Experimental Model Research Articles

Further evaluation of the effectiveness and superiority of hyaluronic acid combined preparations (trehalose, dexpanthenol and coenzyme Q10 & vitamin E) in experimental alkali model.

Further evaluation of the effectiveness and superiority of hyaluronic acid combined preparations (trehalose, dexpanthenol and coenzyme Q10 & vitamin E) in experimental alkali model.

Use of agricultural waste for optimization of protease production by Pleurotus djamor and evaluation of its anthelmintic activity.

Use of agricultural waste for optimization of protease production by Pleurotus djamor and evaluation of its anthelmintic activity.

METTL3-mediated N6-methyladenosine modification contributes to vascular calcification.

METTL3-mediated N6-methyladenosine modification contributes to vascular calcification.

Targeting PARP-1 in ER-positive endocrine-resistant breast cancer.

1083 Background: Resistance to endocrine therapy (ET) in breast cancer (BC) patients is frequently associated with acquired ESR1 gene mutations like the Y537S, which triggers a constitutive estrogen receptor (ERα) activation. Therefore, the identification of novel therapeutic strategies is crucial for the management of ER-positive, ET-resistant BC. In this context, PARP1 poly(ADP-ribose) polymerase 1 (PARP-1) has emerged as a promising therapeutic target, based on its involvement in the regulation of oxidative DNA damage in BC cells. Methods: Data from the METABRIC dataset were used to assess the clinical relevance of PARP-1 in ER-positive BC patients. As experimental models, MCF7 and T47D BC cell lines expressing ERα wild type (wt) or Y537S mutation were used. PARP-1 regulation was investigated by western blotting, immunofluorescence, and chromatin immunoprecipitation (ChIP) assays. Gene expression, promoter assays, and chromatin immunoprecipitation sequencing (ChIP-seq) studies allowed us to analyze the transcriptional activity mediated by ERα. Cell cycle, proliferation and colony formation experiments as well as in vivo studies were performed to evaluate the biological effects of the PARP-1 inhibitor niraparib. Results: We observed that the up-regulation of PARP-1 upon exposure to 17β-estradiol (E 2 ) occurs through ERα in BC cells expressing either ERα wt or Y537S mutation. Moreover, we assessed that the transcriptional activity of ERα relies on PARP-1, as demonstrated by the ability of nirabarib to prevent the transactivation of ERα and the regulation of ERα target genes. In addition, niraparib halted the proliferation and cycle progression of BC cells expressing either ERα wt or Y537S mutation. Of note, niraparib suppressed primary tumor growth in xenograft tumors derived from ERα Y537S mutated MCF7 cells. Conclusions: Our data suggest that crosstalk between PARP-1 and ERα is involved in the proliferative responses of ERα wt or Y537S mutated BC cells. Therefore, targeting PARP-1 could provide a promising strategy to overcome the ET resistance of BC cells.

Piwei Peiyuan Prescription Attenuates the Progression of Chronic Atrophic Gastritis by Eliciting MAPK10-Mediated Mitochondrial Autophagy.

Piwei Peiyuan (PWPY) prescription is a traditional Chinese medicine prescription and has been efficiently used in the clinics to treat chronic atrophic gastritis (CAG) for many years. However, the mechanism of action underlying PWPY for treating CAG remains elusive. A CAG rat animal and cell model was constructed in this study to explore the action mechanism of PWPY prescription in treating CAG. Here we show that PWPY attenuates the progression of CAG by eliciting MAPK10-mediated mitochondrial autophagy. Experimental model of CAG was introduced using N-methyl-n'-nitro-n-nitroguanidine (MNNG). Our histological analyses reveal that MNNG-induced CAG in rat undergoes classical morphological alterations judged by immunohistochemistry and serum level of PGⅠ, PGⅡ, and G17. Importantly, PWPY treatment prevents the progression of MNNG-induced CAG judged by serum level of PGⅠ, PGⅡ, and G17. Interestingly, PWPY treatment inhibits MAPK10 activity judged by biochemical assays and promotes mitochondrial autophagy judged by electron microscopic analyses. Thus, we conclude that PWPY attenuates the progression of MNNG-induced CAG and prevents precancerous lesions by harnessing MAPK10-elicited mitochondrial autophagy. The MNNG-induced experimental CAG model provides a robust platform for further delineating therapeutic targets underlying PWPY regimen.

Betulinic acid protects against lipopolysaccharide and ferrous sulfate-induced oxidative stress, ferroptosis, apoptosis, and neuroinflammation signaling relevant to Parkinson's Disease.

Betulinic acid protects against lipopolysaccharide and ferrous sulfate-induced oxidative stress, ferroptosis, apoptosis, and neuroinflammation signaling relevant to Parkinson's Disease.

Lipidomics reveals different therapeutic potential for natural and synthetic vitamin D formulations in hepatocyte lipotoxicity.

Lipidomics reveals different therapeutic potential for natural and synthetic vitamin D formulations in hepatocyte lipotoxicity.

PHOTODYNAMIC THERAPY FOR PERI-IMPLANTITIS: COMPARATIVE ANALYSES ON IN VITRO MODELS

Chlorin e6 (Ce6) is a Food and Drug Administration-approved photosensitizer that is promising with its low cytotoxicity and effective generation of reactive oxygen species for PDT of bacterial infections. Although the eradication of bacteria by Ce6-mediated antibacterial photodynamic therapy (aPDT) was previously investigated, no previous study has systematically analyzed this treatment method using distinct experimental models in the context of peri-implantitis. This study aims to compare the effectiveness of Ce6-mediated antibacterial aPDT by comparing the outcomes with methylene blue (MB)-mediated protocol as a standard for aPDT in oral applications using two different experimental models. By evaluating these treatments across different conditions, this study intended to provide new insights into their relative efficacy. Additionally, this study investigated the differences in bacterial susceptibility between planktonic and surface-attached states, highlighting how attachment alone may influence treatment resistance. Planktonic Staphylococcus aureus (S. aureus) and S. aureus adhered to roughened titanium discs were treated with non-toxic concentrations of Ce6 and MB, followed by the irradiation using a 660 nm light source at 100 mW/cm2 power density. The treatment outcomes were evaluated using the serial dilution method. Ce6-mediated aPDT could achieve less than a log decrease in normalized colony forming unit (CFU) in planktonic bacteria, while the reduction in normalized CFU in MB-mediated protocol was about 4-log. In the titanium-adhered infection model, the reduction after both protocols was below 1-log, representing a relatively low bactericidal efficacy. In conclusion, Ce6-mediated aPDT is as efficient as the MB-mediated protocol on bacteria adhered to titanium discs. However, both protocols exhibited limited efficacy. These results emphasize the challenge of effectively targeting adhered bacterial populations and suggest the need for optimizing aPDT protocols.

Effective ocular delivery of antioxidant polyphenols using elastin-like polymer nanosystems developed by sustainable process.

Effective ocular delivery of antioxidant polyphenols using elastin-like polymer nanosystems developed by sustainable process.

Pharmacological Blockade of Group II Metabotropic Glutamate Receptors Reduces the Incidence of Brain Tumors Induced by Prenatal Exposure to N-ethyl-N-nitrosourea in Rats.

The study demonstrates that pharmacological blockade of type 3 metabotropic glutamate (mGlu3) receptors at the time of tumor induction significantly reduces the incidence of brain gliomas in rats. The overall survival of patients with high-grade brain gliomas is 14-20 months after current multimodal therapy, including surgery, radiotherapy, and adjuvant chemotherapy. To demonstrate in this experimental model that pharmacological blockade of group II metabotropic glutamate receptors reduces the incidence of brain tumors induced by prenatal exposure to N- ethyl-N-nitrosourea (ENU) in rats. Dams received a single injection of ENU (40 mg/kg, e.v.) at day 20 of pregnancy, combined with 5 daily injections of either saline or the mGlu2/3 receptor antagonist, LY341495 (10 mg/kg) (from day 15 to day 21 of pregnancy). Assessment of brain tumors in the offspring at 5 months of age showed the presence of mixed gliomas (astrocytomas/oligodendrogliomas) in 70% of the ENU + saline group of rats and only in 30% of the ENU + LY341495 group. Tumors in both groups of rats showed a moderate/high expression of the astrocyte marker, GFAP, and the oligodendrocyte marker, OLIG-2, and a low expression of the proliferation marker, Ki-67. However, tumors of the ENU + LY341495 group showed a reduced density of Iba-1+ cells, suggesting a lower extent of neuroinflammation in the tumor microenvironment. These findings strengthen the hypothesis that mGlu3 receptors are candidate drug targets for the treatment of malignant gliomas.

Cutting-edge technologies illuminate the neural landscape of cancer: Insights into tumor development.

Cutting-edge technologies illuminate the neural landscape of cancer: Insights into tumor development.

3'-epi-12β-hydroxyfroside induces autophagic degradation of ABCG2 to overcome drug resistance in lung cancer cells.

3'-epi-12β-hydroxyfroside induces autophagic degradation of ABCG2 to overcome drug resistance in lung cancer cells.

N-glycosylation signature and its relevance in cardiovascular immunometabolism.

N-glycosylation signature and its relevance in cardiovascular immunometabolism.

Effect of Tacrolimus on Development of Experimental Cholesteatoma.

Effect of Tacrolimus on Development of Experimental Cholesteatoma.

Bazi Bushen Capsule Modulates Akkermansia muciniphila and Spermidine Metabolism to Attenuate Brain Aging in SAMP8 Mice.

Bazi Bushen Capsule Modulates Akkermansia muciniphila and Spermidine Metabolism to Attenuate Brain Aging in SAMP8 Mice.

Establishing the electrophysiological feasibility of the rabbit median nerve as an experimental model for carpal tunnel syndrome.

Establishing the electrophysiological feasibility of the rabbit median nerve as an experimental model for carpal tunnel syndrome.

Differential assessment of effects of increasing model complexity in THM coupled models of the FE experiment at Mt. Terri

Differential assessment of effects of increasing model complexity in THM coupled models of the FE experiment at Mt. Terri

Monte Carlo simulation development and implementation of the GiBUU model for neutrino experiments

Monte Carlo simulation development and implementation of the GiBUU model for neutrino experiments

Experimental and kinetic modeling study of iso-dodecane: Pyrolysis and oxidation

Experimental and kinetic modeling study of iso-dodecane: Pyrolysis and oxidation

Removal of nickel ions from industrial wastewater using tms-EDTA-functionalized Ti3C2Tx: Experimental and statistical physics modeling.

Removal of nickel ions from industrial wastewater using tms-EDTA-functionalized Ti3C2Tx: Experimental and statistical physics modeling.