A Fault Tolerant Data Management Scheme for Healthcare Internet of Things in Fog Computing

( Waqar Saeed ),( Zulfiqar Ahmad ),( Ali I. Jehangiri ),( Nader Mohamed ),( Arif I. Umar ),( Jamil Ahmad ) 한국인터넷정보학회 2021 KSII Transactions on Internet and Information Syst Vol.15 No.1

Fog computing aims to provide the solution of bandwidth, network latency and energy consumption problems of cloud computing. Likewise, management of data generated by healthcare IoT devices is one of the significant applications of fog computing. Huge amount of data is being generated by healthcare IoT devices and such types of data is required to be managed efficiently, with low latency, without failure, and with minimum energy consumption and low cost. Failures of task or node can cause more latency, maximum energy consumption and high cost. Thus, a failure free, cost efficient, and energy aware management and scheduling scheme for data generated by healthcare IoT devices not only improves the performance of the system but also saves the precious lives of patients because of due to minimum latency and provision of fault tolerance. Therefore, to address all such challenges with regard to data management and fault tolerance, we have presented a Fault Tolerant Data management (FTDM) scheme for healthcare IoT in fog computing. In FTDM, the data generated by healthcare IoT devices is efficiently organized and managed through well-defined components and steps. A two way fault-tolerant mechanism i.e., task-based fault-tolerance and node-based fault-tolerance, is provided in FTDM through which failure of tasks and nodes are managed. The paper considers energy consumption, execution cost, network usage, latency, and execution time as performance evaluation parameters. The simulation results show significantly improvements which are performed using iFogSim. Further, the simulation results show that the proposed FTDM strategy reduces energy consumption 3.97%, execution cost 5.09%, network usage 25.88%, latency 44.15% and execution time 48.89% as compared with existing Greedy Knapsack Scheduling (GKS) strategy. Moreover, it is worthwhile to mention that sometimes the patients are required to be treated remotely due to non-availability of facilities or due to some infectious diseases such as COVID-19. Thus, in such circumstances, the proposed strategy is significantly efficient.

Mismatched effects of receptor interacting protein kinase-3 on hepatic steatosis and inflammation in non-alcoholic fatty liver disease

Saeed, Waqar Khalid,Jun, Dae Won,Jang, Kiseok,Ahn, Sang Bong,Oh, Ju Hee,Chae, Yeon Ji,Lee, Jai Sun,Kang, Hyeon Tae Baishideng Publishing Group Inc 2018 WORLD JOURNAL OF GASTROENTEROLOGY Vol.24 No.48

<P><B>AIM</B></P><P>To validate the effects of receptor interacting protein kinase-3 (RIP3) deletion in non-alcoholic fatty liver disease (NAFLD) and to clarify the mechanism of action.</P><P><B>METHODS</B></P><P>Wild-type (WT) and RIP3 knockout (KO) mice were fed normal chow and high fat (HF) diets for 12 wk. The body weight was assessed once weekly. After 12 wk, the liver and serum samples were extracted. The liver tissue expression levels of RIP3, microsomal triglyceride transfer protein, protein disulfide isomerase, apolipoprotein-B, X-box binding protein-1, sterol regulatory element-binding protein-1c, fatty acid synthase, cluster of differentiation-36, diglyceride acyltransferase, peroxisome proliferator-activated receptor alpha, tumor necrosis factor-alpha (TNF-α), and interleukin-6 were assessed. Oleic acid treated primary hepatocytes from WT and RIP3KO mice were stained with Nile red. The expression of inflammatory cytokines, including chemokine (C-X-C motif) ligand (CXCL) 1, CXCL2, and TNF-α, in monocytes was evaluated.</P><P><B>RESULTS</B></P><P>RIP3KO HF diet fed mice showed a significant gain in body weight, and liver weight, liver to body weight ratio, and liver triglycerides were increased in HF diet fed RIP3KO mice compared to HF diet fed WT mice. RIP3KO primary hepatocytes also had increased intracellular fat droplets compared to WT primary hepatocytes after oleic acid treatment. RIP3 overexpression decreased hepatic fat content. Quantitative real-time polymerase chain reaction analysis showed that the expression of very-low-density lipoproteins secretion markers (microsomal triglyceride transfer protein, protein disulfide isomerase, and apolipoprotein-B) was significantly suppressed in RIP3KO mice. The overall NAFLD Activity Score was the same between WT and RIP3KO mice; however, RIP3KO mice had increased fatty change and decreased lobular inflammation compared to WT mice. Inflammatory signals (CXCL1/2, TNF-α, and interleukin-6) increased after lipopolysaccharide and pan-caspase inhibitor (necroptotic condition) treatment in monocytes. Neutrophil chemokines (CXCL1, and CXCL2) were decreased, and TNF-α was increased after RIP3 inhibitor treatment in monocytes.</P><P><B>CONCLUSION</B></P><P>RIP3 deletion exacerbates steatosis, and partially inhibits inflammation in the HF diet induced NAFLD model.</P>

Necroptosis: an emerging type of cell death in liver diseases.

Saeed, Waqar Khalid,Jun, Dae Won WJG Press 2014 WORLD JOURNAL OF GASTROENTEROLOGY Vol.20 No.35

<P>Cell death has been extensively evaluated for decades and it is well recognized that pharmacological interventions directed to inhibit cell death can prevent significant cell loss and can thus improve an organ's physiological function. For long, only apoptosis was considered as a sole form of programmed cell death. Recently necroptosis, a RIP1/RIP3-dependent programmed cell death, has been identified as an apoptotic backup cell death mechanism with necrotic morphology. The evidences of necroptosis and protective effects achieved by blocking necroptosis have been extensively reported in recent past. However, only a few studies reported the evidence of necroptosis and protective effects achieved by inhibiting necroptosis in liver related disease conditions. Although the number of necroptosis initiators is increasing; however, interestingly, it is still unclear that what actually triggers necroptosis in different liver diseases or if there is always a different necroptosis initiator in each specific disease condition followed by specific downstream signaling molecules. Understanding the precise mechanism of necroptosis as well as counteracting other cell death pathways in liver diseases could provide a useful insight towards achieving extensive therapeutic significance. By targeting necroptosis and/or other parallel death pathways, a significant cell loss and thus a decrement in an organ's physiological function can be prevented.</P>

Effects of three different cultivars of cruciferous plants on the age‐stage, two‐sex life table traits of Plutella xylostella (L.) (Lepidoptera: Plutellidae)

Waqar Jaleel,Shafqat SAEED,Qamar Saeed,Muhammad Nadir NAQQASH,Muhammad Umair SIAL,Qurat Ul AINE,Lei YANYUAN,Zhao RUI,Yurong HE,Lihua LU 한국곤충학회 2019 Entomological Research Vol.49 No.4

Plutella xylostella is an important pest of cruciferous crops worldwide. However, information regarding the age‐stage, two‐sex life parameters of P. xylostella, which is vital for designing more effective control methods, is currently lacking. The present study reports age‐stage, two‐sex life table parameters for P. xylostella on napa cabbage (Brassica oleracea var. napa), white cabbage (B. oleracea var. capitata), and cauliflower (B. oleracea var. botrytis) under laboratory conditions at 25 ± 2°C, 50–60% relative humidity, and a 16‐h light : 8‐h dark photoperiod. The time for development from an egg to a male or female adult P. xylostella on white cabbage (mean [± SE] 41.15 ± 0.54 and 39.50 ± 0.54 days, respectively) was significantly longer than that on cauliflower and napa cabbage. Furthermore, P. xylostella fecundity on cauliflower (261.90 ± 4.53 eggs female) was significantly highest than on napa cabbage and white cabbage. Intrinsic rate of increase (r) and finite rate of increase (λ) were highest on cauliflower 0.182 day−1 and 1.199 day−1 respectively as comparison to napa cabbage and white cabbage. The highest gross reproductive rate (GRR) and net reproductive rates (R0) of P. xylostella 65.87 and 52.58 respectively on cauliflower then those of other hosts. The findings of the present study indicate that cauliflower is the most suitable cultivar (host) for the development of P. xylostella. Based on these findings, crops like cauliflower can be used as trap crops when napa cabbage and white cabbage are the main crops.

Targeting MLKL Component of Necroptosis Pathway Protects against Hepatic Steatosis

( Waqar Khalid Saeed ),( Dae Won Jun ),( Ki-seok Jang ),( Jae Yoon Jeong ),( Sang Bong Ahn ),( Joo Hyun Sohn ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: We aimed to evaluate the protective effects of MLKL deletion in mouse model of high fat (HF) diet induced steatosis. Methods: 8-9 weeks old C57BL/6 wild type (WT) (n=8) and MLKL-KO (n=6) mice were randomly divided into normal chow (NC) and HF diet groups. NC and HF diet was fed for 12 weeks. The body and diet weight were measured weekly. After 12 weeks the animal were sacrificed, serum and liver samples were collected. Liver weight and liver/body weight ratio was calculated. H&E staining was performed and NAS score was evaluated. Epididymal adipose tissue F4/80 IHC was performed. Liver biopsies of NASH patients were evaluated for MLKL expression. Results: HF diet increased the body and liver weight of the mice. There was no significant difference in body weight of WT and MLKL-KO mice fed on NC and HF diet. MLKL-KO-HF mice only in 12^th week had significantly reduced body weights as compared to WT-HF mice. Interestingly, MLKL-KO animals fed on both NC and HF diet had increased diet intake as compared to corresponding WT groups. After 12 weeks, MLKL-KO animals had reduced liver weights as compared to corresponding WT groups. Accordingly, HF diet fed MLKL-KO animals had decreased serum AST, ALT and TG contents. H&E staining showed increased steatosis in HF diet fed animals. However, MLKL-KO-HF mice had reduced steatosis and NAS score. Adipose tissue F4/80 IHC showed HF fed MLKL-KO group had decreased macrophage associated crown-like structures as compared to WT-HF group. Human NASH liver biopsies showed significantly increased MLKL expression as compared to the normal liver, signifying MLKL induction in NASH patients. Conclusions: Targeting MLKL component of necroptosis pathway significantly decreases liver weight, steatosis and the serum markers of hepatic injury without significantly affecting the overall body weight.

RIP3 Inhibition Promotes Steatosis in High Fat Diet Induced NAFLD

( Waqar Khalid Saeed ),( Dae Won Jun ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: The protective effects of RIP3 inhibition have been reported methionine & choline deficient (MCD) diet induced fibrosis and in ethanol induced hepatic injury; however, the effects of RIP3 inhibition on high fat (HF) diet induced hepatic steatosis and fibrosis have not been evaluated. Methods: 8-9 week old, C57BL/6 (WT) and RIP3KO mice were fed normal chow (NC), HF and MCD diets for 12 weeks. The animals were randomly divided into following groups (n=8): 1) WT-NC 2) WT-HF 3) WT-MCD 4) RIP3KO-NC, RIP3KO-HF and RIP3KO-MCD. The body weight of the animals was evaluated weekly. After 12 weeks, the animals were euthanized, and the liver and blood samples were collected. The liver to body weight ratio, H&E, serum AST, ALT and TG levels were assessed. Liver TG contents were evaluated using commercial kit. Western blot analysis for alpha-SMA, CD36, SREBP1, JNK, p-JNK, p-c-jun, p-peif2a, ATF6-alpha, MLKL, and LC3 were performed. Results: The body weight of animals fed with HF diet increased while MCD diet fed animals decreased. The liver and body weight of RIP3KO-HF mice increased significantly as compared to WT-HF group; moreover, the liver and liver/body weight ratio was also increased in RIP3KO animals. The H&E evaluation showed significantly increased steatosis in HF and MCD diet fed groups. However, the extent of steatosis seemed to be more pronounced in RIP3KO-HF diet group. The serum AST & ALT increased in both HF and MCD diets groups; however, AST and ALT were significantly increased in RIP3KO animals in MCD and HF diet fed groups, respectively. The hepatic TG contents were also significantly increased in RIP3KO-HF group as compared to WT and RIP3KO-MCD groups. Conclusions: RIP3 inhibition in HF diet fed animals promotes steatosis and development of NAFLD.

Synthesis of Novel Quinoxalinone Derivatives by Conventional and Microwave Methods and Assessing their Biological Activity

Waqar Nasir,Munawar Ali Munawar,Ejaz Ahmed,Ahsan Sharif,Saeed Ahmed,Amjad Ayub,Misbahul Ain Khan,Faizul Hassan Nasim 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.10

In this study, twenty-one arylaminoquinoxalinone derivatives were synthesized and their antibacterial activities against Staphylococci aureus, Pseudomonas aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Shigella pneumoniae were evaluated relative to known antibiotics; augmentin, ampicillin, and chloramphenicol. The insecticidal activities of the prepared compounds were also investigated against Tribolium castaneum using permethrin as a standard insecticide. The derivatives were synthesized using both conventional and microwave techniques. Their structures were confirmed using spectral techniques and elemental analysis.

Feasibility and Stability of Liver Biopsy before Treatment for Preclinical Nonalcoholic Fatty Liver Studies

채연지,전대원,Waqar Khalid Saeed,강현태,오주희,이승민,장기석 대한의학회 2019 Journal of Korean medical science Vol.34 No.2

Background: The heterogeneity of histological findings in preclinical diet-induced nonalcoholic fatty liver disease (NAFLD) animal models is highly challenging. Here, we aimed to evaluate the feasibility and stability of repeated liver biopsy in NAFLD animal models. Methods: Heterogeneity of diet-induced NAFLD was evaluated at different time points in 52 high-fat diet (HFD), 35 methionine choline-deficiency diet (MCD), and 166 western diet (WD) induced NAFLD mice. Serial liver biopsies (left lateral, right medial, and left medial lobes) were performed monthly for up to 3 months. Mortality rates and changes in food intake, body weight, and liver enzymes were assessed. Results: At 12 weeks, of the HFD animals, 14% and 30% did not develop steatosis and lobular inflammation, respectively; of the MCD animals, 7% did not develop lobular inflammation; and of the WD animals, 14% and 51% did not develop steatosis and lobular inflammation, respectively. The mortality rate of repeated liver biopsy was 1.62% (2/123 mice died). Repeated liver biopsy can be used to trace disease progression. Although body weight, food intake, and liver enzymes slightly changed after biopsy, all recovered within a week. Repeated liver biopsy did not affect the degrees of inflammation and steatosis of the other liver lobes. Conclusion: The diet-induced NAFLD models were quite heterogeneous. Our results suggest that the repeated liver biopsy before treatment was applicable and stable in this NAFLD animal study.

Novel Necroptosis Pathway in Hepatic Fibrosis: MLKL Ac-tivated Hepatic Stellate Cell via CXCL1/2 and Adhesion Molecules

( Dae Won Jun ),( Waqar K Saeed ),( Eun Jin Kim ),( Jae Ha Kim ),( Jin Hwa Park ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Necroptosis is an emerging new cell death pathway. We evaluated the role of necroptosis in stellate cell activation and its potential for target in hepatic fibrosis. Methods: Wild type, mixed lineage kinase domain like pseudokinase (MLKL) knock-out (KO), and receptor-interacting protein 3 (RIP3) KO mice were evaluated for the degree of fibrosis in common bile duct (CBD) and thioacetamide induced fibrosis models. Hepatic stellate cell activation was evaluated after necroptosis conditions. MLKL inhibitor (necrosulfonamide) treated activated LX-2 cells were investigated for the stellate cells reversion using wound healing assay, α-SMA, collagen1α, and vimentin expressions. Results: Expression of MLKL immunohistochemical stain increased according to the degree of fibrosis in patients with NAFLD. MLKL expression also increased in CBD ligation induced cirrhotic animal model. Both the MLKL-KO and RIP3KO CBD ligated mice had significantly reduced hepatic fibrosis and fibrosis markers including α-SMA, collagen1α, and TIMP-1 compared to CBD ligated wild type mice. Necroptotic stimulation with TNFα and zVAD treatment on stellate cells caused morphological change, increased α-SMA, and cell migration. MLKL inhibitor (necrosulfonamide) reduced stellate cells activation markers including α-SMA, vimentin, and collagen1α. Necrosulfonamide reduced ICAM-1 and VCAM-1 expressions in stellate cell. Conclusions: Necroptosis pathway activated stellate cells, and MLKL inhibitor can reduce stellate cell activation through reducing CXCL1/2 and adhesion molecules.

Basic, Research : Role of 5-hydroxytryptamine Receptor 2A Antagonist in Hepatic Fibrosis

( Dae Won Jun ),( Waqar Khalid Saeed ),( Tae Yeob Kim ),( Joo Hyun Sohn ),( Kang Nyeong Lee ),( Hang Lak Lee ),( Oh Young Lee ),( Byung Chul Yoon ),( Ho Soon Choi ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: The aim of this study was to determine whether 5-HT2A receptor antagonists affect the activation or apoptosis of HSCs in vitro and/or in vivo. Methods: For the in vitro experiments, the viability, apoptosis and wound healing ability of LX-2 cells were examined after treatment with various 5-HT2A receptor antagonists. Levels of HSC activation markers (procollagen type I, α-SMA, TGF-β and Smad 2/3) were measured. For in vivo experiments, rats were divided into three groups: control group, cirrhosis, 5-HT2A antagonist group. Results: 5-HT2A receptors expression was essentially absent in inactive LX-2 cells but was induced in activated LX-2 cells. Expression of the 5-HT2A and 5-HT2B receptors was significantly decreased by sarpogrelate, with a somewhat greater effect on the 5-HT2A receptor. Similar results were obtained with primary hepatic stellate cells. There was a time and dose dependent decrease in sarpogrelate-treated cell proliferation compared to untreated cells (P<0.05). Ketanserin and ritanserin also had anti-proliferative effects. Ketanserin and sarpogrelate significantly increased HSC apoptosis, with the effect strongest for ketanserin in TUNEL assay. The expression of α-SMA was decreased by sarpogrelate in a dose dependent manner. LX-2 cell migration was significantly suppressed in sarpogrelate or ketanserin- treated cultures and wound healing was delayed compared to cultures treated with only PDGF. There was less severe periportal and septal fibrosis in the rats in the treatment group, but the difference was not statistically significant in Masson`s trichrome stain. But expression of α-SMA was lower in the treatment group than in the cirrhotic group (61.0±7.2% vs 136.7±11.7%, P<0.05), and the treatment group expression was lower than in the disease group (58.9±0.8% vs 118.2±18.2%, P<0.05). Conclusions: 5-HT2A receptor antagonists can reduce inflammation and the activation of HSCs in this cirrhotic model.