Pyroptosis and Its Role in Cervical Cancer.

Pyroptosis, an inflammatory programmed cell death, is characterized by the caspase-mediated pore formation of plasma membranes and the release of large quantities of inflammatory mediators. In recent years, the morphological characteristics, induction mechanism and action process of pyroptosis have been gradually unraveled. As a malignant tumor with high morbidity and mortality, cervical cancer is seriously harmful to women's health. It has been found that pyroptosis is closely related to the initiation and development of cervical cancer. In this review the mechanisms of pyroptosis and its role in the initiation, progression and treatment application of cervical cancer are summarized and discussed.

Antitumor Activities of Interleukin-12 in Melanoma.

Melanoma is the most common and serious malignant tumor among skin cancers. Although more and more studies have revolutionized the systematic treatment of advanced melanoma in recent years, access to innovative drugs for melanoma is still greatly restricted in many countries. IL-12 produced mainly by antigen-presenting cells regulates the immune response and affects the differentiation of T cells in the process of antigen presentation. However, the dose-limited toxicity of IL-12 limits its clinical application. The present review summarizes the basic biological functions and toxicity of IL-12 in the treatment of melanoma and discusses the clinical application of IL-12, especially the combination of IL-12 with immune checkpoint inhibitors, cytokines and other therapeutic drugs. We also summarize several promising technological approaches such as carriers that have been developed to improve the pharmacokinetics, efficacy and safety of IL-12 or IL-12 encoding plasmid application.

TcpC Inhibits M1 but Promotes M2 Macrophage Polarization via Regulation of the MAPK/NF-κB and Akt/STAT6 Pathways in Urinary Tract Infection.

TcpC is a multifunctional virulence factor of Uropathogenic Escherichia coli (UPEC). Macrophages can differentiate into two different subsets M1 and M2 that play distinct roles in anti-infection immunity. Here, we investigate the influence of TcpC on M1/M2 polarization and the potential mechanisms. Our data showed that M1 markers CD86 and iNOS were significantly inhibited, while the M2 markers CD163, CD206 and Arg-1 were enhanced in macrophages in kidneys from the TcpC-secreting wild-type CFT073 (CFT073wt)-infected pyelonephritis mouse model, compared with those in macrophages in kidneys from TcpC knockout CFT073 mutant (CFT073Δtcpc)-infected mice. CFT073wt or recombinant TcpC (rTcpC) treatment inhibits LPS + IFN-γ-induced CD80, CD86, TNF-α and iNOS expression, but promotes IL-4-induced CD163, CD206, Arg-1 and IL-10 expression in both human and mouse macrophage cell lines THP-1 and J774A.1. Moreover, rTcpC significantly attenuated LPS + IFN-γ-induced phosphorylation of p38, ERK, p50 and p65 but enhanced IL-4-induced phosphorylation of Akt and STAT6. These data suggest that TcpC inhibits M1 but promotes M2 macrophage polarization by down-regulation of p38, ERK/NF-κB and up-regulation of the Akt/STAT6 signaling pathway, respectively. Our findings not only illuminate the regulatory effects of TcpC on macrophage M1/M2 polarization and its related signaling pathways, but also provide a novel mechanism underlying TcpC-mediated immune evasion of macrophage-mediated innate immunity.

Comparative Analysis of Phytochemical Profiles and Antioxidant Activities between Sweet and Sour Wampee (Clausena lansium) Fruits.

As a local medicine and food, wampee fruit, with abundant bioactive compounds, is loved by local residents in Southern China. Titratable acid (TA), total sugar (TS), and total phenolic and flavonoid contents were detected, and phytochemical profiles and cellular antioxidant activities were analyzed by the HPLC and CAA (cellular antioxidant activity) assay in five sweet wampee varieties and five sour wampee varieties. Results showed that the average TS/TA ratio of sweet wampee varieties was 29 times higher than sour wampee varieties, while TA content was 19 times lower than sour wampee varieties. There were much lower levels of total phenolics, flavonoids, and antioxidant activities in sweet wampee varieties than those in sour wampee varieties. Eight phytochemicals were detected in sour wampee varieties, including syringin, rutin, benzoic acid, 2-methoxycinnamic acid, kaempferol, hesperetin, nobiletin, and tangeretin, while just four of them were detected in sweet wampee varieties. Syringin was the only one that was detected in all the sour wampee varieties and was not detected in all sweet wampee varieties. Correlation analysis showed significant positive correlations between TA with phenolics, flavonoids, and total and cellular (PBS wash) antioxidant activities, while there were significant negative correlations between TS/TA with phenolic and cellular (no PBS wash) antioxidant activities. This suggested that the content of titratable acid in wampee fruit might have some relationship with the contents of phenolics and flavonoids. Sour wampee varieties should be paid much attention by breeders for their high phytochemical contents and antioxidant activities for cultivating germplasms with high health care efficacy.

TcpC inhibits toll-like receptor signaling pathway by serving as an E3 ubiquitin ligase that promotes degradation of myeloid differentiation factor 88.

TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase.

E3 ligase Nedd4l promotes antiviral innate immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3.

Ubiquitination is one of the most prevalent protein posttranslational modifications. Here, we show that E3 ligase Nedd4l positively regulates antiviral immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3. Deficiency of Nedd4l significantly impairs type I interferon and proinflammatory cytokine production induced by virus infection both in vitro and in vivo. Nedd4l deficiency inhibits virus-induced ubiquitination of TRAF3, the binding between TRAF3 and TBK1, and subsequent phosphorylation of TBK1 and IRF3. Nedd4l directly interacts with TRAF3 and catalyzes K29-linked ubiquitination of Cys56 and Cys124, two cysteines that constitute zinc fingers, resulting in enhanced association between TRAF3 and E3 ligases, cIAP1/2 and HECTD3, and also increased K48/K63-linked ubiquitination of TRAF3. Mutation of Cys56 and Cys124 diminishes Nedd4l-catalyzed K29-linked ubiquitination, but enhances association between TRAF3 and the E3 ligases, supporting Nedd4l promotes type I interferon production in response to virus by catalyzing ubiquitination of the cysteines in TRAF3.

FUT4siRNA augments the chemosensitivity of non-small cell lung cancer to cisplatin through activation of FOXO1-induced apoptosis.

BACKGROUND: Increased fucosylation is associated with the chemoresistance phenotype. Meanwhile, fucosyltransferase IV (FUT4) amounts are frequently elevated in lung cancer and may be related to increased chemoresistance. METHODS: In the present work, FUT4's role in cisplatin-induced apoptosis was assessed in A549 and H1975 cells, respectively. To clarify whether the FUT4 gene attenuates chemosensitivity in tumor cells, we constructed FUT4siRNA and evaluated its effects on cisplatin-induced apoptosis and cell growth inhibition. Cell viability, apoptosis, migration and invasion assay were conducted to investigate cisplatin sensitivity. The activation of EGFR/AKT/FOXO1 signaling were measured by western blot. The translocation of FOXO1 was assessed by IFC using Laser Scanning Confocal Microscope. RESULTS: We found that FUT4 knockdown dose-dependently increased cisplatin-associated cytotoxicity. Furthermore, FUT4 silencing induced apoptosis and inhibited proliferation in A549 and H1975 cells by suppressing Akt and FOXO1 phosphorylation induced by cisplatin administration, which resulted in nuclear translocation of FOXO1. CONCLUSION: These results suggested FUT4 might control chemoresistance to cisplatin in lung cancer by suppressing FOXO1-induced apoptosis.

Effects of stem cells on non-ischemic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AIMS: To assess the impacts of stem cell therapy on clinical outcomes in patients with non-ischemic cardiomyopathy (NICM). The effect of stem cell therapy on prognosis is unclear and controversial. METHODS: The authors performed a systematic review and meta-analysis of the effects of autologous stem cell transplantation in patients with NICM on a composite outcome of all-cause mortality and heart transplantation, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), New York Heart Association (NYHA) classification, 6-minute walk test (6-MWT) distance and serum brain natriuretic peptide (BNP) level, considering studies published before March 19, 2020. RESULTS: Twelve trials with 623 subjects met inclusion criteria. Compared with the control group, stem cell therapy improved LVEF (weighted mean difference [WMD], 4.08%, 95% confidence interval [CI], 1.93-6.23, P = 0.0002) and 6-MWT distance (WMD, 101.49 m, 95% CI, 45.62-157.35, P = 0.0004) and reduced BNP level (-294.94 pg/mL, 95% CI, -383.97 to -205.90, P < 0.00001) and NYHA classification (-0.70, 95% CI, -0.98 to -0.43, P < 0.00001). However, LVEDD showed no significant difference between the two groups (WMD, -0.09 cm, 95% CI, -0.23 to 0.06, P = 0.25). In 10 studies (535 subjects) employing the intracoronary route for cell delivery, mortality and heart transplantation were decreased (risk ratio [RR], 0.73, 95% CI, 0.52-1.00, P = 0.05). Furthermore, in four studies (248 subjects) with peripheral CD34+ cells, either all-cause mortality (RR, 0.44, 95% CI, 0.23-0.86, P = 0.02) or mortality and heart transplantation (RR, 0.45, 95% CI, 0.27-0.77, P = 0.003) improved in the treatment group compared with the control. The trial sequential analysis suggested the information size of LVEF, 6-WMT and BNP has been adequate for evidencing the benefits of stem cells on NICM. However, to determine the potential survival benefit, more clinical data are required to make the statistical significance in meta-analysis more conclusive. CONCLUSIONS: This meta-analysis demonstrates that stem cell therapy may improve survival, exercise capacity and cardiac ejection fraction in NICM, which suggests that stem cells are a promising option for NICM treatment.

Autophagy inhibits the mesenchymal stem cell aging induced by D-galactose through ROS/JNK/p38 signalling.

Autophagy and cellular senescence are two critical responses of mammalian cells to stress and may have a direct relationship given that they respond to the same set of stimuli, including oxidative stress, DNA damage, and telomere shortening. Mesenchymal stem cells (MSCs) have emerged as reliable cell sources for stem cell transplantation and are currently being tested in numerous clinical trials. However, the effects of autophagy on MSC senescence and corresponding mechanisms have not been fully evaluated. Several studies demonstrated that autophagy level increases in aging MSCs and the downregulation of autophagy can delay MSC senescence, which is inconsistent with most studies that showed autophagy could play a protective role in stem cell senescence. To further study the relationship between autophagy and MSC senescence and explore the effects and mechanisms of premodulated autophagy on MSC senescence, we induced the up- or down-regulation of autophagy by using rapamycin (Rapa) or 3-methyladenine, respectively, before MSC senescence induced by D-galactose (D-gal). Results showed that pretreatment with Rapa for 24 hours remarkably alleviated MSC aging induced by D-gal and inhibited ROS generation. p-Jun N-terminal kinases (JNK) and p-38 expression were also clearly decreased in the Rapa group. Moreover, the protective effect of Rapa on MSC senescence can be abolished by enhancing the level of ROS, and p38 inhibitor can reverse the promoting effect of H2 O2 on MSC senescence. In summary, the present study indicates that autophagy plays a protective role in MSC senescence induced by D-gal, and ROS/JNK/p38 signalling plays an important mediating role in autophagy-delaying MSC senescence.

Bifidobacterium lactis BB-12 Attenuates Macrophage Aging Induced by D-Galactose and Promotes M2 Macrophage Polarization.

Immunosenescence comprises a set of dynamic changes occurring in innate and adaptive immune systems, and macrophage aging plays an important role in innate and adaptive immunosenescence. However, function and polarization changes in aging macrophages have not been fully evaluated, and no effective method for delaying macrophage senescence is currently available. The results of this study reveal that D-galactose (D-gal) can promote J774A.1 macrophage senescence and induce macrophage M1 polarization differentiation. Bifidobacterium lactis BB-12 can significantly inhibit J774A.1 macrophage senescence induced by D-gal. IL-6 and IL-12 levels in the BB-12 groups remarkably decreased compared with that in the D-gal group, and the M2 marker, IL-10, and Arg-1 mRNA levels increased in the BB-12 group. BB-12 inhibited the expression of p-signal transducer and activator of transcription 1 (STAT1) and promoted p-STAT6 expression. In summary, the present study indicates that BB-12 can attenuate the J774A.1 macrophage senescence and induce M2 macrophage polarization, thereby indicating the potential of BB-12 to slow down immunosenescence and inflamm-aging.

[Effects of resveratrol on aging of mesenchymal stem cells and its mechanism].

OBJECTIVE: To investigate the effects of resveratrol (Res) on aging of marrow mesenchymal stem cells (MSCs), and to explore its mechanism. METHODS: MSCs were isolated from young SD rats and cultured in vitro. The optimal D-gal concentration for induction of MSCs senescence was determined. Then MSCs were randomly divided into four groups, namely the control group, 10µmol/L, 50µmol/L and 100µmol/L Res groups. After the cells were treated with different concentration of Res for 48 h, the senescence-associated changes were examined with senescence-associated-ß-galactosidase (SA-ß-gal) staining; the expression of p53, p16 and γ-H2AX was evaluated by Western blot. The total active oxygen species (ROS) level was determined by flow cytometry with DCFH-DA staining. In order to assess the effect of Res on the mitochondrial function, MitoSox Red staining was used to detect mitochondrial ROS levels in each group, mitochondrial membrane potential was detected by JC-1 assay, mPTP method was used to detect mitochondrial membrane channel opening level, and Western blot was used to detect the expression level of cytoplasmic cytochrome C (Cyt-C). RESULTS: D-gal 10 and 50 g/L significantly increased the number of SA-ß-gal positive cells and the level of mitochondrial ROS (all P<0.01). Therefore, 10 g/L D-gal was used to induce the senescence of MSCs in subsequent experiment. Compared with the control group, the number of SA-ß-gal positive cells in Res groups significantly decreased (all P<0.01), the expression of p53, p16 and γ-H2AX decreased, and the total and mitochondrial ROS level also decreased (all P<0.01). Moreover, mitochondrial membrane potential, open level of mitochondrial membrane channels and the levels of cytoplasm Cyt-C in the Res treatment groups decreased compared with the control group (P<0.05 or P<0.01). CONCLUSIONS: Resveratrol can protect the mitochondrial function of MSCs, and effectively delay the MSC senescence.

Zinc Coordinated Cationic Polymers Break Up the Paradox between Low Molecular Weight and High Transfection Efficacy.

Cationic polymers have emerged as appealing nonviral gene vectors for decades, which, however, suffer from the paradox between low molecular weight and high transfection efficacy. Low molecular weight cationic polymers (LCPs) are well cell tolerated but are perplexed by orders-of-magnitude less efficacy compared to their macromolecular counterparts. The deficiency mainly lies in weak DNA binding of polymers and difficulty in endosomal escape of formulated polyplexes. Herein, we demonstrate that, through zinc (Zn) coordinated modification of LCPs, the high transfection efficiency and low molecular weight (thus low cytotoxicity) can be achieved simultaneously. The Zn coordinated ligand shows a high affinity to phosphate components and therefore will largely benefit the DNA packaging and endosomal membrane destabilization, addressing the defects of LCPs in gene delivery. Zn coordinative functionalization of LCPs breaks up the "efficacy-toxicity" paradox and provides great promise for the development of clinically efficient and safe nonviral gene vectors.

Impact of Leaf Development Stages on Polyphenolics Profile and Antioxidant Activity in Clausena lansium (Lour.) Skeels.

Clausena lansium (Lour.) Skeels, commonly known as "wampee," is an excellent food ingredient of medicinal value. Effects of leaf developmental stages on the composition of phenolics, flavonoids, and antioxidant activity were investigated. Phenolics composition was studied using HPLC-PAD, whereas antioxidant activity was estimated by oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays. Increase in bound flavonoids, quercetin, and cellular antioxidant activity was observed in bound and free fractions at different stages of leaf development. Predominantly, quercetin and ferulic acid contents were high in free and bound fractions of old leaves. In addition, phenolic components depicted highly significant positive association (p < 0.05) with antioxidant activity. Overall, old leaves of wampee have utility value similar to leaf buds, so they could be a more sustainable and economical source of bioactive compounds for commercial application in nutraceutical and pharmaceutical industries.

TAOK1 negatively regulates IL-17-mediated signaling and inflammation.

Interleukin 17 (IL-17) is an important cytokine that can induce tissue inflammation and is involved in the pathogenesis of numerous autoimmune diseases. However, the regulation of its signaling transduction has not been well described. In this study, we report that thousand and one kinase 1 (TAOK1) functions as a negative regulator of IL-17-mediated signal transduction and inflammation. TAOK1 knockdown promotes IL-17-induced cytokine and chemokine expression and the activation of mitogen-activated protein kinases and nuclear factor-κB. We further demonstrate that TAOK1 interacts with IL-17 receptor A (IL-17RA) independent of its kinase activity, and TAOK1 dose-dependently prevents the formation of the IL-17R-Act1 (nuclear factor activator 1, also known as tumor necrosis factor receptor-associated factor 3 interacting protein 2) complex. Consistent with this, TAOK1 deficiency exacerbates colitis in the 2,4,6-trinitrobenzenesulfonic acid)-induced experimental model of inflammatory bowel disease, likely by its promotion of the IL-17-mediated signaling pathway. TAOK1 expression is decreased in the colons of ulcerative colitis patients. In conclusion, these findings suggest that TAOK1 is involved in the development of IL-17-related autoimmune disorders.

Zinc Coordination Substitute Amine: A Noncationic Platform for Efficient and Safe Gene Delivery.

Amines have been extensively involved in vector design thus far, however, their clinical translation has been impeded by several obstacles: cytotoxicity, polyplex serum instability and low efficacy in vivo. In pursuit of functional groups to substitute amines in vector design to address these disadvantages is of great significance. Herein, we report well-tailored noncationic copolymers that contain hydrophilic, hydrophobic, and zinc coordinative moieties through reversible addition-fragmentation chain transfer (RAFT) polymerization for efficient and safe gene delivery. These polymers are capable of condensing DNA, enabling the formation of uncharged polyplexes. Especially, the zinc coordinative ligand can simultaneously benefit strong DNA binding, robust cellular uptake, efficacious endosomal destabilization, low cytotoxicity, and avoidance of serum protein adsorption. The coordinative module holds great promise to substitute amines and inspires the development of next-generation gene vectors. More importantly, the coordinative copolymers illuminate the possibility and potential of noncationic gene delivery systems for clinical applications.

High glucose induces the aging of mesenchymal stem cells via Akt/mTOR signaling.

It has previously been demonstrated that glucose is important in the process of stem cell aging. However, the mechanisms of cell senescence induced by high glucose (HG) remain to be elucidated. The preliminary study indicated that D­galactose induced mesenchymal stem cell (MSCs) aging. The present study demonstrated, following treatment with 11.0 or 22.0 mM HG for 14 days, that HG significantly promoted MSCs aging and the expression levels of phosphorylated (p-)phosphatidylinositol 3-kinase/protein kinase B (Akt) and p­mammalian target of rapamycin signaling (mTOR) in the HG groups were increased compared with the control group. However, following Akt inhibition with 1.0 or 10.0 nM MK­2206, which is an Akt­specific small molecule inhibitor, the senescence­cell value in the HG group was significantly decreased compared with the control group. These results indicated that HG induced MSCs senescence and this effect was primarily mediated via the Akt/mTOR signaling pathway.

Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: A novel mechanism in muscle-bone communication.

Muscle and bone are closely associated in both anatomy and function, but the mechanisms that coordinate their synergistic action remain poorly defined. Myostatin, a myokine secreted by muscles, has been shown to inhibit muscle growth, and the disruption of the myostatin gene has been reported to cause muscle hypertrophy and increase bone mass. Extracellular vesicle-exosomes that carry microRNA (miRNA), mRNA, and proteins are known to perform an important role in cell-cell communication. We hypothesized that myostatin may play a crucial role in muscle-bone interactions and may promote direct effects on osteocytes and on osteocyte-derived exosomal miRNAs, thereby indirectly influencing the function of other bone cells. We report herein that myostatin promotes expression of several bone regulators such as sclerostin (SOST), DKK1, and RANKL in cultured osteocytic (Ocy454) cells, concomitant with the suppression of miR-218 in both parent Ocy454 cells and derived exosomes. Exosomes produced by Ocy454 cells that had been pretreated with myostatin could be taken up by osteoblastic MC3T3 cells, resulting in a marked reduction of Runx2, a key regulator of osteoblastic differentiation, and in decreased osteoblastic differentiation via the down-regulation of the Wnt signaling pathway. Importantly, the inhibitory effect of myostatin-modified osteocytic exosomes on osteoblast differentiation is completely reversed by expression of exogenous miR-218, through a mechanism involving miR-218-mediated inhibition of SOST. Together, our findings indicate that myostatin directly influences osteocyte function and thereby inhibits osteoblastic differentiation, at least in part, through the suppression of osteocyte-derived exosomal miR-218, suggesting a novel mechanism in muscle-bone communication.

Berberine Protects Human Umbilical Vein Endothelial Cells against LPS-Induced Apoptosis by Blocking JNK-Mediated Signaling.

Endothelial dysfunction is a critical factor during the initiation of atherosclerosis. Berberine has a beneficial effect on endothelial function; however, the underlying mechanisms remain unclear. In this study, we investigated the effects of berberine on lipopolysaccharide- (LPS-) induced apoptosis in human umbilical vein endothelial cells (HUVECs) and the molecular mechanisms mediating the effect. The effects of berberine on LPS-induced cell apoptosis and viability were measured with 5-ethynyl-2'-deoxyuridine staining, flow cytometry, and Cell Counting Kit-8 assays. The expression and/or activation of proapoptotic and antiapoptotic proteins or signaling pathways, including caspase-3, poly(ADP-ribose) polymerase, myeloid cell leukemia-1 (MCL-1), p38 mitogen-activated protein kinase, C-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase, were determined with western blotting. The malondialdehyde levels, superoxide dismutase (SOD) activity, and production of proinflammatory cytokines were measured with enzyme-linked immunosorbent assays. The results demonstrated that berberine pretreatment protected HUVECs from LPS-induced apoptosis, attenuated LPS-induced injury, inhibited LPS-induced JNK phosphorylation, increased MCL-1 expression and SOD activity, and decreased proinflammatory cytokine production. The effects of berberine on LPS-treated HUVECs were prevented by SP600125, a JNK-specific inhibitor. Thus, berberine might be a potential candidate in the treatment of endothelial cell injury-related vascular diseases.

Evodiamine induces apoptosis and enhances apoptotic effects of erlotinib in wild-type EGFR NSCLC cells via S6K1-mediated Mcl-1 inhibition.

Erlotinib is effective in NSCLC patients with known drug-sensitizing EGFR mutations, but its clinical efficacy in patients with wild-type EGFR or acquired resistance to erlotinib remains modest. Evodiamine is a chemical extracted from the Evodia rutaecarpa (Juss.) Benth, we showed that evodiamine could induce anti-proliferation and apoptosis in four wild-type EGFR NSCLC cell lines, and combining evodiamine with erlotinib might successfully inhibit cell proliferation and survival in wild-type EGFR NSCLC cells, characterized as erlotinib-resistant. In addition, evodiamine plus erlotinib significantly increased the apoptotic rate of NSCLC cells, as compared to single agent treatment alone. Further investigation of the mechanism underlying these effects revealed that evodiamine plus erlotinib might downregulate Mcl-1 expression through the mTOR/S6K1 control of its translation. Thus, our study has revealed evodiamine as a pertinent sensitizer to erlotinib and the strategy of combining erlotinib with evodiamine appears to be an attractive option for reversing resistance to erlotinib.

[Research progress in kidney dendritic cells].

Kidney dendritic cells(DC) play important roles in the pathogenesis of kidney diseases. Kidney DC presents anti-inflammatory effects in certain kidney diseases, sometimes presents pro-inflammation in other diseases, and sometimes their effects are changing in different stages of the disease, suggesting that the differentiation and function of kidney DC may be influenced by microenvironment. This article reviews the origin and distribution of kidney DC subsets and their roles in the pathogenesis of kidney diseases such as lupus nephritis and pyelonephritis, and the functional regulation of kidney DC by proximal tubule epithelial cells.