Search

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is a rapidly progressing infectious disease with a high fatality rate caused by a novel bunyavirus (SFTSV). The role of lipids in viral infections is well-documented; however, the specific alterations in lipid metabolism during SFTSV infection remain elusive. This study aims to elucidate the lipid metabolic dysregulations in the early stages of SFTS patients. Methods This study prospectively collected peripheral blood sera from 11 critical SFTS patients, 37 mild SFTS patients, and 23 healthy controls during the early stages of infection for lipidomics analysis. A systematic bioinformatics analysis was conducted from three aspects integrating lipid differential expressions, lipid differential correlations, and lipid-clinical indices correlations to reveal the serum lipid metabolic dysregulation in SFTSV-infected individuals. Results Our findings reveal significant lipid metabolic dysregulation in SFTS patients. Specifically, compared to healthy controls, SFTS patients exhibited three distinct modes of lipid differential expression: increased levels of lipids including phosphatidylserine (PS), hexosylceramide (HexCer), and triglycerides (TG); decreased levels of lipids including lysophosphatidylcholine (LPC), acylcarnitine (AcCa), and cholesterol esters (ChE); and lipids showing “dual changes” including phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Finally, based on lipid metabolic pathways and literature analysis, we systematically elucidated the potential mechanisms underlying lipid metabolic dysregulation in the early stage of SFTSV infection. Conclusions Our study presents the first global serum lipidome profile and reveals the lipid metabolic dysregulation patterns in the early stage of SFTSV infection. These findings provide a new basis for the diagnosis, treatment, and further investigation of the disease.

AbstractLiver fibrosis is a key pathological process shared by the progression of various chronic liver diseases. Treatment of liver fibrosis can effectively block the occurrence and development of hepatic cirrhosis or even carcinoma. Currently, there is no effective drug delivery vehicle for curing liver fibrosis. In this study, we designed matrine (MT)-loaded mannose 6-phosphate (M6P) modified human serum albumin (HSA) conjugated solid lipid nanoparticles (SLN), named M6P-HSA-MT-SLN for treatment of hepatic fibrosis. We demonstrated that M6P-HSA-MT-SLN exhibited controlled and sustained release properties and good stability over 7 days. The drug release experiments showed that M6P-HSA-MT-SLN exhibited slow and controlled drug release characteristics. In addition, M6P-HSA-MT-SLN showed a significant targeted ability to fibrotic liver. Importantly, in vivo studies indicated that M6P-HSA-MT-SLN could significantly improve histopathological morphology and inhibit the fibrotic phenotype. In addition, in vivo experiments demonstrate that M6P-HSA-MT-SLN could reduce the expression of fibrosis markers and alleviate the damage of liver structure. Hence, the M6P-HSA-MT-SLN provide a promising strategy to deliver therapeutic agents to fibrotic liver to prevent liver fibrosis.

Abstract The biological functions and toxic effects of reactive oxygen species (ROS) are generally entangled. A large amount of ROS may cause oxidative damage to cell biomolecules, leading to cell death. Tumor treatment can be carried out by using the toxicity of ROS, and various nanosystems related to ROS have been designed. In fact, the level of active oxygen in the biological microenvironment can be regulated in advanced therapeutics via designed nanoscale engineering, which can open up a new direction of treatment with specific simplicity. In this progress report, the authors first introduced how ROS causes cell death. Then, recent studies on converting the inherent toxicity from ROS into advanced treatment tools are highlighted.

The transmembrane protein Crumbs (Crb), a key regulator of apical polarity, has a known involvement in establishment of the apical zonula adherens in epithelia, although the precise mechanism remains elusive. The zonula adherens are required to maintain the integrity and orderly arrangement of epithelia. Loss of the zonula adherens leads to morphogenetic defects in the tissues derived from epithelium. In this study, we revealed that the intracellular tail of Crb2a promoted the apical distribution of adherens junctions (AJs) in zebrafish retinal and lens epithelia, but caused assembly into unstable punctum adherens-like adhesion plaques. The extracellular region of Crb2a guided the transformation of AJs from the punctum adherens into stable zonula adherens. Accordingly, a truncated form of Crb2a lacking the extracellular region (Crb2aΔEX) could only partially rescue the retinal patterning defects in crb2a null mutant zebrafish (crb2am289). By contrast, constitutive over-expression of Crb2aΔEX disrupted the integrity of the outer limiting membrane in photoreceptors, which is derived from the zonula adherens of the retinal neuroepithelium. This study demonstrated that both the extracellular region and the intracellular tail of Crb2a are required to guide the formation of the apical zonula adherens.

Background and objective Lung cancer is a malignant tumor with high mortality rates. This study aims to develop potential candidates of integrin αvβ3 imaging agents, which can facilitate the diagnosis and treatment of lung cancer. Methods The T7 peptide was labeled with carbonyl technetium. The thin layer chromatography with acetone as the development system was performed to investigate the purity and stability of 99mTc-T7. The binding affinity of 99mTc-T7 with NCI-H157 tumor cells was determined. The biodistribution of 99mTc-T7 in nude mice bearing non-small cell lung carcinoma was observed after injection of 99mTc-T7 at 0.5 h, 1 h, 2 h, 4 h, and 8 h, and the radioactive ratio of tumor (T) and non-tumor tissues (NT) was calculated. Results 99mTc labeled T7 had high radiochemical purity of more than 90%, which does not require further purification, with good stability in vitro. The association and dissociation constant (KD) of 99mTc-T7 with NCI-H157 tumor cells was 196.1 nM. 99mTc-T7 was mainly metabolism through the internal organs with rapid blood removal. Moreover, the uptake in tumor tissue was significantly higher than the muscle with tumor/muscle ratio of 5.8. In addition, the 99mTc-T7 exhibited a transient accumulation in the lungs. Conclusion The 99mTc-T7 could be prepared using a simple method, had high labeling rate and good stability, and could be accumulated at tumor site. Thus, 99mTc-T7 is a potential lung cancer SPECT/CT imaging agent.

Adherens junction remodeling regulated by apical polarity proteins constitutes a major driving force for tissue morphogenesis, although the precise mechanism remains inconclusive. Here, we report that, in zebrafish, the Crumbs complex component MPP5a interacts with small GTPase Rab11 in Golgi to transport cadherin and Crumbs components synergistically to the apical domain, thus establishing apical epithelial polarity and adherens junctions. In contrast, Par complex recruited byMPP5a is incapable of interacting with Rab11 but might assemble cytoskeleton to facilitate cadherin exocytosis. In accordance, dysfunction of MPP5a induces an invasive migration of epithelial cells. This adherens junction remodeling pattern is frequently observed in zebrafish lens epithelial cells and neuroepithelial cells. The data identify an unrecognized MPP5a-Rab11 complex and describe its essential role in guiding apical polarization and zonula adherens formation in epithelial cells. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effects of Na+/H+ exchanger regulatory factor 1 (NHERF1) gene knockdown, using short-hairpin RNA (shRNA), on the malignant behaviors of prostate cancer cells. A pSuper.puro NHERF1 shRNA vector was transfected into PC-3M prostate cancer cells using Lipofectamine 2000. Stable cell lines were obtained and NHERF1 knockdown was verified through western blot analysis. MTT assays were then used to measure PC-3M cell proliferation; in addition, cell migration was assessed using a wound healing assay. Flow cytometry was employed in order to determine the effects of NHERF1 knockdown on apoptosis. Expression levels of apoptotic pathway proteins B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein were then determined by western blot analysis. The results demonstrated that shRNA knockdown of NHERF1 significantly suppressed the proliferation of PC-3M cells by >50%. In addition, knockdown of NHERF1 significantly inhibited the migration of PC-3M cells. PC-3M cells harboring NHERF1 shRNA exhibited significantly increased apoptosis, with an ~4-fold increase compared with that of the parental PC-3M cells and cells transfected with an empty vector. Furthermore, the results revealed that knockdown of NHERF1 reduced the protein expression of Bcl-2, although the expression of Bax was unaltered. In conclusion, NHERF1 knockdown using shRNA inhibited the proliferation and migration of PC-3M cells and promoted apoptosis, highlighting the role of NHERF1 in prostate cancer progression. [ABSTRACT FROM AUTHOR]

Background and objective Lung cancer is a malignant tumor with high mortality rates. This study aims to develop potential candidates of integrin αvβ3 imaging agents, which can facilitate the diagnosis and treatment of lung cancer. Methods The T7 peptide was labeled with carbonyl technetium. The thin layer chromatography with acetone as the development system was performed to investigate the purity and stability of 99mTc-T7. The binding affinity of 99mTc-T7 with NCI-H157 tumor cells was determined. The biodistribution of 99mTc-T7 in nude mice bearing non-small cell lung carcinoma was observed after injection of 99mTc-T7 at 0.5 h, 1 h, 2 h, 4 h, and 8 h, and the radioactive ratio of tumor (T) and nontumor tissues (NT) was calculated. Results 99mTc labeled T7 had high radiochemical purity of more than 90%, which does not require further purification, with good stability in vitro. The association and dissociation constant (KD) of 99mTc-T7 with NCI-H157 tumor cells was 196.1 nM. 99mTc-T7 was mainly metabolism through the internal organs with rapid blood removal. Moreover, the uptake in tumor tissue was significantly higher than the muscle with tumor/muscle ratio of 5.8. In addition, the 99mTc-T7 exhibited a transient accumulation in the lungs. Conclusion The 99mTc-T7 could be prepared using a simple method, had high labeling rate and good stability, and could be accumulated at tumor site. Thus, 99mTc-T7 is a potential lung cancer SPECT/CT imaging agent. [ABSTRACT FROM AUTHOR]