila...Articular cartilage and subchondral bones were used to be the samples for studying effects of drugs in the joint degenerative diseases such as osteoarthritis. Because of the deposition of mineral salts, articular cartilage and subchondral bones require decalcification process to soften the tissues. EDTA is a chelating agent that is commonly used to remove mineral salts, but this step is time-consuming and can take as long as 45 days. Commercial ultrasonic cleaner and microwave oven were reported to reduce the decalcification timing. The aim of this study is to determine and compare the decalcification of human articular cartilage and subchondral bone using EDTA together with ultrasonic cleaner or microwave oven. Hundred pieces of articular cartilage and subchondral bones obtained from osteoarthritis patients undergone total-knee-replacement were divided into 10 groups according to decalcification method (ultrasonic cleaner or microwave) and timing (2, 4, 6, 8, and 10 h). In each group, all cartilage and subchondral bone pieces were decalcified and sectioned, and subsequently stained with haematoxylin and eosin, Von Kossa, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, or caspase-3 immunohistochemistry. The optimal timing of decalcification of articular cartilage and subchondral bones using EDTA together with ultrasonic cleaner was at 8 and 10 h, while the timing using EDTA together with microwave oven was more than 10 h. Clear TUNEL and caspase-3 signals were obtained from samples decalcified using EDTA together with ultrasonic cleaner for 8 h. In summary, to our knowledge, this is the first study that compared EDTA decalcification between ultrasonic cleaner and microwave oven. Here, we report a new methodology for decalcification for articular cartilage and subchondral bones that reduces decalcification time from weeks to hours and is suitable for further pathological analyses.
Mitochondria-associated endoplasmic reticulum membranes (MAMs) are dynamic suborganelle membranes that physically couple endoplasmic reticulum (ER) and mitochondria to provide a platform for exchange of intracellular mol...Mitochondria-associated endoplasmic reticulum membranes (MAMs) are dynamic suborganelle membranes that physically couple endoplasmic reticulum (ER) and mitochondria to provide a platform for exchange of intracellular molecules and crosstalk between the two organelles. Dysfunctions of mitochondria and ER and imbalance of intracellular homeostasis have been discovered in the research of toxics. Cellular activities such as oxidative stress, ER stress, Ca transport, autophagy, mitochondrial fusion and fission, and apoptosis mediated by MAMs are closely related to the toxicological effects of various toxicants. These cellular activities mediated by MAMs crosstalk with each other. Regulating the structure and function of MAMs can alleviate the damage caused by toxicants to some extent. In this review, we discuss the relationships between MAMs and the mechanisms of toxicological effects, and highlight MAMs as a potential target for protection against toxicants.
One of the areas of science which has immensely advanced in the recent years is nanotechnology. This area broadly revolves around matter at scales between 1 and 100 nm, where peculiar phenomena make way for cutting-edge...One of the areas of science which has immensely advanced in the recent years is nanotechnology. This area broadly revolves around matter at scales between 1 and 100 nm, where peculiar phenomena make way for cutting-edge applications. Today, nanotechnology has a daily impact on human life with numerous and varied possible advantages. Nanosensors are one of the products of nanotechnology and any sensor that uses nanoscale phenomena qualifies to be known as a nanosensor. Nanosensors have proven very useful in a number of sectors including medical applications, food quality analysis and agricultural controlling process, etc. One of the major human healthcare applications of nanosensors is for disease diagnosis. With the aid of nanosensors, numerous neurodegenerative disorders and inflammatory diseases are commonly identified and treated of late. Alzheimer's disease (AD) and inflammatory bowel disease fall under the categories of neurodegenerative illnesses and inflammatory diseases. There are more than 20 million cases of (AD) making it the most prevalent neurological condition globally and "inflammatory bowel disease" (IBD) refers to a variety of conditions that cause persistent inflammation of the digestive tract. Here we present a comprehensive account on the utility of nanosensors for the diagnosis and treatment of (AD) and (IBD).