• Title/Summary/Keyword: Cascades

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Individualized Therapy to Manage Quadriplegic Spastic Cerebral Palsy with Unani Treatment Modalities

  • Fahmida Kousar;Arshiya Sultana;Shahzadi Sultana;Taseen Banu;Arfa Begum
    • CELLMED
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    • v.13 no.14
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    • pp.16.1-16.14
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    • 2023
  • Objective: Cerebral palsy (CP) is a neurodevelopment disorder attributed to an insult or injury to the developing brain with abnormalities in muscular tone, movement and motor skill. Improvement in quality of life and ameliorating symptoms can be achieved. Therefore, this case report details a distinctive approach to treating a 5-year-old male child with quadriplegic spastic cerebral palsy utilizing Unani treatment modalities. Methods: The treatment regimen commenced with 'Habb Ayarij for constipation followed by Sharbat Ustukhuddus administered orally. Notably, Sharbat Ustukhuddus was combined with Melia Azedarach L. leaves vapour bath. Subsequently, Roghan Babunna douche was performed followed by Dalk Layyin andcontinued until symptomatic improvement was observed. Majun Falasfa, Khamira Marwareed and Khameera Gauzaban were administered for 30 days. The therapeutic outcome included anthropometrical measurements, developmental milestones, spasm/reflex scale, and muscle power grading. Results and conclusion: Over the course of a 2-year follow-up, several clinical findings emerged. These included notable improvements in anthropometric measurements, developmental milestones such as improved head control and sitting ability, and a reduction in spasticity of the upper limbs, along with decreased muscle spasms. The therapeutic outcome of this individualized and holistic approach is potentially due to the multifaceted properties of medicinal plants (Musakkin wa Muharrik wa Muqawwi-i- A'sab wa Dimāgh, Munawwim, Dafi-i-Tashannuj, Muqawwi-i-Qalb-i-Ruh). Furthermore, the use of Dalk and Naṭūl was instrumental in providing nourishment to musculoskeletal cells and initiating intracellular signaling cascades. While these findings are encouraging, further research in the form of case series andrandomized controlled trials is warranted to validate the efficacy of this unique holistic approach.

An In Silico Drug Repositioning Strategy to Identify Specific STAT-3 Inhibitors for Breast Cancer

  • Sruthy Sathish
    • Journal of Integrative Natural Science
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    • v.16 no.4
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    • pp.123-131
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    • 2023
  • Breast cancer continues to pose a substantial worldwide health challenge, thereby requiring the development of innovative strategies to discover new therapeutic interventions. Signal Transducer and Activator of Transcription 3 (STAT-3) has been identified as a significant factor in the development of several types of cancer, including breast cancer. This is primarily attributed to its diverse functions in promoting tumour formation and conferring resistance to therapeutic interventions. This study presents an in silico drug repositioning approach that focuses on identifying specific inhibitors of STAT-3 for the purpose of treating breast cancer. We initially examined the structural and functional attributes of STAT-3, thereby elucidating its crucial involvement in cellular signalling cascades. A comprehensive virtual screening was performed on a diverse collection of drugs that have been approved by the FDA from zinc15 database. Various computational techniques, including molecular docking, cross docking, and cDFT analysis, were utilised in order to prioritise potential candidates. This prioritisation was based on their predicted binding energies and outer molecular orbital reactivity. The findings of our study have unveiled a Dihydroergotamine and Paritaprevir that have been approved by the FDA and exhibit considerable promise as selective inhibitors of STAT-3. In conclusion, the utilisation of our in silico drug repositioning approach presents a prompt and economically efficient method for the identification of potential compounds that warrant subsequent experimental validation as selective STAT-3 inhibitors in the context of breast cancer. The present study highlights the considerable potential of employing computational strategies to expedite the drug discovery process. Moreover, it provides valuable insights into novel avenues for targeted therapeutic interventions in the context of breast cancer treatment.

Identification and in silico analysis of two types of serpin genes from expressed sequence tags (ESTs) of the Oriental land snail, Nesiohelix samarangae (동양달팽이 (Nesiohelix samarangae) 의 expressed sequence tags (ESTs) 로부터 분리한 2종류의 Serpin 유전자 분석)

  • Park, So Young;Jeong, Ji Eun;Hwang, Hee Ju;Wang, Tae Hun;Park, Eun Bi;Kim, Yong Min;Lee, Jun-Sang;Han, Yeon Soo;Yang, Seung-Ha;Lee, Yong Seok
    • The Korean Journal of Malacology
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    • v.30 no.2
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    • pp.155-163
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    • 2014
  • Serpins are a group of proteins involved in the regulation of serine and other type of proteases, and have been identified in many kinds of organisms from invertebrates to vertebrates. Serpins are known to regulate the proteolytic cascades of the innate immune pathways in addition to their roles in blood coagulation, angiogenesis, fibrinolysis, inflammation and tumor suppression. In this study, we have isolated two partial serpin gene fragments from expressed sequence tags (ESTs) of Nesiohelix samarangae. Dotplot analysis indicates that they are of two different types, Ns-serpin type 1 and Ns-serpin type 2. Ns-serpin type 1 has 819 bp coding region (272 amino acids), whereas Ns-serpin type 2 has 555 bp coding region (185 amino acids). Molecular phylogenetic analysis shows that the identified serpins have high similarities to their counterparts in the California see slug, Aplysia californica. Yet, the precise biological and immunological roles of these Ns-serpins remain to be further investigated using RNA interference and other molecular techniques.

Apoptosis Induced by BARODON® in Human Gastric Cancer Cells (BARODON® 에 의한 Human Gastric Adenocarcinoma AGS 세포고사)

  • Jo Eun-Hye;Choi Soo-Il;Kim Soo-Rim;Cho Sung-Dae;Ahn Nam-Shic;Jung Ji-Won;Yang Se-Ran;Park Joon-Suk;Hwang Jae-Woong;Park Yong-Ho;Lee Yong-Soon;Kang Kyung-Sun
    • Toxicological Research
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    • v.21 no.2
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    • pp.107-113
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    • 2005
  • [ $BARODON^{(R)}$ ] is a multi-purpose, high functional alkali solution made by mixing and liquid-ionizing silicon, calcium, sodium, borax, organic carbon chemicals and silver. In this study, we have investigated the apoptotic potential and mechanistic insights of $BARODON^{(R)}$ in human gastric cancer cell line (AGS cells). In MTT assay, $BARODON^{(R)}$ reduced cell viability in AGS cells. Morphological features of apoptosis with marked cytoplasmic vacuolation and appearance of apoptotic peaks in flow cytometry were observed in AGS cells with$BARODON^{(R)}$ treatment. In addition, $BARODON^{(R)}$ induced apoptosis of stomach cancer cell is related to bax up-regulation, caspase 7 protease activation and subsequent cleavage of poly (ADP-ribose) polymerase (PARP). These results suggest that BARODON can induce the apoptosis of AGS cells through modulation of bcl-2 family and the activation of intrinsic caspase cascades, indicating that it is potentially useful as a anti-cancer agent.

Enzymatically Modified Isoquercitrin Attenuates High-Fat Diet-Induced Obesity (효소 처리된 Isoquercitrin이 고지방식이에 의해 비만이 유도된 마우스의 체중감소에 미치는 영향)

  • Min, Yeojin;Park, Taesun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.4
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    • pp.474-483
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    • 2016
  • Enzymatically modified isoquercitrin (EMIQ) is a mixture of quercetin glycodsides consisting of isoquercitrin and its ${\alpha}-glucosylated$ derivatives containing one to seven additional linear glucose moieties. The aim of this study was to assess whether or not EMIQ attenuates high-fat diet (HFD)-induced body weight gain and changes in plasma indices of obesity in mice. Male C57BL/6N mice were fed chow diet, HFD, and HFD containing 1.2% EMIQ for 10 weeks. EMIQ significantly (P<0.05) reduced body weight gain (-21%), total visceral fat-pad weights (-31%), and plasma levels of triglycerides (-17%), total cholesterol (-19%), and free fatty acids (-26%) in HFD-fed mice. EMIQ significantly increased protein kinase A (PKA) expression in the epididymal adipose tissue of HFD-fed mice. Expression of adipogenesis-related genes significantly decreased, whereas expression of fatty acid oxidation-related and thermogenesis-related genes increased in epididymal adipose tissue of EMIQ-fed mice compared with HFD-fed mice. These results suggest that the protective effects of EMIQ against HFD-induced adiposity in mice appear to be associated with PKA-mediated signaling cascades involved in adipogenesis, fatty acid oxidation, and thermogenesis in adipose tissue.

Protective Effects of Omija-tang on $H_2O_2$-induced apoptotic death of H9c2 cardiomyoblast cells (오미자탕(五味子湯)이 심근세포에 미치는 영향)

  • Han, Myoung-Ah;Choi, Woo-Jung;Kim, Dong-Woung;Jung, Dae-Young;Shin, Sun-Ho;Choi, Jin-Young
    • The Journal of Internal Korean Medicine
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    • v.23 no.2
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    • pp.181-190
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    • 2002
  • The water extract of Omija-tang(OMJT) has been traditionally used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of OMJT protects cells from such damage. Therefore, this study was conducted to investigate the protective mechanisms of OMJT on $H_2O_2$-induced toxicity in H9c2 cardiomyoblast cells. Treatment of $H_2O_2$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. The characteristics of $H_2O_2$-induced death of H9c2 showed apparent apoptotic features, such as DNA fragmentation. However, OMJT significantly reduced both $H_2O_2$-induced cell death and chromatin fragmentation. The decrease of Bcl-XL expression by $H_2O_2$ was inhibited by OMJT. In addition, the increase of Bcl-XS and Bax expression were also inhibited by OMJT. In particular, Fas expression, which is generally recognized as cell death inducing signal by Fas/FasL interaction, was markedly increased by $H_2O_2$ in a time-dependent manner, whereas this increase was completely prevented by OMJT. The combined treatment of OMJT and $H_2O_2$ in H9c2 cells also reduced activation of caspase-9 and caspase-3 like protease. Taken together, this study indicates that the protective effects of the water extract of OMJT against oxidative damage may be mediated by the modulation of BcI-XL/S and Bax expression by way of the regulation of mitochondrial membrane potential and caspase cascades.

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Time-series Analysis of Pyroclastic Flow Deposit and Surface Temperature at Merapi Volcano in Indonesia Using Landsat TM and ETM+ (Landsat TM과 ETM+를 이용한 인도네시아 메라피 화산의 화산쇄설물 분포와 지표 온도 시계열 분석)

  • Cho, Minji;Lu, Zhong;Lee, Chang-Wook
    • Korean Journal of Remote Sensing
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    • v.29 no.5
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    • pp.443-459
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    • 2013
  • Located on Java subduction zone, Merapi volcano is an active stratovolcano with a volcanic activity cycle of 1-5 years. Merapi's eruptions were relatively small with VEI 1-3. However, the most recent eruption occurred in 2010 was quite violent with VEI 4 and 386 people were killed. In this study, we have attempted to study the characteristics of Merapi's eruptions during 18 years using optical Landsat images. We have collected a total of 55 Landsat images acquired from July 6, 1994 to September 1, 2012 to identify pyroclastic flows and their temporal changes from false color images. To extract areal extents of pyroclastic flows, we have performed supervised classification after atmospheric correction by using COST model. As a result, the extracted dimensions of pyroclastic flows are nearly identical to the CVP monthly reports. We have converted the thermal band of Landsat TM and ETM+ to the surface temperature using NASA empirical formula and calculated time-series of the mean surface temperature in the area of peak temperature surrounding the crater. The mean surface temperature around the crater repeatedly showed the tendency to rapidly rise before eruptions and cool down after eruptions. Although Landsat satellite images had some limitations due to weather conditions, these images were useful tool to observe the precursor changes in surface temperature before eruptions and map the pyroclastic flow deposits after eruptions at Merapi volcano.

Topographic Phase Correction of MAl (Multiple Aperture SAR Interferometry) Interferogram (MAI (Multiple Aperture SAR Interferometry) 간섭도의 지형위상보정)

  • Jung, Hyung-Sup;Lu, Zhong
    • Korean Journal of Remote Sensing
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    • v.27 no.2
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    • pp.171-180
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    • 2011
  • MAI (multiple aperture SAR interferometry) method has been recently developed to improve the measurement accuracy of along-track surface deformation. By means of split-beam SAR processing, this novel technique produces forward- and backward-looking interferograms, which are combined to generate an MAI interferogram. The along-track surface deformation can then be derived from the MAI interferogram. The achieved accuracy of the along-track surface deformation is approximately 8 cm for interferograms with a coherence of 0.6. It is commonly recognized that the topographic phase on an MAI interferogram can be ignored. However, in this paper, we have generated an MAI interferogram from an ALOS P ALSAR interferometric pair spanning the 2010 Haiti earthquake, and shown that the topographic phase distortion on the MAI interferogram can reach to about $3.45{\times}10^{-4}$ rad./m. This distortion corresponds to an along-track surface deformation of about 98 cm. We have proposed an efficient method to remove the topographic phase distortion. After correcting the distortion, the topographic phase distortion on the MAI interferogram is reduced to about $7.82{\times}10^{-6}$ rad./m. This means that the proposed method can effectively remove the topographic distortion on the MAI interferogram to improve along-track surface deformation measurement.

Action and Signaling of Lysophosphatidylethanolamine in MDA-MB-231 Breast Cancer Cells

  • Park, Soo-Jin;Lee, Kyoung-Pil;Im, Dong-Soon
    • Biomolecules & Therapeutics
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    • v.22 no.2
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    • pp.129-135
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    • 2014
  • Previously, we reported that lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) via type 1 lysophosphatidic acid (LPA) receptor ($LPA_1$) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like $LPA_1/CD97-G_{i/o}$ proteins-phospholipase $C-IP_3-Ca^{2+}$ increase in these cells. In the present study, we further investigated actions of LPE not only in the $[Ca^{2+}]_i$ increasing effect but also in cell proliferation and migration in MDA-MB-231 breast cancer cells. We utilized chemically different LPEs and a specific inhibitor of $LPA_1$, AM-095 in comparison with responses in SK-OV3 ovarian cancer cells. It was found that LPE-induced $Ca^{2+}$ response in MDA-MB-231 cells was evoked in a different manner to that in SK-OV3 cells in terms of structural requirements. AM-095 inhibited LPE-induced $Ca^{2+}$ response and cell proliferation in MDA-MB-231 cells, but not in SK-OV3 cells, supporting $LPA_1$ involvement only in MDA-MB-231 cells. LPA had significant effects on cell proliferation and migration in MDA-MB-231 cells, whereas LPE had less or no significant effect. However, LPE modulations of MAPKs (ERK1/2, JNK and p38 MAPK) was not different to those by LPA in the cells. These data support the involvement of LPA1 in LPE-induced $Ca^{2+}$ response and cell proliferation in breast MDA-MB-231 cells but unknown GPCRs (not $LPA_1$) in LPE-induced responses in SK-OV3 cells. Furthermore, although LPE and LPA utilized $LPA_1$, LPA utilized more signaling cascades than LPE, resulting in stronger responses by LPA in proliferation and migration than LPE in MDA-MB-231 cells.

Nanopharmaceutical Approach for Enhanced Anti-cancer Activity of Betulinic Acid in Lung-cancer Treatment via Activation of PARP: Interaction with DNA as a Target -Anti-cancer Potential of Nano-betulinic Acid in Lung Cancer-

  • Das, Jayeeta;Samadder, Asmita;Das, Sreemanti;Paul, Avijit;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.19 no.1
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    • pp.37-44
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    • 2016
  • Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.