Experimental and molecular pathology最新文献

Introduction

Although wound refers to simple cut in the skin, most wounds don't heal because of the various local and systemic factors that lead to its complexity and chronicity. Thus, prior understanding of the status of the wound is necessary and methods that can differentiate between the healing and non-healing wounds at a much earlier stage is crucial for a successful treatment.

Methods

The current study aims at differentiating Acute Wound Fibroblasts (AWFs) and Chronic Wound Fibroblasts (CWFs) based on differential expression of fibroblast specific markers such as Vimentin and Alpha Smooth Muscle Actin (α-SMA) and compare its cell cycle and proliferation.

Results

Immunostaining and western blotting analysis showed that, AWFs and CWFs differentially expressed vimentin and α-SMA, with AWFs and CWFs showing higher expression of vimentin and α-SMA respectively. AWFs showed higher distributions in G0/G1 (67.43% vs. 62.16%), S phase (22.61% vs. 8.51%) compared to CWFs. However, AWFs showed decreased distributions compared to CWFs in G2 + M phase (8.14% vs. 10.6%). Thus, it was observed that CWFs showed cell cycle arrest in the G1/G0 phase and inhibited DNA synthesis, which was further confirmed by reduced proliferation of CWFs. We suggest that, differential expression of the cell specific markers can be attributed to its pathophysiological status and chronicity of the wound and reduced proliferation rate of CWFs is due to lesser expression of vimentin, which is a key protein for in vitro cell proliferation.

Conclusions

Outcome of the study serve as an immunological tool to guide the chronicity of the wound, which helps to understand the wound towards design of personalized care. The findings also represent a promising opportunity to gain insight into how cell cycle arrest can impact on wound healing and clinical outcomes.

Background

A growing number of genetic and cancer biology investigations have found that the tachykinin NK1 Receptor plays an important role in cancer cell proliferation and survival. In this study. The present study was designed to evaluate the inhibition of cell growth by 17-trifluoromethyl phenyl trinor prostaglandin F2α with NK1 receptor in breast cancer cell lines.

Materials and methods

MDB-MB-468 and MCF-7 breast cancer cell lines were used in the experiment were blocked with PGF2a. Cell proliferation and apoptosis were analyzed to evaluate the cytotoxic effect. Cell cycle distribution, Caspase-3 enzyme activity, Bad and Bax protein expression through flow cytometry and molecular docking were carried out to analyze the NK1 receptor activity.

Results

We found that PGF2a has a high binding affinity towards NK1 Receptor from molecular docking studies. It exerted cytotoxic and antiproliferative effects against MDB-MB-468 and MCF-7 breast cancer cell lines. Our data found that treatment of cells with 17-TPGF2 resulted in cell death and showed that increased expression of Caspase-3, Bad, and Bax protein and further induces G2 cell cycle arrest.

Conclusion

Overall this study investigates the NK1 receptor antagonistic effect of PGF2 against breast cancer cell lines. However, further studies are needed to better characterize the application of NK1 receptor inhibition in clinical cancer treatment and cytotoxicity effect.

Doxorubicin (Dox), a powerful chemotherapeutic agent, has been shown to cause cardiotoxicity and neurotoxicity. Ranolazine, a drug that is commonly used to treat patients with chronic angina, has been shown to reduce toxicity from Dox therapy. Therefore, the present study aims to investigate the mechanisms behind the protective effects of ranolazine on the heart and brain in Dox-treatment. Twenty-four male Wistar rats received 6 doses of either 0.9% normal saline (0.9% NSS, i.p., n = 8) or Dox (3 mg/kg, i.p., n = 16). All Dox-treated rats were assigned into 2 groups to receive vehicle (0.9% NSS, orally; n = 8) or ranolazine (305 mg/kg/day, orally; n = 8) for 30 consecutive days. Following the treatments, left ventricular (LV) function and cognition were determined. Animals were euthanized, then the heart and brain were collected for further analysis. Dox induced systemic oxidative stress/inflammation, and cardiac injury evidenced by mitochondrial dysfunction, mitochondrial dynamic imbalance, and apoptosis, resulting in LV dysfunction. Ranolazine significantly improved LV function via attenuating cardiac injury. Dox also caused brain pathologies as indicated by increased brain inflammation, impaired blood-brain barrier integrity, brain mitochondrial dysfunction, microglial dysmorphology, hippocampal dysplasticity, and increased apoptosis, resulting in cognitive decline. Ranolazine exerted neuroprotective effects by suppressing brain pathologies and restoring cognitive function. These findings suggest that ranolazine has a potential role in cardio- and neuro-protection against chemotherapy.

The human body consists of countless cells with the possibility of excessive and uncontrolled proliferation under certain dysregulated circumstances that could cause abnormal states such as cancer. Phosphatidylinositol 3 kinase (PI3K) and its downstream target, Protein kinase B or AKT, play a critical role in cell survival, proliferation, differentiation, migration, and metabolism. Research studies have examined the aberrant expression of signaling molecules that regulate PI3K/AKT pathway with the purpose of target discovery. The present review aims to recapitulate the relationship between the PI3K/AKT signaling pathway and factors contributing to initiation and development of various cancers. In addition, therapeutic interventions regulating this signaling pathway have been summarized.