Pub Date : 2024-02-01DOI: 10.3390/biologics4010004
L. Nosetti, Claudio Tirelli, F. Marino, M. Gaiazzi, Lucia Sacchi, Mara De Amici, F. Barocci, R. Maio, M. Cosentino, Luigi Nespoli
Introduction: Obstructive Sleep Apnea (OSA) in children is characterized by repeated episodes of partial or complete obstruction of the upper airways that impair normal ventilation and cause hypoxia and sleep disruption. These episodes activate innate and adaptive immunity resulting in the production of proinflammatory cytokines: IL-1β, IL-6, TNF-α, and reactive oxygen species. The hypothalamic–pituitary–adrenal (HPT) axis is also activated with alteration of the circadian rhythm of cortisol synthesis. OSA in children, and even more in adults, induces a systemic inflammatory condition that contributes to the genesis of clinical complications: poor growth, learning disabilities, cardiovascular changes, insulin resistance, and metabolic syndrome. Methods: A total of 42 non-obese children (age 1–15 years) were enrolled among those sent to our sleep center to perform full polysomnography (PSG). After PSG, 6 children did not show OSA (controls), 20 had mild OSA (m OSA), and 16 had medium-severe OSA (MS OSA). In vitro IL-1β, TNF-α, and serum cortisol levels were measured at 2 and 8 am in the analyzed groups. Results: Cortisol levels did not differ between controls and OSA children. At 2 am, there were no differences between controls and OSA in TNF-α production, whereas at 8 am, TNF-α was reduced in MS-OSA. IL-1β production showed no differences between OSA and controls. Conclusions: In our population, only TNF-α production is suppressed in MS-OSA: this might indicate a role of OSA severity in inducing inflammation. In adults, the phenomenon is more pronounced due to the habitual greater severity/duration of OSA, presence of comorbidities (cardiovascular and metabolic), and different immune system function.
导言：儿童阻塞性睡眠呼吸暂停（OSA）的特点是反复发作的上呼吸道部分或完全阻塞，影响正常通气，导致缺氧和睡眠障碍。这些发作会激活先天性和适应性免疫，导致促炎细胞因子的产生：IL-1β、IL-6、TNF-α 和活性氧。下丘脑-垂体-肾上腺（HPT）轴也会随着皮质醇合成昼夜节律的改变而被激活。儿童的 OSA 会诱发全身性炎症，成人的情况更为严重，从而导致临床并发症：发育不良、学习障碍、心血管变化、胰岛素抵抗和代谢综合征。研究方法在被送往睡眠中心进行全面多导睡眠图检查的儿童中，共选取了 42 名非肥胖儿童（1-15 岁）。PSG检查后，6名儿童未发现OSA（对照组），20名儿童患有轻度OSA（m OSA），16名儿童患有中重度OSA（MS OSA）。分析组分别在凌晨 2 点和 8 点测量了体外 IL-1β、TNF-α 和血清皮质醇水平。结果显示对照组和 OSA 儿童的皮质醇水平没有差异。凌晨2点，TNF-α的产生在对照组和OSA之间没有差异，而在早晨8点，TNF-α在MS-OSA中有所减少。IL-1β的产生在OSA和对照组之间没有差异。结论在我们的人群中，只有 TNF-α 的产生在 MS-OSA 中受到抑制：这可能表明 OSA 的严重程度在诱发炎症方面起了作用。在成人中，这种现象更为明显，原因是OSA的习惯性严重程度/持续时间更长、存在合并症（心血管和代谢）以及免疫系统功能不同。
{"title":"Cytokines and Obstructive Sleep Apnea in Childhood: Study of a Group of Children","authors":"L. Nosetti, Claudio Tirelli, F. Marino, M. Gaiazzi, Lucia Sacchi, Mara De Amici, F. Barocci, R. Maio, M. Cosentino, Luigi Nespoli","doi":"10.3390/biologics4010004","DOIUrl":"https://doi.org/10.3390/biologics4010004","url":null,"abstract":"Introduction: Obstructive Sleep Apnea (OSA) in children is characterized by repeated episodes of partial or complete obstruction of the upper airways that impair normal ventilation and cause hypoxia and sleep disruption. These episodes activate innate and adaptive immunity resulting in the production of proinflammatory cytokines: IL-1β, IL-6, TNF-α, and reactive oxygen species. The hypothalamic–pituitary–adrenal (HPT) axis is also activated with alteration of the circadian rhythm of cortisol synthesis. OSA in children, and even more in adults, induces a systemic inflammatory condition that contributes to the genesis of clinical complications: poor growth, learning disabilities, cardiovascular changes, insulin resistance, and metabolic syndrome. Methods: A total of 42 non-obese children (age 1–15 years) were enrolled among those sent to our sleep center to perform full polysomnography (PSG). After PSG, 6 children did not show OSA (controls), 20 had mild OSA (m OSA), and 16 had medium-severe OSA (MS OSA). In vitro IL-1β, TNF-α, and serum cortisol levels were measured at 2 and 8 am in the analyzed groups. Results: Cortisol levels did not differ between controls and OSA children. At 2 am, there were no differences between controls and OSA in TNF-α production, whereas at 8 am, TNF-α was reduced in MS-OSA. IL-1β production showed no differences between OSA and controls. Conclusions: In our population, only TNF-α production is suppressed in MS-OSA: this might indicate a role of OSA severity in inducing inflammation. In adults, the phenomenon is more pronounced due to the habitual greater severity/duration of OSA, presence of comorbidities (cardiovascular and metabolic), and different immune system function.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"16 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139884615","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}
Pub Date : 2024-01-25DOI: 10.3390/biologics4010002
Paul M. Boylan, Megan E. Fleischman, Nathan A. Pinner, Joseph Andrew Woods, Adam Welch
Background: Patients living with chronic obstructive pulmonary disease (COPD) are at risk for lower respiratory tract infections caused by respiratory syncytial virus (RSV). The first RSV vaccines were approved in 2023 for adults ages 60 years and older. The safety and efficacy of the RSV vaccines and their clinical implications in patients living with COPD, apart from composite comorbidity results, are under-reported. Methods: This rapid review aimed to collect and report data pertaining to RSV vaccine safety and efficacy in patients living with COPD. Resources searched included Ovid MEDLINE, EMBASE, International Pharmaceutical Abstracts, published peer-reviewed abstracts, ClinicalTrials.gov, and the United States Food and Drug Administration (FDA) website. Results: Seven records were included: five research manuscripts and two ongoing clinical trials. Patients living with COPD were included in RSV vaccine clinical trials, but outcomes of RSV vaccine safety and efficacy in patients living with COPD were grossly unreported. Conclusions: Future clinical trials of patients living with COPD and subgroup analyses of patients living with COPD within existing studies evaluating RSV vaccine safety and efficacy are necessary to substantiate outcomes in this population.
{"title":"Respiratory Syncytial Virus Vaccines for the Prevention of Lower Respiratory Tract Infections in Patients Living with Chronic Obstructive Pulmonary Disease: A Rapid Review","authors":"Paul M. Boylan, Megan E. Fleischman, Nathan A. Pinner, Joseph Andrew Woods, Adam Welch","doi":"10.3390/biologics4010002","DOIUrl":"https://doi.org/10.3390/biologics4010002","url":null,"abstract":"Background: Patients living with chronic obstructive pulmonary disease (COPD) are at risk for lower respiratory tract infections caused by respiratory syncytial virus (RSV). The first RSV vaccines were approved in 2023 for adults ages 60 years and older. The safety and efficacy of the RSV vaccines and their clinical implications in patients living with COPD, apart from composite comorbidity results, are under-reported. Methods: This rapid review aimed to collect and report data pertaining to RSV vaccine safety and efficacy in patients living with COPD. Resources searched included Ovid MEDLINE, EMBASE, International Pharmaceutical Abstracts, published peer-reviewed abstracts, ClinicalTrials.gov, and the United States Food and Drug Administration (FDA) website. Results: Seven records were included: five research manuscripts and two ongoing clinical trials. Patients living with COPD were included in RSV vaccine clinical trials, but outcomes of RSV vaccine safety and efficacy in patients living with COPD were grossly unreported. Conclusions: Future clinical trials of patients living with COPD and subgroup analyses of patients living with COPD within existing studies evaluating RSV vaccine safety and efficacy are necessary to substantiate outcomes in this population.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"21 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139598372","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}
Pub Date : 2023-12-22DOI: 10.3390/biologics4010001
S. Pujhari
Arboviruses are a group of viruses that are transmitted by arthropods, such as mosquitoes, and cause significant morbidity and mortality worldwide. Currently, there are only a few options, with restricted use, for effective vaccines against these viruses. However, recent advances in arboviral vaccine development have shown promising innovations that have potential in preclinical and clinical studies. Insect-specific viruses have been explored as a novel vaccine platform that can induce cross-protective immunity against related arboviruses. Nanoparticle-based vaccines have also been developed to enhance the immunogenicity and stability of viral antigens. Additionally, vaccines against mosquito salivary proteins that can modulate the host immune response and interfere with arboviral transmission are being explored. Synonymous recoding, such as random codon shuffling, codon deoptimization, and codon-pair deoptimization, is being investigated as a strategy to attenuate the replication of arboviruses in vertebrate cells, reducing the risk of reverting to wild-type virulence. Finally, mRNA vaccines have been developed to rapidly generate and express viral antigens in the host cells, eliciting robust and durable immune responses. The challenges and opportunities for arboviral vaccine development are outlined, and future directions for research and innovation are discussed.
{"title":"Recent Advances in Arboviral Vaccines: Emerging Platforms and Promising Innovations","authors":"S. Pujhari","doi":"10.3390/biologics4010001","DOIUrl":"https://doi.org/10.3390/biologics4010001","url":null,"abstract":"Arboviruses are a group of viruses that are transmitted by arthropods, such as mosquitoes, and cause significant morbidity and mortality worldwide. Currently, there are only a few options, with restricted use, for effective vaccines against these viruses. However, recent advances in arboviral vaccine development have shown promising innovations that have potential in preclinical and clinical studies. Insect-specific viruses have been explored as a novel vaccine platform that can induce cross-protective immunity against related arboviruses. Nanoparticle-based vaccines have also been developed to enhance the immunogenicity and stability of viral antigens. Additionally, vaccines against mosquito salivary proteins that can modulate the host immune response and interfere with arboviral transmission are being explored. Synonymous recoding, such as random codon shuffling, codon deoptimization, and codon-pair deoptimization, is being investigated as a strategy to attenuate the replication of arboviruses in vertebrate cells, reducing the risk of reverting to wild-type virulence. Finally, mRNA vaccines have been developed to rapidly generate and express viral antigens in the host cells, eliciting robust and durable immune responses. The challenges and opportunities for arboviral vaccine development are outlined, and future directions for research and innovation are discussed.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"33 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139165082","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}
Pub Date : 2023-12-12DOI: 10.3390/biologics3040022
Theodoros Karalis
Hyaluronan is one of the major components of the extracellular matrix and is involved in the regulation of multiple processes in both human physiology and disease. In human cancers, hyaluronan metabolism displays remarkable alterations, leading to the accumulation of large amounts of hyaluronan matrices in the tumoural tissues. The altered levels of hyaluronan in the tumours stem from the enhanced expression and activity of hyaluronan synthases in both tumour and stromal cells. Moreover, hyaluronidase activity is also upregulated in cancer, leading to the generation of lower molecular weight hyaluronan fragments that in turn assist tumour growth, neo-angiogenesis and the metastatic cascade. Hyaluronan accumulation in malignant tissues not only assists tumour growth and metastases but is also associated with worse outcomes in cancer patients. Therefore, targeting hyaluronan synthesis emerges as an interesting strategy that might be employed for cancer treatment. This review article summarises current evidence and discusses ways to move forward in the field of targeting hyaluronan synthesis for cancer therapy.
{"title":"Targeting Hyaluronan Synthesis in Cancer: A Road Less Travelled","authors":"Theodoros Karalis","doi":"10.3390/biologics3040022","DOIUrl":"https://doi.org/10.3390/biologics3040022","url":null,"abstract":"Hyaluronan is one of the major components of the extracellular matrix and is involved in the regulation of multiple processes in both human physiology and disease. In human cancers, hyaluronan metabolism displays remarkable alterations, leading to the accumulation of large amounts of hyaluronan matrices in the tumoural tissues. The altered levels of hyaluronan in the tumours stem from the enhanced expression and activity of hyaluronan synthases in both tumour and stromal cells. Moreover, hyaluronidase activity is also upregulated in cancer, leading to the generation of lower molecular weight hyaluronan fragments that in turn assist tumour growth, neo-angiogenesis and the metastatic cascade. Hyaluronan accumulation in malignant tissues not only assists tumour growth and metastases but is also associated with worse outcomes in cancer patients. Therefore, targeting hyaluronan synthesis emerges as an interesting strategy that might be employed for cancer treatment. This review article summarises current evidence and discusses ways to move forward in the field of targeting hyaluronan synthesis for cancer therapy.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"90 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139182115","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}
Pub Date : 2023-11-29DOI: 10.3390/biologics3040021
Sarfaraz K. Niazi, Matthias Magoola
Therapeutic proteins treat many acute and chronic diseases that were until recently considered untreatable. However, their high development cost keeps them out of reach of most patients around the world. One plausible solution to lower-cost manufacturing is to adopt newer technologies like using Escherichia coli to express larger molecules, including full-length antibodies, generally relegated to Chinese Hamster Ovary (CHO) cells, adopt continuous manufacturing, and convert the manufacturing to cell-free synthesis. The advantages of using E. coli include a shorter production cycle, little risk of viral contamination, cell host stability, and a highly reproducible post-translational modification.
{"title":"Advances in Escherichia coli-Based Therapeutic Protein Expression: Mammalian Conversion, Continuous Manufacturing, and Cell-Free Production","authors":"Sarfaraz K. Niazi, Matthias Magoola","doi":"10.3390/biologics3040021","DOIUrl":"https://doi.org/10.3390/biologics3040021","url":null,"abstract":"Therapeutic proteins treat many acute and chronic diseases that were until recently considered untreatable. However, their high development cost keeps them out of reach of most patients around the world. One plausible solution to lower-cost manufacturing is to adopt newer technologies like using Escherichia coli to express larger molecules, including full-length antibodies, generally relegated to Chinese Hamster Ovary (CHO) cells, adopt continuous manufacturing, and convert the manufacturing to cell-free synthesis. The advantages of using E. coli include a shorter production cycle, little risk of viral contamination, cell host stability, and a highly reproducible post-translational modification.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139212475","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}
Pub Date : 2023-11-15DOI: 10.3390/biologics3040020
Sarfaraz K. Niazi, Matthias Magoola
Recombinant technology has been around for nearly three quarters of a century and has revolutionized protein therapy. However, the cost of developing recombinant therapeutic proteins and the manufacturing infrastructure keeps their cost unaffordable for most patients. Proteins are produced in the body via messenger RNA (mRNA) translation. This process can be readily replicated through administering a chemical nucleic acid product to manufacture the same protein recombinantly. The progress made in creating these proteins ex vivo in a cell-free system also offers a lower-cost option to produce therapeutic proteins. This article compares these alternative methods for recombinant protein production, assessing their respective advantages and limitations. While developers and regulatory agencies may encounter significant challenges in navigating product approval, including many unresolved intellectual property issues, these technologies are now proven and offer the most logical solution to making therapeutic proteins accessible to most patients.
{"title":"mRNA and Synthesis-Based Therapeutic Proteins: A Non-Recombinant Affordable Option","authors":"Sarfaraz K. Niazi, Matthias Magoola","doi":"10.3390/biologics3040020","DOIUrl":"https://doi.org/10.3390/biologics3040020","url":null,"abstract":"Recombinant technology has been around for nearly three quarters of a century and has revolutionized protein therapy. However, the cost of developing recombinant therapeutic proteins and the manufacturing infrastructure keeps their cost unaffordable for most patients. Proteins are produced in the body via messenger RNA (mRNA) translation. This process can be readily replicated through administering a chemical nucleic acid product to manufacture the same protein recombinantly. The progress made in creating these proteins ex vivo in a cell-free system also offers a lower-cost option to produce therapeutic proteins. This article compares these alternative methods for recombinant protein production, assessing their respective advantages and limitations. While developers and regulatory agencies may encounter significant challenges in navigating product approval, including many unresolved intellectual property issues, these technologies are now proven and offer the most logical solution to making therapeutic proteins accessible to most patients.","PeriodicalId":505652,"journal":{"name":"Biologics","volume":"8 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139271647","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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