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The phytochemical investigation on the n-BuOH fraction of the Cinnamomum camphora extract led to the isolation and identification of 37 secondary metabolites. Among them, compound 1, named as camphodiol A, was a new phenylpropanoid glycoside, while compounds 2 - 10 , 12 , 13 , 16–25 , 27 , and 29 - 37 were firstly isolated from this plant. The isolates were evaluated for their α -glucosidase inhibitory activities, and compounds 9 , 12 - 25 , 27 and 29 showed potent activities with IC 50 values ranging from 0.26 to 113.87 μM. The molecular docking analysis indicated that compound 22 could bind within the active pocket of the α -glucosidase through the hydrogen bonding and π-π interaction. These results demonstrated that the utilization of C. camphora leaves may have potential beneficial effects for the treatment of diabetes mellitus. [Display omitted] • Chemical investigation on the leaves of C. camphora was performed. • A new phenylpropanoid glycoside, camphodiol A (1), was isolated and identified. • Compounds 9 , 12 - 25 , 27 , and 29 showed potent α -glucosidase inhibitory activities. • Compound 22 could bind within the active pocket of the α -glucosidase. [ABSTRACT FROM AUTHOR]

Food spoilage leads to the annual huge wastage of food. There is a pressing need for safe, multifunctional food preservation packaging to curb this wastage and prevent contamination. In this study, we present a novel, cross-linked P-GL hydrogel film with a smooth surface microstructure, derived from polyvinyl alcohol (PVA), gallic acid (GA), and lysozyme (L). This hydrogel film serves as an exceptional packaging material for food preservation, displaying an ability to completely block UV light and efficiently impede the penetration of water vapor and O 2. Remarkably, the P-GL hydrogel film exhibits a fracture strength of approximately 37.9 MPa, demonstrating superior water solubility, thermal stability, and mechanical properties. Also, this P-GL hydrogel film can effectively eliminate E. coli and S. aureus. The P-GL hydrogel film has proven to be successful in mitigating the spoilage of blueberries through coating and covering treatments, outperforming commercial plastic wrap. As a result, the shelf life of blueberries can be extended to 20 days. Our work provides innovative insights that could potentially drive the use of safe and multifunctional hydrogel films in the food preservation packaging industry. [Display omitted] • A cross-linked P-GL hydrogel film was successful designed by polyvinyl alcohol (PVA), gallic acid (GA), and lysozyme (L). • The P-GL hydrogel film possess safe and multifunctional properties, exemplified by its impressive fracture strength of 37.9 MPa. • The multifunctional P-GL hydrogel film could mitigate the spoilage of blueberries and extend the shelf life of blueberries to 20 days, outperforming commercial plastic wrap. [ABSTRACT FROM AUTHOR]

Abstract: A series of 3-alkoxy(phenyl)thiophosphorylamido-2-(per-O-acetylglycosyl-1′-imino)thiazolidine-4-one derivatives were prepared by the reaction of 1-alkoxy(phenyl)thiophosphoryl-4-(per-O-acetylglycosyl) thiosemicarbazides with ethyl bromoacetate. 1H/13C HMBC measurements corroborated by X-ray crystallographic results revealed the exclusive regioselectivity of these ring closures toward the N-2 position of the thiosemicarbazide moiety. The bioactivity data of 3a–k suggest that the thiazolidine-4-one ring is critical for the herbicidal and fungicidal activities. [Copyright &y& Elsevier]

Abstract: To develop novel biologically active organic compounds possessing a sugar moiety, a series of 2-phenylsulfonylhydrazono-3-(2′,3′,4′,6′-tetra-O-acetyl-β-d-glucopyranosyl)thiazolidine-4-one were synthesized via reaction of the thiosemicarbazide with ethyl bromoacetate. Their chemical structures were characterized by 1H and 13C NMR spectroscopy, elemental analysis and MS. The bioassay results indicated that some of these compound exhibit moderate fungicidal and herbicidal activities. Furthermore, the effect of various solvents at reflux temperature on the reactions of ethyl bromoacetate with the related thiosemicarbazides was investigated. [Copyright &y& Elsevier]

Abstract: A series of TEMPO (2,2′,6,6′-tetramethylpiperidinyl-1-oxy) derivatives were studied as mediators of laccase (from Trametes versicolor) in the oxidation of benzyl alcohol and 1-phenylethyl alcohol. TEMPO (1), 4-hydroxy-TEMPO (2) and 4-acetylamino-TEMPO (4) turned out to be the most active mediators for laccase. In addition, 4-acetylamino-TEMPO and 4-hydroxy-TEMPO were more active in the oxidation of 1-phenylethanol compared to TEMPO. For these mediators kinetic isotope effects in the range of 2.1–3.2 were observed for α-monodeutero-p-methylbenzyl alcohol oxidation. These values are consistent with a mechanism involving oxoammonium intermediacy. Competition experiments between benzyl alcohol and 1-phenylethanol showed that TEMPO and its derivatives react faster with primary alcohols than with secondary alcohols, also in line with the proposed mechanism. [Copyright &y& Elsevier]

Investigations into the separate reactions of a dynamic kinetic resolution and the combined reactions revealed that the overall sequence is highly susceptible to the water content of the reaction mixture. While the racemization and formation of mandelonitrile as well as its kinetic resolution proceeded rapidly when performed independently, the dynamic kinetic resolution was severely hampered by the undesired formation of acetic acid during the reaction. The utilization of drying reagents and neutralizing agents in order to suppress the formation of acetic acid or its consequences were investigated. [Copyright &y& Elsevier]

Three new ruthenium-based catalytic systems are described which are capable of catalyzing the racemization of chiral secondary alcohols. In addition, one of these systems, [TosN(CH2)2NH2]RuCl(p-cymene)/TEMPO, was able to catalyze the in situ racemization during enzymatic resolution, i.e. dynamic kinetic resolution. [Copyright &y& Elsevier]

Graphical abstract Highlights • Novel anthranilic diamides derivatives Ia-k were designed and synthesized. • LC 50 value of If against diamondback moth was 0.0046 mg L−1, better than that of the commercial chlorantraniliprole. • Sulfone group in the title compounds played an important role in the insecticidal activity. • Ryanodine receptor (RyR) is the potential biochemical target of these novel title compounds. Abstract Anthranilic diamide insecticide could control lepidopteran pests by selectively binding and activating insect ryanodine receptors (RyRs), and the unique mode of action is different from other conventional insecticides. In order to discover new anthranilic diamide insecticide as ryanodine receptors activators, a series of 11 novel anthranilic diamides derivatives (Ia-k) were synthesized and confirmed by melting point, 1H NMR, 13C NMR and elemental analyses. The preliminary bioactivity revealed that most title compounds showed moderate to remarkable activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). Especially, compounds Ia and If , which exhibited 100% larvicidal activity against oriental armyworm at 1.0 mg L−1, and comparable to that of chlorantraniliprole (100% at 1 mg L−1). If displayed 60% insecticidal activity against diamondback moth at 0.01 mg L−1, better than chlorantraniliprole (45% at 0.01 mg L−1). The preliminary structure activity relationships were discussed. In addition, the calcium imaging experiment indicated that the insect ryanodine receptor is the potential target of If. [ABSTRACT FROM AUTHOR]

A series of novel anthranilic diamides derivatives ( 7a–s ) containing halogen, trifluoromethyl group and cyano group were designed, synthesized, and characterized by melting point, 1 H NMR, 13 C NMR and elemental analyses. The bioactivity revealed that most of them showed moderate to excellent activities against oriental armyworm ( Mythimna separata ) and diamondback moth ( Plutella xylostella ). Above all, the larvicidal activity of 7o against oriental armyworm was 100% and 40% at 0.25 and 0.1 mg L −1 , comparable to that of the standard chlorantraniliprole (100%, 0.25 mg L −1 and 20%, 0.1 mg L −1 ). What is more, 7o against diamondback moth displayed 90% insecticidal activity at 0.01 mg L −1 , superior to chlorantraniliprole (45%, 0.01 mg L −1 ). The experiments 7o on the American cockroach (Periplaneta Americana) heart beating rates (Dorsal vessel) and contractile force were compared with chlorantraniliprole. In addition, 7o could affect the calcium homeostasis in the central neurons of the third larvae of oriental armyworm, which revealed that the ryanodine receptor is the potential target of 7o . The density functional theory (DFT) calculation results revealed the amide bridge, the benzene ring of anthraniloyl moiety and pyrazole ring might play an important role in the insecticidal activity through hydrophobic interactions and π-π conjugations. [ABSTRACT FROM AUTHOR]

Ethno-pharmacological relevance Paridis Rhizoma is a Chinese medicinal herb that has been used in liver disease treatment for thousands of years. Our previous studies found that Paridis Rhizoma saponins (PRS) are the critical components of Paridis Rhizoma which has good liver protection effect. However, the anti-hepatic fibrosis effect and the mechanism of PRS have seldom been reported. Aim of the study To investigate the potential of PRS in the treatment of experimental liver fibrosis and the underlying mechanism. Materials and methods The chemical feature fingerprint of PRS was analyzed by UPLC-PDA. A total of 40 Male Sprague–Dawley (SD) rats were randomly divided into the control group, the model group, the PRS high dose group (PRS H) and the PRS low dose group (PRS L) with 10 rats in each group. The model, PRS H and L groups as liver fibrosis models were established with carbon tetrachloride (CCl 4 ) method. PRS H and L groups were adopted PRS (300 and 150 mg/kg d −1 ) treatment since the twelfth week of modeling till the sixteenth week. Pathological changes in hepatic tissue were examined using hematoxylin and eosin (H&E) and MASSON trichrome staining. Immunohistochemical analysis was performed to determine the protein expression of the RASAL1. RT-PCR and western blotting were used to detect the expression of ERK1/2 mRNA and protein. Results Four saponins in PRS were identified from 19 detected chromatographic peaks on UPLC-PDA by comparing to the standard compounds. PRS can improve the degeneration and necrosis of hepatic tissue, reduce the extent of its fibrous hyperplasia according to H&E and MASSON staining detection. As was detected in PRS H and L groups, PRS down-regulated p-ERK1/2 mRNA and RASAL1 protein, and up-regulated the level of p-ERK1/2 mRNA and RASAL1 protein. Conclusion These results demonstrated that PRS can attenuate CCl 4 -induced liver fibrosis through the regulation of RAS/ERK1/2 signal pathway. [ABSTRACT FROM AUTHOR]

Previous studies have shown that testes-specific protease 50 (TSP50), a pro-oncogene overexpressed in many types of tumors, could promote cell proliferation, invasion, tumorigenesis, and tumor metastasis, suggesting that it is a potential cancer therapeutic target in drug discovery. Here, a luciferase assay system driven by the TSP50 gene promoter was used to screen the inhibitor of expression of TSP50. The study found that cardamonin, a flavone compound, could efficiently inhibit the expression of TSP50 in both mRNA and protein levels. Further results revealed that cardamonin also efficiently inhibited the viability of TSP50 high-expressing cancer cells by inducing G2/M-phase arrest and mitochondrial-dependent apoptosis. Surprisingly, knocking down the expression of TSP50 gene had the same effects as treatment with cardamonin. Moreover, it has been found that cardamonin had an inhibitory potency on TSP50 high-expressing tumor growth in vivo. In contrast, overexpression of TSP50 greatly decreased the cell sensitivity to the inhibitory effect of cardamonin and reversed the decreased tumor-inhibitory effect of cardamonin. Additionally, both TSP50 interference and treatment with cardamonin could suppress p65 nuclear translocation, and overexpression of TSP50 reversed the suppressive effect of cardamonin on p65 nuclear translocation. Taken together, these results suggest that cardamonin inhibited cell viability and tumorigenesis at least partially via blocking the activation of TSP50-mediated nuclear factor-kappaB signaling pathway, and cardamonin may be a promising anticancer drug candidate in the development of a novel agent for TSP50 high-expressing cancer cells. [ABSTRACT FROM AUTHOR]

Psoriasis is a multifactorial skin disease that inconveniences many patients. Considering the side effects and drug resistance of the current therapy, it is urgent to discover more effective and safer anti-psoriatic drugs. In the present study, we screened over 250 traditional Chinese medicine compounds for their ability to inhibit the cell viability of cultured human HaCaT keratinocytes, a psoriasis-relevant in vitro model, and found that periplogenin was highly effective. Mechanistic studies revealed that apoptosis and autophagy were not induced by periplogenin in HaCaT cells. However, periplogenin caused PI to permeate into cells, increased lactate LDH release and rapidly increased the number of necrotic cells. Additionally, the typical characteristics of necrosis were observed in the periplogenin-treated HaCaT cells. Notably, the necroptosis inhibitor Nec-1 and NSA were able to rescue the cells from necrotic cell death, supporting that necroptosis was involved in periplogenin-induced cell death. Furthermore, the ROS levels were elevated in the periplogenin-treated cells, NAC (an antioxidant) and Nec-1 could inhibit the ROS levels, and NAC could attenuate necroptotic cell death, indicating that the periplogenin-induced necroptotic cell death was mediated by oxidative stress. More importantly, in the murine models of TPA-induced epidermal hyperplasia and IMQ-induced skin inflammation, topical administration of periplogenin ameliorated skin lesions and inflammation. In sum, our results indicate, for the first time, that periplogenin is a naturally occurring compound with potent anti-psoriatic effects in vitro and in vivo , making it a promising candidate for future drug research. [ABSTRACT FROM AUTHOR]

Testes-specific protease 50 (TSP50) is a novelly identified pro-oncogene and it shares a similar enzymatic structure with many serine proteases. Our previous results suggested that TSP50 could promote tumorigenesis through degradation of IκBα protein and activating NF-κB signaling, and the threonine mutation in its catalytic triad could depress TSP50-mediated cell proliferation. However, whether the two other residues in the catalytic triad of TSP50 play a role in maintaining protease activity and tumorigenesis, and the mechanisms involved in this process remain unclear. Here, we constructed and characterized three catalytic triad mutants of TSP50 and found that all the mutants could significantly depress TSP50-induced cell proliferation and colony formation in vitro and tumor formation in vivo, and the aspartic acid at position 206 in the catalytic triad played a more crucial role than threonine and histidine in this process. Mechanistic studies revealed that the mutants in the catalytic triad abolished the enzyme activity of TSP50, but did not change the cellular localization. Furthermore, our data indicated that all the three mutants suppressed activation of NF-κB signal by preventing the interaction between TSP50 and the NF-κB:IκBα complex. Most importantly, we demonstrated that TSP50 could interact with IκBα protein and cleave it directly as a new protease in vitro. [ABSTRACT FROM AUTHOR]

Highlights: [•] Alantolactone is a novel and efficient inhibitor of TSP50 expression. [•] Alantolactone produced cytotoxic effects on the cells which had high levels expression of endogenous TSP50. [•] Alantolactone induced cell apoptosis via mitochondrial-dependent pathway. [•] Alantolactone triggers cell apoptosis by inhibiting TSP50 expression. [ABSTRACT FROM AUTHOR]

Abstract: A pair of new dibenz[cd,lm]perylene derivatives, juglanperylenone A (1a) and juglanperylenone B (1b), along with ten known compounds, including four anthraquinones (2–5), two coumarins (6–7) and four triterpenoids (8–11), were isolated from the stem bark of Juglans mandshurica Maxim. Their structures were elucidated on the basis of spectroscopic evidence, including 1D and 2D NMR, HR-TOF-MS, and by comparison with literature data. In addition, the chemotaxonomic significance of the isolates was also discussed in this paper. [Copyright &y& Elsevier]

Abstract: One new flavonoid, named (R)-2-hydroxynaringenin (1), along with fifteen known compounds, including six flavonoids (2–7), six lignans (8–13), two phenolic glycosides (14–15) and one alkaloid (16) were isolated from the roots of Zizyphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou. Their structures were established on the basis of spectroscopic evidence, including 1D and 2D NMR, circular dichroism (CD) curve analysis, and by comparison with literature data. Compounds 2, 3 and 8–16 were found in Z. jujuba Mill. var. spinosa for the first time, while compounds 8, 10 and 13–15 were new to the Rhamnaceae family. In addition, the chemotaxonomic significance of the isolates was discussed in this paper. [Copyright &y& Elsevier]

Abstract: Purpose: To determine whether the apparent diffusion coefficient (ADC) correlates with histopathologic findings and whether ADC values can be used to differentiate benign from atypical/malignant meningiomas. Materials and methods: MR images were reviewed retrospectively in 138 patients with meningiomas treated between September 1997 and July 2003. The ADC values were measured in the lesions and peritumoral edema, and the normalized ADC (NADC) ratios were calculated using the formula NADC=ADC of the tumor/ADC of the normal white matter. The ADC findings were compared with the histopathologic findings after resection using the World Health Organization criteria (2007). Results: Meningiomas were histologically graded as malignant (9%), atypical (14%) and benign (77%). Of the 138 meningiomas, 32 (23%) were atypical (n =19) or malignant (n =13), whereas 106 (77%) were typical. The mean ADC values were statistically different between typical and atypical/malignant meningiomas (0.97±0.21×10−3 mm2/s vs 0.85±0.17×10−3 mm2/s). The mean NADC ratios were also significantly lower in the atypical/malignant group (1.09±0.23) than in the benign group (1.24±0.25; P =0.002<0.05). The mean ADC values and NADC ratios did not differ significantly among fibrous, meningothelial, transitional and atypical tumors (P >0.05). The mean ADC values and NADC ratios were higher in the angiomatous and secretory subgroups than in the fibrous, meningothelial, transitional, atypical and malignant subgroups (P <0.05). The ADC values and NADC ratios were the lowest in the malignant subgroup, and the difference between atypical and malignant meningiomas was statistically significant (P <0.05). Conclusions: Meningioma subgroups displayed different ADC values from each other. Thus, ADC values may provide a useful supplement to the information obtained from conventional contrast-enhanced MR imaging, enhancing the ability of medical professionals to differentiate among the subgroups of meningiomas. [Copyright &y& Elsevier]

Abstract: Due to the increasing incidence of cancer, a leading cause of death worldwide, discovery of new therapeutic drugs is urgently needed. By screening for agents with low toxicity that selectively target cancer cells, we found that 6-[(1-naphthylmethyl) sulfanyl]-9H-purine (NMMP), a derivative of 6-mercaptopurine (6-MP), could reduce the viability of five human cancer cell lines. Further study suggested that NMMP inhibition of the proliferation of hepatocellular carcinoma (HepG2) cells was associated with G2/M phase cell cycle arrest, and reduced cyclin-dependent kinase (CDK) 4 and cyclin B1/D1 levels. In addition, NMMP induced cell apoptosis, as determined by TUNEL assay. Immunoblot analysis revealed that the expression of cleaved caspase-9 and caspase-3 as well as the ratio of Bax/Bcl-2 protein increased significantly. Overall, our results suggest that NMMP exerts anti-tumor activities through induction of G2/M phase arrest and mitochondria-dependent cell apoptosis, implicating its potential therapeutic value for the treatment of cancer. [Copyright &y& Elsevier]

Abstract: The high biological activity of dehydroabietylamine derivatives has been reported previously. In this study, we aimed to screen 73 dehydroabietylamine derivatives as potential candidate inhibitors in liver cancer cells. Initially, the compounds structural activity relationship analysis was explored and N-benzoyl-12-nitrodehydroabietylamine-7-one (compound 81) was shown to have significant growth inhibitory activity in the human liver carcinoma cell line, HepG2. Further research into the anti-proliferative effect on HepG2 cells mediated by compound 81 was undertaken. The results suggest that compound 81 effectively induced apoptosis in HepG2 cells characterized by nuclear staining of DAPI, TUNEL assay and the activation of caspase-3. A decreased level of anti-apoptotic protein Bcl-2 and increased apoptotic Bax were also observed. Furthermore, Ki-67 protein staining and the BrdU incorporation assay showed that compound 81 significantly inhibited the proliferation of HepG2 cells. Cell cycle components analysis found that expression of cyclin D1 and cyclin B1 was reduced in HepG2 cells with compound 81 treatment, whereas the content of p21Waf1/Cip1 was increased. Taken together, our data indicate that compound 81 induces apoptosis and inhibits proliferation in HepG2 cells, and may be a promising candidate in the development of a novel class of antitumor agents. [Copyright &y& Elsevier]

Abstract: Multidrug resistance is a serious obstacle encountered in cancer treatment. Since drug resistance in human cancer is mainly associated with overexpression of the multidrug resistance gene 1 (MDR1), the promoter of the human MDR1 gene may be a target for multidrug resistance reversion drug screening. In the present study, HEK293T cells were transfected with pGL3 reporter plasmids containing the 2kb of MDR1 promoter, and the transfected cells were used as models to screen for candidate multidrug resistance inhibitors from over 300 purified naturally occurring compounds extracted from plants and animals. Dioscin was found to have an inhibiting effect on MDR1 promoter activity. The resistant HepG2 cell line (HepG2/adriamycin) was used to validate the activity of multidrug resistance reversal by Dioscin. Results showed that Dioscin could decrease the resistance degree of HepG2/adriamycin cells, and significantly inhibit P-glycoprotein expression, as well as increase the accumulation of adriamycin in HepG2/adriamycin cells as measured by Flow Cytometric analysis. These results suggest that Dioscin is a potent multidrug resistance reversal agent and may be a potential adjunctive agent for tumor chemotherapy. [Copyright &y& Elsevier]

Abstract: SLC5A8 (Solute carrier family 5, member 8), proposed to be a potential tumor suppressor gene, is down-regulated by epigenetic changes in some colorectal cancer cells, and ectopic expression of SLC5A8 in SLC5A8-deficient colon cancer cell lines leads to suppression of the colony-forming ability of these cells. Activin A, a member of the transforming growth factor-β (TGF-β) superfamily, has been shown to inhibit the proliferation of a variety of tumor (and normal) human cell types. However, the mechanism(s) by which activin A exerts its inhibitory effects are not yet understood. In this study, we showed that activin A up-regulated SLC5A8 expression in colorectal cancer RKO cells and human embryonic kidney (HEK) 293T cells. To elucidate the underlying mechanism involved in this process, we investigated the activation of the Smad signaling pathway, and analyzed the effects of dominant negative Smad3 and Smad2 proteins on activin A-induced SLC5A8 expression. The results indicated that activin A-induced SLC5A8 expression was dependent on activation of Smad3. Further analysis showed that activin A induced SLC5A8 expression via transcriptional activation. Deletion analysis indicated that the CAGA elements located within the -273/-222 region of the human SLC5A8 promoter were responsive to activin A. Taken together, our results strongly suggest that activin A up-regulates SLC5A8 expression through the Smad signaling pathway, which also partially explains the inhibitory effects of activin A in RKO cells. [Copyright &y& Elsevier]

Abstract: Butyrate has been shown to display anti-cancer activity through the induction of apoptosis in various cancer cells. However, the underlying mechanism involved in butyrate-induced apoptosis is still not fully understood. Here, we investigated the cytotoxicity mechanism of butyrate in human colon cancer RKO cells. The results showed that butyrate induced a strong growth inhibitory effect against RKO cells. Butyrate also effectively induced apoptosis in RKO cells, which was characterized by DNA fragmentation, nuclear staining of DAPI, and the activation of caspase-9 and caspase-3. The expression of anti-apoptotic protein Bcl-2 decreased, whereas the apoptotic protein Bax increased in a dose-dependent manner during butyrate-induced apoptosis. Moreover, treatment of RKO cells with butyrate induced a sustained activation of the phosphorylation of c-jun N-terminal kinase (JNK) in a dose- and time-dependent manner, and the pharmacological inhibition of JNK MAPK by SP600125 significantly abolished the butyrate-induced apoptosis in RKO cells. These results suggest that butyrate acts on RKO cells via the JNK but not the p38 pathway. Butyrate triggered the caspase apoptotic pathway, indicated by an enhanced Bax-to-Bcl-2 expression ratio and caspase cascade reaction, which was blocked by SP600125. Taken together, our data indicate that butyrate induces apoptosis through JNK MAPK activation in colon cancer RKO cells. [Copyright &y& Elsevier]

Abstract: The human SLC5A8 gene is a tumor suppressor. Its silencing may contribute to the carcinogenesis and progression of various tumors, which makes this gene an attractive molecular marker and a potential target for diagnosis and therapy. Little is known about transcriptional mechanisms controlling SLC5A8 gene expression. To better understand the molecular mechanisms regulating SLC5A8 expression, we characterized the 5′-regulatory region and a part of exon 1. Luciferase reporter assays of deletion mutants of SLC5A8 promoter demonstrated that a 295-bp region is essential for the basal promoter activity of the SLC5A8 gene. Further analysis indicated that the CCAAT boxes and GC boxes were involved in positive regulation of SLC5A8 promoter. Overexpression of two transcription factors, CCAAT/enhancer binding protein beta (C/EBPβ) and specific transcription factor 1 (Sp1), upregulated the activities of the human SLC5A8 promoter and protein expression, suggesting that both C/EBPβ and Sp1 transcription factors might have functions in SLC5A8 transcription. Taken together, our results elucidate the mechanism underlying the regulation of SLC5A8 gene transcription and also define a novel regulatory sequence that may be used to increase expression of the SLC5A8 gene in cancer gene therapy. [Copyright &y& Elsevier]

Abstract: Multidrug resistance (MDR) is a serious obstacle encountered in cancer treatment. In this study, we established an in vitro multiple drug resistant HepG2 cell line (HepG2/ADM), and characterized its MDR. This model was used to screen potential candidate chemosensitisers from over 200 purified naturally occurring compounds extracted from plants and animals. Cantharidin was found to have a significant reversal on MDR in our model. Further, our results showed that Cantharidin could significantly inhibit P-gp (P-glycoprotein) expression, mRNA transcription, as well as MDR1 promoter activity. These results suggest that Cantharidin is a novel and potent MDR reversal agent and may be a potential adjunctive agent for tumor chemotherapy. [Copyright &y& Elsevier]

• Convallatoxin has potential therapeutic value for the treatment of psoriasis. • Convallatoxin induces HaCaT cell death through necroptosis. • Convallatoxin promotes necroptotic cell death through oxidative stress. • Convallatoxin ameliorates skin inflammation and hyperplasia in TPA- and IMQ-induced psoriasis-like mouse models. Psoriasis is considered an immune-mediated inflammatory skin disorder that affects the quality of life of nearly four percent of the world population. Considering the side effects of existing therapeutic drugs and the urgent need for new drug development, we screened more than 250 traditional Chinese medicine compounds to identify drugs that significantly reduced the viability of human HaCaT keratinocytes, a psoriasis-related model cell line. Convallatoxin (CNT) was found to be a highly effective inhibitor of HaCaT cell viability. Subsequent mechanistic studies revealed that CNT induced HaCaT cell death by necroptosis rather than by apoptosis. CNT destroyed the membrane integrity of HaCaT cells, as detected by nuclear propidium iodide (PI) staining and lactate dehydrogenase (LDH) release. Additionally, the intercellular levels of adenosine triphosphate (ATP) were lower in HaCaT cells treated with CNT than in control HaCaT cells, and typical necroptosis-associated characteristics were observed by electron microscopy in cells treated with CNT. Furthermore, compared with control HaCaT cells, CNT-treated HaCaT cells produced more reactive oxygen species (ROS), but this effect was inhibited by the antioxidants N-acetyl-cysteine (NAC), diphenyleneiodonium chloride (DPI), and apocynin and the necroptosis inhibitor Nec-1. In addition, antioxidant treatment attenuated necroptotic cell death, suggesting that CNT-induced HaCaT necroptosis is mediated by oxidative stress. More importantly, CNT ameliorated skin lesions and inflammation in imiquimod (IMQ)- and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced psoriasis-like mouse models. In conclusion, our results demonstrate that CNT is cytotoxic against HaCaT cells in vitro and exerts antipsoriatic activities in two mouse models of psoriasis in vivo, making CNT a potential promising candidate drug for future research. [ABSTRACT FROM AUTHOR]

Psoriasis is a common dermatosis causing considerable inconvenience to 4% of the general population. Traditional psoriasis treatments often cause side effects, drug resistance and complications, necessitating development of safer and more effective treatments. In this study, we screened over 600 natural compounds to identify viability inhibitors of human HaCaT keratinocytes cultured in vitro. The results showed that nitidine chloride was a highly effective inhibitor. Further studies revealed that nitidine chloride inhibited HaCaT proliferation and induced S phase cell cycle arrest; these effects were associated with reduced DNA synthesis, decreased Ki67, cyclin A, and cyclin D1 levels, and increased p53 protein expression. Nitidine chloride also significantly downregulated bcl-2 and upregulated bax, cleaved caspase-9 and cleaved caspase-3. Mechanistic studies revealed that nitidine chloride-induced apoptosis involved the c-Jun N-terminal kinase (JNK) pathway. More importantly, in 12-O-tetradecanoyl-phorbol-13-acetate (TPA)- and imiquimod (IMQ)-induced epidermal hyperplasia and inflammation models, nitidine chloride inhibited topical edema in mouse ear and back skin, substantially reducing tissue thickness and weight. In some cases, nitidine chloride also ameliorated conditions caused by TPA and IMQ, such as angiogenesis and infiltration of large numbers of inflammatory cells around blood vessels. Additionally, nitidine chloride inhibited the expression of various proinflammatory cytokines in the two animal models. In conclusion, our results are the first to demonstrate that nitidine chloride inhibits the proliferation of HaCaT cells, induces apoptosis partly via the JNK signaling pathway in vitro and ameliorates skin lesions and inflammation in vivo, making it an appropriate candidate for psoriasis treatment. [ABSTRACT FROM AUTHOR]