The potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[alpha]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs

Wild Panax ginseng C.A. Meyer (WG) is a well-known medicinal herb. In this study, the protective effects of a water extract from the root of WG on benzo[alpha]pyrene (BP)-induced hepatotoxicity and the mechanism of these effects were investigated for the first time. The effects of WG on liver toxicities induced by BP were assessed by blood biochemical and histopathological analyses. BP caused severe liver injury in rats, as indicated by elevated plasma ALT, AST and LPO levels. Pretreatment with WG for 4 weeks completely abrogated increases in the ALT, AST and LPO levels when challenged with BP. Reductions in GSH content and GST activity by BP were reversed by WG. These protective effects of WG against BP-induced toxicity were consistent with the results of histopathological examinations. We next examined the effects of WG on the gene expression of the enzymes that metabolize BP in H4IIE cells. CYP1A1 mRNA and protein expression were increased by BP. WG moderately inhibited BP-induced CYP1A1 gene expression. Moreover, GSTA2, GSTA3 and GSTM2 gene expressions were significantly increased by WG through the Nrf2/antioxidant responsive element pathway for enzyme induction. In summary, WG is efficacious in protecting against BP-induced hepatotoxicity as results of metabolic regulations through both the inhibition of metabolic enzyme activation and the enhancement of electrophilic detoxification, implying that WG should be considered a potential chemopreventive agent

In vitro and in vivo Induction of p53-Dependent Apoptosis by Extract of Euryale ferox Salisb in A549 Human Caucasian Lung Carcinoma Cancer Cells Is Mediated Through Akt Signaling Pathway

Lung cancer is one of the leading causes of death, and mortality rates have steadily been increasing. Recently, several studies were conducted to develop novel, physiologically active compounds from medicinal plant extracts. Several plant-derived extracts and molecules regulate and inhibit signaling molecules associated with the growth and proliferation of cancer cells. Euryale ferox salisb is a medicinal plant that is effective against different types of cancers. In this study, we investigated the apoptotic effects of E. ferox salisb extract (ESE) in A549 lung cancer cells, exerted by the inhibition of the Akt protein and activation of the p53 protein. Our results show that ESE induces apoptosis via the regulation of mitochondrial outer membrane potential and generation of reactive oxygen species (ROS). We demonstrate that apoptosis is induced in a p53-dependent manner when cells are treated with pifithrin-α (a p53 inhibitor) and LY294002 (an Akt inhibitor). The apoptotic effects from ESE were observed in vivo in Balb/c-nu mice bearing A549 xenografts. Altogether, these results suggest that E. ferox salisb extracts exert anti-cancer effects in a p53-dependent manner

Chemical Modification of the Human Ether-a-go-go-related gene(HERG) K* Current by the Amino-Group Reagent Trinitrobenzene Sulfonic Acid

We investigated the effects of trinitrobenzene sulfonic acid (TNBS), an amino-group reagent, on the humanether-a-go-go-related gene (HERG) K+ channels expressed inXenopus oocytes. TNBS neutralizes the positively charged amino-agroups of peptideN-terminal and lysine residues. External application of TNBS at 10 mM for 5 min irreversibly shifted the curves for currents at the end of the pulse and tail currents of HERG to a more negative potential and decreased the maximal amplitude of the Itail curve (Itail, max). TNBS had little effect on either the activated current-voltage relationship or the reversal potential of HERG current, indicating that TNBS did not change ion selectivity properties. TNBS shifted the time constant curves of both activation and deactivation of the HERG current to a more hyperpolarized potential; TNBS's effect was greater on channel opening than channel closing. External H+ is known to inhibit HERG current by shifting V1/2 to the right and decreasing Itail, max. TNBS enhanced the blockade of external H+ by exaggerating the effect of H+ on Itail, max, not on V1/2. Our data provide evidence for the presence of essential amino-groups that are associated with the normal functioning of the HERG channel and evidence that these groups modify the blocking effect of external H+ on the current.We are grateful to Dr. Jokubas Ziburkus for reading and editing this manuscript and to Hee-Kyung Hong for technical support. Ji-Hyun Yun was the recipient of the BK21 fellowship for graduate students in 2006. This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (R04- 2003-000-10007-0)

IL-10 Mediates Rosiglitazone-Induced Kidney Protection in Cisplatin Nephrotoxicity

Cisplatin, a major anti-neoplastic drug, is known to be nephrotoxic and inflammation-inducing. A peroxisome proliferator-activated receptor gamma agonist, regulating lipid metabolism, has known to have anti-inflammatory effect, but the protection mechanisms in various kidney injuries are not fully understood. The purpose of this study was to examine the reno-protective effect of rosiglitazone on cisplatin nephrotoxicity in mice focusing on inflammation and apoptosis. Male BALB/c mice were pretreated with rosiglitazone (10 mg/kg) or vehicle through daily intraperitoneal injection for 3 days and then were given a single injection of cisplatin (20 mg/kg). Cisplatin induced a significant rise in blood urea nitrogen and creatinine levels, and tubular cell damage with marked tissue inflammation. Tissue cytokines and chemokines measured by a cytometric bead array showed increased TNF-α, IL-6, MCP-1, and IFN-γ levels, while IL-10, an anti-inflammatory cytokine, was significantly decreased by cisplatin treatment. However, rosiglitazone pretreatment substantially reversed the depressed IL-10 level with simultaneous suppression of proinflammatory cytokines and chemokines. This tissue cytokine and chemokine milieu was associated with marked attenuation of kidney injury elicited by cisplatin. These findings suggest that the rosiglitazone-mediated renoprotective effect in cisplatin nephrotoxicity of mice is partially mediated by upregulation of anti-inflammatory IL-10 production

Sacropelvic Fixation for Adult Deformity Surgery Comparing Iliac Screw and Sacral 2 Alar-Iliac Screw Fixation: Systematic Review and Updated Meta-Analysis

Objective Two commonly used techniques for spinopelvic fixation in adult deformity surgery are iliac screw (IS) and sacral 2 alar-iliac screw (S2AI) fixations. In this article, we systematically meta-analyzed the complications of sacropelvic fixation for adult deformity surgery comparing IS and S2AI. Methods The PubMed, Embase, Web of Science, and Cochrane clinical trial databases were systematically searched until March 29, 2023. The proportion of postoperative complications, including implant failure, revision, screw prominence, and wound complications after sacropelvic fixation, were pooled with a random-effects model. Subgroup analyses for the method of sacropelvic fixation were conducted. Results Ten studies with a total of 1,931 patients (IS, 925 patients; S2AI, 1,006 patients) were included. The pooled proportion of implant failure was not statistically different between the IS and S2AI groups (21.9% and 18.9%, respectively) (p = 0.59). However, revision was higher in the IS group (21.0%) than that in the S2AI group (8.5%) (p = 0.02). Additionally, screw prominence was higher in the IS group (9.6%) than that in the S2AI group (0.0%) (p < 0.01), and wound complication was also higher in the IS group (31.7%) than that in the S2AI group (3.9%) (p < 0.01). Conclusion IS and S2AI fixations showed that both techniques had similar outcomes in terms of implant failure. However, S2AI was revealed to have better outcomes than IS in terms of revision, screw prominence, and wound complications

Hemophagocytic Syndrome in a Patient with Acute Tubulointerstitial Nephritis Secondary to Hepatitis A Virus Infection

Hepatitis A virus (HAV) infection is generally a self-limited disease, but the infection in adults can be serious, to be often complicated by acute kidney injury (AKI) and rarely by virus-associated hemophagocytic syndrome (VAHS). Our patient, a 48-yr-old man, was diagnosed with HAV infection complicated by dialysis-dependent AKI. His kidney biopsy showed acute tubulointerstitial nephritis with massive infiltration of activated macrophages and T cells, and he progressively demonstrated features of VAHS. With hemodialysis and steroid treatment, he was successfully recovered

Saussurea lappa clarkeDerived costunolide prevents TNF alpha induced breast cancer cell migration and invasion by inhibiting NF-

Saussurea lappa Clarke (SLC) has been used as a traditional medicine in Korea, China, and Japan for the treatment of abdominal pain and tenesmus. Costunolide, a sesquiterpene lactone isolated from SLC, has diverse medicinal effects. However, the anticancer effects of costunolide are still unclear in breast cancer. In this study, we demonstrate that costunolide suppresses tumor growth and metastases of MDA-MB-231 highly metastatic human breast cancer cells via inhibiting TNF -induced NF-B activation. Costunolide inhibited MDA-MB-231 tumor growth and metastases without affecting body weights in the in vivo mouse orthotopic tumor growth assays. In addition, costunolide inhibited in vitro TNF -induced invasion and migration of MDA-MB-231 cells. Costunolide further suppressed TNF -induced NF-B signaling activation, resulting in a reduced expression of MMP-9, a wellknown NF-B-dependent gene to mediate breast cancer cell growth and metastases. Therefore, we conclude that SLC and its derivative costunolide suppress breast cancer growth and metastases by inhibiting TNF -induced NF-B activation, suggesting that costunolide as well as SLC may be promising anticancer drugs, especially for metastatic breast cancer