The amyloid β (Aβ) generation or aggregation plays a crucial role in Alzheimer's disease (AD)... more The amyloid β (Aβ) generation or aggregation plays a crucial role in Alzheimer's disease (AD). Autophagy agonists, which function as the clearance of Aβ, could be the potential drug candidates against AD. In staple food crops, ferulic acid (FA) is an enormously copious and almost ubiquitous phenolic antioxidant. In the present study, FA significantly inhibited Aβ-induced pathological symptoms of paralysis and hypersensitivity to exogenous serotonin, meanwhile restrained Aβ monomers, oligomers, and deposits in AD C. elegans. FA increased the expression of autophagy reporter LGG-1 and enhanced autophagy flux. However, the autophagy inhibitors abolished the restrictive action of FA on the worm paralysis phenotype. According to these results, FA triggered autophagy and ameliorated Aβ-induced pathological symptoms by the autophagy pathway. Moreover, FA activated the HLH-30 transcription factor to nuclear localization, which acts upstream of autophagy in fasted animals, reduced the level of lipids, but affected nor the growth of E.coli OP50, neither animal food intake behavior. These suggest that FA induced a fasting-like effect to activate the autophagy pathway. Additionally, FA ameliorated poly Q aggregations in Huntington's disease worm. Thus, FA could not only affect AD, broadly but also neurodegenerative diseases characterized by misfolded or aggregated proteins.
Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the cen... more Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the central nervous system in the elderly, causing motor impediments and cognitive dysfunctions. Dopaminergic (DA) neuron degeneration and α-synuclein (α-Syn) accumulation in substantia nigra pars compacta are the major contributors to this disease. At present, PD remains untreatable with a huge burden on the quality of life. Therefore, we attempt to explore novel treatment strategies by detecting effective drugs that stop or arrest PD's progression via modifying disease-specific pathways. Chrysin is a flavonoid derived from passion flowers and possesses anti-cancer, anti-inflammatory, anti-oxidant, and anti-depression properties. In the present study, we assessed the neuroprotective potential of chrysin in transgenic Caenorhabditis elegans models of PD. We observed that chrysin reduced the aggregative toxicity of α-Syn and diminished DA neuron degeneration induced by 6-hydroxydopamine (6-OHDA), reduced food-sensing behavioral disabilities, and expanded the nematodes' lifespan. Moreover, chrysin augmented the ubiquitin-like proteasome and superoxide dismutase activities in transgenic C. elegans models. Further, we observed the anti-oxidative role of chrysin by reducing the internal cellular reactive oxygen species levels in 6-OHDA-intoxicated C. elegans. Together, these findings supported chrysin as a possible treatment for PD and encouraged further investigation of chrysin's mechanism of action as a neuroprotective medicine in the future.
Amyloid β induces pathological symptoms in various neurodegenerative disorders. It is the hallmar... more Amyloid β induces pathological symptoms in various neurodegenerative disorders. It is the hallmark of these neurodegenerative disorders, such as Alzheimer's disease, and is reported to induce neurotoxicity leading to neuronal impairment. The continuous development of neurodegenerative disease accompanies pathological changes in amyloid β deposition in the brain. After amyloid β accumulates, the inadequate clearance of amyloid β further accelerates the development of events in the pathological cascade. In eukaryotes, the proteasome is responsible for the degradation of misfolded and damaged proteins to maintain proteostasis. Therefore, screening candidates that preserve proteasomal activity may promote amyloid β homeostasis, which is expected to provide new therapeutic opportunities for these neurodegenerative diseases. Ursolic acid, a natural triterpenoid, has prominent pharmacological antioxidant, anti-inflammatory, neuroprotective, and nontoxic activities. Here, we explored the protective effects of ursolic acid on amyloid β-induced pathological symptoms. This study investigated the therapeutic potential of ursolic acid and its underlying molecular mechanisms using a Caenorhabditis elegans transgenic pathological model. In our study, ursolic acid successfully repressed amyloid β-induced paralysis and hypersensitivity to serotonin in Caenorhabditis elegans. The levels of amyloid β monomers, oligomers, and deposits were decreased after treatment with ursolic acid in transgenic nematodes overexpressing human amyloid β; however, ursolic acid did not affect exogenous transgene transcription and expression levels. Ursolic acid transcriptionally enhanced the ubiquitin-proteasome system and augmented proteasome activity in vivo. However, the proteasome inhibitor MG132 abolished the therapeutic effect of ursolic acid on behavioral paralysis, and Parkinson's disease-related-1 was required for the therapeutic effect of ursolic acid. Our study revealed that ursolic acid prevented amyloid β-induced proteotoxic stress, specifically by reducing the amount of amyloid β and increasing proteasome activity in vivo. Furthermore, the therapeutic effect of ursolic acid on transgenic nematodes expressing amyloid β depended on the increased activity of the proteasome. This work provides an essential supplement to the information on the pharmacological mechanism of ursolic acid.
Neuroprotective Traditional Chinese Medicine (TCM) has been practiced in alternative medicine fro... more Neuroprotective Traditional Chinese Medicine (TCM) has been practiced in alternative medicine from early days. TCM-derived neuroprotective compounds, such as Chrysin, Cannabidiol, Toonasinoids, and β-asaron, exert significant effectiveness's towards Parkinson's disease (PD). Further, these neuroprotective TCM showed antioxidative, anti-inflammatory, anti-tumor, anti-septic, analgesic properties. Recent research showed that the reduction in the reactive oxygen species (ROS) decreased the α-synuclein (α-syn) toxicity and enhanced the dopaminergic neuron regenerations, the main hallmarks of PD. Therefore, the neuroprotective effects of novel TCM due to its antiradical activities needed deep investigations. This review aims to enlighten the neuroprotective TCM and its components with their antioxidative properties to the scientific community for future research. The relevant information on the neuroprotective TCM was gathered from scientific databases (PubMed, Web of Science, Google Scholar, ScienceDirect, SciFinder, Wiley Online Library, ACS Publications, and CNKI). Information was also gained from MS and Ph.D. thesis, books, and online databases. The literature cited in this review dates from 2001 to June 2, 0201. Novel therapies for PD are accessible, mostly rely on Rivastigmine and Donepezil, offers to slow down the progression of disease at an early stage but embraces lots of disadvantages. Researchers are trying to find a potential drug against PD, which is proficient at preventing or curing the disease progress, but still needed to be further identified. Oxidative insult and mitochondrial dysfunction are thought to be the main culprit of neurodegenerations. Reactive oxygen species (ROS) are the only causative agent in all interactions, leading to PD, from mitochondrial dysfunctions, α-syn aggregative toxicity, and DA neurons degenerations. It is evident from the redox balance, which seems an imperative therapeutic approach against PD and was necessary for the significant neuronal activities. Our study is explaining the newly discovered TCM and their neuroprotective and antioxidative properties. But also bring up the possible treatment approaches against PD for future researchers.
2019 IEEE/ACS 16th International Conference on Computer Systems and Applications (AICCSA), 2019
Unsupervised anomaly detection is an important area of research to find abnormal behavior and int... more Unsupervised anomaly detection is an important area of research to find abnormal behavior and integral part of many systems. In this research, a lightweight deep autoencoder based approach is presented to detect anomalies in unsupervised manner. It has the ability to learn the model over the normal patterns and any deviation is considered as an anomaly. Consequently, it can relax the condition to have anomalous data patterns during the training phase of the model. In this work, we examine lightweight autoencoder for anomaly detection task in order to show that simple architecture can show good performance in terms of training, testing time, number of parameters and metrics. We apply autoencoder for binary classification problem (i.e., each data point considered either normal or abnormal). The reconstruction error is used to detect anomalies. The experiments are carried out over the particular class of cyber security domain known as intrusion detection systems. We evaluated our model on standard publicly available benchmarks of KDD-99, NSL-KDD and UNSW-NB15 and achieved F1-score of 0.96, 0.88 and 0.95, respectively. It outperforms by a considerable margin when compared to state-of-the-art methods.
Complex-valued neural networks have many advantages over their real-valued counterparts. Conventi... more Complex-valued neural networks have many advantages over their real-valued counterparts. Conventional digital electronic computing platforms are incapable of executing truly complex-valued representations and operations. In contrast, optical computing platforms that encode information in both phase and magnitude can execute complex arithmetic by optical interference, offering significantly enhanced computational speed and energy efficiency. However, to date, most demonstrations of optical neural networks still only utilize conventional real-valued frameworks that are designed for digital computers, forfeiting many of the advantages of optical computing such as efficient complex-valued operations. In this article, we highlight an optical neural chip (ONC) that implements truly complex-valued neural networks. We benchmark the performance of our complex-valued ONC in four settings: simple Boolean tasks, species classification of an Iris dataset, classifying nonlinear datasets (Circle a...
Indian Journal of Physical Medicine and Rehabilitation, 2012
Heavy back packs carried for prolonged durations can cause different musculoskeletal and neurolog... more Heavy back packs carried for prolonged durations can cause different musculoskeletal and neurological problems especially in the untrained and physically vulnerable individuals. They can cause postural disorders, gait abnormalities, muscular strains, pains and injuries to the brachial plexus and nerves resulting in significant morbidity and at times permanent disability. We report a case of brachial plexus injury in a young soldier wearing back pack for prolonged period. He developed weakness and pain in right shoulder which was not relieved with rest and analgesics. On examination he had weakness in deltoid, biceps and scapular muscles along with numbness in axillary nerve area. Brachial plexus injury (upper trunk) was suspected and confirmed by electrodiagnostic evaluation. His baseline investigations were normal. He was advised rest and avoidance to lift heavy weight. He was managed with electrical muscle stimulation for weak muscles, strengthening exercises and analgesics. He re...
Background— Evidence is sparse about the genetic determinants of major lipids in Pakistanis. Meth... more Background— Evidence is sparse about the genetic determinants of major lipids in Pakistanis. Methods and Results— Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P <10 −13 ), APOA5/ZNF259 (rs651821; P <10 −13 ) and GCKR (rs1260326; P <10 −13 ) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P <10 −9 ). For Pakistanis, these 41 variants explained 6...
The amyloid β (Aβ) generation or aggregation plays a crucial role in Alzheimer's disease (AD)... more The amyloid β (Aβ) generation or aggregation plays a crucial role in Alzheimer's disease (AD). Autophagy agonists, which function as the clearance of Aβ, could be the potential drug candidates against AD. In staple food crops, ferulic acid (FA) is an enormously copious and almost ubiquitous phenolic antioxidant. In the present study, FA significantly inhibited Aβ-induced pathological symptoms of paralysis and hypersensitivity to exogenous serotonin, meanwhile restrained Aβ monomers, oligomers, and deposits in AD C. elegans. FA increased the expression of autophagy reporter LGG-1 and enhanced autophagy flux. However, the autophagy inhibitors abolished the restrictive action of FA on the worm paralysis phenotype. According to these results, FA triggered autophagy and ameliorated Aβ-induced pathological symptoms by the autophagy pathway. Moreover, FA activated the HLH-30 transcription factor to nuclear localization, which acts upstream of autophagy in fasted animals, reduced the level of lipids, but affected nor the growth of E.coli OP50, neither animal food intake behavior. These suggest that FA induced a fasting-like effect to activate the autophagy pathway. Additionally, FA ameliorated poly Q aggregations in Huntington's disease worm. Thus, FA could not only affect AD, broadly but also neurodegenerative diseases characterized by misfolded or aggregated proteins.
Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the cen... more Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the central nervous system in the elderly, causing motor impediments and cognitive dysfunctions. Dopaminergic (DA) neuron degeneration and α-synuclein (α-Syn) accumulation in substantia nigra pars compacta are the major contributors to this disease. At present, PD remains untreatable with a huge burden on the quality of life. Therefore, we attempt to explore novel treatment strategies by detecting effective drugs that stop or arrest PD's progression via modifying disease-specific pathways. Chrysin is a flavonoid derived from passion flowers and possesses anti-cancer, anti-inflammatory, anti-oxidant, and anti-depression properties. In the present study, we assessed the neuroprotective potential of chrysin in transgenic Caenorhabditis elegans models of PD. We observed that chrysin reduced the aggregative toxicity of α-Syn and diminished DA neuron degeneration induced by 6-hydroxydopamine (6-OHDA), reduced food-sensing behavioral disabilities, and expanded the nematodes' lifespan. Moreover, chrysin augmented the ubiquitin-like proteasome and superoxide dismutase activities in transgenic C. elegans models. Further, we observed the anti-oxidative role of chrysin by reducing the internal cellular reactive oxygen species levels in 6-OHDA-intoxicated C. elegans. Together, these findings supported chrysin as a possible treatment for PD and encouraged further investigation of chrysin's mechanism of action as a neuroprotective medicine in the future.
Amyloid β induces pathological symptoms in various neurodegenerative disorders. It is the hallmar... more Amyloid β induces pathological symptoms in various neurodegenerative disorders. It is the hallmark of these neurodegenerative disorders, such as Alzheimer's disease, and is reported to induce neurotoxicity leading to neuronal impairment. The continuous development of neurodegenerative disease accompanies pathological changes in amyloid β deposition in the brain. After amyloid β accumulates, the inadequate clearance of amyloid β further accelerates the development of events in the pathological cascade. In eukaryotes, the proteasome is responsible for the degradation of misfolded and damaged proteins to maintain proteostasis. Therefore, screening candidates that preserve proteasomal activity may promote amyloid β homeostasis, which is expected to provide new therapeutic opportunities for these neurodegenerative diseases. Ursolic acid, a natural triterpenoid, has prominent pharmacological antioxidant, anti-inflammatory, neuroprotective, and nontoxic activities. Here, we explored the protective effects of ursolic acid on amyloid β-induced pathological symptoms. This study investigated the therapeutic potential of ursolic acid and its underlying molecular mechanisms using a Caenorhabditis elegans transgenic pathological model. In our study, ursolic acid successfully repressed amyloid β-induced paralysis and hypersensitivity to serotonin in Caenorhabditis elegans. The levels of amyloid β monomers, oligomers, and deposits were decreased after treatment with ursolic acid in transgenic nematodes overexpressing human amyloid β; however, ursolic acid did not affect exogenous transgene transcription and expression levels. Ursolic acid transcriptionally enhanced the ubiquitin-proteasome system and augmented proteasome activity in vivo. However, the proteasome inhibitor MG132 abolished the therapeutic effect of ursolic acid on behavioral paralysis, and Parkinson's disease-related-1 was required for the therapeutic effect of ursolic acid. Our study revealed that ursolic acid prevented amyloid β-induced proteotoxic stress, specifically by reducing the amount of amyloid β and increasing proteasome activity in vivo. Furthermore, the therapeutic effect of ursolic acid on transgenic nematodes expressing amyloid β depended on the increased activity of the proteasome. This work provides an essential supplement to the information on the pharmacological mechanism of ursolic acid.
Neuroprotective Traditional Chinese Medicine (TCM) has been practiced in alternative medicine fro... more Neuroprotective Traditional Chinese Medicine (TCM) has been practiced in alternative medicine from early days. TCM-derived neuroprotective compounds, such as Chrysin, Cannabidiol, Toonasinoids, and β-asaron, exert significant effectiveness's towards Parkinson's disease (PD). Further, these neuroprotective TCM showed antioxidative, anti-inflammatory, anti-tumor, anti-septic, analgesic properties. Recent research showed that the reduction in the reactive oxygen species (ROS) decreased the α-synuclein (α-syn) toxicity and enhanced the dopaminergic neuron regenerations, the main hallmarks of PD. Therefore, the neuroprotective effects of novel TCM due to its antiradical activities needed deep investigations. This review aims to enlighten the neuroprotective TCM and its components with their antioxidative properties to the scientific community for future research. The relevant information on the neuroprotective TCM was gathered from scientific databases (PubMed, Web of Science, Google Scholar, ScienceDirect, SciFinder, Wiley Online Library, ACS Publications, and CNKI). Information was also gained from MS and Ph.D. thesis, books, and online databases. The literature cited in this review dates from 2001 to June 2, 0201. Novel therapies for PD are accessible, mostly rely on Rivastigmine and Donepezil, offers to slow down the progression of disease at an early stage but embraces lots of disadvantages. Researchers are trying to find a potential drug against PD, which is proficient at preventing or curing the disease progress, but still needed to be further identified. Oxidative insult and mitochondrial dysfunction are thought to be the main culprit of neurodegenerations. Reactive oxygen species (ROS) are the only causative agent in all interactions, leading to PD, from mitochondrial dysfunctions, α-syn aggregative toxicity, and DA neurons degenerations. It is evident from the redox balance, which seems an imperative therapeutic approach against PD and was necessary for the significant neuronal activities. Our study is explaining the newly discovered TCM and their neuroprotective and antioxidative properties. But also bring up the possible treatment approaches against PD for future researchers.
2019 IEEE/ACS 16th International Conference on Computer Systems and Applications (AICCSA), 2019
Unsupervised anomaly detection is an important area of research to find abnormal behavior and int... more Unsupervised anomaly detection is an important area of research to find abnormal behavior and integral part of many systems. In this research, a lightweight deep autoencoder based approach is presented to detect anomalies in unsupervised manner. It has the ability to learn the model over the normal patterns and any deviation is considered as an anomaly. Consequently, it can relax the condition to have anomalous data patterns during the training phase of the model. In this work, we examine lightweight autoencoder for anomaly detection task in order to show that simple architecture can show good performance in terms of training, testing time, number of parameters and metrics. We apply autoencoder for binary classification problem (i.e., each data point considered either normal or abnormal). The reconstruction error is used to detect anomalies. The experiments are carried out over the particular class of cyber security domain known as intrusion detection systems. We evaluated our model on standard publicly available benchmarks of KDD-99, NSL-KDD and UNSW-NB15 and achieved F1-score of 0.96, 0.88 and 0.95, respectively. It outperforms by a considerable margin when compared to state-of-the-art methods.
Complex-valued neural networks have many advantages over their real-valued counterparts. Conventi... more Complex-valued neural networks have many advantages over their real-valued counterparts. Conventional digital electronic computing platforms are incapable of executing truly complex-valued representations and operations. In contrast, optical computing platforms that encode information in both phase and magnitude can execute complex arithmetic by optical interference, offering significantly enhanced computational speed and energy efficiency. However, to date, most demonstrations of optical neural networks still only utilize conventional real-valued frameworks that are designed for digital computers, forfeiting many of the advantages of optical computing such as efficient complex-valued operations. In this article, we highlight an optical neural chip (ONC) that implements truly complex-valued neural networks. We benchmark the performance of our complex-valued ONC in four settings: simple Boolean tasks, species classification of an Iris dataset, classifying nonlinear datasets (Circle a...
Indian Journal of Physical Medicine and Rehabilitation, 2012
Heavy back packs carried for prolonged durations can cause different musculoskeletal and neurolog... more Heavy back packs carried for prolonged durations can cause different musculoskeletal and neurological problems especially in the untrained and physically vulnerable individuals. They can cause postural disorders, gait abnormalities, muscular strains, pains and injuries to the brachial plexus and nerves resulting in significant morbidity and at times permanent disability. We report a case of brachial plexus injury in a young soldier wearing back pack for prolonged period. He developed weakness and pain in right shoulder which was not relieved with rest and analgesics. On examination he had weakness in deltoid, biceps and scapular muscles along with numbness in axillary nerve area. Brachial plexus injury (upper trunk) was suspected and confirmed by electrodiagnostic evaluation. His baseline investigations were normal. He was advised rest and avoidance to lift heavy weight. He was managed with electrical muscle stimulation for weak muscles, strengthening exercises and analgesics. He re...
Background— Evidence is sparse about the genetic determinants of major lipids in Pakistanis. Meth... more Background— Evidence is sparse about the genetic determinants of major lipids in Pakistanis. Methods and Results— Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P <10 −13 ), APOA5/ZNF259 (rs651821; P <10 −13 ) and GCKR (rs1260326; P <10 −13 ) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P <10 −9 ). For Pakistanis, these 41 variants explained 6...
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