Elucidation of the molecular mechanisms involving the initiation and progression of radiation-induced esophageal injury (RIEI) is important for prevention and treatment. Despite ongoing advances, the underlying mechanisms controlling RIEI remain largely unknown. In the present study, RNA-seq was performed to characterize mRNA profiles of the irradiated rat esophagus exposed to 0, 25, or 35 Gy irradiation. Bioinformatics analyses including dose-dependent differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, protein-protein interaction (PPI) network, and immune infiltration were performed. 134 DEGs were screened out with a dose-dependent manner (35 Gy > 25 Gy > control, or 35 Gy < 25 Gy < control). GO and KEGG analyses showed that the most significant mechanism was IL-17 signaling-mediated inflammatory response. 5 hub genes, Ccl11, Cxcl3, Il17a, S100a8, and S100a9, were identified through the intersection of the DEGs involved in inflammatory response, IL-17 pathway, and PPI network. Additionally, immune infiltration analysis showed the activation of macrophages, monocytes, T cells, NKT cells, and neutrophils, among which macrophages, monocytes, and neutrophils might be the main sources of S100a8 and S100a9. Thus, these findings further our understanding on the molecular biology of RIEI and may help develop more effective therapeutic strategies.
{"title":"Transcriptome Profiling Unveils a Critical Role of IL-17 Signaling-Mediated Inflammation in Radiation-Induced Esophageal Injury in Rats","authors":"Jia Yao, Jinkang Zhang, Jinlong Wang, Qiang Lai, Weijun Yuan, Zhongyu Liu, Shuanghua Cheng, Yahui Feng, Zhiqiang Jiang, Yuhong Shi, Sheng Jiang, Wenling Tu","doi":"10.1177/15593258221104609","DOIUrl":"https://doi.org/10.1177/15593258221104609","url":null,"abstract":"Elucidation of the molecular mechanisms involving the initiation and progression of radiation-induced esophageal injury (RIEI) is important for prevention and treatment. Despite ongoing advances, the underlying mechanisms controlling RIEI remain largely unknown. In the present study, RNA-seq was performed to characterize mRNA profiles of the irradiated rat esophagus exposed to 0, 25, or 35 Gy irradiation. Bioinformatics analyses including dose-dependent differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, protein-protein interaction (PPI) network, and immune infiltration were performed. 134 DEGs were screened out with a dose-dependent manner (35 Gy > 25 Gy > control, or 35 Gy < 25 Gy < control). GO and KEGG analyses showed that the most significant mechanism was IL-17 signaling-mediated inflammatory response. 5 hub genes, Ccl11, Cxcl3, Il17a, S100a8, and S100a9, were identified through the intersection of the DEGs involved in inflammatory response, IL-17 pathway, and PPI network. Additionally, immune infiltration analysis showed the activation of macrophages, monocytes, T cells, NKT cells, and neutrophils, among which macrophages, monocytes, and neutrophils might be the main sources of S100a8 and S100a9. Thus, these findings further our understanding on the molecular biology of RIEI and may help develop more effective therapeutic strategies.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44085758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221092379
A. Aisha, Sabahat Zahra, I. M. Tahir, A. Hussain, N. Bano, A. Roobi, N. Afsheen, Yasir Saleem
L-asparaginase is used in chemotherapy for acute lymphoblastic leukemia and other cancers. L-asparaginase derived from bacterial source triggers immune responses. The current study investigates Solanum nigrum as a novel and latent source of L-asparaginase to minimize immunological reactions. The antitumor activity of SN methanol extract was determined using the potato disc assay. InterPro Chimera and InterPro were used to predict the amino acid sequence of L-asparaginase and its anticancer activity. Purification of the enzyme was carried out to homogeneity of 1.51-fold with a recovery of 61.99%. At optimal conditions of 36.5°C, pH 8.6, and 8.5 g/mL substrate, fruit (crude extract) revealed an L-asparaginase titer of 48.23 U/mL. The molecular weight of the enzyme was calculated to be 32 ± 5 kDa using SDS PAGE. The fruit’s total flavonoids and phenolic contents are 0.42 ± .030 g/mL and 94 ± 1.9 mg CAE, respectively. Anti-tumorigenic efficacy was determined to be 66% against Agrobacterium tumefaciens. Additionally, the extract possesses potent antifungal and antibacterial properties. Molecular docking provided the structural motifs and underlying interactions between L-asparaginase, N-acetylglucosamine, murine, and chitin. SN contains high levels of the enzyme L-asparaginase and phytochemicals, making it a potential source of anticancer drugs.
{"title":"Anticancer L-Asparaginase and Phytoactive Compounds From Plant Solanum nigrum Against MDR (Methicillindrug resistant) Staphylococcus aureus and Fungal Isolates","authors":"A. Aisha, Sabahat Zahra, I. M. Tahir, A. Hussain, N. Bano, A. Roobi, N. Afsheen, Yasir Saleem","doi":"10.1177/15593258221092379","DOIUrl":"https://doi.org/10.1177/15593258221092379","url":null,"abstract":"L-asparaginase is used in chemotherapy for acute lymphoblastic leukemia and other cancers. L-asparaginase derived from bacterial source triggers immune responses. The current study investigates Solanum nigrum as a novel and latent source of L-asparaginase to minimize immunological reactions. The antitumor activity of SN methanol extract was determined using the potato disc assay. InterPro Chimera and InterPro were used to predict the amino acid sequence of L-asparaginase and its anticancer activity. Purification of the enzyme was carried out to homogeneity of 1.51-fold with a recovery of 61.99%. At optimal conditions of 36.5°C, pH 8.6, and 8.5 g/mL substrate, fruit (crude extract) revealed an L-asparaginase titer of 48.23 U/mL. The molecular weight of the enzyme was calculated to be 32 ± 5 kDa using SDS PAGE. The fruit’s total flavonoids and phenolic contents are 0.42 ± .030 g/mL and 94 ± 1.9 mg CAE, respectively. Anti-tumorigenic efficacy was determined to be 66% against Agrobacterium tumefaciens. Additionally, the extract possesses potent antifungal and antibacterial properties. Molecular docking provided the structural motifs and underlying interactions between L-asparaginase, N-acetylglucosamine, murine, and chitin. SN contains high levels of the enzyme L-asparaginase and phytochemicals, making it a potential source of anticancer drugs.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47493304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221093275
Muhammad Fiaz Khalid, K. Rehman, Kanwal Irshad, T. Chohan, M. Akash
The aim of current study was to investigate the inhibitory activities of resveratrol and taxifolin against α-amylase, α-glucosidase, and DPP-IV enzymes via in vitro analysis which was further validated by in silico studies. The analysis of molecular docking was also done to determine the binding capabilities of resveratrol and taxifolin with α-amylase, α-glucosidase, and DPP-IV enzymes. Resveratrol and taxifolin having IC50 values, 47.93 ± 5.21 μ M and 45.86 ± 3.78 μ M , respectively, showed weaker effect than acarbose (4.6 ± 1.26 μ M ) on α-amylase but showed significant effect to inhibit α-glucosidase (32.23 ± .556 μ M and 31.26 ± .556 μ M , respectively). IC50 value of resveratrol and taxifolin (5.638 ± .0016 μ M and 6.691 ± .004 μ M ) in comparison to diprotin A (IC50: 7.21 ± .021 μ M ) showed that they have significant inhibitory effect on DPP-IV enzyme. Our results illustrated that resveratrol and taxifolin have potential to prevent the metabolism of carbohydrates via inhibition of α-amylase and α-glucosidase, and prolongs metabolic function of incretin by inhibiting the enzymatic activity of DPP-IV. The results of molecular docking have also revealed that resveratrol and taxifolin have significant affinity to bind with α-amylase, α-glucosidase, and DPP-IV in comparison with standard drugs such as acarbose, miglitol, and diprotin.
{"title":"Biochemical Investigation of Inhibitory Activities of Plant-Derived Bioactive Compounds Against Carbohydrate and Glucagon-Like Peptide-1 Metabolizing Enzymes","authors":"Muhammad Fiaz Khalid, K. Rehman, Kanwal Irshad, T. Chohan, M. Akash","doi":"10.1177/15593258221093275","DOIUrl":"https://doi.org/10.1177/15593258221093275","url":null,"abstract":"The aim of current study was to investigate the inhibitory activities of resveratrol and taxifolin against α-amylase, α-glucosidase, and DPP-IV enzymes via in vitro analysis which was further validated by in silico studies. The analysis of molecular docking was also done to determine the binding capabilities of resveratrol and taxifolin with α-amylase, α-glucosidase, and DPP-IV enzymes. Resveratrol and taxifolin having IC50 values, 47.93 ± 5.21 μ M and 45.86 ± 3.78 μ M , respectively, showed weaker effect than acarbose (4.6 ± 1.26 μ M ) on α-amylase but showed significant effect to inhibit α-glucosidase (32.23 ± .556 μ M and 31.26 ± .556 μ M , respectively). IC50 value of resveratrol and taxifolin (5.638 ± .0016 μ M and 6.691 ± .004 μ M ) in comparison to diprotin A (IC50: 7.21 ± .021 μ M ) showed that they have significant inhibitory effect on DPP-IV enzyme. Our results illustrated that resveratrol and taxifolin have potential to prevent the metabolism of carbohydrates via inhibition of α-amylase and α-glucosidase, and prolongs metabolic function of incretin by inhibiting the enzymatic activity of DPP-IV. The results of molecular docking have also revealed that resveratrol and taxifolin have significant affinity to bind with α-amylase, α-glucosidase, and DPP-IV in comparison with standard drugs such as acarbose, miglitol, and diprotin.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41604833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Actinin alpha 4 (ACTN4) is expressed in the kidney podocytes. ACTN4 gene methylation in patients with diabetic nephropathy (DN) remains high. Underlying mechanism of epigallocatechin-3-gallate (EGCG) inducing ACTN4 demethylation, and its inhibitory effect on DN renal fibrosis remains unclear. Methods: Human podocyte cell line, HPC, was treated with high glucose to establish model of DN. The levels of cytokines, vascular endothelial growth factor (VEGF) and interleukin (IL)-8, and fibrosis markers, alpha smooth muscle actin (α-SMA) and fibronectin (FN), were determined using enzyme-linked immunosorbent assay. HPC cells were treated with EGCG, and cell viability was determined by MTT assay, ACTN4 gene methylation was analyzed by MSP. mRNA and protein expression levels were measured using RT-qPCR and Western blotting, respectively. Results: Actinin alpha 4 gene promoter was hypermethylated in the high glucose-treated groups. EGCG reversed the hypermethylated status of ACTN4, along with the upregulation of ACTN4 levels and downregulation of DNA methyltransferase 1 (DNMT1), NF-κB p65, p-NF-κB p65, IκB-α, VEGF, IL-8, α-SMA, and FN levels (P<.05). Conclusion: Epigallocatechin-3-gallate reduced hypermethylation of ACTN4 in HPC cells by downregulating DNMT1 expression and restoring ACTN4 expression, contributing to the upregulation of the NF-KB p65, p-NF-KB p65, IKB-α, VEGF, IL-8, α-SMA, and FN levels (P<.05).
{"title":"Epigallocatechin Gallate Induces the Demethylation of Actinin Alpha 4 to Inhibit Diabetic Nephropathy Renal Fibrosis via the NF-KB Signaling Pathway In Vitro","authors":"Chunling He, Dong Wang, Ruo-Zhu Wang, Yongli Huang, Xin Huang, ShuMin Shen, J. Lv, Mingcai Wu","doi":"10.1177/15593258221105704","DOIUrl":"https://doi.org/10.1177/15593258221105704","url":null,"abstract":"Actinin alpha 4 (ACTN4) is expressed in the kidney podocytes. ACTN4 gene methylation in patients with diabetic nephropathy (DN) remains high. Underlying mechanism of epigallocatechin-3-gallate (EGCG) inducing ACTN4 demethylation, and its inhibitory effect on DN renal fibrosis remains unclear. Methods: Human podocyte cell line, HPC, was treated with high glucose to establish model of DN. The levels of cytokines, vascular endothelial growth factor (VEGF) and interleukin (IL)-8, and fibrosis markers, alpha smooth muscle actin (α-SMA) and fibronectin (FN), were determined using enzyme-linked immunosorbent assay. HPC cells were treated with EGCG, and cell viability was determined by MTT assay, ACTN4 gene methylation was analyzed by MSP. mRNA and protein expression levels were measured using RT-qPCR and Western blotting, respectively. Results: Actinin alpha 4 gene promoter was hypermethylated in the high glucose-treated groups. EGCG reversed the hypermethylated status of ACTN4, along with the upregulation of ACTN4 levels and downregulation of DNA methyltransferase 1 (DNMT1), NF-κB p65, p-NF-κB p65, IκB-α, VEGF, IL-8, α-SMA, and FN levels (P<.05). Conclusion: Epigallocatechin-3-gallate reduced hypermethylation of ACTN4 in HPC cells by downregulating DNMT1 expression and restoring ACTN4 expression, contributing to the upregulation of the NF-KB p65, p-NF-KB p65, IKB-α, VEGF, IL-8, α-SMA, and FN levels (P<.05).","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49462311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed to investigate the potential protective effects of doxepin on RILI (20 Gy total dose at 3 Gy/min of X-ray irradiation), as well as its underlying mechanism. For animal experiments, such parameters as Immunohistochemistry and hematoxylin and eosin (H&E) staining, WBC (white blood cell), CRP (C-reactive protein), Western blot, and q-PCR were detected. The results indicated that both survival status and weight increase of irradiated rats treated by doxepin (3 mg/kg/day, rat) were higher than those of treated with irradiation alone (Dosing started the day before irradiation). Further, histological examinations showed doxepin could tenuate the radiation injury, as indicated as alveolar inflammatory exudation and there was only mild interstitial inflammation infiltration. Western blotting and q-PCR showed that expression of NF-κβ in X group were higher than that in XMD group. For the first time, we reported doxepin functioned as a radioprotectant candidate, which provide a promising application of doxepin for protecting radiotherapy injuries.
{"title":"The Protective Effects and Mechanism of Doxepin on Radiation–Induced Lung Injury in Rats","authors":"Xinlong Wan, Xuan-Zheng Shi, Mengke Li, Qing Chen, Chang Xue, Guanghui Li, Yeke Huang, Jingwen Yang, Chan Chen, Zhiyi Wang, Shumei Ma, Xiaodong Liu","doi":"10.1177/15593258221107193","DOIUrl":"https://doi.org/10.1177/15593258221107193","url":null,"abstract":"Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed to investigate the potential protective effects of doxepin on RILI (20 Gy total dose at 3 Gy/min of X-ray irradiation), as well as its underlying mechanism. For animal experiments, such parameters as Immunohistochemistry and hematoxylin and eosin (H&E) staining, WBC (white blood cell), CRP (C-reactive protein), Western blot, and q-PCR were detected. The results indicated that both survival status and weight increase of irradiated rats treated by doxepin (3 mg/kg/day, rat) were higher than those of treated with irradiation alone (Dosing started the day before irradiation). Further, histological examinations showed doxepin could tenuate the radiation injury, as indicated as alveolar inflammatory exudation and there was only mild interstitial inflammation infiltration. Western blotting and q-PCR showed that expression of NF-κβ in X group were higher than that in XMD group. For the first time, we reported doxepin functioned as a radioprotectant candidate, which provide a promising application of doxepin for protecting radiotherapy injuries.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46693035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221095977
S. Hassan, Ikrima Khalid, Liaqat Hussain, K. Barkat, I. Khan
Research aimed to develop and evaluate biodegradable, pH-responsive chemically cross-linked Pluronic F127 co-poly- (acrylic acid) nanogels for dermal delivery of Terbinafine HCL (TBH) to increase its permeability and as a new approach to treat skin fungal infections. TBH-loaded nanogels were successfully synthesized from acrylic acid (AA) and Pluronic F127 by free-radical copolymerization technique using N,N′-methylene bisacrylamide (MBA) as crosslinker and ammonium persulphate (APS) as initiator. Prepared nanogels exhibited 93.51% drug entrapment efficiency (DEE), 45 nm particle size, pH-dependent swelling and release behavior. Nanogels were characterized using different physicochemical techniques. The ex-vivo skin retention studies through rat skin showed about 42.34% drug retention from nanogels while 1% Lamisil cream (marketed product) showed about 26.56% drug retention. Moreover, skin irritation studies showed that nanogels were not irritating. Nanogels showed improved in-vitro antifungal activity against Candida albicans compared to commercial product. In-vivo studies on rats infected with Candida albicans confirmed superiority of nanogels over 1% Lamisil for eradication of fungal infection. This confirms that TBH loaded in Pluronic F127 co-poly-(acrylic acid) nanogels provided greater targetibility and cure rates of poorly soluble TBH in animal model and hence nanogels could be a potential carrier for effective topical delivery of TBH for skin fungal infection treatment.
{"title":"Development and Evaluation of pH-Responsive Pluronic F 127 Co-Poly- (Acrylic Acid) Biodegradable Nanogels for Topical Delivery of Terbinafine HCL","authors":"S. Hassan, Ikrima Khalid, Liaqat Hussain, K. Barkat, I. Khan","doi":"10.1177/15593258221095977","DOIUrl":"https://doi.org/10.1177/15593258221095977","url":null,"abstract":"Research aimed to develop and evaluate biodegradable, pH-responsive chemically cross-linked Pluronic F127 co-poly- (acrylic acid) nanogels for dermal delivery of Terbinafine HCL (TBH) to increase its permeability and as a new approach to treat skin fungal infections. TBH-loaded nanogels were successfully synthesized from acrylic acid (AA) and Pluronic F127 by free-radical copolymerization technique using N,N′-methylene bisacrylamide (MBA) as crosslinker and ammonium persulphate (APS) as initiator. Prepared nanogels exhibited 93.51% drug entrapment efficiency (DEE), 45 nm particle size, pH-dependent swelling and release behavior. Nanogels were characterized using different physicochemical techniques. The ex-vivo skin retention studies through rat skin showed about 42.34% drug retention from nanogels while 1% Lamisil cream (marketed product) showed about 26.56% drug retention. Moreover, skin irritation studies showed that nanogels were not irritating. Nanogels showed improved in-vitro antifungal activity against Candida albicans compared to commercial product. In-vivo studies on rats infected with Candida albicans confirmed superiority of nanogels over 1% Lamisil for eradication of fungal infection. This confirms that TBH loaded in Pluronic F127 co-poly-(acrylic acid) nanogels provided greater targetibility and cure rates of poorly soluble TBH in animal model and hence nanogels could be a potential carrier for effective topical delivery of TBH for skin fungal infection treatment.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45894902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221105370
Jie-Ming Dong, Xuan Huang, Li-Ping Ma, Fei Qi, Si-nian Wang, Ziang Zhang, Shi-Nan Wei, Ling Gao, Fang Liu
Objective To evaluate the clinical efficacy and safety of baricitinib, a Janus kinase (JAK) inhibitor, in treating patient with progressing vitiligo, and to further explore the regulation of baricitinib on melanocytes (MCs) in vitro. Methods Four patients with progressing vitiligo were treated with oral baricitinib for a total of 12 weeks. MCs were cultured in vitro and irradiated by high-dose ultraviolet B (UVB, 150mJ/cm2) to make an MC damaged model (MC-Ds). Baricitinib was added at a final concentration of 25 μM. Dopamine staining and NaOH method were used to measure the tyrosinase activity and melanin level, respectively, real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA levels of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1). Results Significant re-pigmentation was observed in the week 12 without obvious side effects. Depigmentation occurred in 2 patients at the 3-month follow-up. Laboratory research found that higher doses of UVB irradiation (150mJ/cm2) could decrease melanin content of MCs, baricitinib (25 μM) could significantly promote tyrosinase activity, melanin content, and TYR, TRP-1 gene expression of MC-Ds. Conclusion Our preliminary study showed that baricitinib was effective and safe in treating progressing vitiligo. Baricitinib could promote tyrosinase activity, melanin content and TYR, TRP1 gene expression of MC-Ds in vitro.
{"title":"Baricitinib is Effective in Treating Progressing Vitiligo in vivo and in vitro","authors":"Jie-Ming Dong, Xuan Huang, Li-Ping Ma, Fei Qi, Si-nian Wang, Ziang Zhang, Shi-Nan Wei, Ling Gao, Fang Liu","doi":"10.1177/15593258221105370","DOIUrl":"https://doi.org/10.1177/15593258221105370","url":null,"abstract":"Objective To evaluate the clinical efficacy and safety of baricitinib, a Janus kinase (JAK) inhibitor, in treating patient with progressing vitiligo, and to further explore the regulation of baricitinib on melanocytes (MCs) in vitro. Methods Four patients with progressing vitiligo were treated with oral baricitinib for a total of 12 weeks. MCs were cultured in vitro and irradiated by high-dose ultraviolet B (UVB, 150mJ/cm2) to make an MC damaged model (MC-Ds). Baricitinib was added at a final concentration of 25 μM. Dopamine staining and NaOH method were used to measure the tyrosinase activity and melanin level, respectively, real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA levels of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1). Results Significant re-pigmentation was observed in the week 12 without obvious side effects. Depigmentation occurred in 2 patients at the 3-month follow-up. Laboratory research found that higher doses of UVB irradiation (150mJ/cm2) could decrease melanin content of MCs, baricitinib (25 μM) could significantly promote tyrosinase activity, melanin content, and TYR, TRP-1 gene expression of MC-Ds. Conclusion Our preliminary study showed that baricitinib was effective and safe in treating progressing vitiligo. Baricitinib could promote tyrosinase activity, melanin content and TYR, TRP1 gene expression of MC-Ds in vitro.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44899400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221095327
Asma Naeem, A. Qureshi, Shafia Arshad, Anila Shehzadi, Asim Kamran, S. Noreen
The primary purpose of the current study was to study the possible pernicious effects of phosphine gas on enzyme activity alterations in Trogoderma granarium to determine its harmfulness to human beings after its prolonged exposure and intake. The saline extract of the adult Khapra beetle was biochemically analyzed at different doses, that is, from 10ppm to 30ppm, to accurately evaluate the effects of various phosphine concentrations (LC30 and LC50) on 2 distinct strains of this insect pest gathered from different godowns of Pakistan as resistant (Chitral [Chi], Haroon Abad [Hbd], and Lahore [Lhr]) and susceptible (Faqeer wali [Fqw], Khanewal [Khw], and Rawalpindi [Rwp]) populations. Our experimental results suggest that the enzyme levels (AcP, AkP, ALAT, ASAT, LDH, and ICDH) seemed to be elevated with increasing dosage of phosphine from 10ppm to 30ppm in the resistant populace of the susceptible ones. It also illustrates that phosphine and its residues can inhibit the workability of certain enzymes that are vital for respiration and neuro reactions in hexapods and mammals. It has detrimental effects of phosphine on human health profile to consume stored food products containing such tenacious enemies.
{"title":"Biochemical Toxic Response of Phosphine on Human Health Estimated From Enzymatic Variance in Trogoderma granarium","authors":"Asma Naeem, A. Qureshi, Shafia Arshad, Anila Shehzadi, Asim Kamran, S. Noreen","doi":"10.1177/15593258221095327","DOIUrl":"https://doi.org/10.1177/15593258221095327","url":null,"abstract":"The primary purpose of the current study was to study the possible pernicious effects of phosphine gas on enzyme activity alterations in Trogoderma granarium to determine its harmfulness to human beings after its prolonged exposure and intake. The saline extract of the adult Khapra beetle was biochemically analyzed at different doses, that is, from 10ppm to 30ppm, to accurately evaluate the effects of various phosphine concentrations (LC30 and LC50) on 2 distinct strains of this insect pest gathered from different godowns of Pakistan as resistant (Chitral [Chi], Haroon Abad [Hbd], and Lahore [Lhr]) and susceptible (Faqeer wali [Fqw], Khanewal [Khw], and Rawalpindi [Rwp]) populations. Our experimental results suggest that the enzyme levels (AcP, AkP, ALAT, ASAT, LDH, and ICDH) seemed to be elevated with increasing dosage of phosphine from 10ppm to 30ppm in the resistant populace of the susceptible ones. It also illustrates that phosphine and its residues can inhibit the workability of certain enzymes that are vital for respiration and neuro reactions in hexapods and mammals. It has detrimental effects of phosphine on human health profile to consume stored food products containing such tenacious enemies.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43107307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221092365
N. Abdel-Aziz, R. Haroun, Hebatallah E. Mohamed
Aim This work aims to investigate whether the pre-exposure to low dose/low dose rate (40 mGy, 2.2 mGy/hour) γ-radiation as a priming dose can produce a protective effect against the subsequent high one (4 Gy, .425 Gy/minute). Methods Rats were divided into Group I (control), Group II (L); exposed to 40 mGy, Group III (H); exposed to 4 Gy, and Group IV (L+H); exposed to 40 mGy 24 hours before the exposure to 4Gy. The molecular and biochemical changes related to oxidative stress, DNA damage, apoptosis, and mitochondrial activity in the liver and testis were studied 4 hours after irradiation. Results Exposure to 40 mGy before 4 Gy induced a significant increase in the levels of Nrf2, Nrf2 mRNA, TAC, and mitochondrial complexes I & II accompanied by a significant decrease in the levels of LPO, 8-OHdG, DNA fragmentation, TNF-α, caspase-3, and caspase-3 mRNA compared with H group. Conclusion Exposure to low-dose γ-radiation before a high dose provides protective mechanisms that allow the body to survive better after exposure to a subsequent high one via reducing the oxidative stress, DNA damage, and apoptosis-induced early after irradiation. However, further studies are required to identify the long-term effects of this low dose.
{"title":"Low-Dose Gamma Radiation Modulates Liver and Testis Tissues Response to Acute Whole Body Irradiation","authors":"N. Abdel-Aziz, R. Haroun, Hebatallah E. Mohamed","doi":"10.1177/15593258221092365","DOIUrl":"https://doi.org/10.1177/15593258221092365","url":null,"abstract":"Aim This work aims to investigate whether the pre-exposure to low dose/low dose rate (40 mGy, 2.2 mGy/hour) γ-radiation as a priming dose can produce a protective effect against the subsequent high one (4 Gy, .425 Gy/minute). Methods Rats were divided into Group I (control), Group II (L); exposed to 40 mGy, Group III (H); exposed to 4 Gy, and Group IV (L+H); exposed to 40 mGy 24 hours before the exposure to 4Gy. The molecular and biochemical changes related to oxidative stress, DNA damage, apoptosis, and mitochondrial activity in the liver and testis were studied 4 hours after irradiation. Results Exposure to 40 mGy before 4 Gy induced a significant increase in the levels of Nrf2, Nrf2 mRNA, TAC, and mitochondrial complexes I & II accompanied by a significant decrease in the levels of LPO, 8-OHdG, DNA fragmentation, TNF-α, caspase-3, and caspase-3 mRNA compared with H group. Conclusion Exposure to low-dose γ-radiation before a high dose provides protective mechanisms that allow the body to survive better after exposure to a subsequent high one via reducing the oxidative stress, DNA damage, and apoptosis-induced early after irradiation. However, further studies are required to identify the long-term effects of this low dose.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"20 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65580558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221097665
Fatima Shahbaz, N. Akhter, M. Shahid, M. Riaz, F. Anjum, F. Hussain
Worldwide, Verbascum thapsus is used for the treatment of various ailments owing to the presence of bioactives of therapeutic potential. Current study was planned to extract bioactives from V thapsus roots using methanol and water as solvents under stimulated effect of ultrasonic waves and characterize them to evaluate their potential benefits. Proximate analysis explored the presence of significant contents of protein, fats, fiber, organic and inorganic minerals. Fourier transform infrared spectra and high-performance liquid chromatography chromatogram indicated the presence of different phytochemicals having antioxidant potential as evidenced by total phenolic contents, total flavonoids content and 2,2-diphenyl-1-picrylhydrazyl activity of both extracts. Both extracts displayed excellent antimicrobial potential against Staphylococcus aureus (S aureus) and Fusarium Solani (F solani). Aqueous and methanolic extracts exhibited higher inhibition of biofilm made by Bacillus subtilis (B subtilis) as 55.09 and 61.58%, respectively in comparison to biofilm of Escherichia coli (E coli) as 48.11 and 36.51%, respectively. Methanol extract exhibited anti-amylase activity (IC50 5.26 ± .31 μg/mL) with an inhibition rate of 68.11% whereas IC50 of aqueous extract was 6.59 ± .53 μg/mL with an inhibition rate of 63.53%. Inhibitory potential against α-glucosidase (IC50 3.70 ± .94 ppm) was demonstrated by methanol extract in comparison to aqueous extract (IC50 7.58 ± .15). The study concluded that V thapsus roots have significant medicinal potential due to the presence of variety of bioactive molecules and can be used in pharmaceutical preparations.
{"title":"Ultrasound Assisted Extraction and Characterization of Bioactives From Verbascum thapsus Roots to Evaluate Their Antioxidant and Medicinal Potential","authors":"Fatima Shahbaz, N. Akhter, M. Shahid, M. Riaz, F. Anjum, F. Hussain","doi":"10.1177/15593258221097665","DOIUrl":"https://doi.org/10.1177/15593258221097665","url":null,"abstract":"Worldwide, Verbascum thapsus is used for the treatment of various ailments owing to the presence of bioactives of therapeutic potential. Current study was planned to extract bioactives from V thapsus roots using methanol and water as solvents under stimulated effect of ultrasonic waves and characterize them to evaluate their potential benefits. Proximate analysis explored the presence of significant contents of protein, fats, fiber, organic and inorganic minerals. Fourier transform infrared spectra and high-performance liquid chromatography chromatogram indicated the presence of different phytochemicals having antioxidant potential as evidenced by total phenolic contents, total flavonoids content and 2,2-diphenyl-1-picrylhydrazyl activity of both extracts. Both extracts displayed excellent antimicrobial potential against Staphylococcus aureus (S aureus) and Fusarium Solani (F solani). Aqueous and methanolic extracts exhibited higher inhibition of biofilm made by Bacillus subtilis (B subtilis) as 55.09 and 61.58%, respectively in comparison to biofilm of Escherichia coli (E coli) as 48.11 and 36.51%, respectively. Methanol extract exhibited anti-amylase activity (IC50 5.26 ± .31 μg/mL) with an inhibition rate of 68.11% whereas IC50 of aqueous extract was 6.59 ± .53 μg/mL with an inhibition rate of 63.53%. Inhibitory potential against α-glucosidase (IC50 3.70 ± .94 ppm) was demonstrated by methanol extract in comparison to aqueous extract (IC50 7.58 ± .15). The study concluded that V thapsus roots have significant medicinal potential due to the presence of variety of bioactive molecules and can be used in pharmaceutical preparations.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46008513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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