Pakistan Journal of Medical Sciences, Dec 31, 1969
Objective: This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegaloviru... more Objective: This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegalovirus (HCMV) in extravillous cytotrophoblast cell line HPT-8 and possible underlying mechanism. Method: Real time PCR and flow cytometry were used to determine B7-H1 mRNA and protein before and after HCMV infection in HPT-8 cells. Western blot analysis was used to determine the level of MAPK phosphorylation in HPT-8 cell lines infected with HCMV. Results: 100TCID50 was found to be the most effective dose, capable of stimulating B7-H1 mRNA and protein expression in HPT-8 cells. When empty control group was considered to have a B7-H1 mRNA value of 1, B7-H1 mRNA was 4.32 in 100TCID50 group. In flow cytometry study, mean fluorescence intensity (MFI) of 100TCID50 group was 16.14, while empty control group was 1.34. Both mRNA and protein expression were found to be significantly increased (P < 0.05) in 100TCID50 group compared to empty control group. The result of Western blot analysis showed increase in B7-H1 expression caused by the extracellular signaling that was related to ERK activation and the ERK inhibitor U0126 was found to reverse this increase. Conclusion: HCMV upregulates B7-H1 expression in human extravillous cytotrophoblast cell line HPT-8, which is related to MAPK activation. Our result would be helpful in finding better therapies against intrauterine HCMV infection.
Abstract Dopant-free hole-transporting materials (HTMs) play a vital role in improving the power ... more Abstract Dopant-free hole-transporting materials (HTMs) play a vital role in improving the power conversion efficiencies (PCEs) and stability for all-inorganic perovskite solar cells (PVSCs). In this work, two donor-acceptor-donor (D-A-D) type HTMs (L2 and L2-T) were designed and synthesized by using a ladder-type heteroacene core. Compared to L2-T with thiophene spacers, L2 presents suitable energy levels, smooth surface morphology, and improved hole mobility. Consequently, CsPbI2Br PVSC based on L2 delivers a decent PCE of 12.41%, which outperforms the counterpart based on L2-T (11.07%). Whereas, the control device based on dopant-free 2,2′,7,7′-tetrakis(N,N-di-p-methoxyphenylamine)-9,9′-spirobifluorene (Spiro-OMeTAD) reveals a relatively low PCE of 9.95%. In addition, both the L2-and L2-T-based devices can maintain over 85% of their original PCEs after 1000 hours storage demonstrating their excellent shelf stability. This work highlights the good potential of the ladder-type heteroacene building block for developing dopant-free HTMs toward high-performance CsPbI2Br PVSCs.
A simple small molecule of BTF is used as a third component in the binary blends of J71:ITIC and ... more A simple small molecule of BTF is used as a third component in the binary blends of J71:ITIC and PM6:Y6 to achieve efficient ternary polymer solar cells with enhanced PCEs of 12.35% and 16.53%, respectively.
Besides an aromatic polycyclic core with extended -conjugation, side-chains and terminal groups ... more Besides an aromatic polycyclic core with extended -conjugation, side-chains and terminal groups are the other two molecular-structure factors which can greatly affect the photovoltaic performance of non-fullerene acceptors. In this work, three dithienocyclopentacarbazole-based non-fullerene acceptors (HCN-C8, HCN-C16, and H2FCN-C16) have been designed and synthesized to investigate the effects of side-chain and fluorination on the photovoltaic properties of non-fullerene acceptors. Among the three acceptors, HCN-C8 and HCN-C16 were designed with the same terminal group of 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (INCN), but with different side-chains of octyl and 2-hexyldecyl appended on the central nitrogen of the dithienocyclopentacarbazole unit, respectively. H2FCN-C16 and HCN-C16 share the same side-chain of 2-hexyldecyl, but the former is designed with the fluorinated INCN in the terminal groups. Although the side-chain has a neglectable effect on the bandgap and energy levels of the resulting non-fullerene acceptors, the replacement of linear octyl chain with the branched 2-hexyldecyl chain leads to a crystallinity change of the resulting acceptors from crystalline to amorphous thereby affecting their phase separation with donor polymers. On the other hand, the non-fullerene acceptor with fluorination on the ending groups shows a decreased optical bandgap with deepened energy levels in comparison with the counterpart without the fluorination. By using a p-type polymer (J71) as the donor material, the best-efficiency polymer solar cell based on H2FCN-C16 exhibited an impressive power conversion efficiency (PCE) of 11.18% with a high short circuit current density (J SC) of 18.62 mA cm-2 , a fill factor (FF) of 66.7%, and an open circuit voltage (V OC) of 0.90 V. The PCE of 11.18 % is the highest among all dithienocyclopentacarbazole-based nonfullerene acceptors reported so far. However, the best-efficiency solar cells based on HCN-C8 and HCN-C16 showed low PCEs of 2.38% and 5.51%, respectively. We further elucidated the important structure-property relationships for these dithienocyclopentacarbazole-based non-fullerene acceptors. These results provide useful guidelines for enhancing the performance of non-fullerene acceptors through fluorination and side-chain engineering.
Novel wide-bandgap copolymers based on ladder-type dithienocyclopentadibenzothiophene were develo... more Novel wide-bandgap copolymers based on ladder-type dithienocyclopentadibenzothiophene were developed for polymer solar cells with 9.46% efficiency and excellent stability.
Diindenocarbazole-based large bandgap polymers were designed and synthesized as short wavelength ... more Diindenocarbazole-based large bandgap polymers were designed and synthesized as short wavelength absorbing materials for PSCs exhibiting an efficiency up to 7.34% and a Voc as large as 0.95 V.
This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegalovirus (HCMV) in... more This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegalovirus (HCMV) in extravillous cytotrophoblast cell line HPT-8 and possible underlying mechanism. Real time PCR and flow cytometry were used to determine B7-H1 mRNA and protein before and after HCMV infection in HPT-8 cells. Western blot analysis was used to determine the level of MAPK phosphorylation in HPT-8 cell lines infected with HCMV. 100TCID50 was found to be the most effective dose, capable of stimulating B7-H1 mRNA and protein expression in HPT-8 cells. When empty control group was considered to have a B7-H1 mRNA value of 1, B7-H1 mRNA was 4.32 in 100TCID50 group. In flow cytometry study, mean fluorescence intensity (MFI) of 100TCID50 group was 16.14, while empty control group was 1.34. Both mRNA and protein expression were found to be significantly increased (P<0.05) in 100TCID50 group compared to empty control group. The result of Western blot analysis showed increase in B7-H1 expression cau...
We investigated the role of G␣q, filamin, Rho, the RhoGEF Lbc, and the C terminus of calcium-sens... more We investigated the role of G␣q, filamin, Rho, the RhoGEF Lbc, and the C terminus of calcium-sensing receptor (CasR) in CasR signaling. We found that Ca 2؉ , Mg 2؉ , or the calcimimetic R isomer of N-(3-[2-chlorophenyl]propyl)-(R)-␣-methyl-3-methoxybenzylamine (NPS-R568) stimulated serum response element (SRE) activity human embryonic kidney 293 cells transfected with CasR and an SRE-luciferase reporter construct. Coexpression of either the dominant negative G␣q(305-359) minigene, regulators of G protein signaling (RGS)2 or RGS4, inhibited CasR-stimulated SRE activity, consistent with CasR activation of G␣q. The cytoskeletal associated Rho protein is involved CasR activation of SRE, as evidenced by CasR-mediated increase in membrane-associated Rho A and by the ability of Clostridium botulinum C3 (C3) exoenzyme to inhibit both CasR and G␣qQL-stimulated SRE activity. Overexpression of the RhoGEF Lbc, lacking either the Dbl-homology or Pleckstrin homology domain, as well as the filamin peptide (1530-1875) inhibited CasRmediated activation of SRE. A carboxyl-terminal CasR minigene, CasR(906-980), encoding a filamin binding region, also blocked CasR-and G␣qQL-stimulated SRE activity. Potential interactions between CasR, RhoGEF Lbc, Rho A, G␣q, and filamin were demonstrated by reciprocal coimmunoprecipitation studies. Our results suggest that the C terminus of CasR may interact with filamin to create a cytoskeletal scaffold necessary for the spatial organization of G␣q, RhoGEF Lbc, and Rho signaling pathways upstream of SRE activation.
Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone format... more Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone formation surrounding the implant is relatively slow after inserting the implant. The current study assessed the effects of bone marrow stromal cells (BMSCs) with forced expression of special AT-rich sequence-binding protein 2 (SATB2) on the osseointegration of titanium implants. To determine whether SATB2 overexpression in BMSCs can enhance the osseointegration of implants, BMSCs were infected with the retrovirus encoding Satb2 (pBABE-Satb2) and were locally applied to bone defects before implanting the titanium implants in the mouse femur. Seven and twentyone days after implantation, the femora were isolated for immunohistochemical (IHC) staining, haematoxylin eosin (H&E) staining, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and micro-computed tomography (μCT) analysis. IHC staining analysis revealed that SATB2-overexpressing BMSCs were intensely distributed in the bone tissue surrounding the implant. Histological analysis showed that SATB2overexpressing BMSCs significantly enhanced new bone formation and bone-to-implant contact 3 weeks after implantation. Real-time qRT-PCR results showed that the local delivery of SATB2-overexpressing BMSCs enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins in the implantation sites. μCT analysis demonstrated that SATB2-overexpressing BMSCs significantly increased the density of the newly formed bone surrounding the implant 3 weeks postoperatively. These results conclude that local delivery of SATB2-overexpressing BMSCs significantly accelerates osseointegration of titanium implants. These results provide support for future pharmacological and clinical applications of SATB2, which accelerates bone regeneration around titanium implants.
To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage dev... more To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Prolifera...
Balancing the process of bone formation and resorption is important in the maintenance of healthy... more Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone‐like peptide. Recent studies have reported the involvement of irisin in many physiological and pathological conditions with bone mineral density changes, including osteopenia and osteoporotic fractures. In this study, we generated the first line of Osx‐Cre:FNDC5/irisin KO mice, in which FNDC5/irisin was specifically deleted in the osteoblast lineage. Gene and protein expressions of irisin were remarkably decreased in bones but no significant differences in other tissues were observed in knockout mice. FNDC5/irisin deficient mice showed a lower bone density and significantly delayed bone development and mineralization from early‐stage to adulthood. Our phenotypical analysis exhibited decreased osteoblast‐related gene expression and increased osteoclast‐re...
Central adiponectin (APN) in either the globular (gAPN) or full-length (fAPN) forms decrease symp... more Central adiponectin (APN) in either the globular (gAPN) or full-length (fAPN) forms decrease sympathetic tone and increase trabecular bone mass in mice through the hypothalamus. It is known that cannabinoid type-1 (CB1) receptors are expressed in the hypothalamic ventromedial nucleus (VMN) and participate in energy metabolism by controlling sympathetic activity. However, whether central APN could influence endocannabinoid signaling through CB1 receptor to regulate bone metabolism has not been characterized. Here we demonstrate that gAPN downregulated CB1 expression in embryonic mouse hypothalamus N1 cells in vitro. gAPN
Specific microRNAs (miRs) and the Wnt signaling pathway play critical roles in regulating bone de... more Specific microRNAs (miRs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous studies revealed the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to use nano-materials to efficiently deliver miR-335-5p into osteogenic cells for tissue engineering applications. We synthesized and screened a library of 12 candidate nano-lipidoids，of which L8 was identified as the preferred biodegradable lipidoid for miRNA molecule delivery into cells. We then investigated whether a lipidoid-miRNA formulation of miR-335-5-p (LMF-335) could successfully deliver miR-335-5-p into cells to promote osteogenesis in vitro and calvarial bone healing in vivo. Transfection of C3H10T1/2 cells and bone marrow stromal cells (BMSCs) with LMF-335 led to decreased expression of DKK1 and increased expression of the key osteogenic genes. LMF-335 and LMF-335-transfected...
Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III dom... more Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain-containing 5 (FNDC5) protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression, leading to an increase in total body energy expenditure by augmented UCP1-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone–tendon interface. Exercise also increased expression of osteogenic markers in ...
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 29, 2017
MicroRNAs (miRNAs) and the Wnt signaling pathway play critical roles in regulating bone developme... more MicroRNAs (miRNAs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous study revealed high expression of miR-335-5p in osteoblasts and hypertrophic chondrocytes in mouse embryos and the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to investigate the effects of miR-335-5p constitutive overexpression on bone formation and regeneration in vivo. To that end, we generated a transgenic mouse line specifically overexpressing miR-335-5p in osteoblasts lineage by the osterix promoter and characterized its bone phenotype. Bone histomorphometry and μCT analysis revealed higher bone mass and increased parameters of bone formation in transgenic mice than in wild-type littermates. Increased bone mass in transgenic mice bones also correlated with enhanced expression of osteogenic differentiation markers. Upon osteogenic induction, bone marrow s...
DICER is the central enzyme that cleaves precursor microRNAs (miRNAs) into 21-25 nucleotide duple... more DICER is the central enzyme that cleaves precursor microRNAs (miRNAs) into 21-25 nucleotide duplex in cell lineage differentiation, identity and survival. In the current study, we characterized the specific bone metabolism genes and corresponding miRNAs and found that DICER and Runt-related transcription factor 2 (Runx2) expressions increased simultaneously during osteogenic differentiation. Luciferase assay showed that Runx2 significantly increased the expression levels of DICER luciferase promoter reporter. Our analysis also revealed weaker DICER expression in embryos of Runx2 knock out mice (Runx2 -/-) compared with that of Runx2 +/- and Runx2 +/+ mice. We further established the calvarial bone critical-size defect (CSD) mouse model. The bone marrow stromal cells (BMSCs) transfected with siRNA targeting DICER were combined with silk scaffolds and transplanted into calvarial bone CSDs. Five weeks post-surgery, micro-CT analysis revealed impaired bone formation and repairing in cal...
Emerging evidence suggests an important role for epigenetic mechanisms in modulating signals duri... more Emerging evidence suggests an important role for epigenetic mechanisms in modulating signals during macrophage polarization and inflammation. JMJD3, a JmjC family histone demethylase necessary for M2 polarization is also required for effective induction of multiple M1 genes by lipopolysaccharide (LPS). However, the effects of JMJD3 to inflammation in the context of obesity remains unknown. To address this deficiency, we firstly examined the expression of JMJD3 in macrophage isolated from bone marrow and adipose tissue of diet induced obesity (DIO) mice. The results indicated that JMJD3 was down-regulated in obesity. Adiponectin (APN), a factor secreted by adipose tissue which is down-regulated in obesity, functions to switch macrophage polarization from M1 to M2, thereby attenuating chronic inflammation. Intriguingly, our results indicated that APN contributed to JMJD3 up-regulation, reduced macrophage infiltration in obese adipose tissue, and abolished the up-regulation of JMJD3 in...
Adiponectin (APN) is an adipocyte-secreted adipokine that exerts well-characterized antidiabetic ... more Adiponectin (APN) is an adipocyte-secreted adipokine that exerts well-characterized antidiabetic properties. Patients with type 2 diabetes (T2D) are characterized by reduced APN levels in circulation and impaired stem cell and progenitor cell mobilization from the bone marrow for tissue repair and remodeling. In this study, we found that APN regulates the mobilization and recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to participate in tissue repair and regeneration. APN facilitated BMSCs migrating from the bone marrow into the circulation to regenerate bone by regulating stromal cell-derived factor (SDF)−1 in a mouse bone defect model. More importantly, we found that systemic APN infusion ameliorated diabetic mobilopathy of BMSCs, lowered glucose concentration, and promoted bone regeneration in diet-induced obesity mice. In vitro studies allowed us to identify Smad1/5/8 as a novel signaling mediator of APN receptor (AdipoR)−1 in BMSCs and osteoblasts. APN stimula...
American journal of physiology. Endocrinology and metabolism, Jan 15, 2014
Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis a... more Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulin-sensitizing properties. The peripheral or central effects of APN regulating bone metabolism are beginning to be explored but are still not clearly understood. In the present study, we found that APN-knockout (APN-KO) mice fed a normal diet exhibited decreased trabecular structure and mineralization and increased bone marrow adiposity compared with wild-type (WT) mice. APN intracerebroventricular infusions decreased uncoupling protein 1 (UCP1) expression in brown adipose tissue, epinephrine and norepinephrine serum levels, and osteoclast numbers, whereas osteoblast osteogenic marker expression and trabecular bone mass increased in APN-KO and WT mice. In addition, centrally administered APN increased hypothalamic tryptophan hydroxylase 2 (TPH2), cocaine- and amphetamine-regulated transcript (CART), and 5-hydroxytryptamine (serotonin) receptor 2C (Htr2C)...
Pakistan Journal of Medical Sciences, Dec 31, 1969
Objective: This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegaloviru... more Objective: This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegalovirus (HCMV) in extravillous cytotrophoblast cell line HPT-8 and possible underlying mechanism. Method: Real time PCR and flow cytometry were used to determine B7-H1 mRNA and protein before and after HCMV infection in HPT-8 cells. Western blot analysis was used to determine the level of MAPK phosphorylation in HPT-8 cell lines infected with HCMV. Results: 100TCID50 was found to be the most effective dose, capable of stimulating B7-H1 mRNA and protein expression in HPT-8 cells. When empty control group was considered to have a B7-H1 mRNA value of 1, B7-H1 mRNA was 4.32 in 100TCID50 group. In flow cytometry study, mean fluorescence intensity (MFI) of 100TCID50 group was 16.14, while empty control group was 1.34. Both mRNA and protein expression were found to be significantly increased (P < 0.05) in 100TCID50 group compared to empty control group. The result of Western blot analysis showed increase in B7-H1 expression caused by the extracellular signaling that was related to ERK activation and the ERK inhibitor U0126 was found to reverse this increase. Conclusion: HCMV upregulates B7-H1 expression in human extravillous cytotrophoblast cell line HPT-8, which is related to MAPK activation. Our result would be helpful in finding better therapies against intrauterine HCMV infection.
Abstract Dopant-free hole-transporting materials (HTMs) play a vital role in improving the power ... more Abstract Dopant-free hole-transporting materials (HTMs) play a vital role in improving the power conversion efficiencies (PCEs) and stability for all-inorganic perovskite solar cells (PVSCs). In this work, two donor-acceptor-donor (D-A-D) type HTMs (L2 and L2-T) were designed and synthesized by using a ladder-type heteroacene core. Compared to L2-T with thiophene spacers, L2 presents suitable energy levels, smooth surface morphology, and improved hole mobility. Consequently, CsPbI2Br PVSC based on L2 delivers a decent PCE of 12.41%, which outperforms the counterpart based on L2-T (11.07%). Whereas, the control device based on dopant-free 2,2′,7,7′-tetrakis(N,N-di-p-methoxyphenylamine)-9,9′-spirobifluorene (Spiro-OMeTAD) reveals a relatively low PCE of 9.95%. In addition, both the L2-and L2-T-based devices can maintain over 85% of their original PCEs after 1000 hours storage demonstrating their excellent shelf stability. This work highlights the good potential of the ladder-type heteroacene building block for developing dopant-free HTMs toward high-performance CsPbI2Br PVSCs.
A simple small molecule of BTF is used as a third component in the binary blends of J71:ITIC and ... more A simple small molecule of BTF is used as a third component in the binary blends of J71:ITIC and PM6:Y6 to achieve efficient ternary polymer solar cells with enhanced PCEs of 12.35% and 16.53%, respectively.
Besides an aromatic polycyclic core with extended -conjugation, side-chains and terminal groups ... more Besides an aromatic polycyclic core with extended -conjugation, side-chains and terminal groups are the other two molecular-structure factors which can greatly affect the photovoltaic performance of non-fullerene acceptors. In this work, three dithienocyclopentacarbazole-based non-fullerene acceptors (HCN-C8, HCN-C16, and H2FCN-C16) have been designed and synthesized to investigate the effects of side-chain and fluorination on the photovoltaic properties of non-fullerene acceptors. Among the three acceptors, HCN-C8 and HCN-C16 were designed with the same terminal group of 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (INCN), but with different side-chains of octyl and 2-hexyldecyl appended on the central nitrogen of the dithienocyclopentacarbazole unit, respectively. H2FCN-C16 and HCN-C16 share the same side-chain of 2-hexyldecyl, but the former is designed with the fluorinated INCN in the terminal groups. Although the side-chain has a neglectable effect on the bandgap and energy levels of the resulting non-fullerene acceptors, the replacement of linear octyl chain with the branched 2-hexyldecyl chain leads to a crystallinity change of the resulting acceptors from crystalline to amorphous thereby affecting their phase separation with donor polymers. On the other hand, the non-fullerene acceptor with fluorination on the ending groups shows a decreased optical bandgap with deepened energy levels in comparison with the counterpart without the fluorination. By using a p-type polymer (J71) as the donor material, the best-efficiency polymer solar cell based on H2FCN-C16 exhibited an impressive power conversion efficiency (PCE) of 11.18% with a high short circuit current density (J SC) of 18.62 mA cm-2 , a fill factor (FF) of 66.7%, and an open circuit voltage (V OC) of 0.90 V. The PCE of 11.18 % is the highest among all dithienocyclopentacarbazole-based nonfullerene acceptors reported so far. However, the best-efficiency solar cells based on HCN-C8 and HCN-C16 showed low PCEs of 2.38% and 5.51%, respectively. We further elucidated the important structure-property relationships for these dithienocyclopentacarbazole-based non-fullerene acceptors. These results provide useful guidelines for enhancing the performance of non-fullerene acceptors through fluorination and side-chain engineering.
Novel wide-bandgap copolymers based on ladder-type dithienocyclopentadibenzothiophene were develo... more Novel wide-bandgap copolymers based on ladder-type dithienocyclopentadibenzothiophene were developed for polymer solar cells with 9.46% efficiency and excellent stability.
Diindenocarbazole-based large bandgap polymers were designed and synthesized as short wavelength ... more Diindenocarbazole-based large bandgap polymers were designed and synthesized as short wavelength absorbing materials for PSCs exhibiting an efficiency up to 7.34% and a Voc as large as 0.95 V.
This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegalovirus (HCMV) in... more This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegalovirus (HCMV) in extravillous cytotrophoblast cell line HPT-8 and possible underlying mechanism. Real time PCR and flow cytometry were used to determine B7-H1 mRNA and protein before and after HCMV infection in HPT-8 cells. Western blot analysis was used to determine the level of MAPK phosphorylation in HPT-8 cell lines infected with HCMV. 100TCID50 was found to be the most effective dose, capable of stimulating B7-H1 mRNA and protein expression in HPT-8 cells. When empty control group was considered to have a B7-H1 mRNA value of 1, B7-H1 mRNA was 4.32 in 100TCID50 group. In flow cytometry study, mean fluorescence intensity (MFI) of 100TCID50 group was 16.14, while empty control group was 1.34. Both mRNA and protein expression were found to be significantly increased (P<0.05) in 100TCID50 group compared to empty control group. The result of Western blot analysis showed increase in B7-H1 expression cau...
We investigated the role of G␣q, filamin, Rho, the RhoGEF Lbc, and the C terminus of calcium-sens... more We investigated the role of G␣q, filamin, Rho, the RhoGEF Lbc, and the C terminus of calcium-sensing receptor (CasR) in CasR signaling. We found that Ca 2؉ , Mg 2؉ , or the calcimimetic R isomer of N-(3-[2-chlorophenyl]propyl)-(R)-␣-methyl-3-methoxybenzylamine (NPS-R568) stimulated serum response element (SRE) activity human embryonic kidney 293 cells transfected with CasR and an SRE-luciferase reporter construct. Coexpression of either the dominant negative G␣q(305-359) minigene, regulators of G protein signaling (RGS)2 or RGS4, inhibited CasR-stimulated SRE activity, consistent with CasR activation of G␣q. The cytoskeletal associated Rho protein is involved CasR activation of SRE, as evidenced by CasR-mediated increase in membrane-associated Rho A and by the ability of Clostridium botulinum C3 (C3) exoenzyme to inhibit both CasR and G␣qQL-stimulated SRE activity. Overexpression of the RhoGEF Lbc, lacking either the Dbl-homology or Pleckstrin homology domain, as well as the filamin peptide (1530-1875) inhibited CasRmediated activation of SRE. A carboxyl-terminal CasR minigene, CasR(906-980), encoding a filamin binding region, also blocked CasR-and G␣qQL-stimulated SRE activity. Potential interactions between CasR, RhoGEF Lbc, Rho A, G␣q, and filamin were demonstrated by reciprocal coimmunoprecipitation studies. Our results suggest that the C terminus of CasR may interact with filamin to create a cytoskeletal scaffold necessary for the spatial organization of G␣q, RhoGEF Lbc, and Rho signaling pathways upstream of SRE activation.
Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone format... more Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone formation surrounding the implant is relatively slow after inserting the implant. The current study assessed the effects of bone marrow stromal cells (BMSCs) with forced expression of special AT-rich sequence-binding protein 2 (SATB2) on the osseointegration of titanium implants. To determine whether SATB2 overexpression in BMSCs can enhance the osseointegration of implants, BMSCs were infected with the retrovirus encoding Satb2 (pBABE-Satb2) and were locally applied to bone defects before implanting the titanium implants in the mouse femur. Seven and twentyone days after implantation, the femora were isolated for immunohistochemical (IHC) staining, haematoxylin eosin (H&E) staining, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and micro-computed tomography (μCT) analysis. IHC staining analysis revealed that SATB2-overexpressing BMSCs were intensely distributed in the bone tissue surrounding the implant. Histological analysis showed that SATB2overexpressing BMSCs significantly enhanced new bone formation and bone-to-implant contact 3 weeks after implantation. Real-time qRT-PCR results showed that the local delivery of SATB2-overexpressing BMSCs enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins in the implantation sites. μCT analysis demonstrated that SATB2-overexpressing BMSCs significantly increased the density of the newly formed bone surrounding the implant 3 weeks postoperatively. These results conclude that local delivery of SATB2-overexpressing BMSCs significantly accelerates osseointegration of titanium implants. These results provide support for future pharmacological and clinical applications of SATB2, which accelerates bone regeneration around titanium implants.
To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage dev... more To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Prolifera...
Balancing the process of bone formation and resorption is important in the maintenance of healthy... more Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone‐like peptide. Recent studies have reported the involvement of irisin in many physiological and pathological conditions with bone mineral density changes, including osteopenia and osteoporotic fractures. In this study, we generated the first line of Osx‐Cre:FNDC5/irisin KO mice, in which FNDC5/irisin was specifically deleted in the osteoblast lineage. Gene and protein expressions of irisin were remarkably decreased in bones but no significant differences in other tissues were observed in knockout mice. FNDC5/irisin deficient mice showed a lower bone density and significantly delayed bone development and mineralization from early‐stage to adulthood. Our phenotypical analysis exhibited decreased osteoblast‐related gene expression and increased osteoclast‐re...
Central adiponectin (APN) in either the globular (gAPN) or full-length (fAPN) forms decrease symp... more Central adiponectin (APN) in either the globular (gAPN) or full-length (fAPN) forms decrease sympathetic tone and increase trabecular bone mass in mice through the hypothalamus. It is known that cannabinoid type-1 (CB1) receptors are expressed in the hypothalamic ventromedial nucleus (VMN) and participate in energy metabolism by controlling sympathetic activity. However, whether central APN could influence endocannabinoid signaling through CB1 receptor to regulate bone metabolism has not been characterized. Here we demonstrate that gAPN downregulated CB1 expression in embryonic mouse hypothalamus N1 cells in vitro. gAPN
Specific microRNAs (miRs) and the Wnt signaling pathway play critical roles in regulating bone de... more Specific microRNAs (miRs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous studies revealed the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to use nano-materials to efficiently deliver miR-335-5p into osteogenic cells for tissue engineering applications. We synthesized and screened a library of 12 candidate nano-lipidoids，of which L8 was identified as the preferred biodegradable lipidoid for miRNA molecule delivery into cells. We then investigated whether a lipidoid-miRNA formulation of miR-335-5-p (LMF-335) could successfully deliver miR-335-5-p into cells to promote osteogenesis in vitro and calvarial bone healing in vivo. Transfection of C3H10T1/2 cells and bone marrow stromal cells (BMSCs) with LMF-335 led to decreased expression of DKK1 and increased expression of the key osteogenic genes. LMF-335 and LMF-335-transfected...
Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III dom... more Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain-containing 5 (FNDC5) protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression, leading to an increase in total body energy expenditure by augmented UCP1-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone–tendon interface. Exercise also increased expression of osteogenic markers in ...
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 29, 2017
MicroRNAs (miRNAs) and the Wnt signaling pathway play critical roles in regulating bone developme... more MicroRNAs (miRNAs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous study revealed high expression of miR-335-5p in osteoblasts and hypertrophic chondrocytes in mouse embryos and the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to investigate the effects of miR-335-5p constitutive overexpression on bone formation and regeneration in vivo. To that end, we generated a transgenic mouse line specifically overexpressing miR-335-5p in osteoblasts lineage by the osterix promoter and characterized its bone phenotype. Bone histomorphometry and μCT analysis revealed higher bone mass and increased parameters of bone formation in transgenic mice than in wild-type littermates. Increased bone mass in transgenic mice bones also correlated with enhanced expression of osteogenic differentiation markers. Upon osteogenic induction, bone marrow s...
DICER is the central enzyme that cleaves precursor microRNAs (miRNAs) into 21-25 nucleotide duple... more DICER is the central enzyme that cleaves precursor microRNAs (miRNAs) into 21-25 nucleotide duplex in cell lineage differentiation, identity and survival. In the current study, we characterized the specific bone metabolism genes and corresponding miRNAs and found that DICER and Runt-related transcription factor 2 (Runx2) expressions increased simultaneously during osteogenic differentiation. Luciferase assay showed that Runx2 significantly increased the expression levels of DICER luciferase promoter reporter. Our analysis also revealed weaker DICER expression in embryos of Runx2 knock out mice (Runx2 -/-) compared with that of Runx2 +/- and Runx2 +/+ mice. We further established the calvarial bone critical-size defect (CSD) mouse model. The bone marrow stromal cells (BMSCs) transfected with siRNA targeting DICER were combined with silk scaffolds and transplanted into calvarial bone CSDs. Five weeks post-surgery, micro-CT analysis revealed impaired bone formation and repairing in cal...
Emerging evidence suggests an important role for epigenetic mechanisms in modulating signals duri... more Emerging evidence suggests an important role for epigenetic mechanisms in modulating signals during macrophage polarization and inflammation. JMJD3, a JmjC family histone demethylase necessary for M2 polarization is also required for effective induction of multiple M1 genes by lipopolysaccharide (LPS). However, the effects of JMJD3 to inflammation in the context of obesity remains unknown. To address this deficiency, we firstly examined the expression of JMJD3 in macrophage isolated from bone marrow and adipose tissue of diet induced obesity (DIO) mice. The results indicated that JMJD3 was down-regulated in obesity. Adiponectin (APN), a factor secreted by adipose tissue which is down-regulated in obesity, functions to switch macrophage polarization from M1 to M2, thereby attenuating chronic inflammation. Intriguingly, our results indicated that APN contributed to JMJD3 up-regulation, reduced macrophage infiltration in obese adipose tissue, and abolished the up-regulation of JMJD3 in...
Adiponectin (APN) is an adipocyte-secreted adipokine that exerts well-characterized antidiabetic ... more Adiponectin (APN) is an adipocyte-secreted adipokine that exerts well-characterized antidiabetic properties. Patients with type 2 diabetes (T2D) are characterized by reduced APN levels in circulation and impaired stem cell and progenitor cell mobilization from the bone marrow for tissue repair and remodeling. In this study, we found that APN regulates the mobilization and recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to participate in tissue repair and regeneration. APN facilitated BMSCs migrating from the bone marrow into the circulation to regenerate bone by regulating stromal cell-derived factor (SDF)−1 in a mouse bone defect model. More importantly, we found that systemic APN infusion ameliorated diabetic mobilopathy of BMSCs, lowered glucose concentration, and promoted bone regeneration in diet-induced obesity mice. In vitro studies allowed us to identify Smad1/5/8 as a novel signaling mediator of APN receptor (AdipoR)−1 in BMSCs and osteoblasts. APN stimula...
American journal of physiology. Endocrinology and metabolism, Jan 15, 2014
Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis a... more Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulin-sensitizing properties. The peripheral or central effects of APN regulating bone metabolism are beginning to be explored but are still not clearly understood. In the present study, we found that APN-knockout (APN-KO) mice fed a normal diet exhibited decreased trabecular structure and mineralization and increased bone marrow adiposity compared with wild-type (WT) mice. APN intracerebroventricular infusions decreased uncoupling protein 1 (UCP1) expression in brown adipose tissue, epinephrine and norepinephrine serum levels, and osteoclast numbers, whereas osteoblast osteogenic marker expression and trabecular bone mass increased in APN-KO and WT mice. In addition, centrally administered APN increased hypothalamic tryptophan hydroxylase 2 (TPH2), cocaine- and amphetamine-regulated transcript (CART), and 5-hydroxytryptamine (serotonin) receptor 2C (Htr2C)...
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Papers by Qisheng Tu