Effect of sinapic acid against carbon tetrachloride-induced acute hepatic injury in rats

Acute hepatic inflammation is regarded as a hallmark of early stage fibrosis, which can progress to extensive fibrosis and cirrhosis. Sinapic acid is a phenylpropanoid compound that is abundant in cereals, nuts, oil seeds, and berries and has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the anti-inflammatory effect of sinapic acid in carbon tetrachloride (CCl₄)-induced acute hepatic injury in rats. Sinapic acid was administered orally (10 or 20 mg/kg) to rats at 30 min and 16 h before CCl₄ intoxication. Sinapic acid treatment of rats reduced CCl₄-induced abnormalities in liver histology, serum alanine transaminase and aspartate transaminase activities, and liver malondialdehyde levels. In addition, sinapic acid treatment significantly attenuated the CCl₄-induced production of inflammatory mediators, including tumor necrosis factor-alpha and interleukin-1β mRNA levels, and increased the expression of nuclear factor-kappa B (NF-κB p65). Sinapic acid exhibited strong free radical scavenging activity in vitro. Thus, sinapic acid protected the rat liver from CCl₄-induced inflammation, most likely by acting as a free radical scavenger and modulator of NF-κB p65 activation and proinflammatory cytokine expression. Sinapic acid may thus have potential as a therapeutic agent for suppressing hepatic inflammation.     

Celecoxib suppresses hepatoma stemness and progression by up-regulating PTEN

Celecoxib, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, can prevent several types of cancer, including hepatocellular carcinoma (HCC). Here we show that celecoxib suppressed the self-renewal and drug-pumping functions in HCC cells. Besides, celecoxib depleted CD44 + /CD133 + hepatic cancer stem cells (hCSC). Prostaglandin E2 (PGE2) and CD133 overexpression did not reverse the celecoxib-induced depletion of hCSC. Also, celecoxib inhibited progression of rat Novikoff hepatoma. Moreover, a 60-day celecoxib program increased the survival rate of rats with hepatoma. Histological analysis revealed that celecoxib therapy reduced the abundance of CD44 + /CD133 + hCSCs in hepatoma tissues. Besides, the hCSCs depletion was associated with elevated apoptosis and blunted proliferation and angiogenesis in hepatoma. Celecoxib therapy activated peroxisome proliferator-activated receptor γ (PPARγ) and up-regulated PTEN, thereby inhibiting Akt and disrupting hCSC expansion. PTEN gene delivery by adenovirus reduced CD44/CD133 expression in vitro and hepatoma formation in vivo. This study suggests that celecoxib suppresses cancer stemness and progression of HCC via activation of PPARγ/PTEN signaling.     

Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression

Hepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical outcome. Our previous work has shown that eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was identified to be an independent risk factor for poor disease-specific survival among HCC patients. Both in vitro and in vivo assays indicated that ablation of endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a main component of the vascular basement membrane (BM), we subsequently investigated the effect of EIF5A2 on tumor vasculature remodeling using complementary approaches, including fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken together, our results indicate that EIF5A2 silencing increases tumor vessel wall continuity, increases blood perfusion and improves tumor oxygenation. Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and JNK/c-Jun pathways. Conclusion: This study highlights an important role of EIF5A2 in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential therapeutic target in the treatment of HCC.     

Integrating psychiatry and primary care improves acceptability to mental health services among Chinese Americans

The objective of this study was to investigate whether integrating psychiatry and primary healthcare improves referral to and treatment acceptability of mental health services among Chinese Americans. The "Bridge Project," a program to enhance collaboration between primary care and mental health services for low-income Chinese immigrants was implemented at South Cove Community Health Center in Boston. The project consisted of conducting training seminars to primary care physicians to enhance recognition of common mental disorders, using a primary care nurse as the "bridge" to facilitate referrals to the Behavioral Health Department of the same facility, and co-locating a psychiatrist in the primary care clinic to provide onsite evaluation and treatment. The rate of mental health service referrals and successful treatment engagement before and during the project were compared. During the 12-month period of the Bridge Project, primary care physicians referred 64 (1.05% of all clinic patients) patients to mental health services, a 60% increase (chi(2)=4.97, P<.05) in the percentage of clinic patients referred in the previous 12 months. Eighty-eight percent of patients referred during the project showed up for psychiatric evaluation, compared to 53% (chi(2)=15.3, P<.001) in the previous 12 months. Integrating psychiatry and primary care is effective in improving access to mental health services and in increasing treatment engagement among low-income immigrant Chinese Americans.     

Contamination of ART culture Media–The role of semen and strategies for prevention

ObjectiveMicrobial contamination of ART culture media is rare but serious. We examined our own experience and conducted a review of the literature with a view to preventing its occurrence and recurrence.Case reportA total of 12 cases were recorded during January 2006 to March 2019. The contaminations were caused by semen and were shown to be bacteria that were resistant to the prophylactic antibiotics used in the medium. After the procedures were cancelled due to contaminations, nine husbands received antibiotic treatment, while nine couples changed over to the ICSI program. Eventually, eight couples concluded the study with live birth deliveries, and there was no recurrence of contamination.ConclusionART laboratories should preserve all sperm suspension samples until embryo transfer has been completed for the purpose of checking whether contamination has occurred. In addition to antibiotic treatment, implementation of the ICSI procedure during the next ART cycle has already been proven to be effective. In the future, the zona-removal technique may be considered as another potential option.