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Papers by Julia Zhong

Background: Extrinsic injury can evoke intrinsic stimulation subquently initiate physiological re... more Background: Extrinsic injury can evoke intrinsic stimulation subquently initiate physiological repair process. Several kinds of injury have been studied to promote hair growth and skin pigmentation. In this study, we ask if proper injury could be employed to create local stimuli subsquently to induce hair regeneration and vitiligo repigmentation.Methods: We firstly manufactured a novel designed device to precisely control all micro-injury parameters. Then the most appropriate micro-injury extent was evaluated without over-damage to skin. The effects of micro-injury on hair regeneration and vitiligo repigmentation were examined by macroscopical observation, histological staining, gene and protein expression analysis.Results: We discover that proper micro-injury effectively induces hair regeneration by activating the hair follicle stem cell proliferation and migration downwards to hair matrix, finally shifting the hair follicle stage from telogen into anagen. On vitiligo model mice, m...

Frontiers in Cell and Developmental Biology

Light has attracted special attention as a stimulus for triggered drug delivery systems (DDS) due... more Light has attracted special attention as a stimulus for triggered drug delivery systems (DDS) due to its intrinsic features of being spatially and temporally tunable. Ultraviolet A (UVA) radiation has recently been used as a source of external light stimuli to control the release of drugs using a “switch on- switch off” procedure. This review discusses the promising potential of UVA radiation as the light source of choice for photo-controlled drug release from a range of photo-responsive and photolabile nanostructures via photo-isomerization, photo-cleavage, photo-crosslinking, and photo-induced rearrangement. In addition to its clinical use, we will also provide here an overview of the recent UVA-responsive drug release approaches that are developed for phototherapy and skin photoprotection.

Antioxidants & Redox Signaling

AIMS Drug-induced liver injury, especially acetaminophen-induced liver injury, is a leading cause... more AIMS Drug-induced liver injury, especially acetaminophen-induced liver injury, is a leading cause of liver failure worldwide. Mouse models were used to evaluate the effect of microelement selenium levels on the cellular redox environment and consequent hepatotoxicity of acetaminophen (APAP). RESULTS APAP treatment affected mouse liver selenoprotein thioredoxin reductase (TrxR) activity and glutathione level in a dose- and time-dependent manner. Decrease of mouse liver TrxR activity and glutathione level was an early event, and occurred concurrently with liver damage. The decreases of ratio of GSH/GSSG, TrxR activity and the increase of protein S-glutathionylation were correlated with the APAP-induced hepatotoxicity. Moreover, in APAP-treated mice both mild deprivation or excess supplementation with selenium increased the severity of liver injury compared to that observed in mice with normal dietary selenium levels. An increase in the oxidation state of the TrxR-mediated system, including cytosolic thioredoxin1 (Trx1) and peroxiredoxin1/2, and mitochondrial Trx2 and Prx3, were found in the livers from mice reared on selenium-deficient and excess selenium-supplemented diets upon APAP-treatment. INNOVATION This work demonstrates that both Trx and GSH systems are susceptible to APAP toxicity in vivo, and that the thiol-dependent redox environment is a key factor in determining the extent of APAP-induced hepatotoxicity. Dietary selenium and selenoproteins play critical roles in protecting mice against APAP overdose. CONCLUSION APAP treatment in mice interrupts the function of the Trx and GSH system which are the main enzymatic antioxidant systems, in both cytosol and mitochondria. Dietary selenium deficiency and excess supplementation both increase the risk of APAP-induced hepatotoxicity.

International Immunopharmacology

BACKGROUND Cumulative evidence suggests that in allergic diseases, oxidative stress and inflammat... more BACKGROUND Cumulative evidence suggests that in allergic diseases, oxidative stress and inflammation could often be detected. Therefore, the antioxidant/anti-inflammatory heme oxygenase (HO)-1 was recognized as a protective factor in allergic disorders. However, the precise underlying mechanisms of HO-1-based protection are not yet completely understood. In addition, miRNAs, a class of non-coding RNA, have been confirmed to associate with immunologic and inflammatory disorders in allergy recently. In addition, abundant studies have verified there is a complex connection between HO-1 and miRNAs. Thus, in this review, the combination of HO-1 and miRNAs (e.g. miR-155) in anti-allergy would be introduced. METHODS To further confirm our hypothesis, GEO sequencing datasets of atopic dermatitis children were analyzed. The miR-548a-3p might regulate the cellular response to hydrogen peroxide through HO-1 and HIF-1pathway. Meanwhile, this article reviews the latest knowledge and studies on the protective mechanisms of miRNA-HO-1 in allergy. RESULTS In brief, we supposed that miRNAs/HO-1 could mediate allergy through oxidative stress pathways, transcription factors and immune cell functions such as mast cell maturation, chemokine expression in T cell and dendritic cell degranulation. Although the detailed mechanism needs further research, this review may reveal the potential application of miRNAs and HO-1 in genetic therapies of allergic disease and provide new biomarkers. CONCLUSION This article examines the latest knowledge and studies on the protective roles and mechanisms of miRNA-HO-1 in allergy. Moreover, via bioinformatics analysis of GEO dataset, it was demonstrated that miRNAs (e.g. miR-205, miR-203, and miR-483-5p) could regulate allergy process through HO-1.

Oxidative Medicine and Cellular Longevity

Autophagy is an essential cellular process that maintains balanced cell life. Restriction in auto... more Autophagy is an essential cellular process that maintains balanced cell life. Restriction in autophagy may induce degenerative changes in humans. Natural or pathological aging of susceptible tissues has been linked with reduced autophagic activity. Skin photoaging is an example of such pathological condition caused by ambient solar UV radiation exposure. The UV-induced production of reaction oxygen species (ROS) has been linked to the promotion and progression of the photoaging process in exposed tissues. Accordingly, it has been suggested that autophagy is capable of delaying the skin photoaging process caused by solar ultraviolet (UV), although the underlying mechanism is still under debate. This review highlights several plausible mechanisms by which UV-induced ROS activates the cellular signaling pathways and modulates the autophagy. More specifically, the UV-mediated regulation of autophagy and age-related transcription factors is discussed to pinpoint the contribution of autop...

Oxidative Medicine and Cellular Longevity

Ultraviolet (UV) irradiation can be considered as a double-edged sword: not only is it a crucial ... more Ultraviolet (UV) irradiation can be considered as a double-edged sword: not only is it a crucial environmental factor that can cause skin-related disorders but it can also be used for phototherapy of skin diseases. Inducible heme oxygenase-1 (HO-1) in response to a variety of stimuli, including UV exposure, is vital to maintain cell homeostasis. Heme oxygenase-2 (HO-2), another member of the heme oxygenase family, is constitutively expressed. In this review, we discuss how heme oxygenase (HO), a vital rate-limiting enzyme, participates in heme catabolism and cytoprotection. Phylogenetic analysis showed that there may exist a functional differentiation between HO-1 and HO-2 during evolution. Furthermore, depending on functions in immunomodulation and antioxidation, HO-1 participates in disease progression, especially in pathogenesis of skin diseases, such as vitiligo and psoriasis. To further investigate the particular role of HO-1 in diseases, we summarized the profile of the HO enz...

Materials Science and Engineering: C

Polymorphous light eruption (PLE) is one of the acquired idiopathic photodermatosis mainly induce... more Polymorphous light eruption (PLE) is one of the acquired idiopathic photodermatosis mainly induced by immoderate UV radiation. In order to realize UV protection and medicine administration simultaneously for polymorphous light eruption protection and therapy, Acetyl-11-keto-β-boswellic acid (AKBA) loaded Zinc Oxide (ZnO) nanoparticles of which drug release behavior is UV-controlled has been successfully synthesized. Such nanoparticles can not only reflect UV but also transfer the energy to release AKBA which presents an excellent antioxidant and anti-inflammatory effects. In addition, they are biocompatible to HaCaT cells. As a result, they have a great potential in combining UV protection and medicine administration simultaneously for PLE protection and therapy.

Free Radical Research

Abstract Ultraviolet A (UVA) irradiation is a potential environmental stressor, which contributes... more Abstract Ultraviolet A (UVA) irradiation is a potential environmental stressor, which contributes to inflammation, photoaging, and carcinogenesis. UVA causes endoplasmic reticulum stress, hence phosphorylates the α subunit of eIF2. Meanwhile, UVA also induces expression of haem oxygenase-1 (HO-1) and nuclear factor erythroid-derived two related factor 2 (Nrf2) in human skin cells. In mouse JB6 cell, we found high dose UVA could change cell morphology, cause cell viability loss. UVA irradiation activated phosphorylation of eIF2α and Nrf2-HO-1 pathway in a dose-dependent manner. Besides, modulation of eIF2α phosphorylation status could alter expression pattern of Nrf2-HO-1 signalling. Salubrinal, a selective inhibitor of eIF2α dephosphorylation, increased the S phase in cell cycle of JB6 cells after UVA irradiation, suggesting phosphorylation status of eIF2α may affect cellular homeostasis under UVA irradiation. The study directed to further acknowledge about the relationship of UVA-induced eIF2α phosphorylation and Nrf2-HO-1 pathway, which may play a role in phototherapy and photo protection.

Cell Communication and Signaling

Background: Despite therapeutic advancements (e.g. B-RAF inhibitors) targeting cutaneous melanoma... more Background: Despite therapeutic advancements (e.g. B-RAF inhibitors) targeting cutaneous melanoma, many cellular processes, including inducible heme oxygenase 1 (HO-1), counteract treatments for malignancies. So there is an urgent need to find biological treatment targets, develop new therapeutic approaches and achieve longer responses. This study aimed to explore the relationship of HO-1 and B-Raf via mediating ERK1/2 signaling on cell cycle in melanoma. Methods: Immunohistochemistry was applied to evaluate the levels of HO-1 and B-Raf expression in melanoma tissues and adjacent healthy tissues. Co-immunoprecipitation (Co-IP) assessed the interaction of HO-1 with B-Raf. Further study overexpression and knock-down of HO-1 in A375 cell lines, especially knockout HO-1 using CRISPR-Cas9, verified HO-1 regulate cell proliferation in vivo and in vitro. Finally, Western blot analysis and qRT-PCR were performed to investigate the mechanisms by which HO-1 mediates cell cycle by B-RAF-ERK1/2 signaling. Results: First, histology and Co-IP show that HO-1 interacts with B-Raf directly in melanoma tissue. Further study illustrated that HO-1 overexpression promotes melanoma cell proliferation while HO-1 reduction represses melanoma cell proliferation because of HO-1 affects cell cycle. Mechanistic studies revealed that HO-1 was associated with a marked activation of B-RAF-ERK1/2 signaling and led to CDK2/cyclin E activation, thereby promoting melanoma proliferation. Conclusions: Our result reveals a previously unknown mechanism that the HO-1-B-RAF-ERK axis plays an important role in melanoma cell proliferation. Therapeutic target on HO-1 could be a novel method for treating melanoma.

Current Research Journal of Biological Sciences

The present study conducted in district Bahawalpur of Southern Punjab province, Pakistan to enlis... more The present study conducted in district Bahawalpur of Southern Punjab province, Pakistan to enlist the medicinal plants and their uses among local people. Previous studies focus primarily on the exploration of medicinal plants of Cholistan desert while rest of the area remained un-explored. The ethno-medicinal survey was conducted regularly for a period of 10 years and tries to eradicate the errors in the utilizations of the plants and to finally to document ethno-medicinal uses of plant species through questionnaire and personal interviews during field trips. Plants with their correct nomenclature were arranged by family name, vernacular name, parts used and ethnomedicinal uses. For the identification of plants we used field guides and flora of Pakistan and as a result 123 plant species currently under utilization by local people were identified. Previously we collected all the plant specimens, after careful identification we preserved and mounted on herbarium sheets, were placed in the department of Botany, Govt. Sadiq Egerton College, Bahawalpur, Pakistan. The study will provide a baseline for future studies relating to pharmacological, chemical isolations, taxonomic and well as biochemical studies by giving a quick approach to the specific plant species.

Journal of biological engineering, 2018

Generation of reactive oxygen species (ROS), triggered by ultraviolet radiation (UVR), is associa... more Generation of reactive oxygen species (ROS), triggered by ultraviolet radiation (UVR), is associated with carcinogenesis of the skin. UV irradiation induced superoxide anion (O2) is the key ROS involved in the cellular damage. The cytoprotective efficacy of an unknown anti-oxidant compound can be evaluated by analyzing the production of O2 from treated cells. In this study, a glass carbon electrode functionalized with nanotube@DNA-Mn3(PO4)2 composite was applied to quantitative determination of generation of highly unstable O2 from the melanoma A375 cell line following UVR(UV, UVA and UVB). In addition, the cytoprotective efficacy of anti-oxidant α-tocopherol was evaluated by quantifying the production of O2. The results showed that, UVR triggers generation of O2 in melanoma A375 cells, and α-tocopherol is effective in diminishing the production of O2 following UV irradiation. By comparing the conventional cell-survival assays results, we found that our simple and quick electrochemi...

Cell communication and signaling : CCS, Jan 15, 2018

The extensive involvement of microRNA (miRNA) in the pathophysiology of psoriasis is well documen... more The extensive involvement of microRNA (miRNA) in the pathophysiology of psoriasis is well documented. However, in order for this information to be useful in therapeutic manipulation of miRNA levels, it is essential that detailed functional mechanisms are elucidated. This study aimed to explore the effects of IL-6 targeting by let-7b and ERK1/2 mediated signaling on keratinocyte differentiation in psoriasis. Following imiquimod cream (IMQ) application to let-7b (keratinocyte-specific let-7b overexpression mouse) and control mice for 7 days, we analyzed erythema, scaling and thickening of skin. A dual luciferase reporter assay and bioinformatics was carried out to detect target gene of let-7b. Additionally, the differentiation markers were measured. Immunohistochemistry analyses demonstrate a relationship of let-7b with IL-6 and ERK signaling. we found let-7b inhibits acanthosis and reduces the disease severity by treatment with IMQ compared to wild-type mice. Further study illustrate...

Cellular signalling, Jan 27, 2018

The tyrosine phosphatases family member PTEN is a tumor suppressor which is widely expressed thro... more The tyrosine phosphatases family member PTEN is a tumor suppressor which is widely expressed throughout the body and is involved in a variety of biological functions. PTEN is known to be frequently mutated or downregulated in human cancers. However, the underlying molecular mechanism remains largely unknown. Here, using a proteomic approach, we identified the E3 ubiquitin ligase HRD1, which was previously reported to be involved in endoplasmic reticulum associated degradation (ERAD), as one of the PTEN-interacting proteins. We also found that HRD1 promoted PTEN degradation by positively regulating its ubiquitination. In addition, suppression of HRD1 expression resulted in the inhibition of the growth, migration and invasion of hepatocellular carcinoma in vitro and in vivo. Finally, we detected a negative correlation between HRD1 and PTEN expression in human hepatocellular carcinoma. From these results we propose a novel molecular mechanism of HRD1 to promote hepatocellular tumorigen...

Materials science & engineering. C, Materials for biological applications, 2018

Infection associated with orthopedic implants is the chief cause of implant failure. An important... more Infection associated with orthopedic implants is the chief cause of implant failure. An important consideration to prevent the infection at implants is to inhibit the biofilm formation for the initial 6 h. Therefore, we fabricated hyaluronidase-sensitive multilayers of chitosan (Chi)/sodium hyaluronate-lauric acid (SL) onto the surface of bone morphogenetic protein 2 (BMP2) loaded titanium nanotube (TNT) via spin-assisted layer-by-layer technique. The results of both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (H NMR) confirmed the successful synthesis of SL. The multilayer structure on BMP2 loaded TNT was characterized by field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and water contact angle, respectively. The release profiles confirmed that hyaluronidase could trigger the release of lauric acid (LA) from the SL multilayer and accelerate the release of BMP2 in the system. The hyaluronidase-sensitive-multilayer-c...

Oxidative medicine and cellular longevity, 2018

Brusatol (BR) is a potent inhibitor of Nrf2, a transcription factor that is highly expressed in c... more Brusatol (BR) is a potent inhibitor of Nrf2, a transcription factor that is highly expressed in cancer tissues and confers chemoresistance. UVA-generated reactive oxygen species (ROS) can damage both normal and cancer cells and may be of potential use in phototherapy. In order to provide an alternative method to treat the aggressive melanoma, we sought to investigate whether low-dose UVA with BR is more effective in eliminating melanoma cells than the respective single treatments. We found that BR combined with UVA led to inhibition of A375 melanoma cell proliferation by cell cycle arrest in the G1 phase and triggers cell apoptosis. Furthermore, inhibition of Nrf2 expression attenuated colony formation and tumor development from A375 cells in heterotopic mouse models. In addition, cotreatment of UVA and BR partially suppressed Nrf2 and its downstream target genes such as HO-1 along with the PI3K/AKT pathway. We propose that cotreatment increased ROS-induced cell cycle arrest and cel...

Oncotarget

Locoregional lymph nodes metastasis in oral tongue squamous cell carcinoma represents one of impo... more Locoregional lymph nodes metastasis in oral tongue squamous cell carcinoma represents one of important and common prognostic factors for poor clinical outcome. The human Telomerase Reverse Transcriptase (hTERT) is one of key players in cancer metastasis and stemness, but its exact function in tongue squamous cell carcinoma remains unknown. Here, we aim to understand the role of hTERT by utilizing the CRISPR/Cas9 gene editing system to deplete hTERT in the SCC-15 cell line. Functional comparison of SCC-15 control and knockout cells (hTERT −/−) showed that loss of hTERT suppressed cell proliferation and migration/invasion. Furthermore, hTERT depletion significantly decreased tumorigenesis, including alterations in cellular morphology that areindicative for epithelial-mesenchymal transition (EMT). Mechanistically we demonstrated that the hTERT knockout attenuates NF-κB signaling via a negative feedback regulation in tumorprogression. From these results we propose a novel molecular mechanism of hTERT to promote SCC-15 invasion and metastasis via NF-κB activation. We conclude that targeting hTERT may represent a new therapeutic strategy to improve therapy and survival of tongue squamous cell carcinoma patients.

Skin pharmacology and physiology, 2017

Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress wi... more Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis. The aim of this study is to investigate the protective effect of acetyl-11-keto-β-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes. HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined. AKBA reduces UVA irradiation-induced cell viability loss, accompanied by a decreased production of UVA-induced ROS, decreased malondialdehyde, and increased superoxide dismutase expression. In addition, AKBA increased basal and UVA-induced levels of Nrf2 (NF-E2-related factor 2), the redox-sensitive factor, and its target genes NQO1 and heme oxygenase-1 (HO-1), whereas expression of the transcriptional repressor Bach1 (BTB and CNC homology...

Experimental dermatology, Feb 11, 2016

Wound healing is a complex process involves proliferation and migration of keratinocyte for closu... more Wound healing is a complex process involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family let-7b, have been expressed in mammalian skin but its exact role in keratinocyte migration is still not in knowledge. Here we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2BP2. Overexpression of let-7b led to reduced HaCaT cell migration while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. By using bioinformatics prediction software and a reporter gene assay, we found that IGF2BP2 was a target of let-7b, which contributes to keratinocyte migration. Introduction of an expression vector of IGF2BP2 also rescued let-7b-induced m...

Clinical and Experimental Metastasis, Apr 1, 2009

Des-gamma-carboxy prothrombin (DCP) is an aberrant prothrombin produced by hepatocellular carcino... more Des-gamma-carboxy prothrombin (DCP) is an aberrant prothrombin produced by hepatocellular carcinoma (HCC) cells. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. However, the role of DCP in the development of angiogenesis is not well understood. Herein, we report the effects of DCP on growth and migration of human vascular endothelial cells. DCP significantly stimulated the proliferation of HUVEC (ECV304) cells in a dose and time dependent manner, as measured by the MTT assay. A continuous rapid migration of ECV304 cells was observed in the presence of DCP measured by the scratch wound assay. The continuous rapid invasive activity, measured by transwell chamber assay also showed that DCP increased endothelial cells migration through the reconstituted extracellular matrix (Matrigel). Further, the tube formation of vascular endothelial cells on 3-D Matrigel showed an increased number of branch points of ECV304 cells induced by DCP in a dose dependent manner. The levels of vascular endothelial cell growth-related angiogenic factors and matrix metalloproteinase were also examined. DCP significantly stimulated the expression levels of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 (latent and active). Together, these data suggest that DCP is a novel type of vascular endothelial growth factor that possesses potent mitogenic and migrative activities in angiogenesis of HCC.

Background: Extrinsic injury can evoke intrinsic stimulation subquently initiate physiological re... more Background: Extrinsic injury can evoke intrinsic stimulation subquently initiate physiological repair process. Several kinds of injury have been studied to promote hair growth and skin pigmentation. In this study, we ask if proper injury could be employed to create local stimuli subsquently to induce hair regeneration and vitiligo repigmentation.Methods: We firstly manufactured a novel designed device to precisely control all micro-injury parameters. Then the most appropriate micro-injury extent was evaluated without over-damage to skin. The effects of micro-injury on hair regeneration and vitiligo repigmentation were examined by macroscopical observation, histological staining, gene and protein expression analysis.Results: We discover that proper micro-injury effectively induces hair regeneration by activating the hair follicle stem cell proliferation and migration downwards to hair matrix, finally shifting the hair follicle stage from telogen into anagen. On vitiligo model mice, m...

Frontiers in Cell and Developmental Biology

Light has attracted special attention as a stimulus for triggered drug delivery systems (DDS) due... more Light has attracted special attention as a stimulus for triggered drug delivery systems (DDS) due to its intrinsic features of being spatially and temporally tunable. Ultraviolet A (UVA) radiation has recently been used as a source of external light stimuli to control the release of drugs using a “switch on- switch off” procedure. This review discusses the promising potential of UVA radiation as the light source of choice for photo-controlled drug release from a range of photo-responsive and photolabile nanostructures via photo-isomerization, photo-cleavage, photo-crosslinking, and photo-induced rearrangement. In addition to its clinical use, we will also provide here an overview of the recent UVA-responsive drug release approaches that are developed for phototherapy and skin photoprotection.

Antioxidants & Redox Signaling

AIMS Drug-induced liver injury, especially acetaminophen-induced liver injury, is a leading cause... more AIMS Drug-induced liver injury, especially acetaminophen-induced liver injury, is a leading cause of liver failure worldwide. Mouse models were used to evaluate the effect of microelement selenium levels on the cellular redox environment and consequent hepatotoxicity of acetaminophen (APAP). RESULTS APAP treatment affected mouse liver selenoprotein thioredoxin reductase (TrxR) activity and glutathione level in a dose- and time-dependent manner. Decrease of mouse liver TrxR activity and glutathione level was an early event, and occurred concurrently with liver damage. The decreases of ratio of GSH/GSSG, TrxR activity and the increase of protein S-glutathionylation were correlated with the APAP-induced hepatotoxicity. Moreover, in APAP-treated mice both mild deprivation or excess supplementation with selenium increased the severity of liver injury compared to that observed in mice with normal dietary selenium levels. An increase in the oxidation state of the TrxR-mediated system, including cytosolic thioredoxin1 (Trx1) and peroxiredoxin1/2, and mitochondrial Trx2 and Prx3, were found in the livers from mice reared on selenium-deficient and excess selenium-supplemented diets upon APAP-treatment. INNOVATION This work demonstrates that both Trx and GSH systems are susceptible to APAP toxicity in vivo, and that the thiol-dependent redox environment is a key factor in determining the extent of APAP-induced hepatotoxicity. Dietary selenium and selenoproteins play critical roles in protecting mice against APAP overdose. CONCLUSION APAP treatment in mice interrupts the function of the Trx and GSH system which are the main enzymatic antioxidant systems, in both cytosol and mitochondria. Dietary selenium deficiency and excess supplementation both increase the risk of APAP-induced hepatotoxicity.

International Immunopharmacology

BACKGROUND Cumulative evidence suggests that in allergic diseases, oxidative stress and inflammat... more BACKGROUND Cumulative evidence suggests that in allergic diseases, oxidative stress and inflammation could often be detected. Therefore, the antioxidant/anti-inflammatory heme oxygenase (HO)-1 was recognized as a protective factor in allergic disorders. However, the precise underlying mechanisms of HO-1-based protection are not yet completely understood. In addition, miRNAs, a class of non-coding RNA, have been confirmed to associate with immunologic and inflammatory disorders in allergy recently. In addition, abundant studies have verified there is a complex connection between HO-1 and miRNAs. Thus, in this review, the combination of HO-1 and miRNAs (e.g. miR-155) in anti-allergy would be introduced. METHODS To further confirm our hypothesis, GEO sequencing datasets of atopic dermatitis children were analyzed. The miR-548a-3p might regulate the cellular response to hydrogen peroxide through HO-1 and HIF-1pathway. Meanwhile, this article reviews the latest knowledge and studies on the protective mechanisms of miRNA-HO-1 in allergy. RESULTS In brief, we supposed that miRNAs/HO-1 could mediate allergy through oxidative stress pathways, transcription factors and immune cell functions such as mast cell maturation, chemokine expression in T cell and dendritic cell degranulation. Although the detailed mechanism needs further research, this review may reveal the potential application of miRNAs and HO-1 in genetic therapies of allergic disease and provide new biomarkers. CONCLUSION This article examines the latest knowledge and studies on the protective roles and mechanisms of miRNA-HO-1 in allergy. Moreover, via bioinformatics analysis of GEO dataset, it was demonstrated that miRNAs (e.g. miR-205, miR-203, and miR-483-5p) could regulate allergy process through HO-1.

Oxidative Medicine and Cellular Longevity

Autophagy is an essential cellular process that maintains balanced cell life. Restriction in auto... more Autophagy is an essential cellular process that maintains balanced cell life. Restriction in autophagy may induce degenerative changes in humans. Natural or pathological aging of susceptible tissues has been linked with reduced autophagic activity. Skin photoaging is an example of such pathological condition caused by ambient solar UV radiation exposure. The UV-induced production of reaction oxygen species (ROS) has been linked to the promotion and progression of the photoaging process in exposed tissues. Accordingly, it has been suggested that autophagy is capable of delaying the skin photoaging process caused by solar ultraviolet (UV), although the underlying mechanism is still under debate. This review highlights several plausible mechanisms by which UV-induced ROS activates the cellular signaling pathways and modulates the autophagy. More specifically, the UV-mediated regulation of autophagy and age-related transcription factors is discussed to pinpoint the contribution of autop...

Oxidative Medicine and Cellular Longevity

Ultraviolet (UV) irradiation can be considered as a double-edged sword: not only is it a crucial ... more Ultraviolet (UV) irradiation can be considered as a double-edged sword: not only is it a crucial environmental factor that can cause skin-related disorders but it can also be used for phototherapy of skin diseases. Inducible heme oxygenase-1 (HO-1) in response to a variety of stimuli, including UV exposure, is vital to maintain cell homeostasis. Heme oxygenase-2 (HO-2), another member of the heme oxygenase family, is constitutively expressed. In this review, we discuss how heme oxygenase (HO), a vital rate-limiting enzyme, participates in heme catabolism and cytoprotection. Phylogenetic analysis showed that there may exist a functional differentiation between HO-1 and HO-2 during evolution. Furthermore, depending on functions in immunomodulation and antioxidation, HO-1 participates in disease progression, especially in pathogenesis of skin diseases, such as vitiligo and psoriasis. To further investigate the particular role of HO-1 in diseases, we summarized the profile of the HO enz...

Materials Science and Engineering: C

Polymorphous light eruption (PLE) is one of the acquired idiopathic photodermatosis mainly induce... more Polymorphous light eruption (PLE) is one of the acquired idiopathic photodermatosis mainly induced by immoderate UV radiation. In order to realize UV protection and medicine administration simultaneously for polymorphous light eruption protection and therapy, Acetyl-11-keto-β-boswellic acid (AKBA) loaded Zinc Oxide (ZnO) nanoparticles of which drug release behavior is UV-controlled has been successfully synthesized. Such nanoparticles can not only reflect UV but also transfer the energy to release AKBA which presents an excellent antioxidant and anti-inflammatory effects. In addition, they are biocompatible to HaCaT cells. As a result, they have a great potential in combining UV protection and medicine administration simultaneously for PLE protection and therapy.

Free Radical Research

Abstract Ultraviolet A (UVA) irradiation is a potential environmental stressor, which contributes... more Abstract Ultraviolet A (UVA) irradiation is a potential environmental stressor, which contributes to inflammation, photoaging, and carcinogenesis. UVA causes endoplasmic reticulum stress, hence phosphorylates the α subunit of eIF2. Meanwhile, UVA also induces expression of haem oxygenase-1 (HO-1) and nuclear factor erythroid-derived two related factor 2 (Nrf2) in human skin cells. In mouse JB6 cell, we found high dose UVA could change cell morphology, cause cell viability loss. UVA irradiation activated phosphorylation of eIF2α and Nrf2-HO-1 pathway in a dose-dependent manner. Besides, modulation of eIF2α phosphorylation status could alter expression pattern of Nrf2-HO-1 signalling. Salubrinal, a selective inhibitor of eIF2α dephosphorylation, increased the S phase in cell cycle of JB6 cells after UVA irradiation, suggesting phosphorylation status of eIF2α may affect cellular homeostasis under UVA irradiation. The study directed to further acknowledge about the relationship of UVA-induced eIF2α phosphorylation and Nrf2-HO-1 pathway, which may play a role in phototherapy and photo protection.

Cell Communication and Signaling

Background: Despite therapeutic advancements (e.g. B-RAF inhibitors) targeting cutaneous melanoma... more Background: Despite therapeutic advancements (e.g. B-RAF inhibitors) targeting cutaneous melanoma, many cellular processes, including inducible heme oxygenase 1 (HO-1), counteract treatments for malignancies. So there is an urgent need to find biological treatment targets, develop new therapeutic approaches and achieve longer responses. This study aimed to explore the relationship of HO-1 and B-Raf via mediating ERK1/2 signaling on cell cycle in melanoma. Methods: Immunohistochemistry was applied to evaluate the levels of HO-1 and B-Raf expression in melanoma tissues and adjacent healthy tissues. Co-immunoprecipitation (Co-IP) assessed the interaction of HO-1 with B-Raf. Further study overexpression and knock-down of HO-1 in A375 cell lines, especially knockout HO-1 using CRISPR-Cas9, verified HO-1 regulate cell proliferation in vivo and in vitro. Finally, Western blot analysis and qRT-PCR were performed to investigate the mechanisms by which HO-1 mediates cell cycle by B-RAF-ERK1/2 signaling. Results: First, histology and Co-IP show that HO-1 interacts with B-Raf directly in melanoma tissue. Further study illustrated that HO-1 overexpression promotes melanoma cell proliferation while HO-1 reduction represses melanoma cell proliferation because of HO-1 affects cell cycle. Mechanistic studies revealed that HO-1 was associated with a marked activation of B-RAF-ERK1/2 signaling and led to CDK2/cyclin E activation, thereby promoting melanoma proliferation. Conclusions: Our result reveals a previously unknown mechanism that the HO-1-B-RAF-ERK axis plays an important role in melanoma cell proliferation. Therapeutic target on HO-1 could be a novel method for treating melanoma.

Current Research Journal of Biological Sciences

The present study conducted in district Bahawalpur of Southern Punjab province, Pakistan to enlis... more The present study conducted in district Bahawalpur of Southern Punjab province, Pakistan to enlist the medicinal plants and their uses among local people. Previous studies focus primarily on the exploration of medicinal plants of Cholistan desert while rest of the area remained un-explored. The ethno-medicinal survey was conducted regularly for a period of 10 years and tries to eradicate the errors in the utilizations of the plants and to finally to document ethno-medicinal uses of plant species through questionnaire and personal interviews during field trips. Plants with their correct nomenclature were arranged by family name, vernacular name, parts used and ethnomedicinal uses. For the identification of plants we used field guides and flora of Pakistan and as a result 123 plant species currently under utilization by local people were identified. Previously we collected all the plant specimens, after careful identification we preserved and mounted on herbarium sheets, were placed in the department of Botany, Govt. Sadiq Egerton College, Bahawalpur, Pakistan. The study will provide a baseline for future studies relating to pharmacological, chemical isolations, taxonomic and well as biochemical studies by giving a quick approach to the specific plant species.

Journal of biological engineering, 2018

Generation of reactive oxygen species (ROS), triggered by ultraviolet radiation (UVR), is associa... more Generation of reactive oxygen species (ROS), triggered by ultraviolet radiation (UVR), is associated with carcinogenesis of the skin. UV irradiation induced superoxide anion (O2) is the key ROS involved in the cellular damage. The cytoprotective efficacy of an unknown anti-oxidant compound can be evaluated by analyzing the production of O2 from treated cells. In this study, a glass carbon electrode functionalized with nanotube@DNA-Mn3(PO4)2 composite was applied to quantitative determination of generation of highly unstable O2 from the melanoma A375 cell line following UVR(UV, UVA and UVB). In addition, the cytoprotective efficacy of anti-oxidant α-tocopherol was evaluated by quantifying the production of O2. The results showed that, UVR triggers generation of O2 in melanoma A375 cells, and α-tocopherol is effective in diminishing the production of O2 following UV irradiation. By comparing the conventional cell-survival assays results, we found that our simple and quick electrochemi...

Cell communication and signaling : CCS, Jan 15, 2018

The extensive involvement of microRNA (miRNA) in the pathophysiology of psoriasis is well documen... more The extensive involvement of microRNA (miRNA) in the pathophysiology of psoriasis is well documented. However, in order for this information to be useful in therapeutic manipulation of miRNA levels, it is essential that detailed functional mechanisms are elucidated. This study aimed to explore the effects of IL-6 targeting by let-7b and ERK1/2 mediated signaling on keratinocyte differentiation in psoriasis. Following imiquimod cream (IMQ) application to let-7b (keratinocyte-specific let-7b overexpression mouse) and control mice for 7 days, we analyzed erythema, scaling and thickening of skin. A dual luciferase reporter assay and bioinformatics was carried out to detect target gene of let-7b. Additionally, the differentiation markers were measured. Immunohistochemistry analyses demonstrate a relationship of let-7b with IL-6 and ERK signaling. we found let-7b inhibits acanthosis and reduces the disease severity by treatment with IMQ compared to wild-type mice. Further study illustrate...

Cellular signalling, Jan 27, 2018

The tyrosine phosphatases family member PTEN is a tumor suppressor which is widely expressed thro... more The tyrosine phosphatases family member PTEN is a tumor suppressor which is widely expressed throughout the body and is involved in a variety of biological functions. PTEN is known to be frequently mutated or downregulated in human cancers. However, the underlying molecular mechanism remains largely unknown. Here, using a proteomic approach, we identified the E3 ubiquitin ligase HRD1, which was previously reported to be involved in endoplasmic reticulum associated degradation (ERAD), as one of the PTEN-interacting proteins. We also found that HRD1 promoted PTEN degradation by positively regulating its ubiquitination. In addition, suppression of HRD1 expression resulted in the inhibition of the growth, migration and invasion of hepatocellular carcinoma in vitro and in vivo. Finally, we detected a negative correlation between HRD1 and PTEN expression in human hepatocellular carcinoma. From these results we propose a novel molecular mechanism of HRD1 to promote hepatocellular tumorigen...

Materials science & engineering. C, Materials for biological applications, 2018

Infection associated with orthopedic implants is the chief cause of implant failure. An important... more Infection associated with orthopedic implants is the chief cause of implant failure. An important consideration to prevent the infection at implants is to inhibit the biofilm formation for the initial 6 h. Therefore, we fabricated hyaluronidase-sensitive multilayers of chitosan (Chi)/sodium hyaluronate-lauric acid (SL) onto the surface of bone morphogenetic protein 2 (BMP2) loaded titanium nanotube (TNT) via spin-assisted layer-by-layer technique. The results of both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (H NMR) confirmed the successful synthesis of SL. The multilayer structure on BMP2 loaded TNT was characterized by field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and water contact angle, respectively. The release profiles confirmed that hyaluronidase could trigger the release of lauric acid (LA) from the SL multilayer and accelerate the release of BMP2 in the system. The hyaluronidase-sensitive-multilayer-c...

Oxidative medicine and cellular longevity, 2018

Brusatol (BR) is a potent inhibitor of Nrf2, a transcription factor that is highly expressed in c... more Brusatol (BR) is a potent inhibitor of Nrf2, a transcription factor that is highly expressed in cancer tissues and confers chemoresistance. UVA-generated reactive oxygen species (ROS) can damage both normal and cancer cells and may be of potential use in phototherapy. In order to provide an alternative method to treat the aggressive melanoma, we sought to investigate whether low-dose UVA with BR is more effective in eliminating melanoma cells than the respective single treatments. We found that BR combined with UVA led to inhibition of A375 melanoma cell proliferation by cell cycle arrest in the G1 phase and triggers cell apoptosis. Furthermore, inhibition of Nrf2 expression attenuated colony formation and tumor development from A375 cells in heterotopic mouse models. In addition, cotreatment of UVA and BR partially suppressed Nrf2 and its downstream target genes such as HO-1 along with the PI3K/AKT pathway. We propose that cotreatment increased ROS-induced cell cycle arrest and cel...

Oncotarget

Locoregional lymph nodes metastasis in oral tongue squamous cell carcinoma represents one of impo... more Locoregional lymph nodes metastasis in oral tongue squamous cell carcinoma represents one of important and common prognostic factors for poor clinical outcome. The human Telomerase Reverse Transcriptase (hTERT) is one of key players in cancer metastasis and stemness, but its exact function in tongue squamous cell carcinoma remains unknown. Here, we aim to understand the role of hTERT by utilizing the CRISPR/Cas9 gene editing system to deplete hTERT in the SCC-15 cell line. Functional comparison of SCC-15 control and knockout cells (hTERT −/−) showed that loss of hTERT suppressed cell proliferation and migration/invasion. Furthermore, hTERT depletion significantly decreased tumorigenesis, including alterations in cellular morphology that areindicative for epithelial-mesenchymal transition (EMT). Mechanistically we demonstrated that the hTERT knockout attenuates NF-κB signaling via a negative feedback regulation in tumorprogression. From these results we propose a novel molecular mechanism of hTERT to promote SCC-15 invasion and metastasis via NF-κB activation. We conclude that targeting hTERT may represent a new therapeutic strategy to improve therapy and survival of tongue squamous cell carcinoma patients.

Skin pharmacology and physiology, 2017

Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress wi... more Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis. The aim of this study is to investigate the protective effect of acetyl-11-keto-β-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes. HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined. AKBA reduces UVA irradiation-induced cell viability loss, accompanied by a decreased production of UVA-induced ROS, decreased malondialdehyde, and increased superoxide dismutase expression. In addition, AKBA increased basal and UVA-induced levels of Nrf2 (NF-E2-related factor 2), the redox-sensitive factor, and its target genes NQO1 and heme oxygenase-1 (HO-1), whereas expression of the transcriptional repressor Bach1 (BTB and CNC homology...

Experimental dermatology, Feb 11, 2016

Wound healing is a complex process involves proliferation and migration of keratinocyte for closu... more Wound healing is a complex process involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family let-7b, have been expressed in mammalian skin but its exact role in keratinocyte migration is still not in knowledge. Here we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2BP2. Overexpression of let-7b led to reduced HaCaT cell migration while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. By using bioinformatics prediction software and a reporter gene assay, we found that IGF2BP2 was a target of let-7b, which contributes to keratinocyte migration. Introduction of an expression vector of IGF2BP2 also rescued let-7b-induced m...

Clinical and Experimental Metastasis, Apr 1, 2009

Des-gamma-carboxy prothrombin (DCP) is an aberrant prothrombin produced by hepatocellular carcino... more Des-gamma-carboxy prothrombin (DCP) is an aberrant prothrombin produced by hepatocellular carcinoma (HCC) cells. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. However, the role of DCP in the development of angiogenesis is not well understood. Herein, we report the effects of DCP on growth and migration of human vascular endothelial cells. DCP significantly stimulated the proliferation of HUVEC (ECV304) cells in a dose and time dependent manner, as measured by the MTT assay. A continuous rapid migration of ECV304 cells was observed in the presence of DCP measured by the scratch wound assay. The continuous rapid invasive activity, measured by transwell chamber assay also showed that DCP increased endothelial cells migration through the reconstituted extracellular matrix (Matrigel). Further, the tube formation of vascular endothelial cells on 3-D Matrigel showed an increased number of branch points of ECV304 cells induced by DCP in a dose dependent manner. The levels of vascular endothelial cell growth-related angiogenic factors and matrix metalloproteinase were also examined. DCP significantly stimulated the expression levels of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 (latent and active). Together, these data suggest that DCP is a novel type of vascular endothelial growth factor that possesses potent mitogenic and migrative activities in angiogenesis of HCC.