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Article: Effects of isoflurane and xylazine on inducing cerebral ischemia by the model of middle cerebral artery occlusion in mice.

Won, Jinyoung / Khan, Zeeshan Ahmad / Hong, Yonggeun

2023 Volume 39, Issue 1, Page(s) 11

Abstract: Preclinical ischemic stroke studies extensively utilize the intraluminal suture method of middle cerebral artery occlusion (MCAo). General anesthesia administration is an essential step for MCAo, but anesthetic agents can lead to adverse effects causing ... ...

Abstract	Preclinical ischemic stroke studies extensively utilize the intraluminal suture method of middle cerebral artery occlusion (MCAo). General anesthesia administration is an essential step for MCAo, but anesthetic agents can lead to adverse effects causing death and making a considerable impact on inducing cerebral ischemia. The purpose of this study was to comparatively assess the effect of isoflurane and xylazine on transient cerebral ischemia in a mouse model of MCAo. Twenty animals were randomly divided into four groups: sham group (no MCAo), control group (MCAo under isoflurane, no agent till reperfusion), isoflurane group (MCAo under isoflurane continued till reperfusion), xylazine group (MCAo under isoflurane, and administration of xylazine till reperfusion). The survival rate, brain infarct volume, and neurologic deficits were studied to assess the effect of isoflurane and xylazine on the stroke model. Our results showed that the body weight showed statistically significant change before and 24 h after surgery in the control and Isoflurane groups, but no difference in the Xylazine group. Also, the survival rate, brain infarct volume, and neurologic deficits were slightly reduced in the isoflurane group at 24 h after reperfusion injury. However, the xylazine and control groups showed similar BIV and neurologic deficits. Interestingly, a high survival rate was observed in the xylazine group. Our results indicate that the modified method of inhalation anesthetics combined with xylazine can reduce the risk of mortality and develop a reproducible MCAo model with predictable brain ischemia. In addition, extended isoflurane anesthesia after MCAo is associated with the risk of mortality.
Language	English
Publishing date	2023-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2623220-0
ISSN	2233-7660 ; 1738-6055
ISSN (online)	2233-7660
ISSN	1738-6055
DOI	10.1186/s42826-023-00163-6
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Article ; Online: Neurodegenerative effect of DAPK1 after cerebral hypoxia-ischemia is associated with its post-transcriptional and signal transduction regulations: A systematic review and meta-analysis.

Khan, Zeeshan Ahmad / Sumsuzzman, Dewan Md / Choi, Jeonghyun / Hong, Yonggeun

Ageing research reviews

2022 Volume 76, Page(s) 101593

Abstract: Cerebral hypoxia-ischemia (CHI) causes brain aging, neurological disorders, cognitive decline, motor function impairment, and mortality. Inhibiting death-associated protein kinase 1 (DAPK1) has shown therapeutic potential against CHI, but several reports ...

Abstract	Cerebral hypoxia-ischemia (CHI) causes brain aging, neurological disorders, cognitive decline, motor function impairment, and mortality. Inhibiting death-associated protein kinase 1 (DAPK1) has shown therapeutic potential against CHI, but several reports contradict its protective function, mechanism of activation, and signal transduction. Here, we systematically reviewed the role and the activation mechanism of DAPK1, and quantitatively assess the efficacy of DAPK1 inhibition (DI) methods in neuroprotection, following a CHI in animal models. Embase and PubMed were searched for relevant studies. Overall, 13 studies met the inclusion criteria, and the SYRCLE Risk of bias tool (RoB) tool was used to assess RoB. StataSE 16 was used for meta-analysis and network meta-analysis (NMA). Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated to estimate the effect size. DI was associated with the reduction of brain infarct volume (BIV) [SMD = -1.70, 95% CI (-2.10, -1.30); p = 0.00], neurological score (N.S.), neuronal degeneration, with no change in the level of in cell death [SMD = -0.83, 95% CI (-2.00, 0.35); p = 0.17], indicating the protective role of DI against CHI. No differences were found in DAPK1 mRNA and protein levels [SMD = 0.50, 95% CI (-0.05, 1.04); p = 0.07] {single-study driven; upregulated after exclusion (p = 0.01, I
MeSH term(s)	Animals ; Cell Death ; Death-Associated Protein Kinases/genetics ; Death-Associated Protein Kinases/metabolism ; Humans ; Hypoxia-Ischemia, Brain/genetics ; Network Meta-Analysis ; Neurodegenerative Diseases/genetics ; RNA Processing, Post-Transcriptional ; Signal Transduction
Chemical Substances	DAPK1 protein, human (EC 2.7.11.1) ; Death-Associated Protein Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-02-22
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2022.101593
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Article ; Online: Assessment of functional roles and therapeutic potential of integrin receptors in osteoarthritis: A systematic review and meta-analysis of preclinical studies.

Sumsuzzman, Dewan Md / Khan, Zeeshan Ahmad / Choi, Jeonghyun / Hong, Yonggeun

Ageing research reviews

2022 Volume 81, Page(s) 101729

Abstract: Background: Integrins are heterodimeric transmembrane receptors that mediate a variety of biological function and plays a critical role in osteoarthritis (OA) pathogenesis, which may provide new targets for the development of OA therapies. However, the ... ...

Abstract	Background: Integrins are heterodimeric transmembrane receptors that mediate a variety of biological function and plays a critical role in osteoarthritis (OA) pathogenesis, which may provide new targets for the development of OA therapies. However, the roles of integrins in different stages of OA remain elusive. Objectives: This study aimed to synthesize all published preclinical evidence on the roles of integrin receptors in different stages of OA to identify the potential target for drug development in alleviating OA pathogenesis. Methods: Major electronic databases were used to identify related original articles. The methodological quality of all included studies was appraised using the SYRCLE risk of bias tool. We used the generic inverse variance with random effects model to calculate standardized mean differences (SMDs) and 95% confidence interval (CI). Results: Seventeen studies were included in this systematic review. Integrin α5β1 activation increases the histopathological score both in early [SMD, 6.39; 95%CI (2.90, 9.87); p = 0.0003] and late [SMD, 3.41; 95%CI (2.44, 4.38); p < 0.00001] stage of OA. Integrin α5β1 also increased the core catabolic factors like MMP-3, IL-1β, and TNF-α. Interestingly, the inactivation of α5β1 integrin did not change the histopathological score (p = 0.84). Similarly, β1 integrin notably increased histopathological score at both stages of OA [early; SMD, 7.13; 95%CI (2.01, 12.24); p = 0.006]; [late; SMD, 10.25; 95%CI (5.11, 15.39); p < 0.0001], and increased the MMP-13 levels. However, integrin β1 was upregulated at the early stage and downregulated at the late stage of OA. Furthermore, α2β1 integrin significantly increased histopathological score [SMD, 3.14; 95%CI (2.18, 4.10); p < 0.00001] and MMP-13 [SMD, 2.24; 95%CI (0.07, 4.41); p = 0.04]. Deactivating integrin α1β1 increased histopathological score in late [SMD, 1.53; 95%CI (0.80, 2.26); p < 0.0001], but not in early [SMD, 0.90; 95%CI (-1.65, 3.45); p = 0.49] stage of OA. Conclusion: This study provides evidence that α5β1, α2β1, and α1β1 integrin might be the potential target for future drug development in alleviating OA pathogenesis. Further work is required to establish our findings through activating/deactivating these receptors in different stages of OA.
MeSH term(s)	Humans ; Integrin alpha1beta1 ; Integrin alpha5beta1 ; Integrin beta1 ; Integrins ; Matrix Metalloproteinase 13 ; Matrix Metalloproteinase 3 ; Osteoarthritis/drug therapy ; Osteoarthritis/metabolism ; Tumor Necrosis Factor-alpha
Chemical Substances	Integrin alpha1beta1 ; Integrin alpha5beta1 ; Integrin beta1 ; Integrins ; Tumor Necrosis Factor-alpha ; Matrix Metalloproteinase 13 (EC 3.4.24.-) ; Matrix Metalloproteinase 3 (EC 3.4.24.17)
Language	English
Publishing date	2022-09-08
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Review ; Systematic Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2022.101729
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Article ; Online: Suppression of DAPK1 reduces ischemic brain injury through inhibiting cell death signaling and promoting neural remodeling.

Won, Jinyoung / Lee, Seunghoon / Ahmad Khan, Zeeshan / Choi, Jeonghyun / Ho Lee, Tae / Hong, Yonggeun

Brain research

2023 Volume 1820, Page(s) 148588

Abstract: The role of death-associated protein kinase1 (DAPK1) in post-stroke functional recovery is controversial, as is its mechanism of action and any neural remodeling effect after ischemia. To assess the debatable role of DAPK1, we established the middle ... ...

Abstract	The role of death-associated protein kinase1 (DAPK1) in post-stroke functional recovery is controversial, as is its mechanism of action and any neural remodeling effect after ischemia. To assess the debatable role of DAPK1, we established the middle cerebral artery occlusion (MCAo) model in DAPK1 knockout mice and Sprague-Dawley (SD) rats. We identified that the genetic deletion of the DAPK1 as well as pharmacological inhibition of DAPK1 showed reduced brain infarct volume and neurological deficit. We report that DAPK1 inhibition (DI) reduces post-stroke neuronal death by inhibiting BAX/BCL2 and LC3/Beclin1 mediated apoptosis and autophagy, respectively. Histological analysis displayed a reduction in nuclear condensation, neuronal dissociation, and degraded cytoplasm in the DI group. The DI treatment showed enhanced dendrite spine density and neurite outgrowth, upregulated neural proliferation marker proteins like brain-derived neurotrophic factor, and reduced structural abnormalities of the cortical pyramidal neurons. This research shows that DAPK1 drives cell death, its activation exacerbates functional recovery after cerebral ischemia and shows that oxazolone-based DI could be an excellent candidate for stroke and ischemic injury intervention.
Language	English
Publishing date	2023-09-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2023.148588
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Article: Effect of Daily Coffee Consumption on the Risk of Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Nila, Irin Sultana / Villagra Moran, Vanina Myuriel / Khan, Zeeshan Ahmad / Hong, Yonggeun

Journal of lifestyle medicine

2023 Volume 13, Issue 2, Page(s) 83–89

Abstract: Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder that affects millions of individuals globally. The identification of the lifestyle factors that potentially help prevent or postpone disease onset is of interest to the researchers. ...

Abstract	Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder that affects millions of individuals globally. The identification of the lifestyle factors that potentially help prevent or postpone disease onset is of interest to the researchers. Although the study results are inconsistent, one such factor that has been extensively studied is coffee consumption. Therefore, this meta-analysis primarily aimed to investigate the effects of coffee consumption on the risk of AD. Pubmed, Embase, and Web of Science (Only Writing Web of Science is Fine) databases were searched for relevant studies with the keywords in various combinations, including "coffee", "caffeine", and "Alzheimer's disease". This meta-analysis included 11 studies. The relative risk (RR) with 95% confidence intervals (CI) was calculated to estimate the effect size. The study used the restricted maximum-likelihood method for a generic-inverse-variance analysis with random-effect (when heterogeneity, I
Language	English
Publishing date	2023-08-25
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	3021714-3
ISSN	2288-1557 ; 2234-8549
ISSN (online)	2288-1557
ISSN	2234-8549
DOI	10.15280/jlm.2023.13.2.83
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Article ; Online: Transparent Rule Enablement Based on Commonization Approach in Heterogeneous IoT Edge Networks.

Jin, Wenquan / Hong, Yong-Geun / Song, Jaeseung / Kim, Jaeho / Kim, Dohyeun

Sensors (Basel, Switzerland)

2023 Volume 23, Issue 19

Abstract: The paradigm of the Internet of Things (IoT) and edge computing brings a number of heterogeneous devices to the network edge for monitoring and controlling the environment. For reacting to events dynamically and automatically in the environment, rule- ... ...

Abstract	The paradigm of the Internet of Things (IoT) and edge computing brings a number of heterogeneous devices to the network edge for monitoring and controlling the environment. For reacting to events dynamically and automatically in the environment, rule-enabled IoT edge platforms operate the deployed service scenarios at the network edge, based on filtering events to perform control actions. However, due to the heterogeneity of the IoT edge networks, deploying a consistent rule context for operating a consistent rule scenario on multiple heterogeneous IoT edge platforms is difficult because of the difference in protocols and data formats. In this paper, we propose a transparent rule enablement, based on the commonization approach, for enabling a consistent rule scenario in heterogeneous IoT edge networks. The proposed IoT Edge Rule Agent Platform (IERAP) deploys device proxies to share consistent rules with IoT edge platforms without considering the difference in protocols and data formats. Therefore, each device proxy only considers the translation of the corresponding platform-specific and common formats. Also, the rules are deployed by the corresponding device proxy, which enables rules to be deployed to heterogeneous IoT edge platforms to perform the consistent rule scenario without considering the format and underlying protocols of the destination platform.
Language	English
Publishing date	2023-10-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s23198282
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Article ; Online: Differential role of melatonin in healthy brain aging: a systematic review and meta-analysis of the SAMP8 model.

Sumsuzzman, Dewan Md / Khan, Zeeshan Ahmad / Choi, Jeonghyun / Hong, Yonggeun

Aging

2021 Volume 13, Issue 7, Page(s) 9373–9397

Abstract: The relationship between oxidative stress (OS) and cellular senescence (CS) is an important research topic because of the rapidly aging global population. Melatonin (MT) is associated with aging and plays a pivotal role in redox homeostasis, but its role ...

Abstract	The relationship between oxidative stress (OS) and cellular senescence (CS) is an important research topic because of the rapidly aging global population. Melatonin (MT) is associated with aging and plays a pivotal role in redox homeostasis, but its role in maintaining physiological stability in the brain (especially in OS-induced senescence) remains elusive. Here, we systematically reviewed the differential role of MT on OS-induced senescence in the SAMP8 mouse model. Major electronic databases were searched for relevant studies. Pooled mean differences (MDs)/standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to estimate the effect size. Overall, 10 studies met the inclusion criteria. MT treatment was associated with the reduction of lipid peroxidation (SMD = -2.00, 95% CI [-2.91, -1.10];
MeSH term(s)	Aging/metabolism ; Animals ; Brain/metabolism ; Cellular Senescence/physiology ; Disease Models, Animal ; Glutathione Peroxidase/metabolism ; Melatonin/metabolism ; Oxidative Stress/physiology ; Superoxide Dismutase/metabolism
Chemical Substances	Glutathione Peroxidase (EC 1.11.1.9) ; Superoxide Dismutase (EC 1.15.1.1) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2021-04-02
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.202894
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Article ; Online: Recent Advances in Electrochemical and Optical Sensors for Detecting Tryptophan and Melatonin.

Khan, Zeeshan Ahmad / Hong, Paul Jung-Soo / Lee, Christina Hayoung / Hong, Yonggeun

International journal of nanomedicine

2021 Volume 16, Page(s) 6861–6888

Abstract: Tryptophan and melatonin are pleiotropic molecules, each capable of influencing several cellular, biochemical, and physiological responses. Therefore, sensitive detection of tryptophan and melatonin in pharmaceutical and human samples is crucial for ... ...

Abstract	Tryptophan and melatonin are pleiotropic molecules, each capable of influencing several cellular, biochemical, and physiological responses. Therefore, sensitive detection of tryptophan and melatonin in pharmaceutical and human samples is crucial for human well-being. Mass spectrometry, high-performance liquid chromatography, and capillary electrophoresis are common methods for both tryptophan and melatonin analysis; however, these methods require copious amounts of time, money, and manpower. Novel electrochemical and optical detection tools have been subjects of intensive research due to their ability to offer a better signal-to-noise ratio, high specificity, ultra-sensitivity, and wide dynamic range. Recently, researchers have designed sensitive and selective electrochemical and optical platforms by using new surface modifications, microfabrication techniques, and the decoration of diverse nanomaterials with unique properties for the detection of tryptophan and melatonin. However, there is a scarcity of review articles addressing the recent developments in the electrochemical and optical detection of tryptophan and melatonin. Here, we provide a critical and objective review of high-sensitivity tryptophan and melatonin sensors that have been developed over the past six years (2015 onwards). We review the principles, performance, and limitations of these sensors. We also address critical aspects of sensitivity and selectivity, limit and range of detection, fabrication process and time, durability, and biocompatibility. Finally, we discuss challenges related to tryptophan and melatonin detection and present future outlooks.
MeSH term(s)	Biosensing Techniques ; Chromatography, High Pressure Liquid ; Electrochemical Techniques ; Humans ; Mass Spectrometry ; Melatonin ; Nanostructures ; Tryptophan
Chemical Substances	Tryptophan (8DUH1N11BX) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2021-10-11
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2364941-0
ISSN	1178-2013 ; 1176-9114
ISSN (online)	1178-2013
ISSN	1176-9114
DOI	10.2147/IJN.S325099
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Article ; Online: Neurocognitive effects of melatonin treatment in healthy adults and individuals with Alzheimer's disease and insomnia: A systematic review and meta-analysis of randomized controlled trials.

Sumsuzzman, Dewan Md / Choi, Jeonghyun / Jin, Yunho / Hong, Yonggeun

Neuroscience and biobehavioral reviews

2021 Volume 127, Page(s) 459–473

Abstract: Endogenous melatonin levels are inversely associated with age and cognitive deficits. Although melatonin can improve psychopathological behavior disturbances in clinical trials, whether melatonin may also enhance cognitive function remains elusive. This ... ...

Abstract	Endogenous melatonin levels are inversely associated with age and cognitive deficits. Although melatonin can improve psychopathological behavior disturbances in clinical trials, whether melatonin may also enhance cognitive function remains elusive. This study examined cognitive outcomes from randomized trials of melatonin treatment for Alzheimer's disease (AD), insomnia, and healthy-subjects. Twenty-two studies met the inclusion criteria (AD = 9, insomnia = 2, healthy-subjects = 11). AD patients receiving >12 weeks of melatonin treatment improved mini-mental state examination (MMSE) score [MD: 1.82 (1.01; 2.63) p < 0.0001]. Importantly, melatonin significantly improved MMSE score in mild stage of AD [MD: 1.89 (0.96; 2.82) p < 0.0001]. In healthy-subjects, although daytime melatonin treatment notably decreased in accuracy by correct responses [SMD: -0.74 (-1.03; -0.45) p < 0.00001], the reaction-time score on different stimuli (p = 0.37) did not increased. Additionally, by pooling of short-term, spatial, and visual memory scores, melatonin did not reduce memory function (p = 0.08). Meta-analysis of MMSE score suggested that melatonin is effective in treatment for mild stage of AD. Additionally, we propose that melatonin may be preferable to traditional hypnotics in management of insomnia.
MeSH term(s)	Adult ; Alzheimer Disease/drug therapy ; Cognition Disorders ; Humans ; Melatonin/therapeutic use ; Randomized Controlled Trials as Topic ; Sleep Initiation and Maintenance Disorders/drug therapy
Chemical Substances	Melatonin (JL5DK93RCL)
Language	English
Publishing date	2021-05-03
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2021.04.034
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Article ; Online: Pre- and post-conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta-analysis.

Khan, Zeeshan Ahmad / Sumsuzzman, Dewan Md / Choi, Jeonghyun / Kamenos, George / Hong, Yonggeun

CNS neuroscience & therapeutics

2022 Volume 28, Issue 8, Page(s) 1168–1182

Abstract: Background: Toll-like receptor (TLR) agonist polyinosinic-polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear.: Methods: We evaluated ... ...

Abstract	Background: Toll-like receptor (TLR) agonist polyinosinic-polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear. Methods: We evaluated the neuroprotective role of poly I:C by assessing CI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in CI. Our search identified 164 articles and 10 met the inclusion criterion. Results: Poly I:C reduces BIV and N.S. (p = 0.00 and p = 0.03). Interestingly, both pre- and post-conditioning decrease BIV (preC p = 0.04 and postC p = 0.00) and N.S. (preC p = 0.03 and postC p = 0.00). Furthermore, poly I:C upregulates TLR3 [SMD = 0.64; CIs (0.56, 0.72); p = 0.00], downregulates nuclear factor-κB (NF-κB) [SMD = -1.78; CIs (-2.67, -0.88); p = 0.0)], and tumor necrosis factor alpha (TNF-α) [SMD = -16.83; CIs (-22.63, -11.02); p = 0.00]. Conclusion: We showed that poly I:C is neuroprotective and acts via the TLR3/NF-κB/TNF-α pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against CI. Further research on simultaneous activation of TLR3 with poly I:C and suppression of TLR 2/4 might open new vistas for the development of therapeutics against CI.
MeSH term(s)	Animals ; Brain Infarction ; Brain Injuries ; Brain Ischemia/pathology ; Cerebral Infarction ; NF-kappa B/metabolism ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Poly I-C/pharmacology ; Signal Transduction ; Toll-Like Receptor 2 ; Toll-Like Receptor 3/metabolism ; Tumor Necrosis Factor-alpha
Chemical Substances	NF-kappa B ; Neuroprotective Agents ; Toll-Like Receptor 2 ; Toll-Like Receptor 3 ; Tumor Necrosis Factor-alpha ; Poly I-C (O84C90HH2L)
Language	English
Publishing date	2022-05-05
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Systematic Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2423461-8
ISSN	1755-5949 ; 1755-5930
ISSN (online)	1755-5949
ISSN	1755-5930
DOI	10.1111/cns.13851
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