[Renal Pathology and Cytogenetic Examination in Multiple Myeloma Patients with Renal Impairment--Retrospective Analysis].

OBJECTIVE: To explore the renal pathology and cytogenetic features in the multiple myeloma (MM) patients with renal impairment. METHODS: The clinical data of newly diagnosed MM patients with renal impairment in our hospital from January 2009 to January 2019 were analyzed retrospectively, and the relationship between FISH results and results of renal pathological exanimation was analyzed statistically by using SPSS 20.0. RESULTS: A total of 20 patients underwent renal biopsy, included 12 males and 8 females. FISH result showed that out of 20 patients, 7 cases presented interstitial nephritis, among which 3 cases were negative for FISH, and in the remaining cases the rate of IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection was 42.86%, 28.57%, 28.57%, 28.57% and 14.29% respectively, the detection positive rate was statistically significantly lower as compared with total probe positive rate (P＜0.01). There were 6 cases of cast nephropathy, among which IgH rearrangement, the rate of 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection was 66.67%, 50%, 66.67%, 50% and 0% respectively. Compared with the total probe positive rate, there was no statistical significance (P＞0.05). There were 4 cases of acute tubular necrosis, among which the detection rates of IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion was 100%, 50%, 50%, 25% and 25%, respectively. Compared with the total probe positive rate, there was no statistical significance (P＞0.05). There were one case of amyloidosis, and one case of tubular nephropathy with amyloidosis, the detection with 5 probes were all positive. One case of light chain deposition disease was positive for RB1 gene deletion + D13S319 gene deletion. CONCLUSION: FISH in the MM patients with different renal pathological changes is characterized by heterogeneity, which can be used to predict the risk of renal damage and speculate possible renal pathological types to guide prognosis.

Expression of Vsig4 attenuates macrophage-mediated hepatic inflammation and fibrosis in high fat diet (HFD)-induced mice.

The innate immune response contributes to hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). However, the pathogenic mechanism of NAFLD is still poorly understood. The costimulatory molecule V-set and immunoglobulin domain-containing protein-4 (Vsig4), which is exclusively expressed on macrophages, shows significant role in regulating macrophage-mediated inflammation. Here, we attempted to explore if Vsig4 expression was involved in high fat diet (HFD)-induced NAFLD. The results indicated that Vsig4 expression was markedly down-regulated in fatty livers of NAFLD patients and obese mice. Vsig4 knockout accelerated HFD-induced metabolic dysfunction. In addition, the loss of Vsig4 significantly promoted insulin resistance and lipid deposition in liver samples of HFD-challenged mice. Furthermore, HFD-induced inflammation was apparently accelerated in Vsig4 knockout mice by further activating nuclear factor-κB (NF-κB) signaling pathway. Also, Vsig4 deficient mice exhibited greater collagen accumulation in hepatic samples in HFD-challenged mice compared to the WT mice, which was through promoting transforming growth factor-ß1 (TGFß1) signaling. Importantly, we found that lipopolysaccharide (LPS)- or TGFß1-stimulated inflammation and fibrosis in primary hepatocytes and hepatic stellate cells, respectively, were markedly exacerbated by co-culture with condition medium from bone marrow-derived macrophages (BMDMs) with Vsig4 deficiency. Finally, transplantation of bone marrow cells from control mice to Vsig4-knockout mice restored the severity of steatosis, inflammation and fibrosis after HFD feeding. Therefore, loss of Vsig4 accelerated the severity of lipid deposition, fibrosis and the inflammatory response. Vsig4 could be a therapeutic target for NAFLD treatment.

Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice.

BACKGROUNDS: Syngeneic or autologous hematopoietic stem cells transplantation (HSCT) has been proposed to treat autoimmune diseases because of its immunosuppressive and immunomodulatory effects, which can also contribute to posttransplant antirejection therapy. In this study, we explored the tolerogenic effect of syngeneic HSCT on prolonging islet allograft survival. METHODS: C57BL/6 mice received syngeneic HSCT plus preconditioning with sublethal irradiation. Then islets of BALB/c mice were transplanted into the renal subcapsular of C57BL/6 mice after chemically induced into diabetes. RESULTS: HSCT mice exhibited improved islet allograft survival and increased serum insulin compared to control mice. Islet allografts of HSCT mice displayed lower level lymphocyte infiltration and stronger insulin staining than control mice. T cells of HSCT mice proliferated poorly in response to allogeneic splenocytes compared to control mice. Mice appeared reversed interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio to a Th2 immune deviation after syngeneic HSCT. The percentage of CD8(+) T cells was lower, while percentage of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) was higher in HSCT mice than control mice. HSCT mice showed higher percentage of CTLA-4(+) T cells and expression of CTLA-4 mRNA than control mice. Targeting of CTLA-4 by intraperitoneal injection of anti-CTLA-4 mAb abrogated the effect of syngeneic HSCT on prolonging islet allograft survival, inhibiting activity of T cells in response to alloantigen, promoting Th1 to Th2 immune deviation and up regulating CD4(+)CD25(+)Foxp3(+) Tregs. CONCLUSIONS: Syngeneic HSCT plus preconditioning of sublethal irradiation induces tolerance and improves islet allograft survival in fully mismatched mice model. Th1 to Th2 immune deviation, increased CD4(+)CD25(+)Foxp3(+) Tregs and up-regulation of CTLA-4 maybe contribute to the tolerogenic effect induced by syngeneic HSCT.

A highly selective chemosensor for Al(III) and Zn(II) and its coordination with metal ions.

This paper reports a fluorescence chemosensor, N-(benzimidazol-2-yl)salicylaldimine (H2L), for Zn(II) and Al(III) ions. H2L has high selectivity for Al(III) in dimethyl sulfoxide (DMSO) and for Zn(II) in N,N-dimethylformamide (DMF). In methanol, Zn(II) and Al(III) could also be distinguished by H2L with different excitation wavelengths. The fluorescent species [Zn(HL)(H2O)(CH3OH)](+), [Zn(HL)(H2O)(DMF)](+), [Al(HL)2(OH)(H2O)], and [Al(HL)(OH)2(H2O)(DMSO)] formed in solution were established by a combination of experimental and theoretical methods, including Job's plot, (1)H NMR titration, electrospray inonization mass spectrometry (ESI-MS), and B3LYP-SCRF/6-31(d) and TD-B3LYP-SCRF/6-31G* density functional theory methods. The results show that Zn(II) and Al(III) are all coordinated to the imine nitrogen atom and the hydroxyl oxygen atom from H2L, which is the same as the M(2+) ions in the obtained mononuclear complexes [M(HL)2(CH3OH)2] (where M = Cd, Ni, Co, and Mg). The detection limits of H2L for Zn(II) were 5.98 µM in methanol and 5.76 µM in DMF, while the detection limits of H2L for Al(III) were 3.3 µM in methanol and 5.25 µM in DMSO. Furthermore, it is also confirmed that H2L has low toxicity for HeLa cells and could be used to detect Zn(II) and Al(III) ions in living cells by bioimaging.

Hydrogen sulfide treatment promotes glucose uptake by increasing insulin receptor sensitivity and ameliorates kidney lesions in type 2 diabetes.

AIMS: To examine if hydrogen sulfide (H2S) can promote glucose uptake and provide amelioration in type 2 diabetes. RESULTS: Treatment with sodium hydrosulfide (NaHS, an H2S donor) increased glucose uptake in both myotubes and adipocytes. The H2S gas solution showed similar effects. The NaHS effects were blocked by an siRNA-mediated knockdown of the insulin receptor (IR). NaHS also increased phosphorylation of the IR, PI3K, and Akt. In Goto-Kakizaki (GK) diabetic rats, chronic NaHS treatment (30 µmol·kg(-1)·day(-1)) decreased fasting blood glucose, increased insulin sensitivity, and increased glucose tolerance with increased phosphorylation of PI3K and Akt in muscles. Similar insulin-sensitizing effects of NaHS treatment were also observed in Wistar rats. Moreover, glucose uptake was reduced in the cells with siRNA-mediated knockdown of the H2S-generating enzyme cystathionine γ-lyase in the presence or absence of exogenous H2S. Moreover, chronic NaHS treatment reduced oxygen species and the number of crescentic glomeruli in the kidney of GK rats. INNOVATION AND CONCLUSION: This study provides the first piece of evidence for the insulin-sensitizing effect of NaHS/H2S in the both in vitro and in vivo models of insulin resistance. REBOUND TRACK: This work was rejected during a standard peer review and rescued by the Rebound Peer Review (Antoxid Redox Signal 16: 293-296, 2012) with the following serving as open reviewers: Jin-Song Bian, Samuel Dudley, Hideo Kimura, and Xian Wang.

Bone marrow-derived mesenchymal stem cells protect rats from endotoxin-induced acute lung injury.

BACKGROUND: Acute lung injury (ALI) is a serious and common condition for which there are currently no specific strategies for treatment. Recent studies have suggested that bone marrow-derived multipotent mesenchymal stem cells (MSCs) may have therapeutic applications in multiple clinical disorders. We explored the biological effects of MSCs during endotoxin-induced ALI and the mechanisms involved. METHODS: MSCs were isolated from male rat bone marrow and the ALI model was induced by intravenous endotoxin injection. Female rats were sacrificed at 6 hours, 24 hours, 4 days, 1 week and 3 weeks post-injection of MSCs or saline and the lung tissue, bronchoalveolar lavage fluid, and serum were harvested for analysis. We further evaluated the survival of the rats and examined the effects of endotoxin-induced injury on the interaction between alveolar macrophages (AMs) and MSCs in ex vivo. RESULTS: There was a significant decrease in numbers of neutrophils in bronchoalveolar lavage fluid (P < 0.05), and myeloperoxidase activity in the lung (P < 0.01), and of TNF-α and IL-1ß in serum (P < 0.05) in the MSC treated rats at 4 days. Furthermore, MSC treated rats exhibited improved survival, lower lung injury score, higher concentration of IL-10 in the serum and a reduced hydroxyproline content, but these differences were not statistically significant. Moreover, co-cultures of MSCs and AMs had significantly reduced levels of TNF-α, IL-1ß and macrophage inflammatory protein (MIP)-1α and significantly increased levels of IL-10 (P < 0.05) in the culture supernatants. CONCLUSIONS: Treatment with intravenous injection of bone marrow-derived MSCs have beneficial effects on endotoxin-induced ALI in rats. The beneficial effect might be achieved through the engraftment of differentiated MSCs in the lungs and appears derive more from their capacity to secrete soluble factors that modulate immune responses.

Perfluorocarbon attenuates lipopolysaccharide-mediated inflammatory responses of alveolar epithelial cells in vitro.

BACKGROUND: Toll-like receptor-4 (TLR-4) is integrally involved in lipopolysaccharide (LPS) signaling and has a requisite role in the activation of nuclear factor-κB (NF-κB). The exact mechanisms that lend perfluorocarbon (PFC) liquids a cytoprotective effect have yet to be elucidated. Therefore we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated alveolar epithelial cellls (AECs). METHODS: AECs (A549 cells, human lung adenocarcinoma cell line) were divided into four groups: control, PFC, LPS and LPS + PFC (coculture group) groups. Intercellular adhesion molecule-1 (ICAM-1) was detected by ELISA, tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) were detected by radioimmunological methods. The expression of TLR-4 mRNA and protein was detected by real time PCR and Western blotting, respectively. The activation of NF-κB was detected by Western blotting (proteins of I-κBa and NF-κB p65). RESULTS: ICAM-1, TNF-α and IL-8 were significantly increased in LPS-stimulated AECs groups. The expression of TLR-4 mRNA and protein in LPS-stimulated groups was markedly increased. Meanwhile, NF-κB was activated as indicated by the significant degradation of IκB-α and the significant release of NF-κB P65 and its subsequent translocation into the nucleus. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-α and IL-8, the expression of TLR-4 mRNA and the activity of NF-κB. CONCLUSIONS: Taken together, our results demonstrate that LPS can induce AEC-related inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect AECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway, which is indicated by the significant decrease of TLR-4 expression and NF-κB activation.

[Investigation of inflammatory responses of alveolar epithelial cells induced by lipopolysaccharide and mechanism].

OBJECTIVE: Lipopolysaccharide (LPS) can activate alveolar epithelial cells (AECs) and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in the activation of NF-κB. NF-κB is a key intercellular signaling event that mediates cell inflammatory responses. The aim of the study is to investigate in an in vitro model the inflammatory responses of AECs induced by LPS and the probable mechanism underlined the observed inflammatory responses. So cytokines of ICAM-1, TNF-α and IL-8 secreted by LPS-activated AECs were observed. And the initial signal molecule (the expression of TLR-4 mRNA) and the key intracellular steps (the activation of NF-κB) were studied in detail. METHODS: The study was performed on A549 cells (Human lung adenocarcinoma cell line). A549 cells were divided into two groups: control, and LPS interference group. Proinflammatory cytokines ICAM-1, TNF-α and IL-8 were detected by ELISA or radioimmunological methods. The expression of TLR-4 mRNA was detected by real time PCR. The activation of NF-κB was detected by Western blot (proteins of I-κBα and NF-κB p65). RESULTS: Compared with control group, ICAM-1 and TNF-α of LPS-stimulated group were significantly higher and peaked after 2h before gradually declining at 6 and 12 h; IL-8 was higher after 2 h, which continued up to 12 h. The expression of TLR-4 mRNA of LPS group was significantly higher and peaked after 2 h and gradually declining at 6 and 12 h. Meanwhile, NF-κB was activated after 0.5, 2, 6 and 12 h indicated by the significant degradation of IκB-α and the significant release of NF-κB P65 and its subsequent translocation into the nucleus approximately synchronized. CONCLUSION: Taken together, the results demonstrate that LPS can induce AECs inflammatory injury via activating TLR-4 and subsequently activating NF-κB.

KRAS and PIK3CA but not BRAF genes are frequently mutated in Chinese cholangiocarcinoma patients.

Cholangiocarcinoma (CCA) is a rare but lethal malignancy arising from the biliary tract epithelium. It has a poor prognosis largely due to the difficulties of early diagnosis and the lack of effective therapies. It is thus imperative to develop new and effective treatments for CCA, which depends heavily on the mechanistic understanding of the disease. Previous studies have suggested that somatic mutations in KRAS, BRAF, and PIK3CA genes are frequently found in several types of human cancers including colon, breast, and lung carcinomas as well as CCA. Yet, the frequency and the involvement of these oncogenic mutations in CCA in Chinese population have not been investigated. In this study, we evaluated the hotspot mutations of KRAS, BRAF, and PIK3CA genes in 34 Chinese CCA patients. Sequencing analysis revealed 13 (38.2%) and 11 (32.4%) patients bearing KRAS and PIK3CA mutations, in which two (5.9%) of them harbored both KRAS and PIK3CA mutations. Surprisingly, no BRAF mutation was detected in all 34 CCA samples. Our findings indicate that somatic mutations in KRAS and PIK3CA but not BRAF oncogenes are closely associated with the development of CCA in Chinese population and provide new potential targets for future therapeutic treatments of the disease.

[Investigation of inflammatory responses of pulmonary microvascular endothelial cells induced by lipopolysaccharide and mechanism].

OBJECTIVE: Lipopolysaccharide (LPS) can activate pulmonary vascular endothelial cells (PMVECs) and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in the activation of NF-κB. NF-κB is a key intercellular signaling event that mediates cell inflammatory responses. The aim of the study was to investigate in an in vitro model the inflammatory responses of PMVECs induced by LPS and the probable mechanism underlying the observed inflammatory responses. METHODS: The present study was performed on isolated PMVECs from Sprague-Dawley rats. After being identified, PMVECs were divided into 2 groups: a control group, and a LPS (0.01, 0.1, 1, 10 mg/L) intervention group. ICAM-1, TNF-α and IL-8 were detected by ELISA or radioimmunological methods. The expression of TLR-4 mRNA was detected by real time PCR. The activation of NF-κB was detected by Western blot (proteins of I-κBα and NF-κB p65) and immunocytochemical staining (NF-κB p65). RESULTS: Compared with the control group, cytokines secreted from PMVECs-stimulated by LPS were increased in a dose-dependent manner. When stimulated with LPS 10 mg/L for 2, 6 and 12 h, cytokines measured were all increased. ICAM-1 and TNF-α were significantly increased and peaked after 2 h before gradually declining at 6 and 12 h. IL-8 was higher after 2 h, which continued up to 12 h. The expression of TLR-4 mRNA was significantly higher and peaked after 2 h and continued to 12 h (4.34 ± 1.42, 3.62 ± 1.45, 3.32 ± 1.36), which were all higher than that of the control group (1.00 ± 0.00, P < 0.05). Meanwhile, NF-κB was activated at 0.5, 2, 6 and 12 h indicated by the significant degradation of IκB-α and the significant increased release of NF-κB P65 and its subsequent translocation into the nucleus with approximately synchronized. CONCLUSION: Taken together, the results demonstrated that LPS was able to induce PMVECs inflammatory injury via activating TLR-4 and subsequently activating NF-κB.

Gefitinib attenuates murine pulmonary fibrosis induced by bleomycin.

BACKGROUND: Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer (NSCLC), and is generally well tolerated. However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction. This study investigated the effect of gefitinib on lung fibrosis in mice. METHODS: We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib. C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline. Lung tissues were harvested on day 14 or 21 for histology and genetic analysis. RESULTS: The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells. In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR (p-EGFR). Furthermore, quantitative real-time PCR (qRT-PCR) demonstrated that gefitinib inhibited the accumulation of collagens I and III. CONCLUSIONS: These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.

[Study on molecular mechanism of inhibitory effect of baicalin on proliferation of insulinoma cell line in rats].

OBJECTIVE: To investigate the effect of baicalin on insulinoma cell line and the molecular mechanism involved. METHODS: Light microscope, MTT assay, flow cytometry, gene analysis and Western Blot were applied to investigate the effects of baicalin on the cell proliferation, the cell cycle and the involved molecular mechanism. RESULTS: After treatment with baicalin, the number of cells in mitotic stage and the survival rate of cells obviously decreased, and cell proliferation was inhibited in a drug concentration- and acting time-dependent manner, with the appearance of apoptotic insulinoma cells. During the apoptotic process, the activity of caspase-3 was elevated by baicalin in a time-dependent manner; with the increase of the concentration of baicalin, the number of cells in S-phase obviously decreased from 38.2% to 9.4%, while the percentage of cells in G0/G1 phase increased from 56.4% to 85.9%, indicating cells were arrested in G1-phase. Meanwhile, the activity of cyclin gene promoter obviously declined, and the expression of cyclin reduced remarkably. CONCLUSION: Baicalin could induce apoptosis of insulinoma cells, which might be correlated with the activity of caspase-3, and inhibiting proliferation of insulinoma cells in a concentration- and time-dependent manner, in which the action of baicalin in down-regulating the gene transcription and expression of cyclin may play an important role.

[Effects of Notch-1 signaling in bone marrow mesenchymal stem cells differentiating into neurons: experiment in vitro].

OBJECTIVE: To investigate the role of Notch-1 signaling in bone marrow mesenchymal stem cells (MSCs) differentiating into neurons. METHODS: Mice Notch-1 small hairpin RNA (mNotch-1 shRNA) was constructed and transfected into the MSCs obtained from the tibiae of BALB/c mice. MSCs transfected with glyceraldehyde-3-phosphate hydoxygenase (GADPH) shRNA and untransfected MSCs were used as controls. The cell survival rate was detected by ELISA. The MSCs of different groups were cultured in Neurobasal-A medium so as to be induced to differentiate into neurons. Apoptosis of the MSCs was detected by TUNEL. RESULTS: After induction of 6 days the MSCs transfected with mNotch-1 shRNA displayed typical neuronal morphology and high expression of neuron-specific markers: nestin, neuron-specific enolase (NSE), neurofilament 200 (NF 200), and Notch-1 protein, however, gilal fibrillary acidic protein (GFAP), the glia-specific marker, was not detected. The percentage of apoptotic cells in the MSCs transfected with mNotch-1 shRNA was 13.3% +/- 2.3%, significantly higher than those of the MSCs transfected with mGAPH shRNA and untransfected MSCs (4.7% +/- 0.5% and 4.5% +/- 0.4%, both P < 0.01). CONCLUSION: Block of the Notch signal pathway may increase the differentiation of MSCs into neurons.

[Species and distribution of the medicinal plants peculiar to Guizhou].

OBJECTIVE: To review the species and distribution of the medicinal plants peculiar to Guizhou and provide evidence for application, protection and collection. METHOD: Open-air investigation, data collection and specimen identification. RESULT: More than eighty kinds of the medical plants peculiar to Guizhou have been identified. CONCLUSION: Guizhou has a diversity of medicinal plants. The area of distribution of most species is restricted and the population is small. Some of the species have higher medicinal and scientific research values.

[Expression of exogenous gene in bone marrow stromal cells by liposome].

OBJECTIVE: To transform eukaryotic expression vector pEGFP-PDX-1 into marrow stromal cells by liposome and to optimize the conditions of transformation. METHODS: The recombinant vector was identified by enzyme digestion analysis and sequencing. The recombinant plasmid was transformed into bone marrow stromal cells and it changed the quantity of DNA or liposome. The expression of PDX-1 gene in the transformed cells was detected by immunocytochemical staining. RESULTS: Enzyme digestion analysis and sequencing showed that the interesting gene was integreted into the recombinant vector. We obtained satisfactory efficiency of transfection when the ratio of DNA and liposome was 1 : 1 or 1 : 2. The PDX-1 in the transformed cells was expressed by immunocytochemical staining. CONCLUSION: The eukaryotic expression vector pEGFP-PDX-1 was constructed for the first time in China. We have enhanced the efficiency of transfection by optimizing the transformation conditions. It is possible to use the bone marrow stromal cells as seed cells in tissue-engineering.

[Effect of baicalin on the proliferation of insulinoma cell line].

OBJECTIVE: To investigate the effect of baicalin on the proliferation of insulinoma cell line and the molecular mechanism involved. METHODS: Such methods as light microscope, MTT assay, flow cytometry and Western blotting were applied to investigate the effects of baicalin (0, 100, 200, and 400 microg/ml baicalin treated for 24 h or 200 microg/ml baicalin treated at different time points) on the cell proliferation, cell survival rate, the cell cycle and related molecular mechanisms. RESULTS: The number of proliferating cells obviously decreased with the increase of baicalin under the light microscope, and the survival rate of cells decreased as determined by MTT assay. After being treated with baicalin, the number of insulinoma cells in S-phase obviously decreased from 38.2% (0 microg/ml) to 9.4% (400 microg/ml), and the number of cells in phase G1 increased from 56.4% (0 microg/ml) to 85.9% (400 microg/ml). In the meantime, the expression of cyclin D1 was obviously declined by Western blotting. CONCLUSION: Baica-lin can inhibit the proliferation of insulinoma cells, and the down-regulation of the expression of cyclin D1 might also be involved in these events.