Reconfigurable integrated photonic filters for optical signal processing using a silicon photonic platform.

We present a systematic photonic filter design approach by deploying pole-zero optimization. The filter transfer function is derived from its specifications by formulating closed-form optimization objective functions and subsequently translating them into optical design parameters. Two distinct filter examples, namely Chebyshev and elliptic filters, are considered for the design and validation. A compact reconfigurable three-pole photonic filter is fabricated on a silicon photonic platform to illustrate the proposed design technique including transmission tunability. Integrated thermal phase shifters coupled with micro-ring resonators are used to reconfigure filter responses. A well-matched experimental demonstration is presented to validate the proposed tuning method. We achieved a sharp out-of-band edge rejection of at least 20 and 40 dB for the elliptic and Chebyshev filter, respectively.

Fourier Ptychographic Microscopy 10 Years on: A Review.

Fourier ptychographic microscopy (FPM) emerged as a prominent imaging technique in 2013, attracting significant interest due to its remarkable features such as precise phase retrieval, expansive field of view (FOV), and superior resolution. Over the past decade, FPM has become an essential tool in microscopy, with applications in metrology, scientific research, biomedicine, and inspection. This achievement arises from its ability to effectively address the persistent challenge of achieving a trade-off between FOV and resolution in imaging systems. It has a wide range of applications, including label-free imaging, drug screening, and digital pathology. In this comprehensive review, we present a concise overview of the fundamental principles of FPM and compare it with similar imaging techniques. In addition, we present a study on achieving colorization of restored photographs and enhancing the speed of FPM. Subsequently, we showcase several FPM applications utilizing the previously described technologies, with a specific focus on digital pathology, drug screening, and three-dimensional imaging. We thoroughly examine the benefits and challenges associated with integrating deep learning and FPM. To summarize, we express our own viewpoints on the technological progress of FPM and explore prospective avenues for its future developments.

Palmitic acid-activated GPRs/KLF7/CCL2 pathway is involved in the crosstalk between bone marrow adipocytes and prostate cancer.

BACKGROUND: Obesity-induced abnormal bone marrow microenvironment is one of the important risk element for bone metastasis in prostate cancer (PCa). The present study aimed to determine whether obesity-induced elevation in palmitic acid (PA), which is the most abundant of the free fatty acids (FFAs), increased CCL2 via the GPRs/KLF7 pathway in bone marrow adipocytes (BMA) to facilitate PCa growth and metastasis. METHODS: We constructed a bone-tumor bearing mouse model with obesity through high-fat diet, and observed the tumor formation ability of PCa cells. In vitro, observe the effect of PA on the expression level of CCL2 in BMA through GPRs/KLF7 signaling pathway. After co-culture of BMA and PCa cells, CCK8 assay and transwell experiment were used to detect the changes in biological behavior of PCa cells stimulated by BMA. RESULTS: The BMA distribution in the bone marrow cavity of BALB/c nude mice fed with the high-fat diet (HFD) was evidently higher than that in the mice fed with the normal diet (ND). Moreover, HFD-induced obesity promoted KLF7/CCL2 expression in BMA and PCa cell growth in the bone marrow cavity of the mice. In the vitro experiment, a conditioned medium with increased CCL2 obtained from the BMA cultured with PA (CM-BMA-PA) was used for culturing the PCa cell lines, which evidently enhanced the proliferation, invasion, and migration ability. KLF7 significantly increased the CCL2 expression and secretion levels in BMA by targeting the promoter region of the CCL2 gene. In addition, GPR40/120 engaged in the PA-induced high KLF7/CCL2 levels in BMA to facilitate the malignant progression of PC-3 cells. CONCLUSIONS: PA-activated GPRs/KLF7/CCL2 pathway in BMA facilitates prostate cancer growth and metastasis.

The Influence of Carbides on Atomic-Scale Mechanical Properties of Carbon Steel: A Molecular Dynamics Study.

Pearlite is an important structure in carbon steel; however, the influence mechanism of carbides in pearlite on its mechanical properties and microstructure evolution has not yet been fully elucidated. In this work, a ferrite-carbide composite model with various carbide types was constructed to investigate the influence of carbide types via a uniaxial compression deformation using classical molecular dynamics simulations. It was found that the carbide type had little effect on the compressive elastic modulus, but a more obvious effect on the yield strain, yield stress, and flow stress. The maximum compressive elastic modulus was in the Fe2C model, with 300.32 GPa, while the minimum was found in the Fe4C model at 285.16 GPa; the error was 5.32%. There were significant differences in the yield stress, yield strain, and flow stress of the ferrite-carbide model according to the stress-strain curve. Secondly, the type of carbide used affected its elastic constant, especially the bulk modulus and Cauchy pressure. The maximum bulk modulus of the Fe4C model was 199.01 GPa, the minimum value of the Fe3C model was 146.03 GPa, and the difference was 52.98 GPa. The Cauchy pressure calculation results were consistent with the yield strain trend. Additionally, the effective elastic moduli of the composite system were used to verify the accuracy of the calculation results of this work. Thirdly, ferrite-carbide interfaces could act as a resource for dislocation emission. The initial stacking fault forms at ferrite-carbide interfaces and expands into ferrite. The dislocation type and segment in the ferrite-carbide model were significantly different due to the type of carbide used.

Application of the TDFA window in true optical time delay systems.

Recent advances in silicon photonic components operating in the thulium-doped fiber amplifier (TDFA) wavelength regime around 2-µm have shown that these wavelengths hold great promise for on-chip photonic systems. Here we present our work on characterizing a Mach-Zehnder interferometer coupled silicon photonic ring resonator operating in the TDFA window for optical time delay applications. We describe the optical transmission and variable time delay properties of the resonator, including a detailed characterization and comparison of the directional coupler and Mach-Zehnder interferometer base components at both 1930 and 1550 nm wavelengths. The results show tuning of a ring from a 190-ps peak time delay at a resonant extinction ratio of 5.1-dB to a 560-ps peak time delay at an extinction ratio of 11.0-dB, in good agreement with optical models of the device. These results demonstrate significant promise towards the future application of TDFA band devices in optical time delay systems.

[RS102895 inhibits the proliferation, invasion, and migration of PC-3 prostate cancer cells by blocking CCL2/CCR2 pathway].

Objective To investigate the effect of RS102895, a specific C-C motif chemokine receptor 2 (CCR2) antagonist, on the biological behavior of prostate cancer (PCa) cells with different degrees of malignancy. Methods Non-androgen-dependent prostate cancer cells PC-3 and androgen-dependent prostate cancer cells 22RV1 were cultured in vitro. A control group, a recombinant C-C motif chemokine ligand 2 (rCCL2) treatment group, and a rCCL2 combined with RS102895 treatment group were established. Cell proliferation ability was detected by CCK-8 assay, cell invasion and migration abilities were detected by TranswellTM assay, mRNA expressions of cell antigen KI-67 (ki67) and matrix metalloproteinase 2 (MMP2) were detected by real-time quantitative PCR, and protein expression levels of ki67 and MMP2 were detected by Western blotting. Results The proliferation, invasion, and migration abilities of PC-3 cells were significantly enhanced by rCCL2, and the proliferation ability of 22RV1 cells was significantly increased as well. Meanwhile, the mRNA and protein expression levels of ki67 and MMP2 in PC-3 cells were significantly up-regulated by rCCL2. After RS102895 treatment, the above effects of rCCL2 were reversed. Conclusion RS102895 can inhibit the proliferation, invasion, and migration of PC-3 prostate cancer cells by specifically blocking the CCL2/CCR2 pathway and down-regulating the expressions of ki67 and MMP2.

Caprylic acid (C8:0) promotes bone metastasis of prostate cancer by dysregulated adipo-osteogenic balance in bone marrow.

Prostate cancer (PCa) continues to be the most common, noncutaneous cancer in men. Bone is the most frequent site of PCa metastases, and up to 90% of patients with advanced PCa develop bone metastases. An altered bone marrow microenvironment, induced by obesity, is a significant mediator for the bone tropism of PCa. However, the specific molecular mechanisms by which obesity causes changes in the bone marrow microenvironment, leading to PCa bone metastasis, are not fully understood. Our results demonstrate that a high-fat diet (HFD) leads to dyslipidemia and changes in bone marrow of nude mice: an increase in the area and number of adipocytes and a reduction in the area and number of osteoblasts. Moreover, a HFD promoted cyclooxygenase 2 (COX2) expression and inhibited osteoprotegerin (OPG) expression in the bone microenvironment. Additionally, the total level of free fatty acids (FFAs) and caprylic acid (C8:0) was significantly higher in PCa patients with bone metastases. In vitro, caprylic acid (C8:0) promoted bone mesenchymal stem cell (MSC)-derived adipocytic differentiation, COX2 expression, and prostaglandin E2 (PGE2) secretion, whereas osteoblastic differentiation and OPG expression were reduced. Furthermore, caprylic acid (C8:0)-treated adipocytes promoted the invasion and migration of PCa cells. Taken together, our findings suggest caprylic acid (C8:0) promotes bone metastasis of PCa by dysregulated adipo-osteogenic balance of bone marrow.

Free Fatty Acids Promote the Development of Prostate Cancer by Upregulating Peroxisome Proliferator-Activated Receptor Gamma.

INTRODUCTION: As one of the most common forms of cancer that threatens men's health, prostate cancer (PCa) is under a trend of increasing morbidity and mortality in most countries. More and more studies have pointed out that obesity is closely linked to the occurrence and development of PCa, although there are still many undiscovered molecular mechanisms between the two. METHODS: In the present study, we compare serum lipid levels in patients with PCa and normal individuals. PCa cells (PC3 and 22RV1) were cultured in vitro, the TC/TG/HDL/GLU assay kit was used to detect the glucose and lipid metabolism level of PCa cells, the flow cytometry technique was used to detect the proliferation ability of PCa cells, and the Transwell was used to detect the invasion and migration ability of PCa cells. Western blot/quantitative real-time PCR was used to detect peroxisome proliferator-activated receptor γ (PPARγ) and vimentin/vascular endothelial growth factor-A (VEGF-A) expression levels, and immunohistochemistry was used to observe tumor-associated gene expression levels in nude mice. All data were analysed using the Independent samples t-test or rank sum test. RESULTS: We found higher levels of FFA in the serum of patients with PCa. In vitro experiments have demonstrated that high levels of FFA can promote the proliferation, migration and invasion of two PCa cells (PC3 and 22RV1) and affect the energy metabolism of PCa cells. The upregulated PPARγ plays a key role in this process, and vimentin may be involved in this signaling pathway. CONCLUSION: We infer that high levels of FFA may promote PCa development by upregulating PPARγ expression.

High Level of Palmitic Acid Induced Over-Expressed Methyltransferase Inhibits Anti-Inflammation Factor KLF4 Expression in Obese Status.

Our study is based on the establishment of a cohort of human obese omental adipose tissue and the culture of adipocytes in vitro. To observe the effect of high level of free fatty acid (FFA) on the expression of DNA methyltransferases (DNMTs) and the anti-inflammatory factor Kruppel-like factor 4 (KLF4) in adipocytes and evaluate the role of methyltransferases in FFA inhibiting KLF4 expression. A total of 20 normal patients and 20 obese patients were selected for further test. qRT-PCR and western blot were used to detect the mRNA and protein expression levels of DNMT1/DNMT3a/DNMT3b and KLF4 in human adipose tissue and 3T3-L1 adipocytes which stimulated with saturated fatty acid, palmitic acid (PA). Bisulfite sequencing PCR (BSP) detected methylation status of KLF4 gene in human adipose tissue. It was found that the mRNA and protein expression levels of DNMT1 and DNMT3a in the omental tissue of obese individuals were higher than those in normal group, but the expression of KLF4 was decreased. The positive methylation rate of KLF4 promoter region in obese individuals were significantly higher than those in normal individuals, especially at CpG_33 and CpG_34 sites. Meanwhile compared with non-methylated group at CpG_33 and CpG_34 sites of KLF4 promoter region, the DNMT3a mRNA expression in methylated group were significantly increased. A total of 200 µM PA significantly promoted DNMT1, DNMT3a, and DNMT3b and inhibited KLF4 protein expression levels in 3T3-L1 adipocytes. Our findings suggest that under obesity status, the lower expression level of KLF4 of visceral adipose tissue may correlate with palmitic acid promoted DNMTs expression in adipocytes.

Serum FFAs profile analysis of Normal weight and obesity individuals of Han and Uygur nationalities in China.

BACKGROUND: Han and Uygur are the two main nationalities living in Xinjiang, China. There are significant differences in the incidence of metabolic diseases for two nationalities, but the specific reasons are not clear. Obesity is an important risk factor for the development of metabolic syndrome, which may be closely related to the increase of serum free fatty acids (FFAs) content. This study aims to use metabolomics to compare the changes of serum FFAs profiles between normal weight (NW) and obese (OB) individuals of two nationalities, screening out the differential FFAs, predicting and evaluating their relationship with diseases. METHODS: Thirty-four kinds of FFAs in serum were detected by ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) and distinctions in FFAs profiles were evaluated using a metabolomics method while Receiver operating characteristics (ROC) and logistic regression models were used to explore FFAs significant for diagnosing obesity and obesity-associated comorbidities. RESULTS: In the Han nationality, ten kinds of FFAs (C7:0, C8:0, C9:0, C10:0, C11:0, C14:0, C18:2, C20:3, C20:4 and C22:6) showed significant differences between NW and OB individuals. These differential FFAs may be related to hypertension and gestational diabetes mellitus. In the Uygur nationality, C20:3 and C20:5 showed significant differences between NW and OB individuals. C9:0 and C19:0, which were screened out among the female subjects, showed a good ability to predict obesity status in Uygur females (AUC = 0.950). CONCLUSION: In both the Han and Uygur nationalities, the FFAs profiles of NW individuals differed from those of OB individuals. The significantly differential FFAs are closely related to obesity and may be important risk factors for obesity and related metabolic diseases.

Young and old adipocytes have differential influence on the development of osteoblasts.

OBJECTIVE: The aim of the current study was to investigate the effect of adipocytes on the differentiation of osteoblasts at different stages of adipocyte development. METHODS: BMSCs were isolated from 4-week-old male wistar rat femurs and tibias, and flow cytometry was performed. Adipocytes were derived from BMSCs, cell morphology was continually observed from day 21 to day 50. Adipocyte medium was collected once every 2days (d) and ELISA kits were used for detection of triglycerides (TG), tumor necrosis factor-α (TNF-α), and interleukin-6(IL-6) expression level. 21d and 40d old adipocyte and osteoblast cells were co-cultured, and alizarin red staining was performed after 21d. After co-culture, the adherent cells were collected, and the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) was detected by real time PCR. RESULT: Results of cell characterisation showed that the cells had positive expression of CD29 (97.92%) and CD44 (89.32%). With the increase of the induction time of mature adipocytes, the number of adipocyte on 21thd was significantly higher than 40thd, while the volume of adipocyte was significantly lower than 40thd (P<0.05). The levels of TG(2.6±0.83mmol/l VS 3.8±0.66mmol/l), TNF-α(30.5±2.53pg/ml VS 57.6±5.1pg/ml), and IL-6(32.5±1.42pg/ml VS 55.1±5.97pg/ml) secreted by adipocytes increased with induction time: 40thd was significantly higher than 21thd (P<0.01). When 21thd adipocytes and osteoblasts were co-cultured, the number of calcium nodules significantly increased over that of the positive control group, When 40thd adipocytes and osteoblasts were co-cultured, the number of calcium nodules significantly decreased over that of the positive control group (P<0.05). The OPG(68.9±5.39 VS 1.00±0.36) expression was significantly increased, and the expression of RANKL (2.0±0.84 VS 34.4±2.01) was significantly decreased from the 21thd adipocytes co-cultured group compared with the 40thd adipocytes co-cultured group (P<0.001). CONCLUSION: The differential size of adipocytes in the bone marrow can affect bone metabolism by regulating the expression of OPG/RANKL.

The Effect and Mechanism of KLF7 in the TLR4/NF-κB/IL-6 Inflammatory Signal Pathway of Adipocytes.

OBJECTIVE: To investigate the role and possible molecular mechanism of Krüppel-like factor 7 (KLF7) in the TLR4/NF-κB/IL-6 inflammatory signaling pathway activated by free fatty acids (FFA). METHODS: The mRNA and protein expression levels of KLF7 and the factors of TLR4/NF-κB/IL-6 inflammatory signal pathways were detected by qRT-PCR and Western blotting after cell culture with different concentrations of palmitic acid (PA). The expression of KLF7 or TLR4 in adipocytes was upregulated or downregulated; after that, the mRNA and protein expression levels of these key factors were detected. KLF7 expression was downregulated while PA stimulated adipocytes, and then the mRNA and protein expressions of KLF7/p65 and downstream inflammatory cytokine IL-6 were detected. The luciferase reporter assay was used to determine whether KLF7 had a transcriptional activation effect on IL-6. RESULTS: (1) High concentration of PA can promote the expression of TLR4, KLF7, and IL-6 in adipocytes. (2) TLR4 positively regulates KLF7 expression in adipocytes. (3) KLF7 positively regulates IL-6 expression in adipocytes. (4) PA promotes IL-6 expression via KLF7 in adipocytes. (5) KLF7 has a transcriptional activation on IL-6. CONCLUSION: PA promotes the expression of the inflammatory cytokine IL-6 by activating the TLR4/KLF7/NF-κB inflammatory signaling pathway. In addition, KLF7 may directly bind to the IL-6 promoter region and thus activate IL-6.

Post-silking Factor Consequences for N Efficiency Changes Over 38 Years of Commercial Maize Hybrids.

Hybrid selection in maize (Zea mays L.) over the decades has increased post-silking dry matter (PostDM) and nitrogen (PostN) accumulation, often with an accompanying increase in one or more N use efficiency (NUE) metrics such as partial factor productivity (PFP), N conversion efficiency (NCE), and N internal efficiency (NIE). More certainty on the underlying mechanisms of how PostDM and PostN changes over time have contributed to NUE gains or losses in modern-era hybrids can only be realized by directly comparing hybrids of different eras in the context of production-system-relevant management systems. A two-year and two-location field study was conducted in Indiana with two N rates (55 and 220 kg N ha-1), three plant densities (54,000, 79,000, and 104,000 plants ha-1) and eight commercial hybrids that were released by a single seed company from 1967 to 2005. The main treatment effects of N rate, density, and hybrid dominated the PostDM and PostN responses, and there were no significant two-way or three-way interactions. Total dry matter at maturity gains averaged 80 kg ha-1 year-1 of hybrid release when averaged over locations, plant densities and N rates. Total N contents at maturity increased 0.68 kg ha-1 year-1, primarily due to annual increases in grain N content (0.8 kg ha-1 year-1). Post-silking N uptake rate increased 0.44 kg ha-1 year-1 for these era hybrids in more favorable production site-years. Slopes of grain N concentration increases per unit PostN gain were similar for all hybrids. Gains in average PFP over time were considerably higher at the low N rate (0.9 kg ha-1 year-1) than at the high N rate (0.3 kg kg-1 year-1). Hybrid gains in NIE were evident from 1967 to 1994, but not thereafter. The low N rate and higher plant densities also increased relative NIE and NCE values, but without hybrid interactions. There was no consistent trend of NIE or NCE gains in these hybrids primarily because grain and whole-plant N concentrations didn't decline over the decades at either N rate, and because NIE and NCE were often plant-density dependent.

Is the inherent potential of maize roots efficient for soil phosphorus acquisition?

Sustainable agriculture requires improved phosphorus (P) management to reduce the overreliance on P fertilization. Despite intensive research of root adaptive mechanisms for improving P acquisition, the inherent potential of roots for efficient P acquisition remains unfulfilled, especially in intensive agriculture, while current P management generally focuses on agronomic and environmental concerns. Here, we investigated how levels of soil P affect the inherent potential of maize (Zea mays L.) roots to obtain P from soil. Responses of root morphology, arbuscular mycorrhizal colonization, and phosphate transporters were characterized and related to agronomic traits in pot and field experiments with soil P supply from deficiency to excess. Critical soil Olsen-P level for maize growth approximated 3.2 mg kg(-1), and the threshold indicating a significant environmental risk was about 15 mg kg(-1), which represented the lower and upper levels of soil P recommended in current P management. However, most root adaptations involved with P acquisition were triggered when soil Olsen-P was below 10 mg kg(-1), indicating a threshold for maximum root inherent potential. Therefore, to maintain efficient inherent potential of roots for P acquisition, we suggest that the target upper level of soil P in intensive agriculture should be reduced from the environmental risk threshold to the point maximizing the inherent potential of roots.

Insulin-Mimetic Action of Rhoifolin and Cosmosiin Isolated from Citrus grandis (L.) Osbeck Leaves: Enhanced Adiponectin Secretion and Insulin Receptor Phosphorylation in 3T3-L1 Cells.

Citrus grandis (L.) Osbeck (red wendun) leaves have been used in traditional Chinese medicine to treat several illnesses including diabetes. However, there is no scientific evidence supporting these actions and its active compounds. Two flavone glycosides, rhoifolin and cosmosiin were isolated for the first time from red wendun leaves and, identified these leaves are rich source for rhoifolin (1.1%, w/w). In differentiated 3T3-L1 adipocytes, rhoifolin and cosmosiin showed dose-dependent response in concentration range of o.oo1-5 µM and 1-20 µM, respectively, in biological studies beneficial to diabetes. Particularly, rhoifolin and cosmosiin at 0.5 and 20 µM, respectively showed nearly similar response to that 10 nM of insulin, on adiponectin secretion level. Furthermore, 5 µM of rhoifolin and 20 µM of cosmosiin showed equal potential with 10 nM of insulin to increase the phosphorylation of insulin receptor-ß, in addition to their positive effect on GLUT4 translocation. These findings indicate that rhoifolin and cosmosiin from red wendun leaves may be beneficial for diabetic complications through their enhanced adiponectin secretion, tyrosine phosphorylation of insulin receptor-ß and GLUT4 translocation.

Andrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal mesangeal cell lines.

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of Andrographis paniculata Nees are used for various ethnomedical conditions including hyperglycemia and hypertension complications. AIM OF THE STUDY: The purpose of this study is to evaluate the anti-diabetic nephropathy effect of diterpene lactones andrographolide (AP1) and 14-deoxy-11,12-didehydroandrographolide (AP2) from Andrographis paniculata. MATERIALS AND METHODS: MES-13, a SV40-transformed murine glomerular mesangial cell line, was cultured in high concentration of glucose to induce diabetic nephropathy phenotypes, which include secretion of extracellular matrix protein fibronectin, cytokine TGF-ß, states of oxidative stress, and apoptosis marker caspase-3. RESULTS: Our data suggest that addition of compounds AP1 or AP2 reduces the phenotypes indicating diabetic nephropathy in MES-13 cells. The compound AP2 showed potent activity than AP1 in the reduction of apoptosis marker caspase-3, fibrosis marker TGF-ß, and PAI-1. Furthermore, AP1 and AP2 do not have antioxidant ability in acellular environment; however, addition of AP1 and AP2 reduced intracellular oxidative states in high glucose cultured MES-13 cells. CONCLUSION: This is the first report on anti-diabetic nephropathy effect of AP1 and AP2 in part due to the regulation of intracellular signaling transduction, not mere clearance of reactive oxygen species. Thus, this study may be useful for drug development or food supplement for diabetes and nephropathy from Andrographis paniculata.

Effect of flavonol glycosides from Cinnamomum osmophloeum leaves on adiponectin secretion and phosphorylation of insulin receptor-beta in 3T3-L1 adipocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum osmophloeum is used for various ethnomedical conditions in Taiwan including diabetic complications. AIM OF THE STUDY: The aim of present study was to identify the anti-diabetic compounds from C. osmophloeum leaves and evaluate the preliminary molecular basis for their insulin-like effects. MATERIALS AND METHODS: Silica gel column chromatographic purification of MeOH extract from leaves of C. osmophloeum resulted in the isolation of a two kaempferol glycosides CO-1 and CO-2. These two compounds were evaluated for their effects on adiponectin secretion, tyrosine phosphorylation of insulin receptor (IR)-beta and glucose transporter 4 (GLUT4) in differentiated mouse 3T3-L1 adipocytes, and the results were compared with the reference drug insulin. RESULTS: The compound CO-1 at a concentration of 5 microM was able to act as an insulin-mimetic in terms of its ability to increase adiponectin secretion by 12.2-fold, while CO-2 has no such effect up to 20 microM tested. Furthermore, 5 microM of CO-1 and 20 microM of CO-2 showed potential to increase the phosphorylation of IRbeta by 2.3- and 2.1-fold, respectively, in addition to their positive effect on GLUT4 translocation. CO-1 and CO-2 stimulated GLUT4 translocation are reduced by phosphatidylinositol-3-kinase (PI3-K) inhibitor. CONCLUSION: The present study indicates that the insulin-like anti-diabetic mechanism of constituents from C. osmophloeum leaves in part due to enhanced adiponectin secretion, and activation of insulin signaling pathway leading to GLUT4 translocation which involved phosphorylation of IR and activation of PI3-K.

Kaempferitrin activates the insulin signaling pathway and stimulates secretion of adiponectin in 3T3-L1 adipocytes.

The purpose of the current study was to examine the signal transduction pathways activated and adipokine secreted by kaempferitrin stimulation to adipocytes. Activation of insulin receptor beta and insulin receptor substrate 1 was tested in pull-down assays, and phosphorylation of Protein kinase B (PKB/akt) on ser 473 was measured by Western blot. Participation of phosphatidylinositol-3-kinase (PI3-K) in the pathway was tested by addition of wortmannin. GLUT4 translocation was measured on fractions of cell extracts, as well as by confocal imaging on fluorescent immunostained cells. Secreted and cellular adiponectin were measured by Western blot and ELISA. We showed that kaempferitrin treatment resulted in an up-regulated level of phosphorylation on insulin receptor beta and insulin receptor substrate 1, and ser473 site in PKB/akt. PI3-K acted up-stream of PKB/akt phosphorylation and GLUT4 translocation, as inhibitor of PI3-K wortmannin abolished both. GLUT4 translocated to membrane and GLUT4 protein level increased upon kaempferitrin stimulation. Kaempferitrin also stimulated more sustained adiponectin secretion than insulin did. This study provided evidence of the dual effects of kaempferitrin. It improved insulin resistance by the activation of the classical insulin transduction pathway, and increased adiponectin secretion.