Therapeutic Effects of Botanicals Used in Management of Dhiq al-Nafas (Bronchial Asthma): An Evidence Based Review

Ahmad, Taufiq,Parray, Shabir Ahmad,Ahmad, Naseem,Khan, Javed Ahmad,Zohaib, Sharique Cellmed Orthocellular Medicine and Pharmaceutical 2019 셀메드 (CellMed) Vol.9 No.1

Bronchial asthma is one of the most common chronic diseases globally and currently affects approximately 300 million people worldwide. As per scientific data, approximately 10-12% of adults; and 15% of children are affected by the disease. The increasing global prevalence of the disease imposes a high health care costs into its mechanisms and treatment. Unani system of medicine (USM) is a well known traditional therapy for number of diseases since ancient times. Time has proved that USM has a special role in treatment of chronic diseases, due its special Usooleillaj (Line of treatment). Dhiq al-Nafas (bronchial asthma) is also considered as a chronic disease. Since ancient times, the disease was cured by number of single as well as compound formulations by renowned Unani scholars. This review provides a comprehensive summary of medicinal plant throughout the world, with reference to renowned Unani scholars and physicians for treatment of Dhiq al-Nafas. A number of Unani single and compound drugs, highly efficacious and safe drugs are available for the asthma. The data were taken from classical literature of USM, Modern reference books & electronic journals. The recent information was collected from different authentic search engines. This review will provide the centuries therapeutic information's of classical literature and recent scientific studies of 12 herbal drugs mentioned in USM, which will help the academia, clinicians, research scholars and post graduate students from Unani Medicine, Traditional & Complementary Medicine and other related disciplines, having research interest or work in the Unani medicine.

Agglomeration of human dermal fibroblasts with ECM mimicking nano-fragments and their effects on proliferation and cell/ECM interactions

Taufiq Ahmad,신영민,이진규,신혁준,Sajeesh Kumar Madhurakart Perikamana,신흥수 한국공업화학회 2018 Journal of Industrial and Engineering Chemistry Vol.67 No.-

Here, we engineered spheroids by using ECM mimicking nano-fragments (NFs) with fibroblasts and investigated their effect on proliferation and cell/ECM interactions. NF incorporation resulted in formation of a stable spheroid, which improved proliferation and viability of cells by assisting oxygen transport confirmed by LOX-1 staining. In addition, hypoxic and apoptotic genes were significantly downregulated in spheroids with PD-NFs. Furthermore, ECM and cell junction proteins were highly expressed. Overall, our findings suggest that incorporation of NFs within spheroids for assembly with various cell types can be an alternative approach for 3D cell culture in many applications.

Hybrid-spheroids incorporating ECM like engineered fragmented fibers potentiate stem cell function by improved cell/cell and cell/ECM interactions

Ahmad, Taufiq,Lee, Jinkyu,Shin, Young Min,Shin, Hyeok Jun,Madhurakat Perikamana, Sajeesh Kumar,Park, Sun Hwa,Kim, Sung Won,Shin, Heungsoo Elsevier 2017 ACTA BIOMATERIALIA Vol.64 No.-

<P><B>Abstract</B></P> <P>Extracellular matrix (ECM) microenvironment is critical for the viability, stemness, and differentiation of stem cells. In this study, we developed hybrid-spheroids of human turbinate mesenchymal stem cells (hTMSCs) by using extracellular matrix (ECM) mimicking fragmented fibers (FFs) for improvement of the viability and functions of hTMSCs. We prepared FFs with average size of 68.26 µm by partial aminolysis of poly L-lactide (PLLA) fibrous sheet (FS), which was coated with polydopamine for improved cell adhesion. The proliferation of hTMSCs within the hybrid-spheroids mixed with fragmented fibers was significantly increased as compared to that from the cell-only group. Cells and fragmented fibers were homogenously distributed with the presence of pore like empty spaces in the structure. LOX-1 staining revealed that the hybrid-spheroids improved the cell viability, which was potentially due to enhanced transport of oxygen through void space generated by engineered ECM. Transmission electron microscopy (TEM) analysis confirmed that cells within the hybrid-spheroid formed strong cell junctions and contacts with fragmented fibers. The expression of cell junction proteins including connexin 43 and E-cadherin was significantly upregulated in hybrid-spheroids by 16.53 ± 0.04 and 28.26 ± 0.11-fold greater than that from cell-only group. Similarly, expression of integrin α<SUB>2,</SUB> α<SUB>5</SUB>, and β<SUB>1</SUB> was significantly enhanced at the same group by 25.72 ± 0.13, 27.48 ± 0.49, and 592.78 ± 0.06-fold, respectively. In addition, stemness markers including Oct-4, Nanog, and Sox2 were significantly upregulated in hybrid-spheroids by 96.56 ± 0.06, 158.95 ± 0.06, and 115.46 ± 0.47-fold, respectively, relative to the cell-only group. Additionally, hTMSCs within the hybrid-spheroids showed significantly greater osteogenic differentiation under osteogenic media conditions. Taken together, our hybrid-spheroids can be an ideal approach for stem cell expansion and serve as a potential carrier for bone regeneration.</P> <P><B>Statement of Significance</B></P> <P>Cells are spatially arranged within extracellular matrix (ECM) and cell/ECM interactions are crucial for cellular functions. Here, we developed a hybrid-spheroid system incorporating engineered ECM prepared from fragmented electrospun fibers to tune stem cell functions. Conventionally prepared cell spheroids with large diameters (>200 µm) is often prone to hypoxia. In contrast, the hybrid-spheroids significantly enhanced viability and proliferation of human turbinate mesenchymal stem cells (hTMSCs) as compared to spheroid prepared from cell only. Under these conditions, the presence of fragmented fibers also improved maintenance of stemness of hTMSCs for longer time cultured in growth media and demonstrated significantly greater osteogenic differentiation under osteogenic media conditions. Thus, the hybrid-spheroids can be used as a delivery carrier for stem cell based therapy or a 3D culture model for <I>in vitro</I> assay.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Agglomeration of human dermal fibroblasts with ECM mimicking nano-fragments and their effects on proliferation and cell/ECM interactions

Ahmad, Taufiq,Shin, Young Min,Lee, Jinkyu,Shin, Hyeok Jun,Madhurakart Perikamana, Sajeesh Kumar,Shin, Heungsoo THE KOREAN SOCIETY OF INDUSTRIAL AND ENGINEERING 2018 JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY -S Vol.67 No.-

<P><B>Abstract</B></P> <P>Here, we engineered spheroids by using ECM mimicking nano-fragments (NFs) with fibroblasts and investigated their effect on proliferation and cell/ECM interactions. NF incorporation resulted in formation of a stable spheroid, which improved proliferation and viability of cells by assisting oxygen transport confirmed by LOX-1 staining. In addition, hypoxic and apoptotic genes were significantly downregulated in spheroids with PD-NFs. Furthermore, ECM and cell junction proteins were highly expressed. Overall, our findings suggest that incorporation of NFs within spheroids for assembly with various cell types can be an alternative approach for 3D cell culture in many applications.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Stem cell spheroids incorporating fibers coated with adenosine and polydopamine as a modular building blocks for bone tissue engineering

Ahmad, Taufiq,Byun, Hayeon,Lee, Jinkyu,Madhurakat Perikamana, Sajeesh Kumar,Shin, Young Min,Kim, Eun Mi,Shin, Heungsoo Elsevier 2020 Biomaterials Vol.230 No.-

<P><B>Abstract</B></P> <P>Although stem cell spheroids offer great potential as functional building blocks for bottom-up bone tissue engineering, delivery of bioactive signals remain challenging. Here, we engineered adenosine-ligand-modified fiber fragments to create a 3D cell-instructive microenvironment for bone. Briefly, the Poly(ι-lactic acid) (PLLA) nanofiber sheet was partially degraded into fragmented fibers (FFs) through aminolysis and adenosine was stably incorporated via one-step polydopamine coating. The SEM and XPS analysis demonstrated that polydopamine assisted adenosine coating efficiency was significantly increased, which led to high coating efficiency of adenosine and its significant retention. The engineered fibers were then assembled into stable spheroids with human-adipose-derived stem cells (hADSCs). The adenosine in the spheroids effectively stimulated A2bR (1.768 ± 0.08) signaling, which further significantly induced the expression of osteogenic markers such as Runx2 (3.216 ± 0.25), OPN (4.136 ± 0.14), OCN (10.16 ± 0.34), and OSX (2.27 ± 0.11) with improved mineral deposition (1.375 ± 0.05 μg per spheroid). In contrast, the adipogenic differentiation of hADSCs was significantly suppressed within the engineered spheroids. Transplantation of engineered spheroids strongly induced osteogenic differentiation of hADSCs in ectopic subcutaneous tissue. Finally, the bone regeneration was significantly enhanced by implanting AP-FF group (59.97 ± 18.33%) as compared to P-FF (27.96 ± 11.14) and defect only (7.97 ± 3.76%). We propose that stem cell spheroids impregnated with engineered fibers enabling adenosine delivery could be promising building blocks for a bottom-up approach to create large tissues for regeneration of damaged bone.</P>

DELIVERY OF DUAL GROWTH FACTORS USING COACERVATE COATED NANOFIBERS FOR IMPROVEMENT OF SKIN DEFECT

Taufiq AHMAD,Min Suk LEE,Jinkyu LEE,Hee Seok YANG,Kyobum KIM,Heungsoo SHIN 한국생물공학회 2016 한국생물공학회 학술대회 Vol.2016 No.4

Investigation on the Three-Dimensional Nanostructure and the Optical Properties of Hydroxyapatite/Magnetite Nanocomposites Prepared from Natural Resource

Ahmad Taufiq,Yuanita Amalia Hariyanto,Sunaryono,Siriwat Soontaranon 한국물리학회 2019 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.75 No.9

Hydroxyapatite, which has been widely used in the medical eld in the last couple of years, is a superior biomaterial due to its biocompatibility and nontoxicity. Hydroxyapatite requires highly magnetic materials to perform maximally in specic medical elds. In this study, hydroxyap- atite/magnetite composites mainly composed of limestone and natural iron sand were synthesized through a coprecipitation method, and composites having different hydroxyapatite-to-magnetite mass ratios were compared. The crystal structure, particle size, fractal dimension, morphology, functional group, and energy gap were characterized using X-ray diffraction (XRD), synchrotron X-ray scattering (SAXS), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and ultraviolent-visible (UV-Vis) spectroscopy. The research results showed that the hydroxyapatite and magnetite phases had a hexagonal structure and cubic structure, respectively. In general, from the FTIR data analysis, the hydroxyapatite and magnetite particles were iden- tied from the functional groups of phosphate, iron-oxygen, carbonate, and hydroxyl. Moreover, depending on particle size, the samples consisting of 3.7-nm primary particles formed a cluster with a massive three-dimensional structure. Meanwhile, the energy gap showed various values ranging between 3.25 and 3.86 eV.

Fabrication of <i>in vitro</i> 3D mineralized tissue by fusion of composite spheroids incorporating biomineral-coated nanofibers and human adipose-derived stem cells

Ahmad, Taufiq,Shin, Hyeok Jun,Lee, Jinkyu,Shin, Young Min,Perikamana, Sajeesh Kumar Madhurakat,Park, So Yeon,Jung, Hyun Suk,Shin, Heungsoo Elsevier 2018 ACTA BIOMATERIALIA Vol.74 No.-

<P><B>Abstract</B></P> <P>Development of a bone-like 3D microenvironment with stem cells has always been intriguing in bone tissue engineering. In this study, we fabricated composite spheroids by combining functionalized fibers and human adipose-derived stem cells (hADSCs), which were fused to form a 3D mineralized tissue construct. We prepared fragmented poly (ι-lactic acid) (PLLA) fibers approximately 100 μm long by partial aminolysis of electrospun fibrous mesh. PLLA fibers were then biomineralized with various concentrations of NaHCO<SUB>3</SUB> (0.005, 0.01, and 0.04 M) to form mineralized fragmented fibers (mFF1, mFF2, and mFF3, respectively). SEM analysis showed that the minerals in mFF2 and mFF3 completely covered the fiber surface, and surface chemistry analysis confirmed the presence of hydroxyapatite peaks. Additionally, mFFs formed composite spheroids with hADSCs, demonstrating that the cells were strongly attached to mFFs and homogeneously distributed throughout the spheroid. <I>In vitro</I> culture of spheroids in the media without osteogenic supplements showed significantly enhanced expression of osteogenic genes including Runx2 (20.83 ± 2.83 and 22.36 ± 2.18 fold increase), OPN (14.24 ± 1.71 and 15.076 ± 1.38 fold increase), and OCN (4.36 ± 0.41 and 5.63 ± 0.51 fold increase) in mFF2 and mFF3, respectively, compared to the no mineral fiber group. In addition, mineral contents were significantly increased at day 7. Blocking the biomineral-mediated signaling by PSB 603 significantly down regulated the expression of these genes in mFF3 at day 7. Finally, we fused composite spheroids to form a mineralized 3D tissue construct, which maintained the viability of cells and showed pervasively distributed minerals within the structure. Our composite spheroids could be used as an alternative platform for the development of <I>in vitro</I> bone models, <I>in vivo</I> cell carriers, and as building blocks for bioprinting 3D bone tissue.</P> <P><B>Statement of Significance</B></P> <P>This manuscript described our recent work for the preparation of biomimeral-coated fibers that can be assembled with mesenchymal stem cells and provide bone-like environment for directed control over osteogenic differentiation. Biomineral coating onto synthetic, biodegradable single fibers was successfully carried out using multiple steps, combination of template protein coating inspired from mussel adhesion and charge-charge interactions between template proteins and mineral ions. The biomineral-coated single micro-scale fibers (1–2.5 μm in diameter) were then assembled with human adipose tissue derived stem cells (hADSCs). The assembled structure exhibited spheroidal architecture with few hundred micrometers. hADSCs within the spheroids were differentiated into osteogenic lineage <I>in vitro</I> and mineralized in the growth media. These spheroids were fused to form <I>in vitro</I> 3D mineralized tissue with larger size.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Small-Angle X-Ray Scattering Study on PVA/Fe3O4 Magnetic Hydrogels

Sunaryono,Ahmad Taufiq,Edy Giri Rahman Putra,Atsushi Okazawa,Isao Watanabe,Norimichi Kojima,Supagorn Rugmai,Siriwat Soontaranon,Mohammad Zainuri,Triwikantoro,Suminar Pratapa,Darminto 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2016 NANO Vol.11 No.3

A synchrotron small-angle X-ray scattering (SAXS) study on PVA/Fe3O4 magnetic hydrogels has been performed to investigate the effect of clustering on their magnetic properties. The hydrogels were prepared through freezing–thawing (F–T) processes. The structure, morphology and magnetic properties of magnetite (Fe3O4) nanoparticles (NPs) were investigated using X-ray diffractometry (XRD), transmission electron microscopy (TEM) and a superconducting quantum interference device (SQUID) magnetometer, respectively. In this study, SAXS data were used to reveal the structural dimensions of the magnetite and its distribution in the polymer-rich PVA and magnetic hydrogels. As calculated using the Beaucage and Teubner–Strey models, the average of the structural dimensions of the PVA hydrogels was 3.9 nm (crystallites), while the average distance between crystallites was approximately 18 nm. Further analysis by applying a two-lognormal distribution showed that the magnetite NPs comprised secondary particles with a diameter of 9.6 nm that were structured by primary particles (~3.2 nm). A two-lognormal distribution function has also been used in describing the size distributions of magnetite NPs in magnetic hydrogels. The clusters of magnetite NPs in the magnetic hydrogels are significantly reduced from 30.4 nm to 12.8 nm with decreasing concentration of the NPs magnetite from 15 wt.% to 1 wt.%. The saturation magnetization values of the magnetite NPs, the 15% and 1% magnetic hydrogels were 34.67 emu/g, 6.52 emu/g and 0.37 emu/g, respectively.

Delivery of a Cell Patch of Cocultured Endothelial Cells and Smooth Muscle Cells Using Thermoresponsive Hydrogels for Enhanced Angiogenesis

Bak, Seongwoo,Ahmad, Taufiq,Lee, Yu Bin,Lee, Joong-yup,Kim, Eun Mi,Shin, Heungsoo Mary Ann Liebert 2016 Tissue engineering. Part A Vol.22 No.1

<P>Cell-based therapy has been studied as an attractive strategy for therapeutic angiogenesis. However, obtaining a stable vascular structure remains a challenge due to the poor interaction of transplanted cells with native tissue and the difficulty in selecting the optimal cell source. In this study, we developed a cell patch of cocultured human umbilical vein endothelial cells (HUVECs) and smooth muscle cells (SMCs) using thermosensitive hydrogels for regeneration of mature vasculatures. In vitro characterization of HUVECs in the cocultured group revealed the formation of a mesh-like morphology over 5 days of culture. Vascular endothelial growth factor expression was also upregulated in the cocultured group compared with HUVECs only. The cell patch seeded with HUVECs, SMCs, or both cell type was prepared on the synthetic thermosensitive and cell interactive hydrogels, and readily detached from the hydrogel within 10min by expansion of the hydrogel when the temperature was decreased to 4 degrees C. We then investigated the therapeutic effect of the cell patch using a hind limb ischemic model of an athymic mouse. Overall, the group that received a cell patch of cocultured HUVECs and SMCs had a significantly retarded rate of necrosis with a significant increase in the number of arterioles and capillaries for 4 weeks compared with the groups transplanted with only HUVECs or SMCs. Dual staining of smooth muscle alpha actin and human nuclear antigen showed that the implanted cell patch was partially involved in vessel formation. In summary, the simple transplantation of a cocultured cell patch using a hydrogel system could enhance therapeutic angiogenesis through the regeneration of matured vascular structures.</P>