Peroxiredoxin I deficiency increases keratinocyte apoptosis in a skin tumor model via the ROS-p38 MAPK pathway.

Keratinocyte hyperproliferation is an essential link in skin cancer pathogenesis. Peroxiredoxin I (Prx I) is known to regulate cancer cell proliferation, differentiation, and apoptosis, but its role in skin cancer remains unclear. This study aimed to elucidate the role and mechanism of Prx I in skin cancer pathogenesis. Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were used to create a skin tumor model of the initiation/promotion stage of cancer. The role of Prx I in H2O2-induced keratinocyte apoptosis was also investigated. After DMBA/TPA treatment, Prx I deficiency was significantly associated with less skin tumors, lower Bcl-2 expression, and higher p-p38 and cleaved caspase-3 expressions in Prx I knockout tumors than in wild-type controls. H2O2 stimulation caused more cellular apoptosis in Prx I knockdown HaCaT cells than in normal HaCaT cells. The signaling study revealed that Bcl-2, p-p38, and cleaved caspase-3 expressions were consistent with the results in the tumors. In conclusion, the deletion of Prx I triggered the DMBA/TPA-induced skin tumor formation in vivo and in vitro by regulating the reactive oxygen species (ROS)-p38 mitogen-activated protein kinase (MAPK) pathway. These findings provide a theoretical basis for treating skin cancer.

Effects of soil microplastic heterogeneity on plant growth vary with species and microplastic types.

Microplastics are heterogeneously distributed in soils. However, it is unknown whether soil microplastic heterogeneity affects plant growth and root foraging responses and whether such effects vary with plant species and microplastic types. We grew each of seven herbaceous species (Platycodon grandiflorus, Trifolium repens, Portulaca oleracea, Medicago sativa, Taraxacum mongolicum, Perilla frutescenst, and Paspalum notatum) in heterogeneous soil (patches without microplastics and patches with 0.2 % microplastics) and homogeneous soil (patches with 0.1 % microplastics). Three microplastic types were tested: polypropylene (PP), polyacrylonitrile (PAN), and polyester (PET). P. frutescens showed no response to soil microplastic heterogeneity. For P. grandiflora, microplastic heterogeneity tended to decrease its biomass (total, shoot and root) when the microplastic was PAN and also shoot biomass when it was PET, but had no effect when it was PP. For T. repens, microplastic heterogeneity promoted biomass when PAN was used, decreased total and root biomass when PET was used, but showed no effect when PP was used. Microplastic heterogeneity increased biomass of P. oleracea and decreased that of M. sativa when PET was used, but had no effect when PP or PAN was used. For T. mongolicum, microplastic heterogeneity reduced biomass when the microplastic was PAN, tended to increase total and root biomass when it was PP, but showed no effect when it was PET. For P. notatum, microplastic heterogeneity increased biomass when the microplastic was PP, decreased it when PET was used, but had no effect when PAN was used. However, biomass of none of the seven species showed root foraging responses at the patch level. Therefore, soil microplastic heterogeneity can influence plant growth, but such effects depend on species and microplastic types and are not associated with root foraging. Our findings highlight the roles of soil microplastic heterogeneity, which may influence species interactions and community structure and productivity.

Steric Effects on the Photovoltaic Performance of Panchromatic Ruthenium Sensitizers for Dye-Sensitized Solar Cells.

Three new heteroleptic Ru complexes, CYC-B22, CYC-B23C, and CYC-B23T, were prepared as sensitizers for coadsorbent-free, panchromatic, and efficient dye-sensitized solar cells. They are simultaneously functionalized with highly conjugated anchoring and ancillary ligands to explore the electronic and steric effects on their photovoltaic characteristics. The coadsorbent-free device based on CYC-B22 achieved the best power conversion efficiency (PCE) of 8.63% and a panchromatic response extending to 850 nm. The two stereoisomers, CYC-B23C and CYC-B23T coordinated with an unsymmetrical anchoring ligand, display similar absorption properties and the same driving forces for electron injection as well as dye regeneration. Nevertheless, the devices show not only the remarkably distinct PCE (6.64% vs 8.38%) but also discernible stability. The molecular simulation for the two stereoisomers adsorbed on TiO2 clarifies the distinguishable distances (16.9 Å vs 19.0 Å) between the sulfur atoms in the NCS ligands and the surface of the TiO2, dominating the charge recombination dynamics and iodine binding and therefore the PCE and stability of the devices. This study on the steric effects caused by the highly conjugated and unsymmetrical anchoring ligand on the adsorption geometry and photovoltaic performance of the dyes paves a new way for advancing the molecular design of polypyridyl metal complex sensitizers.

The Presence of Testis Determines Aristolochic Acid-Induced Nephrotoxicity in Mice.

Aristolochic acid (AA) is notorious for inducing nephrotoxicity, but the influence of sex on AA-induced kidney injury was not clear. This study sought to investigate sex differences in kidney dysfunction and tubular injury induced by AA. Male and female mice were bilaterally orchiectomized and ovariectomized, respectively. Fourteen days after gonadectomy, the mice were intraperitoneally injected with AA (10 mg/kg body weight/day) daily for 2 days and sacrificed 7 days after the first injection. Body weight, kidney function, and tubular structure were assessed. When compared between male and female non-gonadectomized mice, AA-induced body weight loss was greater in male mice than in female mice. Functional and structural damages in male kidneys were markedly induced by AA injection, but kidneys in AA-injected female mice showed no or mild damages. Ovariectomy had no effect on AA-induced nephrotoxic acute kidney injury in female mice. However, orchiectomy significantly reduced body weight loss, kidney dysfunction, and tubular injury in AA-induced nephrotoxicity in male mice. This study has demonstrated that testis causes AA-induced nephrotoxic acute kidney injury.

Inhibitory Effect of Bovine Adipose-Derived Mesenchymal Stem Cells on Lipopolysaccharide Induced Inflammation of Endometrial Epithelial Cells in Dairy Cows.

Endometritis is a disease that affects reproductive health in dairy cows and causes serious economic damage to the dairy industry world-wide. Although in recent years, the application of mesenchymal stem cell (MSC) therapy for the treatment of inflammatory diseases has attracted much attention, there are few reports of the use of MSCs in dairy cows. In the present study, our objective was to explore the inhibitory effects of bovine adipose-derived mesenchymal stem cells (bAD-MSCs) on lipopolysaccharide (LPS) induced inflammation in bovine endometrial epithelial cells (bEECs) along with the potential underlying molecular mechanisms. We characterized isolated bAD-MSCs using cell surface marker staining and adipogenic/osteogenic differentiation, and analyzed them using immunofluorescence, flow cytometry (surface marker staining), and adipogenic and osteogenic differentiation. Furthermore, to understand the anti-inflammatory effects of bAD-MSCs on LPS induced bEEC inflammation, we used a bAD-MSC/bEEC co-culture system. The results showed that bAD-MSC treatments could significantly decrease LPS induced bEEC apoptosis and pro-inflammatory cytokine expression levels, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Furthermore, our results showed that bAD-MSC treatments could also significantly downregulate LPS induced p38, IkB-a, and JAK1 phosphorylation and Bax protein expression levels, which are closely related to inflammatory progress and cellular apoptosis in bEECs. Our findings demonstrate that bAD-MSCs play an inhibitory role in LPS induced bEEC inflammation and provide new insights for the clinical therapy of endometritis in dairy cows.

Systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome in a 77-year-old man: A case report.

BACKGROUND: Systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are classically thought to cause renal impairment and small vessel vasculitis with different pathophysiologies. Their overlap constitutes a rare rheumatologic disease. To date, only dozens of such cases with biopsy-proven glomerulonephritis have been reported worldwide typically in women of childbearing age. Here, we present a unique clinical case due to its rarity and individualized treatment of a Chinese man in his eighth decade of life. CASE SUMMARY: A 77-year-old man was admitted to several hospitals for shortness of breath and received nonspecific treatments over the past 3 years. As his symptoms were not completely relieved, he visited our hospital for further treatment. Laboratory examinations revealed kidney dysfunction, severe anaemia, hypocom-plementemia, glomerular proteinuria, and microscopic haematuria. Antinuclear antibodies, as well as anti-dsDNA antibodies, were positive. Computed tomography of the chest showed right pleural effusion. Renal biopsy was performed, and histology suggested crescentic glomerulonephritis, pauci-immune type. After treatment with plasmapheresis, glucocorticoid, and cyclo-phosphamide, the disease was in remission, and the patient remained in a stable condition for over 3 years post-hospital discharge. CONCLUSION: Due to its complexity and rarity, SLE and AAV overlap syndrome is easily misdiagnosed. An accurate diagnosis and treatment at the earliest stage may significantly improve the condition and reduce irreversible organ injury.

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits in a young woman: A case report.

BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a newly recognized rare disease. The renal pathology is characterized by prominent manifestations of membranous hyperplasia, which are easy to misdiagnose. The clinical symptoms are severe. Massive proteinuria and hypoproteinemia are conspicuous, and most patients are accompanied by renal insufficiency and microscopic hematuria. CASE SUMMARY: A 27-year-old woman was admitted to a hospital for macroscopic hematuria and proteinuria 4 years prior, and renal biopsy in the hospital suggested moderate-to-severe mesangial proliferating glomerulonephritis (MsPGN). She had taken a glucocorticoid, cyclophosphamide, mycophenolate mofetil, and other treatments and achieved brief partial remission. Recently, the patient visited our hospital due to massive proteinuria. Repeated renal biopsy and re-evaluation of the first biopsy obtained 4 years previously revealed monoclonal immunoglobulin deposition in the glomeruli. A bone marrow examination was performed to exclude hematologic malignancy, and a diagnosis of PGNMID was established. The patient showed remission after four cycles of a bortezomib + cyclophosphamide + dexamethasone scheme. CONCLUSION: PGNMID is usually misdiagnosed as MsPGN or membranoproliferative glomerulonephritis. Although it often occurs in middle-aged and elderly individuals, it cannot be readily excluded in young people, even when serum immunofixation electrophoresis is negative. IgG subtype and light chain staining are necessary when this disease is highly suspected. An accurate diagnosis at the earliest stage may avoid the overuse of glucocorticoids and immunosuppressants.

Curcumin Activates ROS Signaling to Promote Pyroptosis in Hepatocellular Carcinoma HepG2 Cells.

BACKGROUND/AIM: Curcumin is a polyphenol that exerts a variety of pharmacological activities and plays an anti-cancer role in many cancer cells. It was recently reported that gasdermin E (GSDME) is involved in the progression of pyroptosis. MATERIALS AND METHODS: HepG2 cells were treated with various concentrations of curcumin and cell viability was examined using MTT assay, apoptosis was analysed using flow cytometry, reactive oxygen species (ROS) levels using dihydroethidium, LDH release using an LDH cytotoxicity assay, and protein expression using western blot. RESULTS: Curcumin increased the expression of the GSDME N-terminus and proteins involved in pyrolysis, promoted HspG2 cell pyrolysis and increased intracellular ROS levels. Moreover, inhibition of the production of intracellular ROS with n-acetylcysteine (NAC) improved the degree of apoptosis and pyrolysis induced by curcumin. CONCLUSION: Curcumin induces HspG2 cell death by increasing apoptosis and pyroptosis, and ROS play a key role in this process. This study improves our understanding of the potential anti-cancer properties of curcumin in liver cancer.

Goodpasture syndrome and hemorrhage after renal biopsy: A case report.

BACKGROUND: Goodpasture syndrome (GS) is a rare disease, the morbidity of which is estimated to be 0.5-0.8 per million per year. Hemorrhage is the most serious complication in renal biopsy. Despite the fact that both GS and hemorrhage after renal biopsy are rare, it has not been reported that they are likely to occur in the same patient. CASE SUMMARY: A 30-year-old man with diffuse pulmonary hemorrhage and rapid progressive renal function caused by anti-glomerular basement membrane disease presented atypical symptoms without hemoptysis, accompanied by life-threatening hypoxemia. Plasmapheresis was performed, and glucocorticoids and cyclophosphamide were administered. The patient started to show signs of improvement. Percutaneous renal biopsy is an appropriate diagnostic measure that is commonly safe, but this patient experienced hemorrhage after operation, thus necessitating embolization of the renal artery to stop the bleeding. The patient's condition was improved, and the serum anti-glomerular basement membrane antibody level was 106 AU/mL (normal range: < 24 AU/mL) and slowly decreased. His discharge medications were oral daily prednisone (30 mg) and continued maintenance hemodialysis. CONCLUSION: GS is a rare organ-specific autoimmune disease that is invariably ubiquitous in the lung and kidney areas. Renal biopsy is the appropriate procedure for the treatment of GS disease, although it is an invasive measure.

Peroxiredoxin II Inhibits Alcohol-induced Apoptosis in L02 Hepatocytes Through AKT/ß-Catenin Signaling Pathway.

BACKGROUND: Peroxiredoxin II (PRDX2) performs unique roles in cells. It can reduce peroxides through cysteine residues, and helps prevent the effects of oxidative stress on cells. It is closely related to the occurrence and development of various diseases, especially alcoholic liver injury and even liver cancer. The metabolism of alcohol in hepatocytes leads to the increase in the levels of reactive oxygen species (ROS), oxidative stress, injury, and apoptosis. Therefore, this study focused on the investigating the protection conferred by PRDX2 against alcohol-induced apoptosis of hepatocytes. MATERIALS AND METHODS: PRDX2 inhibition of alcohol-induced apoptosis in L02 hepatocytes was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, fluorescence microscopy, flow cytometry, western blotting and hematoxylin and eosin staining. RESULTS: The results showed that the levels of reactive oxygen species, protein kinase B, ß-catenin, B-cell lymphoma-2 (BCL2), BCL-XL, BCL2-associated X, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase in PRDX2-silenced cells were increased significantly after the treatment of cells with ethanol. Similar results were obtained in an in vivo Prdx2-knockout mouse model of alcoholic liver injury. Therefore, PRDX2 may regulate the phosphorylation of the AKT signal protein by eliminating reactive oxygen species from cells, and it inhibits the downstream mitochondria-dependent apoptosis pathway, and, thereby, the apoptosis of cells. CONCLUSION: Thus, PRDX2 may be a potential molecular target for the prevention and treatment of alcoholic liver injury.

The compound 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras-mutated liver cancer cells.

The aim of the present study was to verify the pro-apoptotic anticancer potential of several 5,8-dimethoxy-1,4-phthoquinone (DMNQ) derivatives in Ras-mediated tumorigenesis. MTT assays were used to detect cellular viability and flow cytometry was performed to assess intracellular reactive oxygen species (ROS) levels and apoptosis. The expression levels of proteins were detected via western blotting. Among the 12 newly synthesized DMNQ derivatives, 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione (BZNQ; component #1) significantly reduced cell viability both in mouse NIH3T3 embryonic fibroblasts cells (NC) and H-RasG12V transfected mouse NIH3T3 embryonic fibroblasts cells (NR). Moreover, BZNQ resulted in increased cytotoxic sensitivity in Ras-mutant transfected cells. Furthermore, the reactive oxygen species (ROS) levels in H-RasG12V transfected HepG2 liver cancer cells (HR) were significantly higher compared with the levels in HepG2 liver cancer cells (HC) following BZNQ treatment, which further resulted in increased cellular apoptosis. Eliminating cellular ROS using an ROS scavenger N-acetyl-L-cysteine markedly reversed BZNQ-induced cellular ROS accumulation and cell apoptosis in HC and HR cells. Western blotting results revealed that BZNQ significantly downregulated H-Ras protein expression and inhibited the Ras-mediated downstream signaling pathways such as protein kinase B, extracellular signal-related kinase and glycogen synthase kinase phosphorylation and ß-catenin protein expression. These results indicated that the novel DMNQ derivative BZNQ may be a therapeutic drug for Ras-mediated liver tumorigenesis. The results of the current study suggest that BZNQ exerts its effect by downregulating H-Ras protein expression and Ras-mediated signaling pathways.

[Prevention of diltiazem in tacrolimus-induced nephrotoxicity: experiment with rats].

OBJECTIVE: To study the nephrotoxicity induced by first oral administration of tacrolimus (FK506) and the prevention of diltiazem (Dil). METHODS: 24 Sprague-Dawley male rats were randomly divided into 4 equal groups: control (n = 6), cyclosporine A (CsA) group (receiving CsA 25 mg.kg(-1).d(-1) so as to develop CsA-induced nephropathy model), FK506 group (receiving FK506 0.8 mg.kg(-1).d(-1), the common renal transplantation therapeutic dose, so as to develop FK506-induced nephropathy model), FK506 + Dil group (receiving CsA 0.8 mg.kg(-1).d(-1) and Dil 8 mg.kg(-1).d(-1)), and control group. Four weeks later body weight was measured, blood samples were collected to examine the creatinine, urea nitrogen, and uric acid, and urine samples were collected to examine the 24 h urine protein, uric acid, and creatinine. Then the rats were killed with their kidneys taken out to undergo histopathological examination. RESULTS: The urine creatinine levels of the CsA and FK506 groups were significantly lower than that of the control group (both P < 0.05), however, there was no significant difference in urine creatinine between the FK506 + Dil group and control group. The blood creatinine levels of both CsA and FK506 groups were significantly higher than those of the FK506 + Dil group and control group (all P < 0.05), however, there was no significant difference in blood creatinine between the FK506 + Dil group and control group. The urea nitrogen level of the CsA group was significantly higher than those of the other 3 groups (all P < 0.05). The creatinine clearance rates of the CsA and FK506 groups were both significantly lower than that of the control group (both P < 0.05), and the creatinine clearance rate of the FK506 + Dil group was between those of the FK506 group and control group, however, with significant differences with both of them. Histopathology examination showed cloudy swelling and vacuolization of the renal tubular epithelial cells in the CsA and FK506 groups. However, the pathological changes of the FK506 + Dil group were remarkably milder in comparison with these 2 groups. CONCLUSION: FK506 and CsA at the renal transplantation therapeutic dose induce nephrotoxicity. Diltiazem prevents FK506-induced nephrotoxicity.

Effect of parathyroid hormone on healing in osteoporotic fractures via a phospholipase C-independent pathway.

Objective This study was performed to investigate the effect of parathyroid hormone (PTH) on healing in osteoporotic fractures via a phospholipase C (PLC)-independent pathway and explore the mechanism of PTH-mediated bone formation. Methods Ninety-six 12-week-old C57BL/6J female mice underwent bilateral ovariectomy. One month later, the lower third of the femur was fractured and the mice were treated using saline, PTH(1-28), PTH(1-34), zoledronic acid (ZA), PTH(1-28)+ZA, and PTH(1-34)+ZA. The mice were killed at weeks 2 and 4 in each group. Biomechanical testing and micro-computed tomography were performed. Results The formation and strength of the callus increased in all but the saline group. The mice treated with PTH(1-34) showed a significantly higher ultimate bending force, bending rigidity, bone mineral density, percent bone volume, and trabecular thickness than those treated with PTH(1-28). The PTH(1-34)+ZA group demonstrated the greatest improvements in the ultimate bending force, bending rigidity, bone mineral density, and relative bone volume. Conclusions PTH can promote fracture healing and callus hardness in ovariectomized mice by increasing callus formation and reconstructing trabecular bone via a PLC-independent pathway. PTH combined with ZA has a cumulative effect on the healing of fractures in ovariectomized mice.

Finite element analysis of locking plate and 1/4 tubular plate for first tarsometatarsal joint fracture-dislocation.

Objective The optimal plate for fixation of tarsometatarsal joint injuries is controversial. The objective of this study was to compare the biomechanical characteristics between a locking plate and 1/4 tubular plate for first tarsometatarsal joint fracture-dislocation. Method Finite element analysis was used after establishment of a first tarsometatarsal joint fracture-dislocation model. Two implant simulations using a locking plate and five-hole 1/4 tubular plate were designed to simulate fixation of the fracture-dislocation. The displacement of the first tarsometatarsal articular surface and the stress distribution in the implants were calculated. Results A 700-N load was applied to both models. The minimum displacement of the articular surface in the locking plate and 1/4 tubular plate model was 0.6471 mm and 0.3833 mm, respectively. The maximum principal stress in the locking plate and 1/4 tubular plate was 1.212 × 103 MPa and 1.107 × 103 MPa, respectively. Conclusion Use of a 1/4 tubular plate is recommended for fixation of first tarsometatarsal joint fracture-dislocation after consideration of other factors such as economical issues.