Model Pemberdayaan Ekonomi Dengan Filantropi Islam Dalam Mewujudkan Kesejahteraan Masyarakat

This study aims to: 1) describe the model of community empowerment BAZNAS Makassar, 2) to find out the effectiveness community empowerment model in BAZNAS Makassar, 3) to find the right model of economic community empowerment in BAZNAS Makassar. This study was used field research methods with qualitative methode, which were analyzed descriptively. This study found that the BAZNAS Makassar has programme called Makassar prosperous, in which there are three productive programs: Revolving Fund Assistances, Life Skill Training and ZCD (zakat community development). The prosperous Makassar program has not been maximized in implementing Islamic philanthropy, because of consumptive programs are still larger than productive programs. Regarding the effective empowerment model, BAZNAS Makassar can implement a model of economic empowerment program for coastal areas.[Penelitian ini bertujuan untuk: 1) mendeskripsikan model pemberdayaan masyarakat pada BAZNAS kota Makassar, 2) mengetahui efektifitas model pemberdayaan BAZNAS kota Makassar, 3) menemukan model pemberdayaan ekonomi yang tepat bagi BAZNAS kota Makassar. Studi ini dilakukan dengan menggunakan metode penelitian lapangan (field research) dengan metode kualitatif (qualitative method) yang dilakukan secara deskriptif analisis. Penelitian ini menemukan bahwa program pemberdayaan ekonomi BAZNAS kota Makassar disebut Makassar makmur, di dalamnya terdapat tiga program produktif yaitu Bantuan Dana Bergulir, Pelatihan Life Skill, dan ZCD (zakat community development). Program Makassar makmur belum maksimal dalam menerapkan filantropi Islam, karena program konsumtif masih lebih besar dari program produktif.  Sedangkan untuk Model pemberdayaan yang efektif, BAZNAS kota Makassar dapat melaksanakan model program pemberdayaan ekonomi pesisir.

Model Pemberdayaan Ekonomi Dengan Filantropi Islam Dalam Mewujudkan Kesejahteraan Masyarakat

This study aims to: 1) describe the model of community empowerment BAZNAS Makassar, 2) to find out the effectiveness community empowerment model in BAZNAS Makassar, 3) to find the right model of economic community empowerment in BAZNAS Makassar. This study was used field research methods with qualitative methode, which were analyzed descriptively. This study found that the BAZNAS Makassar has programme called Makassar prosperous, in which there are three productive programs: Revolving Fund Assistances, Life Skill Training and ZCD (zakat community development). The prosperous Makassar program has not been maximized in implementing Islamic philanthropy, because of consumptive programs are still larger than productive programs. Regarding the effective empowerment model, BAZNAS Makassar can implement a model of economic empowerment program for coastal areas.[Penelitian ini bertujuan untuk: 1) mendeskripsikan model pemberdayaan masyarakat pada BAZNAS kota Makassar, 2) mengetahui efektifitas model pemberdayaan BAZNAS kota Makassar, 3) menemukan model pemberdayaan ekonomi yang tepat bagi BAZNAS kota Makassar. Studi ini dilakukan dengan menggunakan metode penelitian lapangan (field research) dengan metode kualitatif (qualitative method) yang dilakukan secara deskriptif analisis. Penelitian ini menemukan bahwa program pemberdayaan ekonomi BAZNAS kota Makassar disebut Makassar makmur, di dalamnya terdapat tiga program produktif yaitu Bantuan Dana Bergulir, Pelatihan Life Skill, dan ZCD (zakat community development). Program Makassar makmur belum maksimal dalam menerapkan filantropi Islam, karena program konsumtif masih lebih besar dari program produktif.  Sedangkan untuk Model pemberdayaan yang efektif, BAZNAS kota Makassar dapat melaksanakan model program pemberdayaan ekonomi pesisir.

Production of lentivirus carrying green fluorescent protein with different promoters for in vitro gene transfer

Many diseases are potential targets for gene therapy using either non-viral or viral vectors. Unlike non-viral methods, viral vectors, such as lentiviruses, have the ability to integrate into the host chromosome, which can lead to long-term transgene expression. Lentiviruses have advantages over other types of viruses due to their capacity to transduce non-dividing cells. An optimized generation of lentiviruses carrying green fluorescent protein (GFP) reporter gene driven by either UbC (LV/UbC/GFP) or CMV (LV/CMV/GFP) promoter is described in this paper. The lentiviruses were produced by co-transfecting lentiviral expression constructs and packaging mix into 293FT lentivirus producer cell lines. Lipofectamine was highly efficient in transfecting the cells compared to Transfast and Polyethyleneimine (PEI). Following cell transfection, syncytia were clearly visible at day 2. Lentiviruses were harvested at days 1, 2 and 3 post-transfection. The highest transduction efficiency was read from LV/CMV/GFP harvested at day 2 post-transfection and LV/UbC/GFP harvested at day 3 post-transfection. Finally, the GFP expression in COS-7 cells was determined at day 2 and day 14 post-transduction for transient and stable GFP expression. It was found that the GFP expression declined overtime. However, the transduction efficiency and duration of the transgene expression in COS-7 cells transduced with LV/CMV/GFP were higher compared to LV/UbC/GFP. In conclusion, we have successfully produced lentiviruses carrying GFP with different promoters and shown that the viruses were able to infect COS-7 cells at different efficiencies. Meanwhile, the generation of the active lentiviruses will allow us to the subsequent analysis of the effect of regulatory elements in future study

Mesenchymal stem cell expressing TRAIL as targeted therapy against sensitised tumour

Tapping into the ability of engineered mesenchymal stem cells (MSCs) to mobilise into the tumour has expanded the scope of cancer treatment. Engineered MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) could serve as a platform for an efficient and targeted form of therapy. However, the presence of cancer stem cells (CSCs) that are resistant to TRAIL and apoptosis may represent a challenge for effective treatment. Nonetheless, with the discovery of small molecular inhibitors that could target CSCs and tumour signalling pathways, a higher efficacy of MSC-TRAIL mediated tumour inhibition can be achieved. This might pave the way for a more effective form of combined therapy, which leads to a better treatment outcome. In this review, we first discuss the tumour-homing capacity of MSCs, its effect in tumour tropism, the different approach behind genetically-engineered MSCs, and the efficacy and safety of each agent delivered by these MSCs. Then, we focus on how sensitisation of CSCs and tumours using small molecular inhibitors can increase the effect of these cells to either TRAIL or MSC-TRAIL mediated inhibition. In the conclusion, we address a few questions and safety concerns regarding the utilization of engineered MSCs for future treatment in patients

The matrix (M) protein of newcastle disease virus binds to human bax through its BH3 domain

The underlying mechanisms by which Newcastle disease virus (NDV) kills cancer cells are still unclear. Recent discoveries have shown that many viruses contain Bcl-2 homology-like domains which enabled their interaction with Bcl-2 family members, and thereby accounting for their virulence and pathogenicity. Alignment of the protein sequences of Malaysian strain of NDV, known as AF2240, with those from members of the human Bcl-2 family showed many similar regions; most notably we found that its matrix (AF2240-M) protein, large (AF2240-L) protein and fusion (AF2240-F) protein all contain BH3-like regions. In addition, there are BH1-like domains in these proteins, where AF2240-F and Mcl-1 share 55% identity within this region. To further investigate our hypothesis that the presence of the BH3-like domains in these proteins may convey cytotoxicity, AF2240-M and AF2240-F genes were cloned into pFLAG and pEGFP.N2 vectors and transfected into HeLa cells. The expression of these constructs promoted cell death. As shown by flow cytometry, AF2240-M protein with deleted BH3-like region showed five-fold decrease in apoptosis. Moreover, the construct containing the N-terminal of AF2240-M showed nearly the same cell death rate as to that of the full-length protein, strongly suggesting that the BH3-like domain within this protein participates in promoting cell death. Moreover, AF2240-M transfection promoted Bax redistribution to mitochondria. Therefore, to determine whether there is any direct interaction between NDV viral proteins with some members of the Bcl-2 family, various constructs were co-transfected into HeLa cells. Co-immunoprecipitation trials showed that the AF2240-M indeed directly interacted with Bax protein via its BH3-domain, as the mutant proteins failed to interact with Bax. AF2240-F failed to interact with any of the tested proteins, although Bcl-XL slowed down the rate of cell death caused by this construct by nearly five-fold. In a parallel experiment, the level of expression of endogenous Bax and Bcl-2 after infection of HeLa cells with NDV was assessed by qRT-PCR, but no statistically significant change was observed. Consequently, the Bax/Bcl-2 ratio at the mRNA level did not alter. Overall, our study has shed additional light into the mechanisms by which NDV induces apoptosis

Generation of hemophilia A mouse induced pluripotent stem cells using polycistronic lentiviral vector in serum- and feeder-free culture conditions

Induced pluripotent stem cells (iPSCs) research has opened up exciting possibilities in many research areas especially in the field of regenerative medicine. The ability to reprogram back somatic cells into embryonic stem (ES)-like state has made patient-specific cells therapy possible unhindered ethical and practical dilemmas associated with the use of embryonic stem cells [1]. There have been several reports on the generation of iPS cells from murine somatic cells in vitro, however, there are still many challenges to overcome; (i) the induction efficiency is extremely low, (ii) multiple transgene integrations which increase the risk of tumorigenicity of iPS cells produced, (iii) partially differentiated iPS colonies due to incomplete reprogramming, (iv) the use of feeder cells and medium containing serum add complexity and variability in nutrients and factors that contribute to cell growth and the maintenance of pluripotency [2,3,4,5]. To overcome these issues, we utilized polycistronic lentiviral vector carrying the Yamanaka’s factors (Oct4, Sox2, Klf4 and c-Myc) for reprogramming of murine fibroblasts in serum- and feeder- free defined culture conditions. In this study, primary fibroblasts from hemophilic A B6;129S4-F8tm1Kaz/J and wild-type C57BL/6 mouse were transduced with an optimal multiplicity of infection of the virus produced. Suspected iPS cell colonies were picked within 20 days post-transduction. The results showed that iPS cells derived from the wild-type mouse fibroblast were successfully generated in serum- and feeder-free defined culture conditions. The generated wild-type mouse iPS cells are similar to embryonic stem cells in many aspects including morphology, their properties of self-renewal and pluripotency, and in vitro differentiation into the three primary germ layers. However, we were not able to generate iPS cells from hemophilia A mouse fibroblast with the similar lentiviral vector using the same reprogramming manner. We obtained neuronal-like morphology instead of the expected pluripotent cell colonies. The emerging of neuronal-like cells post-transduction is speculated as an incomplete reprogramming process [6]. These partially reprogrammed cells could not maintain the stem cells-like characteristic and eventually undergo differentiation. Hence, these data could provide an insight of reprogramming process

Overcoming the challenge of transduction of human T-cells with chimeric antigen receptor (CAR) specific for ERBB2 antigen

Breast cancer is one of the most common malignancies among woman. Decades of scientific study have linked the overexpression of ERBB2 antigen to aggressive tumors. To target aggressive breast cancer, chimeric antigen receptor (CAR) technology can be utilized. For this, human T-cells are transduced with a gene sequence encoding a CAR that is specific for tumor-associated antigens (TAAs). These genetically-engineered CAR transduced T-cells (CAR-T cells) are able to target the tumor antigen without the need for major histocompatibility complex (MHC) recognition, rendering it a potentially universal immunotherapeutic option. However, efficient transduction of therapeutic gene into human T-cells and further cell expansion are challenging. In this study, we reported a successful optimization of a transduction protocol using spinoculation on CD3+ T-cells with different concentrations of lentiviral plasmid encoding the CAR gene. CD3+T-cells were isolated from the peripheral blood mononuclear cells (PBMCs). The constructed CAR gene was inserted into a lentiviral plasmid containing the green fluorescent protein (GFP) tag and lentiviral particles were produced. These lentiviral particles were used to transduce activated T-cells by spinoculation. T-cells were activated using Dynabead-conjugated CD3/CD28 human T-cell activator and interleukin-2 (IL-2) before transduction. CD3+ T-cells were selected and GFP expression, which indicated transduction, was observed. Future studies will focus on in vitro and in vivo models to determine the efficiency of CAR-T cells in specifically targeting ERBB2-expressing cells

Overcoming the challenge of transduction of human T-cells with chimeric antigen receptor (CAR) specific for ERBB2 antigen

Breast cancer is one of the most common malignancies among woman. Decades of scientific study have linked the overexpression of ERBB2 antigen to aggressive tumors. To target aggressive breast cancer, chimeric antigen receptor (CAR) technology can be utilized. For this, human T-cells are transduced with a gene sequence encoding a CAR that is specific for tumor-associated antigens (TAAs). These genetically-engineered CAR transduced T-cells (CAR-T cells) are able to target the tumor antigen without the need for major histocompatibility complex (MHC) recognition, rendering it a potentially universal immunotherapeutic option. However, efficient transduction of therapeutic gene into human T-cells and further cell expansion are challenging. In this study, we reported a successful optimization of a transduction protocol using spinoculation on CD3+ T-cells with different concentrations of lentiviral plasmid encoding the CAR gene. CD3+T-cells were isolated from the peripheral blood mononuclear cells (PBMCs). The constructed CAR gene was inserted into a lentiviral plasmid containing the green fluorescent protein (GFP) tag and lentiviral particles were produced. These lentiviral particles were used to transduce activated T-cells by spinoculation. T-cells were activated using Dynabead-conjugated CD3/CD28 human T-cell activator and interleukin-2 (IL-2) before transduction. CD3+ T-cells were selected and GFP expression, which indicated transduction, was observed. Future studies will focus on in vitro and in vivo models to determine the efficiency of CAR-T cells in specifically targeting ERBB2-expressing cells