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Objectives: The 90-day double-blind phase (DBP) of the Phase 3 EASE study demonstrated accelerated wound healing for Oleogel-S10 (birch triterpenes) versus control gel in epidermolysis bullosa (EB). Here, we report safety and total wound burden results from the 24-month open-label phase (OLP) in which all patients received treatment with Oleogel-S10. Method(s): Total wound burden was assessed using EB Disease Activity and Scarring Index (EBDASI) and Body Surface Area Percentage (BSAP). Data are reported without visit windows to reflect a realworld situation more accurately, particularly considering the COVID- 19 pandemic. Result(s): The patient population was made up of dystrophic EB (n = 178, 86.8%) and junctional EB (n = 25, 12.2%);71.7% (n = 147) of patients were aged <18 years. 141 patients (68.8%) completed the OLP. The mean (SD) treatment duration for all patients was 584.7 (246.1) days. Adverse events were reported in 77.1% of all patients in the OLP versus 81.7% of those receiving Oleogel-S10 in the DBP. Mean BSAP for patients treated with Oleogel-S10 in the DBP reduced from 12.1% at study entry to 6.1% with 27 months of treatment. Similarly, the mean EBDASI skin activity score in the Oleogel-S10 group improved from 19.6 to 15.1 after 27 months. In addition, reductions in both BSAP and EBDASI from OLP baseline were observed in patients who transitioned from control gel to Oleogel-S10 in the OLP. Discussion(s): These data support a reassuring long-term safety profile of Oleogel-S10. Furthermore, the reduction in wound burden previously reported with 15 months of Oleogel-S10 treatment is maintained to the end of OLP. This is encouraging given the nature of this chronic genetic disorder in which there is regular cycling of patients' fragile wounds.
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The Siddha system of medicine is an ancient medical lineage that is practiced primarily in the southern part of India. Siddha system of medicine has been in practice for thousands of years with documented evidence dating back to the 6th century BCE. According to siddha system of medicine's basic fundamental principle, the human body is made up of 96 thathuvam (primary components), which encompass physical, physiological, psychological, and intellectual aspects. Medicine (marunthu) is classified as a wide range of internal and external medicines. The major components of its medical formulations include plant parts, minerals and animal products. Various methods were carried out for the purification process to eliminate the toxins. Choornam, Guligai, Tailam, Parpam, Chendooram, Kattu, Pasai and Poochu are the most common medicines used in Siddha system of medicine for the treatment of various diseases. The pathophysiological classification of diseases is elaborated in detail in the classical Siddha literature. Siddha system of medicine plays an important role in protecting people from diseases such as COVID-19 by providing immune-protecting and immune-boosting medicines in today's world. Mathan tailam and maha megarajanga tailam are the two unique preparations used widely for various skin diseases including chronic wounds and burns. Scientific validation of both medicines will help in understanding their effectiveness against a typical wound condition. In the present study physio-chemical and phytochemical, HPTLC, and GC-MS analyses were carried out and discussed in detail on the multifunctional properties exhibited in the patient communities.
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The COVID-19 pandemic has disrupted healthcare, with its far-reaching effects seeping into chronic disease evaluation and treatment. Our tertiary wound care center was specially designed to deliver the highest quality care to wounded patients. Pre-pandemic, we were able to ensure rapid treatment via validated protocols delivered by a co-localized multidisciplinary team within the hospital setting. The pandemic has disrupted our model's framework, and we have worked to adapt our workflow without sacrificing quality of care. Using the modified Donabedian model of quality assessment, we present an analysis of pre- and intra-pandemic characteristics of our center. In this way, we hope other providers can use this framework for identifying evolving problems within their practice so that quality care can continue to be delivered to all patients.
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BACKGROUND: Previous studies in Dutch young adults revealed that individuals with self-reported impaired wound healing reported poorer mood, increased inattention and impulsivity, poorer quality of life, and poorer immune fitness compared to healthy controls. Another study revealed that the negative impact of lockdowns during the 2019 coronavirus disease (COVID-19) pandemic was significantly more profound among the impaired wound healing group than the control group. The purpose of the current study was to replicate and extend these findings among young adults living in Germany. METHODS: A retrospective, cross-sectional survey was conducted among N = 317 young adults living in Germany, 18-35 years old. They were allocated to the IWH group (N = 66) or the control group (N-251). Participants completed the Attention Control Scale, and mood, quality of life, and immune fitness were assessed with single-item ratings. All assessments were made for (1) the period before the COVID-19 pandemic, (2) the first lockdown period, March-May 2020, (3) the first no-lockdown period, summer 2020, (4) the second lockdown, November 2020 to May 2021, and (5) the second no-lockdown period, summer 2021. RESULTS: The impaired wound healing group reported significantly poorer mood, quality of life, and immune fitness. The effects were evident before the pandemic. The impaired wound healing group scored significantly poorer on attention focusing, but no significant differences between the groups were found for attention shifting. During the pandemic, negative lockdown effects (i.e., further aggravation of mood and immune fitness and lower quality of life) were evident in both groups but significantly more profound in the impaired wound healing group. No differences between the groups were found for the no-lockdown periods. CONCLUSION: Individuals with self-reported impaired wound healing have significantly poorer mood, attention focusing, and immune fitness and report a poorer quality of life than healthy controls. The impact of COVID-19 lockdowns was significantly more profound in the impaired wound-healing group.
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Nitric oxide (NO), a gaseous transmitter extensively present in the human body, regulates vascular relaxation, immune response, inflammation, neurotransmission, and other crucial functions. Nitrite donors have been used clinically to treat angina, heart failure, pulmonary hypertension, and erectile dysfunction. Based on NO's vast biological functions, it further can treat tumors, bacteria/biofilms and other infections, wound healing, eye diseases, and osteoporosis. However, delivering NO is challenging due to uncontrolled blood circulation release and a half-life of under five seconds. With advanced biotechnology and the development of nanomedicine, NO donors packaged with multifunctional nanocarriers by physically embedding or chemically conjugating have been reported to show improved therapeutic efficacy and reduced side effects. Herein, we review and discuss recent applications of NO nanomedicines, their therapeutic mechanisms, and the challenges of NO nanomedicines for future scientific studies and clinical applications. As NO enables the inhibition of the replication of DNA and RNA in infectious microbes, including COVID-19 coronaviruses and malaria parasites, we highlight the potential of NO nanomedicines for antipandemic efforts. This review aims to provide deep insights and practical hints into design strategies and applications of NO nanomedicines.
Subject(s)
COVID-19 , Neoplasms , Male , Humans , Nitric Oxide/therapeutic use , Neoplasms/therapy , Drug Carriers/therapeutic use , Nitric Oxide DonorsABSTRACT
Chronic venous leg ulcers cause significant morbidity in patients and the majority reoccur after resolution. The current standard of care, double layer compression, is not effective in all patients. Interleukin 17A (IL17) antagonist therapy has been shown to promote healing in murine models of chronic wounds. This has not previously been explored in humans. Therefore, we aim to undertake a phase II randomized, double-blinded, placebo-controlled pilot trial to assess whether Ixekizumab, an anti-IL17A therapy, is effective at reducing chronic venous ulcer size. In addition, to determine the feasibility and safety of undertaking a randomized control trial. Patients with a venous leg ulcer not responsive to 4 weeks of compression therapy were recruited. Participant were randomized to receive either Ixekizumab (80mg) or placebo injected subcutaneously every fortnight for 12 weeks while continuing standard of care. From 30 eligible, 4 patients consented, were enrolled and randomized. Initially, COVID-19 risk, medical history and distance from recruiting site were the main causes of exclusion or refusal to participate. All participants completed the 12-week treatment period. At completion, two participants in the Ixekizumab group reduced by >40% and one completely resolved their ulcer. Ulcers in the Ixekizumab group reduced by an average size of 955mm2 to 529mm2at baseline to final review respectively (p-value 0.12). The placebo group reduced in size by <5%.There were no adverse events related to the intervention. This pilot clinical trial investigated a novel treatment for chronic venous ulcers and showed IL17 inhibition does not impede and may improve chronic wound healing. It also showed a lack of major safety issues in using anti-IL17A therapy in this population. Moreover, the findings reinforce the feasibility of a larger trial to more accurately evaluate anti-inflammatory strategies in chronic wounds.Copyright © 2023
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Aim: Diabetic foot ulcers (DFUs) are linked to morbidity, decreased mobility, and feelings of isolation, powerlessness and sadness. The aim of our study was to explore the prevalence of anxiety and depression symptoms in adult patients with DFU. Method(s): We analysed questionnaires completed by patients with DFU attending our University Hospital Multidisciplinary Foot Clinic service over a one-month period in March 2022. The patients had completed three questionnaires, comprising of questions relating to socio-demographic status and care perceptions, the Patient Health Questionnaire-9 (PHQ-9) scale to assess depression, and the Generalized Anxiety Disorder scale (GAD-7) to assess anxiety. Result(s): Of the 60 patients who completed the questionnaires, 35% (n=21) reported anxiety symptoms and 40% (n=24), depressive symptoms. Individuals with comorbidities were three times more likely to report depression relative to those without any comorbidities (OR 3.3;95% CI 1.13-12.56). Younger individuals (less than 50 years), were almost nine times more likely to report anxiety in comparison to those aged 60 years or more (adjusted OR 8.9;95% CI 1.01-86.41), despite adjustment for confounding variables. Conclusion(s): The prevalence of depression and anxiety in this cohort of patients with DFU was low, but those who were affected reported moderate to severe symptoms. Younger individuals and those with comorbid conditions with DFU are more likely to experience an adverse impact on their mental health. This is a crucial factor to consider in the management of people undergoing DFU care. Strategies to reduce anxiety and/or depressive symptoms could impact both quality of life and wound healing. Copyright © 2023 John Wiley & Sons.Copyright © 2023 John Wiley & Sons, Ltd.
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Silymarin, is a phytoactive constituent isolated from the fruits and seeds of Silybum maria-num L Gaetn.), also called milk thistle belonging to the family of Asteracease. The phytoactive has been used to treat several physiological disorders. The objective of this manuscript was to review the therapeutic prospective of silymarin due to its ability to treat several physiological disorders. The da-tabases such as Pubmed, Elsevier, and Google Scholar were reviewed for the investigations or reviews published related to the title. The discussion is focused on the immunomodulatory, chemopreventive, and anti-inflammatory mechanisms of silymarin in various metabolic and dermatological disorders. In addition, the review discusses the different therapeutic potentials of silymarin such as the management of the liver disorder, skin carcinogenesis, cardiovascular disorders, diabetes mellitus, neurodegenera-tive disorders, and several dermatological disorders such as melasma, anti-aging, acne, rosacea, atopic dermatitis, and psoriasis. Silymarin is safe even with a dose higher than the therapeutic dose. Si-lymarin had good potential for the safe and effective treatment of numerous metabolic and dermatological disorders. © 2023 Bentham Science Publishers.
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In recent research, 3D printing has become a powerful technique and has been applied in the last few years to carbon-based materials. A new generation of 3D-printed electrodes, more affordable and easier to obtain due to rapid prototyping techniques, has emerged. We propose a customizable fabrication process for flexible (and rigid) carbon-based biosensors, from biosensor design to printable conductive inks. The electrochemical biosensors were obtained on a 50 µm Kapton® (polyimide) substrate and transferred to a 500 µm PDMS substrate, using a 3D-extrusion-based printing method. The main features of our fabrication process consist of short-time customization implementation, fast small-to-medium batch production, ease of electrochemical spectroscopy measurements, and very good resolution for an extrusion-based printing method (100 µm). The sensors were designed for future integration into a smart wound dressing for wound monitoring and other biomedical applications. We increased their sensibility with electro-deposited gold nanoparticles. To assess the biosensors' functionality, we performed surface functionalization with specific anti-N-protein antibodies for SARS-CoV 2 virus, with promising preliminary results.
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The present article reviews the effects of the textile in the wound healing process, as well as the availability of these products in the market. A brief description of applications is given based on the literature obtained from searching the scientific databases, besides the data obtained from secondary sources, like books and congress proceedings. The historical context of the textiles used in wounds, their general characteristics, particularities in the healing process, and incorporation of new technologies are discussed. It was evidenced that the textiles and associated technologies might influence directly or indirectly the stimulation of collagen, cell migration, angiogenesis, and reduction of pro-inflammatory factors and fibroblasts. However, the mechanisms by which the textiles act in the healing process are not well established in the literature. The interaction among textile engineering, biotechnology, medicine, and pharmacology is essential for the improvement and development of new products with better efficiency and accessibility.
Subject(s)
Textiles , Wound HealingABSTRACT
Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.Copyright © 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences
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The mass casualties caused by the delta variant and the wave of the newer "Omicron" variant of SARS-COV-2 in India have brought about great concern among healthcare officials. The government and healthcare agencies are seeking effective strategies to counter the pandemic. The application of nanotechnology and repurposing of drugs are reported as promising approaches in the management of COVID-19 disease. It has also immensely boomed the search for productive, re-liable, cost-effective, and bio-assimilable alternative solutions. Since ancient times, the traditional-ly employed Ayurvedic bhasmas have been used for diverse infectious diseases, which are now employed as nanomedicine that could be applied for managing COVID-19-related health anomalies. Like currently engineered metal nanoparticles (NPs), the bhasma nanoparticles (BNPs) are also packed with unique physicochemical properties, including multi-elemental nanocrystalline compo-sition, size, shape, dissolution, surface charge, hydrophobicity, and multi-pathway regulatory as well as modulatory effects. Because of these conformational and configurational-based physico-chemical advantages, Bhasma NPs may have promising potential to manage the COVID-19 pandemic and reduce the incidence of pneumonia-like common lung infections in children as well as age-related inflammatory diseases via immunomodulatory, anti-inflammatory, antiviral, and adju-vant-related properties.Copyright © 2023 Bentham Science Publishers.
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Hesperidin has gained major interest recently due to the outbreak of COVID-19. The traction has led to more research being conducted on the compound hesperidin. Recent studies have shown its anti-inflammatory and anti-viral attributes, which have beneficial effects on severe acute respiratory syndrome (SARS-CoV-2). Hesperidin has also shown unique effects on the protein of SARS-CoV-2, which lead to a good preventative measure for SARS-CoV-2. Hesperidin also causes a suppression of appetite, which helps to combat obesity through the release of cholecystokinin. Furthermore, hesperidin has shown cardioprotective properties, which cause an increase in plasma high-density lipoprotein levels and a decrease in plasma low-density lipoprotein levels. Hesperidin is also used in combination with the Japanese herb Rikkunshito, which has shown potential in a discovery of a new drug for gastrointestinal motility as hesperidin can depolarize pacemaker potential in interstitial cells of Cajal (ICC). The chemo-preventive effects of hesperidin are caused by its antioxidant effect, which may prevent tissue necrosis due to oxidative stress. The photo-protective effect of hesperidin can reduce the damage to the skin caused by UV rays. Hesperidin also possesses wound-healing properties.Copyright © 2023 Bentham Science Publishers.
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Background: Coronavirus disease-19 (COVID-19) is an infectious disease that can result in serious respiratory illness. It is associated with extensive systemic inflammation and changes to the lung extracellular matrix (ECM), which may result in diffuse alveolar damage and pulmonary fibrosis. In this study, the aim was to investigate whether ECM remodeling, wound healing, and neutrophil activity is altered in patients with COVID-19, with or without interstitial lung disease (ILD). Method(s): Serum was collected from 72 patients with COVID-19 infection 3 months after diagnosis, 10 of whom developed ILD, and from 16 healthy controls. A panel of neo-epitope specific ELISAs reflecting type III collagen crosslinking (PC3X), type III and VI collagen formation (PRO-C3 and PRO-C6), type I, III, and VI collagen degradation (C1M, C3M, and C6M), fibrin crosslinking (X-FIB), fibrin clot formation (PRO-FIB), elastin degradation (EL-NE and ELP-3), and calprotectin degradation (CPa9-HNE) were assessed in serum of patients. Result(s): Mean serum neo-epitopes PC3X (p<0.0001), PRO-C3 (p=0.0024), C3M (p=0.0085), PRO-FIB (p<0.0001), ELP-3 (p<0.0001), and CPa9-HNE (p<0.0001) were significantly elevated in patients with COVID-19 compared to healthy controls. Additionally, PC3X (p=0.023) and PRO-C3 (p=0.0317) were significantly elevated in COVID-19 patients who developed ILD when compared to those who did not. Conclusion(s): Non-invasive serological biomarkers reflecting tissue remodeling were significantly elevated in patients infected with COVID-19. Additionally, type III collagen crosslinking and formation may differentiate patients who develop ILD consequent to COVID-19 infection.
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The human body is inhabited by trillions of diverse microorganisms collectively called "microbiome" or "microbiota". Microbiota consists of bacteria, viruses, fungi, protozoa, and archaea. Microbiome demonstrates multi-faceted effects on human physical and mental health. Per evidence there is a multi-functional interplay between the whole-body microbiome composition on the epithelial surfaces including skin, nasal and oral cavities, airway, gastro-intestinal and urogenital tracts on one hand and on the other hand, the individual health status. Microbiota composition as well as an option to modulate it - together create a highly attractive operation area for the translational bio/medical research with multi-professional expertise and healthcare-relevant output in the framework of predictive, preventive and personalised medicine (PPPM/3 PM). Advanced PPPM strategies implemented in the microbiome area are expected to significantly improve individual outcomes and overall cost-efficacy of healthcare. According to the accumulated research data, corresponding diagnostic and treatment approaches are applicable to primary care (health risk assessment in individuals with sub-optimal health conditions and prevention of a disease development), secondary care (personalised treatment of clinically manifested disorders preventing a disease progression) and tertiary care (making palliation to an optimal management of non-curable diseases). In the current book, we do highlight the implementation potential of the microbiome-relevant research in the framework of predictive diagnostics, targeted prevention and treatments tailored to the individualised patient profile.Copyright © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.
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Silver has been in medicine for hundreds of years and has proven antimicrobial properties. It was widely used until the Second World War, when antibiotics emerged. Silver nitrate (SN) sticks (75% silver nitrate and 25% potassium nitrate) are currently employed as a topical haemostatic agent for various cutaneous surgical procedures. In the initial phase of the COVID-19 pandemic, faced with a limited supply of personal protective equipment, we used SN stick haemostasis for several skin surgical procedures (including excisions). COVID-19-related guidance from the Trust recommended the avoidance of electrocautery owing to the generation of surgical plume;hence, SN stick haemostasis seemed a pragmatic option. Four female patients with a mean age of 67 years (range 48-75) presented with swelling, erythema and pain at the surgical site within a week of the procedure. Three had ellipse excisions for suspected melanoma and squamous cell carcinomas, and one had a shave excision for possible seborrhoeic keratosis. Postsurgical wound infection was suspected, but repeated microbiological swabs did not grow any pathogens. All patients failed to respond to broad-spectrum oral antibiotics, even after two courses. The inflammatory changes took up to 4 weeks to settle, with topical corticosteroids used for wound healing. On contact with moisture, SN sticks deliver free silver ions that form an eschar as they bind to the tissue and occlude vessels. The longer the tip contacts the tissue, the greater the degree of the resultant caustic action. It is widely used in clinical practice, especially wound care (overgranulation, epibole and delayed healing). A 2020 review found an increased incidence of postoperative pain along with pigmentary changes in surgical wounds treated with SN sticks vs. aluminium chloride hexahydrate and ferric subsulfate. In skin surgery, SN is used to cauterize superficial wounds after curettage and shave excision. It does not generate aerosol and, in a pandemic setting, this particular feature can be valuable. However, the potential to cause aseptic skin inflammation that mimics postoperative infection is noteworthy. There are no evidence-based guidelines for its use in dermatology. We believe that the SN is an effective haemostatic agent but can induce significant tissue inflammation in some patients, particularly if it is used in excisions when the cauterized tissue is closed. If SN-induced haemostasis for excision was to be adopted in clinical practice, our experience suggests that larger studies and guidelines are recommended.
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Introduction: The ongoing pandemic of Severe Acute Respiratory Syndrome coronavirus-2 (SARS COV-2) has jeopardized people's health and the global economy. The infection caused by these viruses inflicts immunosuppression and an unprecedented range of symptoms leading to mortality. At this stage, there are no countermeasures or medicines to overcome rapid disease proliferation and aberrant immunological response. Objective(s): The study aims to determine different immunomodulatory therapeutics that could be potential agents to alleviate viral and other lethal infections and possibly rejuvenate immunological and tissue repair response against this disease. Method(s): A review of the literature was performed by screening different scientific databases to procure various immunomodulatory therapies for the treatment of SAR COV-2. Result(s): A comprehensive literature review indicated that different foods rich in vitamins (A-D), selenium and iron can enhance immunological response against various deleterious infections, whereas different nutritious drinks that include hydrogen-enriched water and green tea alleviate inflammation and elicit wound healing properties. Black cumin seeds and Garlic have a myriad of biological activities due to abundant bioactive phytochemicals that play an important role in the elimination of various bacterial and viral infections. Conclusion(s): These foods/supplements are relatively safe to consume and possess high toxicity profile and could be a potential nutritional intervention in order to create adequate immunity within a population to fight against this prevailing infection.Copyright © 2021 Bentham Science Publishers.