POLLUTION & SKIN: ROLE OF POLYSACCHARIDES From Waste Material to Innovative Cosmeceuticals

Review Article | DOI: https://doi.org/10.31579/2578-8949/093

POLLUTION & SKIN: ROLE OF POLYSACCHARIDES From Waste Material to Innovative Cosmeceuticals

  • Pier Francesco Morganite 1*
  • Xinghua Gao 2
  • Rui Qun Qi 3
  • Maria Beatrice Coltelli 4
  • Bouchra Benjelloun-Mlayah 5
  • Vladimir E Yudin 6
  • Gianluca Morganti 7

1 Academy of History of Health Care Art,00186 Rome, Italy and China Medical University,110001Shenyang, China.

2 Deputy Dermatology Director, the First Hospital, China Medical University, 110001 Shenyang, China.

3 Dermatology department, Key lab of Immunodermatology, China Medical University,110001 Shenyang, China.

4 Department of Civil and Industrial Engineering Interuniversity Consortium of Material Science & Technology, University of Pisa,56122 Pisa, Italy

5 R&D Director, Compagnie Industrielle de la Matiere Vegetable CIMV, Neuilly-Sur-Seine, Ile-de-France.

6 Institute of Macromolecular Compounds, Russian Academy of Sciences 199004 Saint Petersburg, Russia.

7 ISCD Nanoscience Center, 00165 Rome Italy.

*Corresponding Author: Pier Francesco Morganite

Citation: Pier Francesco Morganite, Xinghua Gao, Rui Qun Qi, Maria Beatrice Coltelli, Bouchra Benjelloun-Mlayah at ell. (2022) POLLUTION & SKIN: ROLE OF POLYSACCHARIDES From Waste Material to Innovative Cosmeceuticals. Dermatology and Dermatitis. 7(3); DOI:10.31579/2578-8949/093

Copyright: ©2022 Pier Francesco Morganite, This is an open-access article distributed under the terms of The Creative Commons. Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 02 February 2022 | Accepted: 30 March 2022 | Published: 29 October 2022

Keywords: skin; polysaccharides; chitin nanofibrils; nanolignin; cosmeceuticals, cosmetics; packaging; biodegradability; sustainability; non-woven tissues

Abstract

Skin as principal barrier protects our body from the inside and outside environmental aggressions represented principally from air pollution and the pathogenic microorganisms.The fundamental protective parts of the skin are the Stratum Corneum and the dermal compartment largely composed of dense collagen-rich fibrils which, embedded into the Extracellular matrix, provide structural and mechanical support.This complex structure degrades during the aging processes due to genetic factors and  the environmental polluted environment .To protect and try to rejuvenate the skin both women and men are looking for cosmetic products made by natural ingredients,produced by sustainable technologies and packed by containers able to safeguard human health and the environment. Polysaccharides seem to be the best ingredients to make natural-based active ingredients and carriers for Pharmaceutical and Cosmetic use, being skin- and environmentally-friendly,and obtainable at low cost from the food waste.

At this purpose, a new category of biocosmetic products has been proposed, which are made by smart  non-woven tissue-carriers,

embedded by micro-nanoparticles of nanochitin-nanolignin, encapsulating different active ingredients. Natural polysaccharides used as carriers and active ingredients characterize the different activities of these innovative cosmeceutical-tissues. So doing it could be possible to reduce part of the food waste, safeguarding natural raw materials and biodiversity of our planet for the future generations.

Introduction

Skin is an important multilayered barrier which externally protects the human body from threats, such as infectious microoganisms and chemicals, while internally helps to maintain homeostasis with a reduced 

loss of water [1]. This protective structure, less than 2 mm thick, is composed of several layers: epidermis, dermis and hypodermis (figure 1).

Figure: 1 The skin layers

The outermost epidermis' layer, the stratum corneum (SC), represents the primary barrier to balance the excessive water loss, the ingress of exogenous chemicals and pathogens, as well as to protect from the UV radiation' activity and regulate the transdermal delivery of compounds applied on its surface [1,2]. Keratinocytes, as sentinels of skin homeostasis, are the major cell population of epidermis, representing the first line of immune protection against the microbial infection and expression of the antimicrobial beta defensins involved.

SC is composed of corneocytes, cells filled with keratin fibrils enclosed by an envelope of proteins and surrounded by a lipid' matrix [1-3]. Dermis is largely composed of dense collagen-rich fibrils, which provides structural, and mechanical support to the skin together with hypodermis that, consisting largely of fat, insulates the skin from cold and aiding shock absorption.

Collagen, produced from fibroblasts and embedded into the complex and dynamic extra cellular matrix together with elastin (ECM),provides the main skin' structural and mechanical support, maintaining its fundamental functions for all the lifecycle[1-3].During the aging phenomena this polymer  is fragmented by the activity of complex extracellular and intracellular pathways which, include the activity of the Metalloroteinase-1 (MMP1),impair of collagen integrity, fibroblast attachment and the keratinocytes migration [3]. Skin aging, in fact, is a complex process which is characterized by an alteration of all the ECM components in both dermis and epidermis, involving oxidative, epigenetic and genotoxic stresses, and modified collagen turnover, telomere shortening and mitochondrial dysfunction [3,4].Both genetic factors and  environmental conditions,which include UV exposure and pollution nanoparticulates,provoke changes in the ECM' network organization with  collagen fragmentation, elevated presence of  MMP-1 enzymes,cross linking of amino acids side chains, and the consequent skin wrinkling (figure.2) [3-5].It isn't  to be forgotten  that structural-integrity and functionality of dermis depend primarily  on the intact ECM network with its tightly packed  and well-organized long collagen-1 fibrils [2].Thus to slowdown the aging processes, it results fundamental to live in an healthy environment with  a regular lifestyle which, as previously reported, balance and  influence part of the genetic factors and  skin structure[2,4,5].Regarding the many functions of collagen, it's to remember that its fragments are also mediators of Inflammation during the wound re-epithelialization process,acting as chemoattractants for neutrophils,thus enhancing immune responses and modulating gene expression[6,7]. There fore, with the aim to find solutions for slowdown the skin wrinkling formation as well as to accelerate and remodeling the skin affected by wounds and burns, some authors have proposed the hydrolized collagen that, used by nutracosmeceuticals formulations, have been applied  topically  and/or taken by oral route[7-9].

Figure:  2 Collagen fragmentation in aging skin.

The obtained collagen peptides,in fact, seem to act as antioxidant compounds for their capacity to donate electrons,neutralizing the free radicals' activity in dependence on their molecular weight :the lower the molecular weight the greater their effectiveness [8].

Consequently, the use of natural active ingredients, as collagen, loaded and released from biodegradable natural carriers of products to be applied on the skin and/or taken by oral routes, is among the actual consumers' request [9-11]. People,in fact, are looking for natural cosmetics and skin care with a positive impact on the environment due to the  biodegradable ingredients and packaging materials used for their formulations [12].Thus the necessity to reduce pollution and waste adopting the circular Economy and producing innovative skin- and environmentally-friendly  cosmeceuticals by the use of polysaccharides obtained by food by-products[13-15]

Pollution, climate changing and human health

The level of pollutants are constantly increasing worldwide, causing many health-related problems and risks of microbial and virus infection, such as COVID-19. The WHO 2016 report states that around 7 million people globally and 400,000/580,000  in China only die prematurely  annually, due  directly or indirectly to pollution problems (figure 3)[16].

Figure 3: Pollution is a silent killer (by the courtesy of WHO)

Moreover the long-term exposure to outdoor and indoor fine particulate matter with a size less than 2.5 millimicrons on diameter (PM2.5) represents the largest environmental risk factor for human health with an estimated 4.1 million attributable deaths in 2019[17-9]. Thus, air pollution as well as both water pollution and soil depletion are the principal causes of  the climate change. Thus, the amount of water in rivers has been influenced and, depending on the region and the time of the year, it resulted in more flooding or brought [20]. The worldwide deforestation, is another important cause of climate changing. Forest, in fact, as well as oceans store massive amount of carbon, off setting about 10% of the country's annual greenhouse gas (GHG) emissions, thus helping to mitigate climate change [21]. Thus, pollution, nature loss, and changing climate are inextricably linked together. They need to be urgently slowed investing in natural climate solutions, including better land conservation and management' actions able to increase carbon storage and avoid GHG emissions which are increasing day by day due to the different human activities (Figure 4) [22].

Figure 4: Worldwide GHG emissions by 2018 due to to different human activities.

Moreover, the environmental contaminants have  a negative impact on the skin causing premature aging, pigmented spots and inflammation phenomena. Additionally pollutants, weaken the skin barrier function and penetrating through the skin layers, may cause serious dermatological issues such as atopic dermatitis, psoriasis and other systemic toxicity[23].At this purpose it is also to underline the further plastic waste caused from the COVID-19 pandemic due to  the great quantity of surgical masks and medical dressings used as protective means to avoid the virus infection, estimated to range worldwide 129 billion of face masks and 65 billion of gloves every month[24,25].These protective means, in fact, are prevalently made by the non-degradable  polypropylene (PP) as petrol-derived polymer. As a consequence, it is enormously increasing the interest for natural and biodegradable products, including polysaccharides, which are able to

protect skin and mucous membranes from airborne particulate matter, because of their positive impact on the environment.

Food loss and Role of polysaccharides.

Among the many polymersthenatural polysaccharides and other  macromolecules  such as pullulanchitin, lignin and the natural-derived  synthetic compounds  polylactic acid (PLAand Polyhydroxyalcanoates ,are the more known carriersused in the medical,food and cosmetic fieldsalso as packaging raw materialbecauseof their skinandenvironmentally-friendly effectiveness and safeness [26-28].Food lostand packaging wastein facthas becomea great  problemfor the consequential air pollution thatrepresents a serious global  threat to human healthand welfare. According to Food and AgriculturalOrganization (FAO), in fact,1/3 of the total foodproductionis lost during all the distribution supplychain and harvestingcontributing to theestimated value of around USD 1 trillion annual loss [29]. It has been estimated,in factthat approximately30%-50of food intended for humanconsumption is wasted at different stagesof the food systemwithloss ofproductivityenergy and natural resources[30].This great quantity of food waste is estimated to be further increased  because  directly proportionated tothe increased demand of food producedand consumed from the world population projected to increasefrom 7.8 billion people  in 2020 to 9.9 billion by 2050 and 11 billionby 2100 (figure5)[30-32].

Figure 5 The previsional worldwide increase of population by 2100(by the courtesy of Our World in Data)

On the other hand, packaging constitutes roughly 46% of global plastic waste, increased in the European Union by 9.4% for reaching 77.7 million metric tons (Mt) in 2018, also if municipal waste landfilled decreased by 56% in 2019 from 121 Mt in 1995 (fig 6)[32,33].


 

Figure :6 Changing of generation and disposition of comunal waste

Figure 7: Effectiveness of the CN-LG tissue on the face wrinkling of

However, the use of  food waste as a source of precious raw material to produce goods and packagings, remains an urgent need.Food loss in fact represented from vegetables, fruits, grains, fish and seafood, meat, etc, is rich of biopolymers such as proteins, nucleic acids, and polysaccharides, including alginates, pectins, agar, pullulan, cellulose, lignin and chitin which for their similarities to ECM make them one of the key players in designing scaffolds for tissue engineering[34-38].It is to underline, in fact, that an efficient scaffold to be used for tissue regeneration should be able to allow a platform necessary to assist interactions between cells and the surrounding tissues' bioactive factors [34-38].

And the ability of these natural polymers to generate biological-like scaffolds has been linked to their glycan units [36,37].

At this purpose, it is to remember that polysaccharides are the most abundant naturally occurring macromolecules which, present in all living systems, act as structural materials and supplier of water and energy, playing a crucial role in the survival of both animals and plants [37]. Obtainable from many different sources, such as plants, microorganisms, algae and animals, these polymers are constituted by  long chain units of monosaccharides jointed each other by glycosidic linkages. Due to their physicochemical characteristics and for enhancing their properties, polysaccharides are susceptible to chemical and physical modifications, resulting more stable than proteins and nucleic acids, without being denatured irreversibly by heating [34,36]. Moreover, they possess different properties characterized  by their variable  high or low molecular weight and poly-dispersivity, and a linear or branched structure enriched by functional groups such as hydroxy, carboxy, amine, etc. Thus, some polysaccharides are water-soluble like gum arabic or pullulan, while other like cellulose and chitin are water-insoluble, but all are non-carcinogenic and immunogenic and with a low toxicity being skin- and environmentally-friendly [34,35,37]. Due to their characteristics, it is possible to easily realize physical modifications of these polymers by blending two or more of them to obtain composite compounds whichpossessing physicochemical properties, including porosity, structure, softness, swelling capacity, and elasticity, result similar to biological systems [38,39]. These composites may be also blended with nanomaterials (micro-nanoparticles) extracted from natural sources or chemically synthesized by natural-derived ingredients such as PLA, or obtained by microbiological synthesis as PHAs [40].

At this purpose it is to underline again that utilizing waste by the use of microoganisms (bacteria and algae) to produce polysaccharides not only it will be possible to reduce the environmental pollution, but also to   make different kind of tissues and goods skin- and and environmentally-friendly [41,42]. The actual research, in fact, is working on polymers which, already existing in nature as compounds synthesized by plants or microorganisms, result rapidly biodegraded under natural conditions, also when used to produce bioplastics [43,44].

Chitin Nanofibril-Nanolignin on skin, hair and Mucous Membranes

Recently,the natural polymers Chitin and Lignin  have been complexed each to other, in their micro-nano dimension, for realizing  block polymeric particles useful  to  encapsulate different and selected active ingredients [45].These particles(Pls) may be bound to the natural fibers of non-woven tissue/films by electrospinning [45],casting techniques[ 46] or by extrusion [47].Apart the technology used, it is important to control the  fibers' nature, the incorporation of the actives encapsulated into the realized particles and their bonding onto the tissue/film surface, and naturally effectiveness and safeness of the final product realized [45-56 ].The final obtained dressings may be utilized to make biodegradable advanced medication and surgical masks ,food supplements ,or innovative cosmeceutical-tissues, more or less effective  related to the specific biological characteristics  of the selected and encapsulated active particles and, naturally, the polymers used to make the non-woven tissues[45-56].

At this purpose, by the use of natural polymers and the electrospinning technique it has been realized a non-woven tissues embedded by chitin nanofibrils-nanolignin (CN-LG) particles, encapsulating peptides from fish collagen hydrolysate  together with vitamins C and E .From the first obtained results obtained into a plastic surgery department,this tissue has shown to be effective in  reducing both fine lines and wrinkles on women affected by premature  aging after 60 days of treatment(Figure.7 )(57).It is interesting to underline the recovered anti-aging effect  that some authors have obtained  by the use of fish collagen' peptides [58] used from our group as part of the realized  tissue (59).These peptides, in fact, complexed with chitin nanofibrils(CN) and   applied on the skin by a non-woven innovative tissue, confirm to be effective" not only when used topically(59) but seem to possess the same antiaging effectiveness when taken by oral route (8,58), women affected by photoaging(premature aging)

Figure 8: Significance of Active Ageing

Our studies are going on to deeply understand the mechanism of action of these polypeptides when released from the proposed tissues alone and in combinations with other natural ingredients, including the reported vitamins [57]. Thus, the utilization of these specialized tissues as innovative carriers for a new category of cosmeceutical products may be of high interest, as also reported elsewhere [45-56]. They, in fact, may be formulated as multifunctional cosmetics, having the capacity to load a combination of active ingredients, released at different dose and time. Thus, by the selection of the right natural ingredients encapsulated into the Chitin-lignin (CN-LG) complex it may be possible to formulate and make smart cosmeceutical-tissues characterized for their different effectiveness as skin active-aging (figure 8) [55]and moisturizing, whitening, lipid-balancing and anti-pollution products or as protective and hair repairing agents (figure 9) [56].

Figure: 9 Repairing activity of Chitin nanofibrils on a hair' longitudinally tricloclasy

Moreover, by the use of a specific tissue-diet supplement it could be possible to balance the gut microbiota, favoring the growth of saprophytic microbiota and reducing the presence of the pathogenic ones [60,61]It is to remember, in fact, that mammalian mucosal immune systems play an essential role in maintaining the gut and vaginal homeostasis connected with the global health of the human body. Consequently, gut microbiota affect its own development by stimulating the  innate and adaptive immune responses. Thus, while the external pathogenic microoganisms are eliminated, the indigenous microbes are tolerated [60,61].

Therefore, the formulation of these innovative multifunctional products requires a planned, organized approach for their structural composition [62]Therefore the need to identify the most appropriate and active ingredients which have to be included on the tissue-films' surface  as well as bound to the polymer used.Thus,to yield the designed effect, both selected actives and the carrier' components have to remain stable from the time of the product' production until its use by the consumer, being biodegradable, biocompatible and skin- and environmentally-friendly also.At this purpose,it is necessary to consider molecular size, pH, ionization parameters, melting point, solubility, odor and color of both active ingredients and polymers[62]. Moreover, other than the product formulation,it is also necessary to consider other important factors as, for example, the active ingredients' penetration at level of skin and its structures [62].This includes  region of the body,skin condition and  degree of hydration  as well as size and thickness  of the application site.These factors are needed to understand the time necessary for obtaining  the cosmeceutical-tissue' effectiveness and safeness. The active ingredients, in fact, should penetrate into the skin, but not through the skin and the active ingredients selected have to be compatible and stable into the tissue-carrier, acting synergistically without interacting with each other [63]. They, therefore, need to be delivered to either the skin surface, including stratum corneum, viable epidermis and/or dermis, and not to the systemic circulation. At this purpose it is also to underline the specific characteristics of the CN-LG complex that acts not only as biodegradable carrier, but also as active ingredient (27,64). In fact, on the one hand chitin, hydrolyzed to glucosamine, acetyl glucosamine and glucose from the human enzyme chitotrosidase, is  used as nutrient and energy for the cell growth and reproduction, acting also as antioxidant and antibacterial polymer[27,64,65].On the other hand lignin, acting as antioxidant, antibacterial and UV protective polymer results to be synergistic to the chitin activity [66,67].However, both carriers and  ingredients have to be evaluated in advance to verify their impact on the final formulation. Additionally, these innovative cosmeceutical-tissue result not only stable because packed and distributed at the dry state, but are also free of preservatives, emulsifiers, fragrance, color, and chemical which are often the main cause of allergic and sensitizing phenomena [68,69]. Additionally, these smart tissues, packed into container made by biodegradable paper or aluminium foils, are recyclable and to be considered at zero waste.

Naturally, commercial success of these new category of cosmetics will  depend from their functional properties and the perceived performance characteristics which  have to follow the consumer' request of natural-based  safe and environmental-friendly products, which has been estimated by Statista to reach USD 54.5 billion by 2027(figure.10 )in a global market of USD 511 billion in 2019 (figure 11 )  [70,80].

Figure 10 Natural products market (by the courtesy of Common Thread [80])

Figure:  10

Figure:  11 The worldwide previsional global Beauty and Personal carecosmetic market by 2020-2025(by the courtesy of Common [Thread 80])

Conclusion

Skin, as protective barrier of the body through the SC, is also composed by an extracellular matrix embedding various dermal components, including collagen fibrils and hyaluronic acid (1,2,4,5,23).This complex dynamic system which provides the skin by a structural and mechanical support, undergoes individual physiologic changes with age, including the fragmentation of collagen, with formation of fine lines wrinkles and black spots (72,73).Thus consumers are looking for cosmeceuticals which, natural-based and made by elevated engineered ingredients carriers and sustainable technologies, may be able to neutralize the pollution micro-nanoparticles and slowdown the aging processes ,thus safeguarding health and the environment (71,74,75).Millennials (26-44 years old) and Gen Z (6-25 years old) are the biggest drivers of the actual cosmetic business, doubling the consume of Baby Boomers (57-75 years old).Their purchasing decisions, based on media or on line reviews, consider more important the product effectiveness  with the ingredients and packaging used ,rather than its price. Moreover, they are shifting the focus from aging to longevity (75,76).Thus,COVID-19 pandemic has increased the willingness of all the consumers to pay a premium  for sustainable healthy personal care products and prioritize safety and hygiene (77).Therefore, purchasing decisions are increasingly motivated by the quest for an health and green living with a best life expectancy (78,79).Consequently, the pursuit of prevention and wellbeing is driving innovation, regarding the cosmetic ingredients used for both products and packagings (81-83).The growth rate for consumer goods marketed for sustainability,in fact ,is nearly four timer higher than the market average (82). European customers have understood that the food sector plays a critical,role in climate change and is responsible for about 25% of worldwide GHG emissions,50%of the arable land,and consume most of freshwater (16,33,81)

Therefore, considering polysaccharides as natural, biodegradable and biocompatible polymers obtainable from waste food materials, their use to produce non-woven tissues and films  is certainly in line with the actual consumer requests[83]. Moreover, as previously reported, the obtained polymeric composites easily personalized embedding their fibers by CN-LG micro-nanoparticles encapsulating different active ingredients, may be used to produce not only the proposed antiaging cosmeceutical-tissues, but also biodegradable Facial Beauty and

Surgical masks together with one-day Doctor Dressings [45-56,81-91]. Realizing the proposed products by the use of   it could be possible to reduce pollution and eliminate part of food waste, thus safeguarding natural raw materials and the earth's biodiversity for the future generations.

 

Author contributions: Idea of manuscript PM, GM; writing-original draft PM, MBC; Writing review and editing, PM, MBC, YVE and XG; supervision PM, BB-M,RQQ and MBC. All the authors have read and agree to the publishing version of manuscript

Istitutional Review Board Statement: not applicable

Informed Consent Statement: not applicable

Data Availability Starement: not applicable

Conflict of interest: the authors declare no conflict of interest

References

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad