Aishwarya Vetrivel, Monica Ramasamy, P. Vetrivel, Santhi Natchimuthu, S. Arunachalam, G. Kim, Rajeswari Murugesan
{"title":"Pseudomonas aeruginosa Biofilm Formation and Its Control","authors":"Aishwarya Vetrivel, Monica Ramasamy, P. Vetrivel, Santhi Natchimuthu, S. Arunachalam, G. Kim, Rajeswari Murugesan","doi":"10.3390/biologics1030019","DOIUrl":"https://doi.org/10.3390/biologics1030019","url":null,"abstract":"Microbes are hardly seen as planktonic species and are most commonly found as biofilm communities in cases of chronic infections. Biofilms are regarded as a biological condition, where a large group of microorganisms gets adhered to a biotic or abiotic surface. In this context, Pseudomonas aeruginosa, a Gram-negative nosocomial pathogen is the main causative organism responsible for life-threatening and persistent infections in individuals affected with cystic fibrosis and other lung ailments. The bacteria can form a strong biofilm structure when it adheres to a surface suitable for the development of a biofilm matrix. These bacterial biofilms pose higher natural resistance to conventional antibiotic therapy due to their multiple tolerance mechanisms. This prevailing condition has led to an increasing rate of treatment failures associated with P. aeruginosa biofilm infections. A better understanding of the effect of a diverse group of antibiotics on established biofilms would be necessary to avoid inappropriate treatment strategies. Hence, the search for other alternative strategies as effective biofilm treatment options has become a growing area of research. The current review aims to give an overview of the mechanisms governing biofilm formation and the different strategies employed so far in the control of biofilm infections caused by P. aeruginosa. Moreover, this review can also help researchers to search for new antibiofilm agents to tackle the effect of biofilm infections that are currently imprudent to conventional antibiotics.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46960131","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}
{"title":"Peptides in COVID-19 Clinical Trials—A Snapshot","authors":"K. Hilpert","doi":"10.3390/biologics1030018","DOIUrl":"https://doi.org/10.3390/biologics1030018","url":null,"abstract":"Since the beginning of the COVID-19 pandemic, there has been a strong drive and desire to find effective treatments for and protection against the disease. On the webpage ClinicalTrials.gov, a total of 6505 clinical trials currently (September 2021) investigating various aspects of COVID-19 are registered. Of these, 124 studies involving peptides were identified. These 124 were further evaluated, and 88 trials that used peptides only for routine diagnostics were excluded. The remaining 36 trials were classified into 5 different classes according to their function: immunomodulatory (5 trials), regain homeostasis (10 trials), diagnostics/biomarkers (8 trials), vaccination (9 trials), and antiviral activity (4 trials, all overlap with immunomodulatory activities). In the current review, these 36 trials are briefly described and tabularly summarised. According to the estimated finish date, 14 trials have not yet finished. All of the finished trials are yet to report their results. Seven trials were based in the USA, and Egypt, France, the UK, Turkey, and the Russian Federation conducted three trials each. This review aims to present a snapshot of the current situation of peptides in COVID-19 clinical trials and provides a template to follow up on trials of interest; it does not claim to be a complete overview.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41970478","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}
{"title":"Is the Gut Microbiome a Target for Adjuvant Treatment of COVID-19?","authors":"K. Hilpert","doi":"10.3390/biologics1030017","DOIUrl":"https://doi.org/10.3390/biologics1030017","url":null,"abstract":"High expression of the transmembrane protein angiotensin I converting enzyme 2 (ACE2), more than 100-times higher as in the lung, and transmembrane serine protease 2 (TMPRSS2) in the gastrointestinal tract leads to infection with SARS-CoV-2. According to meta-analysis data, 9.8–20% of COVID-19 patients experience gastrointestinal symptoms, where diarrhoea is the most frequent, and about 50% shed viruses with high titre through their faeces, where a first faecal transmission was reported. Furthermore, gut inflammation, intestinal damage, and weakening of the gut mucosal integrity that leads to increased permeability has been shown in different studies for COVID-19 patients. This can lead to increased inflammation and bacteraemia. Low mucosal integrity combined with low intestinal damage is a good predictor for disease progression and submission to the intensive care unit (ICU). Several pilot studies have shown that the gut microbiome of COVID-19 patients is changed, microbial richness and diversity were lower, and opportunistic pathogens that can cause bacteraemia were enriched compared to a healthy control group. In a large proportion of these patients, dysbiosis was not resolved at discharge from the hospital and one study showed dysbiosis is still present after 3 months post COVID-19. Consequently, there might be a link between dysbiosis of the gut microbiome in COVID-19 patients and chronic COVID-19 syndrome (CCS). Various clinical trials are investigating the benefit of probiotics for acute COVID-19 patients, the majority of which have not reported results yet. However, two clinical trials have shown that a certain combination of probiotics is beneficial and safe for acute COVID-19 patients. Mortality was 11% for the probiotic treatment group, and 22% for the control group. Furthermore, for the probiotic group, symptoms cleared faster, and an 8-fold decreased risk of developing a respiratory failure was calculated. In conclusion, evidence is arising that inflammation, increased permeability, and microbiome dysbiosis in the gut occur in COVID-19 patients and thus provide new targets for adjuvant treatments of acute and chronic COVID-19. More research in this area is needed.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41866891","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}
{"title":"Clinical Efficacy and Safety of Antiviral Drugs in the Extended Use against COVID-19: What We Know So Far","authors":"Md. Jamal Hossain, Tabassum Jannat, Shejuti Rahman Brishty, Urmi Roy, Saikat Mitra, Md. Oliullah Rafi, Md. Rabiul Islam, M. Nesa, Md Ariful Islam, T. Emran","doi":"10.3390/biologics1020016","DOIUrl":"https://doi.org/10.3390/biologics1020016","url":null,"abstract":"Human beings around the globe have been suffering from a devastating novel pandemic and public health emergency, coronavirus disease 2019 (COVID-19), for more than one and a half years due to the deadly and highly pathogenic severe acute respiratory coronavirus 2 (SARS-CoV-2) infection worldwide. Notably, no effective treatment strategy has been approved for the complete recovery of COVID-19 patients, though several vaccines have been rolled out around the world upon emergency use authorization. After the emergence of the COVID-19 outbreak globally, plenty of clinical investigations commenced to screen the safety and efficacy of several previously approved drugs to be repurposed against the SARS-CoV-2 pathogen. This concise review aims at exploring the current status of the clinical efficacy and safety profile of several antiviral medications for the treatment of patients with COVID-19 and other respiratory complications caused by SARS-CoV-2 infection. The paper covers all kinds of human studies (January 2020 to June 2021) except case reports/series to highlight the clear conclusion based on the current clinical evidence. Among the promising repositioned antivirals, remdesivir has been recommended in critical conditions to mitigate the fatality rate and improve clinical conditions. In addition, boosting the immune system is believed to be beneficial in treating COVID-19 patients, so interferon type I might exert immunomodulation through its antiviral effects by stimulating interferon-stimulated gene (ISG). However, more extensive clinical studies covering all ethnic groups globally are warranted based on current data to better understand the clinical efficacy of the currently proposed repurposed drugs against COVID-19.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47945032","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}
{"title":"Implications of Endothelial Cell-Mediated Dysfunctions in Vasomotor Tone Regulation","authors":"Carolina Mangana, Margarida Lorigo, E. Cairrão","doi":"10.3390/biologics1020015","DOIUrl":"https://doi.org/10.3390/biologics1020015","url":null,"abstract":"Cardiovascular diseases (CVD) constitute the major cause of death worldwide and show a higher prevalence in the adult population. The human umbilical cord consistsof two arteries and one vein, both composed of three tunics. The tunica intima, lined with endothelial cells, regulates vascular tone through the production/release of vasoregulatory substances. These substances can be vasoactive factors released by endothelial cells (ECs) that cause vasodilation (NO, PGI2, EDHF, and Bradykinin) or vasoconstriction (ET1, TXA2, and Ang II) depending on the cell type (ECs or SMC) that reacts to the stimulus. Vascular studies using ECs are important for the analysis of cardiovascular diseases since endothelial dysfunction is an important CVD risk factor. In this paper, we will address the morphological characteristics of the human umbilical cord and its component vessels. the constitution of the vascular endothelium, and the evolution of human umbilical cord-derived endothelial cells when isolated. Moreover, the role played by the endothelium in the vasomotor tone regulation, and how it may be associated with the existence of CVD, were discussed.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43830243","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}
B. Y. Nakamatsu, A. Fernandes, Débora da Silva, L. S. Santos, Thamires Rodrigues de Sousa, J. R. Victor
{"title":"Suitable Interpretation of Skin Prick Test and Biomedical Guidance Leads to a Better Clinical State in Atopic Individuals with High Indoor Permanence: Possible Therapeutic Implications","authors":"B. Y. Nakamatsu, A. Fernandes, Débora da Silva, L. S. Santos, Thamires Rodrigues de Sousa, J. R. Victor","doi":"10.3390/biologics1020014","DOIUrl":"https://doi.org/10.3390/biologics1020014","url":null,"abstract":"Indoor conditions contribute to allergen sensitization and multiple allergens reactivity, mainly for inhaled allergens. This study analyzes if Skin Prick Test (SPT) combined with efficient individual biomedical guidance about allergy development’s social, biological, and environmental aspects can yield a better clinical state with therapeutic implications for atopic individuals with high indoor permanence. We recruited atopic and non-atopic volunteers (clinically and in vitro diagnosed) with indoor permanence above 15 h per day and without previous SPT evaluation. The SPT and serum anti-allergen IgE analyses were performed individually in person, demonstrated, and discussed by the practitioners. Six months after, SPT and specific IgE titers determination were repeated, and a questionnaire to evaluate the effectiveness of the practitioner’s orientation was performed. After six months, 14% of atopic volunteers reported changes in their social habits, 30% said that they avoid the development of allergies clinical symptoms, and 68% reported a substantial improvement in their health after being informed mentored about their allergen reactivity. The control non-atopic group, as expected, reported no changes in social habits, the maintenance of total avoidance of allergic symptoms, and almost no improvement of their health. Reduced SPT and serum allergen-specific IgE titers were detected in the atopic individuals corroborating with questionnaire results. Our results indicated that SPT, followed by an individual and efficient discussion about the main biomedical aspects of allergy development, could exert a pronounced therapeutic role in allergy development by high indoor permanence individuals.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45657800","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}
J. Feehan, M. Prakash, L. Stojanovska, M. Flavel, B. Kitchen, V. Apostolopoulos
{"title":"Immunomodulatory Properties of Polyphenol-Rich Sugarcane Extract on Human Monocytes","authors":"J. Feehan, M. Prakash, L. Stojanovska, M. Flavel, B. Kitchen, V. Apostolopoulos","doi":"10.3390/biologics1020013","DOIUrl":"https://doi.org/10.3390/biologics1020013","url":null,"abstract":"As inflammatory lifestyle factors become more prevalent and as the population ages, the management of inflammation will become increasingly relevant. Plant polyphenols are powerful antioxidants that are known to have beneficial effects in a number of diseases with an inflammatory or oxidative component, such as malignancy, cardiovascular disease and arthritis. Polyphenol-rich sugarcane extract (PRSE) is a novel preparation with high concentrations of polyphenolic antioxidants, with some evidence to show benefits in health, but there is limited research investigating its effects on immunomodulation. This study determined the effects of PRSE on human monocyte cells in vitro. We show that PRSE has an immunomodulatory effect in U937 human monocyte cells, altering the expression of cellular surface markers, with an increased expression of CD16 and CD11b, as well as small changes in CD40, CD80, CD80, CD206 and MHCI. It also modulates the profile of secreted cytokines, increasing IL-1β, TNFα, IL-6, IL-8, IL-4 and IL-10. These changes are consistent with the advanced differentiation of the monocyte, as well as the switch from the M1 to M2 phenotype in macrophages. We also demonstrate that this effect is likely to be independent of the NF-κB signalling pathway, suggesting that other mechanisms drive this effect. PRSE exerts an immunomodulatory effect on U937 monocytes in vitro, potentially facilitating the conversion from inflammation to healing. Future studies should identify specific mechanisms underlying the changes and evaluate their effectiveness in animal models of disease.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46556136","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}
{"title":"Biological Treatments in Inflammatory Bowel Disease: A Complex Mix of Mechanisms and Actions","authors":"L. O. Moreno, S. Fernández-Tomé, R. Abalo","doi":"10.3390/biologics1020012","DOIUrl":"https://doi.org/10.3390/biologics1020012","url":null,"abstract":"Inflammatory bowel disease (IBD) is a chronic disease that requires lifelong medication and whose incidence is increasing over the world. There is currently no cure for IBD, and the current therapeutic objective is to control the inflammatory process. Approximately one third of treated patients do not respond to treatment and refractoriness to treatment is common. Therefore, pharmacological treatments, such as monoclonal antibodies, are urgently needed, and new treatment guidelines are regularly published. Due to the extremely important current role of biologics in the therapy of IBD, herein we have briefly reviewed the main biological treatments currently available. In addition, we have focused on the mechanisms of action of the most relevant groups of biological agents in IBD therapy, which are not completely clear but are undoubtfully important for understanding both their therapeutic efficacy and the adverse side effects they may have. Further studies are necessary to better understand the action mechanism of these drugs, which will in turn help us to understand how to improve their efficacy and safety. These studies will hopefully pave the path for a personalized medicine.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45141746","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}
D. Câmara, A. Porcacchia, N. Lizier, P. L. de-Sá-Júnior
{"title":"A COVID-19 Overview and Potential Applications of Cell Therapy","authors":"D. Câmara, A. Porcacchia, N. Lizier, P. L. de-Sá-Júnior","doi":"10.3390/biologics1020011","DOIUrl":"https://doi.org/10.3390/biologics1020011","url":null,"abstract":"The COVID-19 pandemic has already reaped thousands of lives, although many scientific studies already showed the possibility of this scenario. Currently, further attention is provided to patients depicting comorbidities such as respiratory or immunocompromised diseases, hypertension, and diabetes, as these individuals show a worse prognosis. Cell therapies using stem cells and/or defense cells, combined or not with traditional treatment, could be an outstanding strategy for COVID-19 management since these treatments can act by modulating the immune system, reducing proliferation, and favoring the complete elimination of the virus. In this review, we highlight the main molecular characteristics of this novel coronavirus, as well as the main pathognomonic signs of COVID-19. Furthermore, possible cell therapies are pointed out to show alternative treatments against COVID-19 and its sequels.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/biologics1020011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47134480","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}
Abdallah S. Abdelsattar, Anan Safwat, Rana Nofal, Amera Elsayed, Salsabil Makky, A. El-Shibiny
{"title":"Isolation and Characterization of Bacteriophage ZCSE6 against Salmonella spp.: Phage Application in Milk","authors":"Abdallah S. Abdelsattar, Anan Safwat, Rana Nofal, Amera Elsayed, Salsabil Makky, A. El-Shibiny","doi":"10.3390/biologics1020010","DOIUrl":"https://doi.org/10.3390/biologics1020010","url":null,"abstract":"Food safety is very important in the food industry as most pathogenic bacteria can cause food-borne diseases and negatively affect public health. In the milk industry, contamination with Salmonella has always been a challenge, but the risks have dramatically increased as almost all bacteria now show resistance to a wide range of commercial antibiotics. This study aimed to isolate a bacteriophage to be used as a bactericidal agent against Salmonella in milk and dairy products. Here, phage ZCSE6 has been isolated from raw milk sample sand molecularly and chemically characterized. At different multiplicities of infection (MOIs) of 0.1, 0.01, and 0.001, the phage–Salmonella interaction was studied for 6 h at 37 °C and 24 h at 8 °C. In addition, ZCSE6 was tested against Salmonella contamination in milk to examine its lytic activity for 3 h at 37 °C. The results showed that ZCSE6 has a small genome size (<48.5 kbp) and belongs to the Siphovirus family. Phage ZCSE6 revealed a high thermal and pH stability at various conditions that mimic milk manufacturing and supply chain conditions. It also demonstrated a significant reduction in Salmonella concentration in media at various MOIs, with higher bacterial eradication at higher MOI. Moreover, it significantly reduced Salmonella growth (MOI 1) in milk, manifesting a 1000-fold decrease in bacteria concentration following 3 h incubation at 37 °C. The results highlighted the strong ability of ZCSE6 to kill Salmonella and control its growth in milk. Thus, ZCSE6 is recommended as a biocontrol agent in milk to limit bacterial growth and increase the milk shelf-life.","PeriodicalId":93526,"journal":{"name":"Biologics (Basel, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/biologics1020010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42048197","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}