Diana Nurjanah, Fadilah Fadilah, Niluh Putu Indi Dharmayanti
Background: Neuraminidase inhibitor (NAI) is one of anti-influenza drugs recommended for use by the World Health Organization (WHO). However, after treatment with NAI drugs in human, resistance to influenza antiviral drugs is begun to rise. Therefore, identification of compounds from Indonesian herbal plants as natural inhibitors of the influenza virus neuraminidase protein needs to be conducted for the development of new anti-influenza drugs.Materials and methods: The crystal structure of the neuraminidase protein complex used in this study was obtained from the Protein Data Bank (PDB). Structure-based pharmacophore modeling was performed using LigandScout version 4.4.5 software. Indonesian herbal plant compounds were collected from the HerbalDB database. Protein and ligand processing was carried out using Autodock 4.2 software. The 3D interaction visualization was carried out with Autodock software, while 2D interaction visualization was carried out with LigPlot software. To determine the toxicity and drug-likeliness of the ligand, the test ligands that had the best docking results were predicted using SwissADME and AdmetSAR.Results: From the virtual screening results, 24 hits were found, and five compounds had the best binding energy among the 24 tested compounds, these were pollenitin (ΔG=-7.22 kcal/mol), OPC-4:0 (ΔG=-7.11 kcal/mol), 6-hydroxykaempferol (ΔG=-7.08 kcal/mol), 5,8-dihydroxy-7,4'-dimethoxyflavone (ΔG=-7.07 kcal/mol), and 3,5,6,7-tetrahydroxy-4'-methoxyflavone (ΔG=-6.95 kcal/mol). The best five compounds were then chosen for further analysis.Conclusion: OPC-4:0 is found to be the best compound for the NAI based on its binding energy, pharmacokinetics, toxicity, and drug-likeliness. Thus, OPC-4:0 might be a potential candidate as a NAI of HxN2 virus. Keywords: influenza, molecular docking, neuraminidase, resistance, virtual screening
{"title":"Virtual Screening of Indonesian Herbal Compounds with Neuraminidase Inhibitor Activity against N2 Influenza Virus Protein: An in silico Study","authors":"Diana Nurjanah, Fadilah Fadilah, Niluh Putu Indi Dharmayanti","doi":"10.21705/mcbs.v8i2.468","DOIUrl":"https://doi.org/10.21705/mcbs.v8i2.468","url":null,"abstract":"Background: Neuraminidase inhibitor (NAI) is one of anti-influenza drugs recommended for use by the World Health Organization (WHO). However, after treatment with NAI drugs in human, resistance to influenza antiviral drugs is begun to rise. Therefore, identification of compounds from Indonesian herbal plants as natural inhibitors of the influenza virus neuraminidase protein needs to be conducted for the development of new anti-influenza drugs.Materials and methods: The crystal structure of the neuraminidase protein complex used in this study was obtained from the Protein Data Bank (PDB). Structure-based pharmacophore modeling was performed using LigandScout version 4.4.5 software. Indonesian herbal plant compounds were collected from the HerbalDB database. Protein and ligand processing was carried out using Autodock 4.2 software. The 3D interaction visualization was carried out with Autodock software, while 2D interaction visualization was carried out with LigPlot software. To determine the toxicity and drug-likeliness of the ligand, the test ligands that had the best docking results were predicted using SwissADME and AdmetSAR.Results: From the virtual screening results, 24 hits were found, and five compounds had the best binding energy among the 24 tested compounds, these were pollenitin (ΔG=-7.22 kcal/mol), OPC-4:0 (ΔG=-7.11 kcal/mol), 6-hydroxykaempferol (ΔG=-7.08 kcal/mol), 5,8-dihydroxy-7,4'-dimethoxyflavone (ΔG=-7.07 kcal/mol), and 3,5,6,7-tetrahydroxy-4'-methoxyflavone (ΔG=-6.95 kcal/mol). The best five compounds were then chosen for further analysis.Conclusion: OPC-4:0 is found to be the best compound for the NAI based on its binding energy, pharmacokinetics, toxicity, and drug-likeliness. Thus, OPC-4:0 might be a potential candidate as a NAI of HxN2 virus. Keywords: influenza, molecular docking, neuraminidase, resistance, virtual screening","PeriodicalId":514464,"journal":{"name":"Molecular and Cellular Biomedical Sciences","volume":"60 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141663281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metabolic syndrome remains as a major health problem in the world today, with a prevalence of 23.4% in people aged 26-82 years. A high-fat, high-carbohydrate diet and lack of physical activity are considered as one of the triggers for metabolic syndrome. Dysbiosis is a condition where there is an imbalance between pathogenic and non-pathogenic bacteria in the human gut. Currently, an association has been found between dysbiosis and metabolic syndrome. Dysbiosis causes the generation of fermentation products in the form of active metabolites that can modulate hormones and other physiological functions. In metabolic syndrome, low-grade inflammation, energy metabolism, and disruption of the gut brain axis are thought to be the main mechanisms of the development of metabolic syndrome due to dysbiosis. Probiotics may be a promising therapeutic agent in the treatment of metabolic syndrome, by improving dysbiosis to eubiosis. Based on previously conducted clinical trials, it is currently known that probiotics can improve lipid profiles, fasting blood glucose, homeostatic model assessment for insulin resistance (HOMA-IR), vascular cell adhesion molecule 1 (VCAM-1), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and body mass index (BMI). However, the results found are still varied, so a dose ranging study is needed to determine the duration, bacterial composition and dose of probiotics as a therapeutic agent for metabolic syndrome. Keywords: insulin resistance, dysbiosis, gut-brain axis
{"title":"The Prospect of Probiotics to Treat Metabolic Syndrome","authors":"Andika Yusuf Ramadhan, Dewi Selvina Rosdiana","doi":"10.21705/mcbs.v8i2.425","DOIUrl":"https://doi.org/10.21705/mcbs.v8i2.425","url":null,"abstract":"Metabolic syndrome remains as a major health problem in the world today, with a prevalence of 23.4% in people aged 26-82 years. A high-fat, high-carbohydrate diet and lack of physical activity are considered as one of the triggers for metabolic syndrome. Dysbiosis is a condition where there is an imbalance between pathogenic and non-pathogenic bacteria in the human gut. Currently, an association has been found between dysbiosis and metabolic syndrome. Dysbiosis causes the generation of fermentation products in the form of active metabolites that can modulate hormones and other physiological functions. In metabolic syndrome, low-grade inflammation, energy metabolism, and disruption of the gut brain axis are thought to be the main mechanisms of the development of metabolic syndrome due to dysbiosis. Probiotics may be a promising therapeutic agent in the treatment of metabolic syndrome, by improving dysbiosis to eubiosis. Based on previously conducted clinical trials, it is currently known that probiotics can improve lipid profiles, fasting blood glucose, homeostatic model assessment for insulin resistance (HOMA-IR), vascular cell adhesion molecule 1 (VCAM-1), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and body mass index (BMI). However, the results found are still varied, so a dose ranging study is needed to determine the duration, bacterial composition and dose of probiotics as a therapeutic agent for metabolic syndrome. Keywords: insulin resistance, dysbiosis, gut-brain axis","PeriodicalId":514464,"journal":{"name":"Molecular and Cellular Biomedical Sciences","volume":"50 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141663129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sri Lestari Utami, Dorta Simamora, Ira Idawati, Jimmy Hadi Widjaja
Background: Genetics was one of the risk factors for essential hypertension (EH). Research on ACE I/D and A2350G polymorphisms associated with risk factors for hypertension in Indonesia has never been done. Therefore, this study was conducted to analyze the relationship between the genotype and alleles of this gene with EH, body weight, and body mass index (BMI) in Javanese postmenopausal women.Materials and methods: This cross-sectional study involved 69 postmenopausal Javanese women according to several criteria related with hypertension risk factors. The data were obtained from the measurement and questionnaire results, along with Towards Health Card Records. The polymerase chain reaction (PCR) genotyping method used was the restriction fragment length polymorphism and allele-specific.Results: The prevalence of hypertension, prehypertension, and normotension in Javanese postmenopausal women were 0.246, 0.13, and 0.623, respectively. The frequency of BMI classification as underweight, normal, overweight, or obese were 0.029, 0.42, 0.261, and 0.29, respectively. The ACE I/D and A2350G polymorphism variant genotypes and frequencies found were II (0.464), ID (0.522), DD (0.014), and AA (1). Meanwhile, the alleles and their frequencies at ACE I/D gene polymorphism were I (0.725) and D (0.275). The II and ID genotype was mostly found in normotension subjects. The DD genotype was only available in hypertension subjects. There was no association between genotypes and alleles of ACE I/D, hypertension, body weight, and BMI classification (p>0.05). There was an association between these genotypes, alleles, and BMI (p<0.05).Conclusion: ACE I/D polymorphism is susceptible for BMI in Javanese postmenopausal women.Keywords: Javanese postmenopausal, essential hypertension, ACE I/D, ACE A2350G
背景：遗传是本质性高血压（EH）的风险因素之一。在印度尼西亚，与高血压风险因素相关的 ACE I/D 和 A2350G 多态性研究还从未开展过。因此，本研究分析了爪哇绝经后妇女中该基因的基因型和等位基因与 EH、体重和体重指数（BMI）之间的关系：这项横断面研究涉及 69 名绝经后的爪哇妇女，根据与高血压风险因素相关的几项标准进行了研究。数据来自测量和问卷调查结果以及Towards健康卡记录。使用的聚合酶链反应（PCR）基因分型方法是限制性片段长度多态性和等位基因特异性：结果：爪哇绝经后妇女的高血压、高血压前期和正常血压患病率分别为 0.246、0.13 和 0.623。体重指数分为体重不足、正常、超重或肥胖的频率分别为 0.029、0.42、0.261 和 0.29。发现的 ACE I/D 和 A2350G 多态性变异基因型和频率分别为 II (0.464)、ID (0.522)、DD (0.014) 和 AA (1)。同时，ACE I/D 基因多态性的等位基因及其频率分别为 I (0.725) 和 D (0.275)。II 和 ID 基因型大多出现在血压正常者中。DD 基因型只出现在高血压患者中。ACE I/D 基因型和等位基因与高血压、体重和 BMI 分类之间没有关联（P>0.05）。这些基因型、等位基因和体重指数之间存在关联（P<0.05）：结论：ACE I/D 多态性易受爪哇绝经后妇女体重指数的影响：爪哇绝经后，本质性高血压，ACE I/D, ACE A2350G
{"title":"ACE I/D and A2350G Polymorphisms are Correlated with Body Mass Index, but Not with Body Weight and Essential Hypertension: Study in Javanese Postmenopausal Women","authors":"Sri Lestari Utami, Dorta Simamora, Ira Idawati, Jimmy Hadi Widjaja","doi":"10.21705/mcbs.v8i2.426","DOIUrl":"https://doi.org/10.21705/mcbs.v8i2.426","url":null,"abstract":"Background: Genetics was one of the risk factors for essential hypertension (EH). Research on ACE I/D and A2350G polymorphisms associated with risk factors for hypertension in Indonesia has never been done. Therefore, this study was conducted to analyze the relationship between the genotype and alleles of this gene with EH, body weight, and body mass index (BMI) in Javanese postmenopausal women.Materials and methods: This cross-sectional study involved 69 postmenopausal Javanese women according to several criteria related with hypertension risk factors. The data were obtained from the measurement and questionnaire results, along with Towards Health Card Records. The polymerase chain reaction (PCR) genotyping method used was the restriction fragment length polymorphism and allele-specific.Results: The prevalence of hypertension, prehypertension, and normotension in Javanese postmenopausal women were 0.246, 0.13, and 0.623, respectively. The frequency of BMI classification as underweight, normal, overweight, or obese were 0.029, 0.42, 0.261, and 0.29, respectively. The ACE I/D and A2350G polymorphism variant genotypes and frequencies found were II (0.464), ID (0.522), DD (0.014), and AA (1). Meanwhile, the alleles and their frequencies at ACE I/D gene polymorphism were I (0.725) and D (0.275). The II and ID genotype was mostly found in normotension subjects. The DD genotype was only available in hypertension subjects. There was no association between genotypes and alleles of ACE I/D, hypertension, body weight, and BMI classification (p>0.05). There was an association between these genotypes, alleles, and BMI (p<0.05).Conclusion: ACE I/D polymorphism is susceptible for BMI in Javanese postmenopausal women.Keywords: Javanese postmenopausal, essential hypertension, ACE I/D, ACE A2350G","PeriodicalId":514464,"journal":{"name":"Molecular and Cellular Biomedical Sciences","volume":"119 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141665437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oluebube Magnificient Eziefule, W. Arozal, S. Wanandi, M. Louisa, P. Wuyung, Syarifah Dewi, N. Nafrialdi, Yulia Ratna Dewi, Deya Adiby Nabillah
Background: Doxorubicin (DOX), an efficacious chemotherapy drug is compromised by cardiotoxicity, myelosuppression, and hepatotoxicity. Due to the limited success of current treatments for DOX toxicity, there is a pressing need to explore alternative medical interventions, particularly from plant sources. This study was conducted to investigate the potential protective effect of ethanolic extract of Andrographis paniculata leaves (EEAP) against DOX-induced cardiac inflammation, liver toxicity, and anemia.Materials and methods: Sprague-Dawley rats were intraperitoneally injected with DOX at a total dose of 16 mg/kgBW. EEAP was administered orally for 4 weeks at doses of 125, 250, and 500 mg/kgBW/day according to the assigned treatment groups. The mRNA expression levels of interleukin-1β (IL-1β) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) in the heart tissue, along with the concentrations of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and calcium level were examined. Additionally, the hematological parameters (including hematocrit, hemoglobin and red blood cells (RBCs)), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels in blood were also analyzed.Results: EEAP dose-dependently decreased the mRNA expressions of IL-1β (p<0.05), tended to decrease mRNA expression of NLRP3 and the concentrations of NFκB and calcium in heart tissue compared with the DOX-only group. Additionally, EEAP dose-dependently decreased ALP values (p<0.0001) and tended to improve hematological parameters, as well as AST and MDA levels in serum.Conclusion: This extract may prevent DOX-induced cardiac inflammation, anemia, and hepatotoxicity. However, further studies are needed to confirm these findings, including the efficacy profile of the extract in cancer rats treated with DOX.Keywords: doxorubicin, Andrographis paniculata, inflammation, anemia, hepatotoxicity, herbal medicine
{"title":"Andrographis paniculata Ethanolic Extract Improved Doxorubicin-induced Cardiac Inflammation, Alterations in Liver Function Parameters and Anemia","authors":"Oluebube Magnificient Eziefule, W. Arozal, S. Wanandi, M. Louisa, P. Wuyung, Syarifah Dewi, N. Nafrialdi, Yulia Ratna Dewi, Deya Adiby Nabillah","doi":"10.21705/mcbs.v8i2.444","DOIUrl":"https://doi.org/10.21705/mcbs.v8i2.444","url":null,"abstract":"Background: Doxorubicin (DOX), an efficacious chemotherapy drug is compromised by cardiotoxicity, myelosuppression, and hepatotoxicity. Due to the limited success of current treatments for DOX toxicity, there is a pressing need to explore alternative medical interventions, particularly from plant sources. This study was conducted to investigate the potential protective effect of ethanolic extract of Andrographis paniculata leaves (EEAP) against DOX-induced cardiac inflammation, liver toxicity, and anemia.Materials and methods: Sprague-Dawley rats were intraperitoneally injected with DOX at a total dose of 16 mg/kgBW. EEAP was administered orally for 4 weeks at doses of 125, 250, and 500 mg/kgBW/day according to the assigned treatment groups. The mRNA expression levels of interleukin-1β (IL-1β) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) in the heart tissue, along with the concentrations of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and calcium level were examined. Additionally, the hematological parameters (including hematocrit, hemoglobin and red blood cells (RBCs)), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels in blood were also analyzed.Results: EEAP dose-dependently decreased the mRNA expressions of IL-1β (p<0.05), tended to decrease mRNA expression of NLRP3 and the concentrations of NFκB and calcium in heart tissue compared with the DOX-only group. Additionally, EEAP dose-dependently decreased ALP values (p<0.0001) and tended to improve hematological parameters, as well as AST and MDA levels in serum.Conclusion: This extract may prevent DOX-induced cardiac inflammation, anemia, and hepatotoxicity. However, further studies are needed to confirm these findings, including the efficacy profile of the extract in cancer rats treated with DOX.Keywords: doxorubicin, Andrographis paniculata, inflammation, anemia, hepatotoxicity, herbal medicine","PeriodicalId":514464,"journal":{"name":"Molecular and Cellular Biomedical Sciences","volume":"108 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141666024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Puja Singh, Bharti Badlani, Chanchalesh Dehariya, M. Joher
Background: Breast carcinoma is the most common malignancy and demands quick and accurate diagnosis and treatment. Precise diagnosis of breast lesions is made using a triple-test approach: clinical, radiological and cytological. However, multiple steps make the process time-consuming and expensive. In developing countries like India, trained and certified radiologists are extremely overburdened. Fine needle aspiration cytology (FNAC) along with clinical examination can fill the gap. This study aims to correlate cytological, radiological and histological findings and measure their relative accuracies. Based on these findings, a new approach will be proposed to address the above shortcomings.Materials and methods: The FNAC was performed on all cases and reported as per Yokohama cytology. The cytological findings were correlated & validated against radiological and histopathological findings respectively. Relative performance of cytological and radiological findings were established using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. A chi-square test for independence between cytological and radiological findings was performed.Results: The sensitivity, specificity, PPV, NPV, and accuracy for cytological findings come out as 97.60, 90.08, 90.37, 97.52, and 93.75, respectively. Meanwhile, the Radiological findings come out as 96.61, 82.20, 84.44, 96.04, and 89.41, respectively. The chi-square test demonstrates strong interdependence between cytological and radiological findings.Conclusion: FNAC is more accurate, quicker, and cheaper than radiological tests. Hence, FNAC based on the Yokohama system, along with clinical observations, can be used as a primary diagnosis tool in developing countries with limited health resources without making significant compromises on incorrect treatment. If needed, radiology and histopathology can be used for precise diagnosis and treatment.Keywords: FNAC, cytology, breast lesions, Yokohama, radiology, histopathology
{"title":"Correlation between Yokohama Cytological Coding and Radiological Findings and Their Diagnostic Accuracies against Histopathology: A Retrospective Study of Palpable Breast Lesions","authors":"Puja Singh, Bharti Badlani, Chanchalesh Dehariya, M. Joher","doi":"10.21705/mcbs.v8i2.439","DOIUrl":"https://doi.org/10.21705/mcbs.v8i2.439","url":null,"abstract":"Background: Breast carcinoma is the most common malignancy and demands quick and accurate diagnosis and treatment. Precise diagnosis of breast lesions is made using a triple-test approach: clinical, radiological and cytological. However, multiple steps make the process time-consuming and expensive. In developing countries like India, trained and certified radiologists are extremely overburdened. Fine needle aspiration cytology (FNAC) along with clinical examination can fill the gap. This study aims to correlate cytological, radiological and histological findings and measure their relative accuracies. Based on these findings, a new approach will be proposed to address the above shortcomings.Materials and methods: The FNAC was performed on all cases and reported as per Yokohama cytology. The cytological findings were correlated & validated against radiological and histopathological findings respectively. Relative performance of cytological and radiological findings were established using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. A chi-square test for independence between cytological and radiological findings was performed.Results: The sensitivity, specificity, PPV, NPV, and accuracy for cytological findings come out as 97.60, 90.08, 90.37, 97.52, and 93.75, respectively. Meanwhile, the Radiological findings come out as 96.61, 82.20, 84.44, 96.04, and 89.41, respectively. The chi-square test demonstrates strong interdependence between cytological and radiological findings.Conclusion: FNAC is more accurate, quicker, and cheaper than radiological tests. Hence, FNAC based on the Yokohama system, along with clinical observations, can be used as a primary diagnosis tool in developing countries with limited health resources without making significant compromises on incorrect treatment. If needed, radiology and histopathology can be used for precise diagnosis and treatment.Keywords: FNAC, cytology, breast lesions, Yokohama, radiology, histopathology","PeriodicalId":514464,"journal":{"name":"Molecular and Cellular Biomedical Sciences","volume":"125 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141666301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glioblastoma multiforme (GBM), a highly aggressive and malignant form of brain cancer, continues to pose a significant challenge in the field of oncology. Despite ongoing advancements in treatment strategies, the prognosis for GBM patients remains grim, with a 5-year survival rate hovering around 5%. The management of GBM involves multiple therapeutic approaches, including immunotherapy, but optimal treatment outcomes in terms of overcoming tumor recurrence and resistance have not been achieved. A key factor contributing to therapy resistance and the progression of GBM is the tumor's ability to evade the immune system, referred to as immune escape from cancer. This phenomenon reflects the tumor cells' efforts to adapt and survive the body's immune response. The release and expression of molecules like TGF-ß, IL-10, PD-L1, and NKG2DL by GBM cells impact the activation, recognition, and elimination of tumor cells by the immune system. Additionally, the involvement of cells such as MDSCs, Tregs, and TAMs plays a role in inhibiting the immune system's function, thereby promoting the development of GBM cells. A better comprehension of GBM's immune escape, supported by technological advances, will significantly aid in the future management of GBM patients' treatment.Keywords: glioblastoma multiforme, GBM, cancer immunity, immune evasion, immune escape, immunotherapy
{"title":"Evasion of the Immune System by Glioblastoma Multiforme: An Obstacle to Achieving Effective Therapies","authors":"Kevin Johanes Kawengian, S. Wanandi","doi":"10.21705/mcbs.v8i2.434","DOIUrl":"https://doi.org/10.21705/mcbs.v8i2.434","url":null,"abstract":"Glioblastoma multiforme (GBM), a highly aggressive and malignant form of brain cancer, continues to pose a significant challenge in the field of oncology. Despite ongoing advancements in treatment strategies, the prognosis for GBM patients remains grim, with a 5-year survival rate hovering around 5%. The management of GBM involves multiple therapeutic approaches, including immunotherapy, but optimal treatment outcomes in terms of overcoming tumor recurrence and resistance have not been achieved. A key factor contributing to therapy resistance and the progression of GBM is the tumor's ability to evade the immune system, referred to as immune escape from cancer. This phenomenon reflects the tumor cells' efforts to adapt and survive the body's immune response. The release and expression of molecules like TGF-ß, IL-10, PD-L1, and NKG2DL by GBM cells impact the activation, recognition, and elimination of tumor cells by the immune system. Additionally, the involvement of cells such as MDSCs, Tregs, and TAMs plays a role in inhibiting the immune system's function, thereby promoting the development of GBM cells. A better comprehension of GBM's immune escape, supported by technological advances, will significantly aid in the future management of GBM patients' treatment.Keywords: glioblastoma multiforme, GBM, cancer immunity, immune evasion, immune escape, immunotherapy","PeriodicalId":514464,"journal":{"name":"Molecular and Cellular Biomedical Sciences","volume":"103 46","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141666138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Vitamin D deficiency results in various problems, like rickets, osteomalacia, heart problems, cancer, diabetes, and autoimmune diseases. Hypocalcemia is a common disorder among preterm infants, indicating vitamin D deficiency. This study was conducted to analyze the association of vitamin D deficiency with hypocalcemia in preterm infants.Materials and methods: A cross-sectional study was performed in preterm infants born in our hospital from December 2022 to May 2023. Venous blood was collected within the first 24 hours to assess vitamin D and calcium levels. Chi-square test and logistic regression analysis were used to assess the association of gestational age, sex, birth weight, and vitamin D with the incidence of hypocalcemia. The significance was determined with p<0.05.Results: There were 40 preterm newborns, comprising 37.5% moderately preterm, 20% very preterm, and 42.5% extremely preterm. Most subjects were female (52.5%). Low birth weight, very low birth weight, and extremely low birth weight occurred in 55%, 27.5%, and 17.5%, respectively. Vitamin D insufficiency and deficiency were observed in 20% and 80% subjects, respectively. Most subjects had hypocalcemia (62.5%). Chi-square test obtained a significant association of vitamin D deficiency with hypocalcemia (p=0.029).Conclusion: Vitamin D deficiency is significantly associated with the incidence of hypocalcemia in preterm infants.Keywords: Vitamin D, hypocalcemia, preterm neonates
背景：缺乏维生素 D 会导致各种问题，如佝偻病、骨软化症、心脏病、癌症、糖尿病和自身免疫性疾病。低钙血症是早产儿中常见的一种疾病，表明早产儿缺乏维生素 D。本研究旨在分析维生素 D 缺乏与早产儿低钙血症的关系：本研究对 2022 年 12 月至 2023 年 5 月期间在我院出生的早产儿进行了横断面研究。在最初 24 小时内采集静脉血以评估维生素 D 和钙的水平。采用卡方检验和逻辑回归分析评估胎龄、性别、出生体重和维生素 D 与低钙血症发生率的关系。P<0.05为显著性：40名早产新生儿中，37.5%为中度早产，20%为极早产，42.5%为极早产。大多数受试者为女性（52.5%）。低出生体重儿、极低出生体重儿和极低出生体重儿分别占 55%、27.5% 和 17.5%。维生素 D 不足和缺乏的受试者分别占 20% 和 80%。大多数受试者有低钙血症（62.5%）。通过卡方检验发现，维生素 D 缺乏与低钙血症有显著关联（P=0.029）：结论：维生素 D 缺乏与早产儿低钙血症的发生率明显相关：维生素 D 低钙血症 早产新生儿
{"title":"Vitamin D Deficiency is Associated with Hypocalcemia in Preterm Infants","authors":"Nabiel Nabiel, Hari Wahyu Nugroho, A. Moelyo","doi":"10.21705/mcbs.v8i2.473","DOIUrl":"https://doi.org/10.21705/mcbs.v8i2.473","url":null,"abstract":"Background: Vitamin D deficiency results in various problems, like rickets, osteomalacia, heart problems, cancer, diabetes, and autoimmune diseases. Hypocalcemia is a common disorder among preterm infants, indicating vitamin D deficiency. This study was conducted to analyze the association of vitamin D deficiency with hypocalcemia in preterm infants.Materials and methods: A cross-sectional study was performed in preterm infants born in our hospital from December 2022 to May 2023. Venous blood was collected within the first 24 hours to assess vitamin D and calcium levels. Chi-square test and logistic regression analysis were used to assess the association of gestational age, sex, birth weight, and vitamin D with the incidence of hypocalcemia. The significance was determined with p<0.05.Results: There were 40 preterm newborns, comprising 37.5% moderately preterm, 20% very preterm, and 42.5% extremely preterm. Most subjects were female (52.5%). Low birth weight, very low birth weight, and extremely low birth weight occurred in 55%, 27.5%, and 17.5%, respectively. Vitamin D insufficiency and deficiency were observed in 20% and 80% subjects, respectively. Most subjects had hypocalcemia (62.5%). Chi-square test obtained a significant association of vitamin D deficiency with hypocalcemia (p=0.029).Conclusion: Vitamin D deficiency is significantly associated with the incidence of hypocalcemia in preterm infants.Keywords: Vitamin D, hypocalcemia, preterm neonates","PeriodicalId":514464,"journal":{"name":"Molecular and Cellular Biomedical Sciences","volume":"44 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141663851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ery Hermawati, Mitra Handini, M. I. Ilmiawan, Mahyarudin Mahyarudin
Background: Cerebellum is one of the vital components of the brain that will be affected by ischemia-reperfusion (IR) injury. IR injury will increase free radicals, which in turn can trigger apoptosis and cell death. Therefore, this study was conducted to examine the effect of chlorogenic acid administration on apoptosis and the number of cells in the cerebellum of rats with global ischemic transients.Materials and methods: Wistar rats were divided into five groups: sham-operated (C1), IR (C2), IR + 15 mg/kgBW chlorogenic acid (T1), IR + 30 mg/kgBW chlorogenic acid (T2), and IR + 60 mg/kgBW chlorogenic acid (T3). C2, T1, T2, and T3 groups received bilateral common carotid occlusion (BCCO) surgery to induce IR injury. Thirty minutes after BCCO surgery, T1, T2, and T3 rats were administered chlorogenic acid in various doses intraperitoneally. RNA extraction and real-time polymerase chain reaction (PCR) measurements were then performed on NeuN, Bcl2, Bax, caspase 3, as well as on GAPDH as housekeeping genes.Results: There were significant differences in NeuN expressions between groups, with the highest expression shown in C1 followed by T3. Bcl2 expressions were also significantly different between groups, and rats in C1 and T3 showed to be significantly higher compared to C2, while T1 was significantly lower than C1. However, Bax and caspase 3 expressions showed no significant differences.Conclusion: Chlorogenic acid in 60 mg/kgBW dose increases NeuN expression and Bcl2 mRNA expression after transient global ischemia. These increases might correlate with the heightened level of protection against apoptosis in the cerebellum, hence showing its potential in protecting neuron cells.Keywords: transient global ischemia, chlorogenic acid, cerebellum, apoptosis
{"title":"Chlorogenic Acid Protects Cell Death in the Cerebellum through Anti-Apoptotic Protein Bcl2 in Transient Global Ischemia Cases","authors":"Ery Hermawati, Mitra Handini, M. I. Ilmiawan, Mahyarudin Mahyarudin","doi":"10.21705/mcbs.v8i1.411","DOIUrl":"https://doi.org/10.21705/mcbs.v8i1.411","url":null,"abstract":"Background: Cerebellum is one of the vital components of the brain that will be affected by ischemia-reperfusion (IR) injury. IR injury will increase free radicals, which in turn can trigger apoptosis and cell death. Therefore, this study was conducted to examine the effect of chlorogenic acid administration on apoptosis and the number of cells in the cerebellum of rats with global ischemic transients.Materials and methods: Wistar rats were divided into five groups: sham-operated (C1), IR (C2), IR + 15 mg/kgBW chlorogenic acid (T1), IR + 30 mg/kgBW chlorogenic acid (T2), and IR + 60 mg/kgBW chlorogenic acid (T3). C2, T1, T2, and T3 groups received bilateral common carotid occlusion (BCCO) surgery to induce IR injury. Thirty minutes after BCCO surgery, T1, T2, and T3 rats were administered chlorogenic acid in various doses intraperitoneally. RNA extraction and real-time polymerase chain reaction (PCR) measurements were then performed on NeuN, Bcl2, Bax, caspase 3, as well as on GAPDH as housekeeping genes.Results: There were significant differences in NeuN expressions between groups, with the highest expression shown in C1 followed by T3. Bcl2 expressions were also significantly different between groups, and rats in C1 and T3 showed to be significantly higher compared to C2, while T1 was significantly lower than C1. However, Bax and caspase 3 expressions showed no significant differences.Conclusion: Chlorogenic acid in 60 mg/kgBW dose increases NeuN expression and Bcl2 mRNA expression after transient global ischemia. These increases might correlate with the heightened level of protection against apoptosis in the cerebellum, hence showing its potential in protecting neuron cells.Keywords: transient global ischemia, chlorogenic acid, cerebellum, apoptosis","PeriodicalId":514464,"journal":{"name":"Molecular and Cellular Biomedical Sciences","volume":" 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140387444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rima Haifa, Cynthia Retna Sartika, Ahmad Faried, Y. E. Hadisaputri, A. Chouw, Andi Wijaya, M. Barliana
Dendritic cell (DC) vaccines, as immunotherapy agents, can gather up and transport cancer-related antigens to T lymphocytes, activating anti-tumor effector responses. After being activated by DC, cytotoxic T lymphocyte cells (CTL) will secrete the cytolytic granzyme B that can effectively induce rapid apoptosis of target cells. On the other hand, DC also secrete several cytokines and a large number of exosomes, which together operate as a whole antigen-presenting entity. The efficacy of the vaccine’s treatment may be affected by the sources used for DC vaccines. Umbilical cord blood (UCB) from healthy donors can be employed when autologous cancer patient’s peripheral blood (PB) cannot be used as a source for isolating DC due to genetic abnormalities. Comparing UCB to other sources, there is a painless method of collecting sources as opposed to PB, which necessitates a venipuncture or leukapheresis procedure to isolate the blood. Many studies related to the use of PB-DC have been carried out, but research on potential comparisons between PB-DC and UCB-DC is still very limited. In this review, the potential of PB- and UCB-derived DC and their secretomes for cancer will be discussed.Keywords: dendritic cells, vaccines, umbilical cord blood, peripheral blood
树突状细胞（DC）疫苗作为免疫治疗药物，可将与癌症相关的抗原聚集并运送到T淋巴细胞，激活抗肿瘤效应反应。细胞毒性 T 淋巴细胞（CTL）被 DC 激活后，会分泌细胞溶解性颗粒酶 B，能有效诱导靶细胞快速凋亡。另一方面，DC 还能分泌多种细胞因子和大量外泌体，它们共同构成一个完整的抗原递呈实体。疫苗的治疗效果可能会受到 DC 疫苗来源的影响。当自体癌症患者的外周血（PB）因基因异常而无法用作分离直流电的来源时，可以使用健康供体的脐带血（UCB）。与其他来源相比，UCB 的采集方法无痛苦，而 PB 则需要通过静脉穿刺或白细胞分离手术来分离血液。与使用 PB-DC 相关的研究已经开展了很多，但有关 PB-DC 和 UCB-DC 潜在比较的研究仍然非常有限。本综述将讨论脐带血和外周血中的树突状细胞及其分泌物对癌症的潜在作用。
{"title":"Potency of Peripheral Blood- and Umbilical Cord Blood-derived Dendritic Cells and Their Secretomes as Vaccines for Cancer","authors":"Rima Haifa, Cynthia Retna Sartika, Ahmad Faried, Y. E. Hadisaputri, A. Chouw, Andi Wijaya, M. Barliana","doi":"10.21705/mcbs.v8i1.358","DOIUrl":"https://doi.org/10.21705/mcbs.v8i1.358","url":null,"abstract":"Dendritic cell (DC) vaccines, as immunotherapy agents, can gather up and transport cancer-related antigens to T lymphocytes, activating anti-tumor effector responses. After being activated by DC, cytotoxic T lymphocyte cells (CTL) will secrete the cytolytic granzyme B that can effectively induce rapid apoptosis of target cells. On the other hand, DC also secrete several cytokines and a large number of exosomes, which together operate as a whole antigen-presenting entity. The efficacy of the vaccine’s treatment may be affected by the sources used for DC vaccines. Umbilical cord blood (UCB) from healthy donors can be employed when autologous cancer patient’s peripheral blood (PB) cannot be used as a source for isolating DC due to genetic abnormalities. Comparing UCB to other sources, there is a painless method of collecting sources as opposed to PB, which necessitates a venipuncture or leukapheresis procedure to isolate the blood. Many studies related to the use of PB-DC have been carried out, but research on potential comparisons between PB-DC and UCB-DC is still very limited. In this review, the potential of PB- and UCB-derived DC and their secretomes for cancer will be discussed.Keywords: dendritic cells, vaccines, umbilical cord blood, peripheral blood","PeriodicalId":514464,"journal":{"name":"Molecular and Cellular Biomedical Sciences","volume":" 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140387533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuberculosis is caused by Mycobacterium tuberculosis infection. During M. tuberculosis infection, there is a decrease in the partial pressure of oxygen in the granuloma microenvironment, which causes the hypoxia-inducible factor (HIF) to become stable. HIF functions as a transcription factor that regulates the expression of genes crucial for metabolic adaptation in hypoxic conditions. Recent research suggests that HIF plays a vital role in infectious and inflammatory conditions. Several studies have demonstrated that HIF signaling can enhance macrophages antimicrobial activity and bactericidal effect against M. tuberculosis, such as increasing macrophage autophagy, enhancing the effects of rifampicin, inhibiting p38 MAPK signaling, enhancing the regulation of effector antimicrobial pathways mediated by human β defensin 2 (hBD2) and vitamin D receptor (VDR), redirecting energy metabolism to glycolysis, and producing various cytokines. All these responses ultimately result in the inhibition of intracellular M. tuberculosis growth. HIF has therapeutic implications, potentially being a new candidate for host-directed therapy as a complement to existing antituberculosis drugs. Understanding the role of HIF in macrophages during M. tuberculosis infection and comprehending the host-pathogen relationship with M. tuberculosis is advantageous for developing future therapies.Keywords: Mycobacterium tuberculosis, macrophages, hypoxia-inducible factor
{"title":"The Role of Hypoxia-inducible Factor in Mycobacterium tuberculosis-infected Macrophages","authors":"Nina Fitriana, F. C. Iswanti, Mohamad Sadikin","doi":"10.21705/mcbs.v8i1.405","DOIUrl":"https://doi.org/10.21705/mcbs.v8i1.405","url":null,"abstract":"Tuberculosis is caused by Mycobacterium tuberculosis infection. During M. tuberculosis infection, there is a decrease in the partial pressure of oxygen in the granuloma microenvironment, which causes the hypoxia-inducible factor (HIF) to become stable. HIF functions as a transcription factor that regulates the expression of genes crucial for metabolic adaptation in hypoxic conditions. Recent research suggests that HIF plays a vital role in infectious and inflammatory conditions. Several studies have demonstrated that HIF signaling can enhance macrophages antimicrobial activity and bactericidal effect against M. tuberculosis, such as increasing macrophage autophagy, enhancing the effects of rifampicin, inhibiting p38 MAPK signaling, enhancing the regulation of effector antimicrobial pathways mediated by human β defensin 2 (hBD2) and vitamin D receptor (VDR), redirecting energy metabolism to glycolysis, and producing various cytokines. All these responses ultimately result in the inhibition of intracellular M. tuberculosis growth. HIF has therapeutic implications, potentially being a new candidate for host-directed therapy as a complement to existing antituberculosis drugs. Understanding the role of HIF in macrophages during M. tuberculosis infection and comprehending the host-pathogen relationship with M. tuberculosis is advantageous for developing future therapies.Keywords: Mycobacterium tuberculosis, macrophages, hypoxia-inducible factor","PeriodicalId":514464,"journal":{"name":"Molecular and Cellular Biomedical Sciences","volume":" 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140387737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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