Caveolin-1 plays an important role in prostatic carcinogenesis and metastasis. Stromal expression of caveolin-1 in PCa is lowered in relation to BPH and HGPIN. In PCa; stromal caveolin-1 was associated with good prognostic parameters. Epithelial caveolin-1 is significantly increased in PCa than BPH and HGPIN. It is associated with clinically aggressive disease. Caveolin-1 may play a role in angiogenesis.
Background: Worldwide growing rates of obesity are correlated with the rising prevalence of nonalcoholic fatty liver disease (NAFLD) with limited available therapeutics. Aim: The present study was undertaken to investigate the modulatory effects of dietary supplementation fisetin on hepatocyte nuclear factor 4 α (HNF4α) gene expression, hepatic lipin-1 signaling, thioredoxin-interacting protein (TXNIP) levels, poly-(ADP-ribose)-polymerase-1 (PARP-1) activity, as well as some oxidative stress parameters in a rat model of high-fat/high-sucrose (HFHS) induced NAFLD.Methods: Sixty male albino rats were allocated into four equal groups: normal control group, fisetin-treated control group, NAFLD group, and fisetin-treated NAFLD group. Gene expression levels of HNF4-α were estimated using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), while Lipin-1, TXNIP levels, and PARP-1 activity were estimated by enzyme-linked immunosorbent assay (ELISA); lipid profile, hepatic lipid contents, hepatic lipoperoxides, fatty acid synthase activity, and total antioxidant capacity were also assessed colorimetrically.Results: Fisetin ameliorated HFHS-induced NAFLD; where it suppressed hepatic lipid accumulation, upregulated HNF4-α /lipin-1 signaling, mitigated oxidative stress, inhibited reactive oxygen species (ROS)-mediated TXNIP induction, and PARP-1 activation. In conclusion, fisetin could confer protection against NAFLD and impede its progression. However,additional experimental scrutiny is needed to verify these findings.
K E Y W O R D Sfisetin, hepatocyte nuclear factor 4 α, lipin-1, nonalcoholic fatty liver disease, poly-(ADP-ribose)polymerase-1, thioredoxin-interacting protein
Head and neck squamous cell carcinoma is diagnosed at late stages. The prevalence of metastatic lesions directly correlates with poor patient outcome. The progression to metastatic disease requires changes in the tumor microenvironment. Within the microenvironment, infiltrating immune cells facilitate the spread of tumor cells. Tumor-infiltrating lymphocytes play an important role in the response of tumors to therapy. Tumor-associated macrophages are the main cellular component in stroma of many tumors. The goal of cancer treatment is to abolish cell proliferation and to induce aptoptosis. Apoptosis is a key mechanism of tumor cell elimination. The Bcl2 protein itself is a product of a proto-oncogene and has an antiapoptotic action. The study used immunohistochemical staining of CD68, CD3, Bcl2 to measure macrophages, lymphocytes and evaluate apoptosis in 25 included cases; 5 cases of non specific dermatitis, 5 normal skin and 15 head and neck squamous cell carcinoma (HNSCC) graded into 5 well, 5 moderately and 5 poorly differentiated. CD68+ve macrophages were significantly higher in moderately differentiated HNSCC than well differentiated tumors. Poorly differentiated showed significantly lower CD68+ve macrophages than moderately differentiated tumors. CD3 +ve lymphocytes were significantly higher in well differentiated followed by moderate and poorly differentiated. CD3+ve lymphocytes were significantly higher in cases of dermatitis than HNSCC cases. Poorly differentiated SCC showed higher Bcl2 positivity followed by moderately differentiated. Well differentiated SCC showed the least Bcl2 positivity. This difference was significant. Our results showed tumor infiltrating macrophage and lymphocyte can predict the progression and prognosis of HNSCCs and the involvement of Bcl2 in HNSCC tumorigenesis.
Maspin (Mammary serine protease inhibitor) is a tumor suppressor serine. Its clinical significance and role in breast carcinoma are contradictory and inconclusive. Researches demonstrated that the function of maspin differs according to its subcellular localization. This study was conducted to investigate the expression of maspin in invasive ductal carcinoma (IDC) of the breast with special emphasis on its subcellular localization and to evaluate its prognostic role in relation to clinicopathological parameters and microvessel density (MVD) of the tumor. The expression of maspin was evaluated immunohistochemically in 45 IDC cases. The positive rate of maspin expression was 73.3%. Maspin positivity was significantly related to higher tumor grade (p value = 0.041), nodal metastasis (p value = 0.044), perineural invasion (p value = 0.047), and high CD34+MVD (p value = 0.002). Nuclear maspin was detected in 36.6% whereas cytoplasmic maspin was detected in 63.4% of maspin positive cases. A significant inverse relationship was observed between nuclear maspin and high tumor grade (p value = 0.016), and nodal metastasis (p value = 0.047). These results suggest that maspin expression has a prognostic role in breast cancer. Maspin expression is related to increased angiogenesis. Subcellular localization of maspin can strongly affect cancer prognosis. Cytoplasmic maspin relates to poor prognostic parameters whereas nuclear maspin relates to good prognostic ones.
This study aimed to investigate the protective effects of berberine (BBR) against D-galactose (D-gal)-induced renal aging in rats, pointing to its ability to modulate phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt signalling, and to attenuate oxidative stress, inflammation and apoptosis. Renal aging was induced by subcutaneous injection of D-gal for six consecutive weeks along with simultaneous oral administration of BBR and compared to control rats and rats received individual doses of either drug. BBR treatment significantly reduced the serum levels of urea and creatinine, retrieved the alterations in kidney histopathology, and restored redox balance evidenced by alleviations of the level of malondialdehyde, 8-hydroxy-2'-deoxyguanosine and activating heme oxygenase-1 enzyme. Moreover, it markedly reduced the serum levels of pro-inflammatory mediators, along with down-regulation of PTEN expression, enhanced Akt activity, as well as significantly higher immunostaining of the anti-apoptotic marker (Bcl-2). These findings hold a great promise for the use of BBR as a protecting agent against renal aging.
The aim of this study was to investigate the protective effect of montelukast (MTK) against prednisolone‐induced hepatic injury in rats. Twenty‐eight male albino rats were categorized into four equal groups. Group I served as the control group; group II: rats orally received prednisolone (5 mg·kg−1·d−1) for 30 days; groups III and IV: rats orally received MTK at 10 and 20 mg·kg−1·d−1, respectively, simultaneously with prednisolone for 30 days. Serum liver enzymes, hepatic mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic markers were evaluated, and the results were confirmed by histopathological examination. MTK showed significant hepatic protection evidenced by alleviated histological lesion and improvement of mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic changes induced by prednisolone, with more profound protection in higher MTK dose (20 mg·kg−1). In view of these findings, we can conclude that MTK may have hepatoprotective potential, beyond its therapeutic value for asthmatic patients during their course of corticosteroid therapy.
Currently, there are no curative treatment options for mycosis fungoides (MF) and Sézary syndrome (SS) other than stem cell transplant. Understanding the interplay between tumor cells and tumor microenvironment could aid in the development of new therapies. Tumor-associated macrophages (TAMs) mostly have M2 phenotype that promotes tumor progression. This study investigated CD68+ and CD163+ TAMs as well as CD163/CD68 ratio in skin lesions from different stages of MF, large-plaque parapsoriasis, and SS. Moreover, we analyzed serum levels of sCD163 and CCL22 in correlation with TAMs count and CD163/CD68 ratio. CD68+ and CD163+ TAMs count significantly increased as the disease progressed. CD163/ CD68 ratio was highest at MF tumor stage and SS indicating M2 polarization with disease progression. Significant positive correlations were detected between serum levels of sCD163 and CCL22 and CD68+ and CD163+ TAMs count and CD163/ CD68 ratio. We concluded that TAMs play an important role in MF progression. High CD163/CD68 ratio in tumor stage MF and SS indicates M2 polarization of TAMs with tumor progression. CD163/CD68 ratio should be considered in assessing TAMs rather than total TAMs count. Also, sCD163 and CCL22 serum levels reflect M2 load and thus could be used as markers to assess disease progression.
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