Secreted Protein Acidic and Rich in Cysteine (SPARC) to Manage Coronavirus Disease-2019 (COVID-19) Pandemic and the Post-COVID-19 Health Crisis.

Coronavirus disease-2019 (COVID-19) has had and will have impacts on public health and health system expenses. Indeed, not only it has led to high numbers of confirmed COVID-19 cases and hospitalizations, but its consequences will remain even after the end of the COVID-19 crisis. Therefore, therapeutic options are required to both tackle the COVID-19 crisis and manage its consequences during the post COVID-19 era. Secreted protein acidic and rich in cysteine (SPARC) is a biomolecule that is associated with various properties and functions that situate it as a candidate which may be used to prevent, treat and manage COVID-19 as well as the post-COVID-19-era health problems. This paper highlights how SPARC could be of such therapeutic use.

Secreted Protein Acidic and Rich in Cysteine (SPARC)-Mediated Exercise Effects: Illustrative Molecular Pathways against Various Diseases.

The strong benefits of exercise, in addition to the development of both the therapeutic applications of physical activity and molecular biology tools, means that it has become very important to explore the underlying molecular patterns linking exercise and its induced phenotypic changes. Within this context, secreted protein acidic and rich in cysteine (SPARC) has been characterized as an exercise-induced protein that would mediate and induce some important effects of exercise. Herein, we suggest some underlying pathways to explain such SPARC-induced exercise-like effects. Such mechanistic mapping would not only allow us to understand the molecular processes of exercise and SPARC effects but would also highlight the potential to develop novel molecular therapies. These therapies would be based on mimicking the exercise benefits via either introducing SPARC or pharmacologically targeting the SPARC-related pathways to produce exercise-like effects. This is of a particular importance for those who do not have the ability to perform the required physical activity due to disabilities or diseases. The main objective of this work is to highlight selected potential therapeutic applications deriving from SPARC properties that have been reported in various publications.

Mapping Genetics and Epigenetics to Explore the Pathways beyond the Correlated Ageing Phenotype.

Ageing is defined by the decline in the biological and physiological functions over time, which leads to health problems and increases risks of diseases. The modern societies are characterised by an ageing population, which represents challenges for the healthcare system. Within this context, there is a need to better understand the biological mechanisms beyond ageing in order to optimise geriatric therapies and medical approaches. Herein, we suggest exploring the genetic and epigenetic patterns related to ageing and correlate them with the ageing-related phenotype of the biological entities in order to establish mechanistic links and map the molecular pathways. Such links would have diverse implications in basic research, in clinics, as well as for therapeutic studies.

In Vitro Mimicking of Obesity-Induced Biochemical Environment to Study Obesity Impacts on Cells and Tissues.

Obesity represents a heavy burden for modern healthcare. The main challenge facing obesity research progress is the unknown underlying pathways, which limits our understanding of the pathogenesis and developing therapies. Obesity induces specific biochemical environments that impact the different cells and tissues. In this piece of writing, we suggest mimicking obesity-induced in vivo biochemical environments including pH, lipids, hormones, cytokines, and glucose within an in vitro environment. The concept is to reproduce such biochemical environments and use them to treat the tissue cultures, explant cultures, and cell cultures of different biological organs. This will allow us to clarify how the obesity-induced biochemistry impacts such biological entities. It would also be important to try different environments, in terms of the compositions and concentrations of the constitutive elements, in order to establish links between the effects (impaired regeneration, cellular inflammation, etc.) and the factors constituting the environment (hormones, cytokines, etc.) as well as to reveal dose-dependent effects. We believe that such approaches will allow us to elucidate obesity mechanisms, optimize animal models, and develop therapies as well as novel tissue engineering applications.

Tricking the Brain with Leptin to Limit Post Liposuction and Post Bariatric Surgery Weight Regain?

Obesity represents a medical challenge for modern therapists. The main difficulty is that once obesity is established, it is hard to reverse. It is believed that once an increased body weight/adiposity content is reached it becomes the "reference" that energy mechanisms adjust towards keeping. Thus, following a weight loss, such as following liposuction/bariatric surgery, the metabolic balance would target this "reference" that represents the previously reached body weight/adiposity content. On the other hand, medical procedures of liposuction and bariatric surgery reduce the level of the adipocytes-produced hormone leptin. This leptin level reduction leads to an increase in food intake and a decrease in energy expenditure. Therefore, the reduced leptin would be among the signals received by the brain to trigger weight regain via processes aiming to re-establish the pre-liposuction/pre-bariatric surgery body weight or adiposity content. We suggest administering leptin so that the brain does not detect the post- liposuction/post-bariatric surgery weight loss; thus, limiting the signals toward weight regain, leading to a better weight control.

Genetic Expression between Ageing and Exercise: Secreted Protein Acidic and Rich in Cysteine as a Potential "Exercise Substitute" Antiageing Therapy.

Ageing is the effect of time on biological entities. It represents a risk factor for a variety of diseases and health disorders; thus, therapeutic options are required to tackle ageing issues. Modern geriatric medicine prescribes exercise to counteract ageing effects. This work presents secreted protein acidic and rich in cysteine (SPARC) as a potential antiageing therapy. Indeed, SPARC declines with ageing, exercise induces SPARC, and SPARC overexpression in mice mimics exercise. Thus, we hypothesize that SPARC is an exercise-induced factor that is beyond-at least part of-the antiageing effects induced by exercise. This could become a potential antiageing therapy for the elderly that counteracts ageing by mimicking the effects of exercise without needing to perform exercise. This is of particular importance because ageing usually reduces mobility and age-related diseases can reduce the ability to perform the required physical activity. On the other hand, the possibilities of mimicking exercise benefits via SPARC are not limited to ageing, and can be applied in various contexts in which exercise cannot be performed because of physical disabilities, health disorders, or limited mobility.

Secreted Protein Acidic and Rich in Cysteine as an Exercise-Induced Gene: Towards Novel Molecular Therapies for Immobilization-Related Muscle Atrophy in Elderly Patients.

Long periods of immobilization, among other etiologies, would result is muscle atrophy. Exercise is the best approach to reverse this atrophy. However, the limited or the non-ability to perform the required physical activity for such patients and the limited pharmacological options make developing novel therapeutic approaches a necessity. Within this context, secreted protein acidic and rich in cysteine (SPARC) has been characterized as an exercise-induced gene. Whereas the knock-out of this gene leads to a phenotype that mimics number of the ageing-induced and sarcopenia-related changes including muscle atrophy, overexpressing SPARC in mice or adding it to muscular cell culture produces similar effects as exercise including enhanced muscle mass, strength and metabolism. Therefore, this piece of writing aims to provide evidence supporting the potential use of SPARC/SPARC as a molecular therapy for muscle atrophy in the context of immobilization especially for elderly patients.

Secreted Protein Acidic and Rich in Cysteine (Sparc) KO Leads to an Accelerated Ageing Phenotype Which Is Improved by Exercise Whereas SPARC Overexpression Mimics Exercise Effects in Mice.

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein implicated in various functions, including metabolism, tissue regeneration, and functional homeostasis. SPARC/Sparc declines with ageing but increases with exercise. We aim to verify two hypotheses: (1) SPARC deficiency leads to an ageing-like phenotype (metabolic decline, muscle loss, etc.), and (2) SPARC overexpression would mimic exercise, counteract ageing, and improve age-related changes. Our mice experiments are divided into two parts. First, we explore the consequences of Sparc knockout (KO) and compare them to the ageing effects. We also observe the effects of exercise. In the second part, we study the effects of SPARC overexpression and compare them to the exercise benefits. At the end, we make an analysis of the results to point out the analogies between Sparc KO and the ageing-like phenotype on the one hand and make comparisons between SPARC overexpression and exercise in the context of exercise counteracting ageing. The measurements were mainly related to tissue weights, adiposity, metabolism, and muscle strength. The main findings are that Sparc KO reduced glucose tolerance, muscle glucose transporter expression, and abdominal adipose tissue weight but increased glycogen content in the muscle. SPARC overexpression increased muscle strength, muscle mass, and expressions of the muscle glucose transporter and mitochondrial oxidative phosphorylation but lowered the glycemia and the adiposity, especially in males. Collectively, these findings, and the data we have previously reported, show that Sparc KO mice manifest an ageing-like phenotype, whereas SPARC overexpression and exercise generate similar benefits. The benefits are towards counteracting both the SPARC deficiency-induced ageing-like phenotype as well as reversing the age-related changes. The potential applications of these findings are to build/optimize Sparc KO-based animal models of various health conditions and, on the other hand, to develop therapies based on introducing SPARC or targeting SPARC-related pathways to mimic exercise against age-related and metabolic disorders.

Exercise, Diet and Sleeping as Regenerative Medicine Adjuvants: Obesity and Ageing as Illustrations.

Regenerative medicine uses the biological and medical knowledge on how the cells and tissue regenerate and evolve in order to develop novel therapies. Health conditions such as ageing, obesity and cancer lead to an impaired regeneration ability. Exercise, diet choices and sleeping pattern have significant impacts on regeneration biology via diverse pathways including reducing the inflammatory and oxidative components. Thus, exercise, diet and sleeping management can be optimized towards therapeutic applications in regenerative medicine. It could allow to prevent degeneration, optimize the biological regeneration and also provide adjuvants for regenerative medicine.

DNA Damage as a Mechanistic Link between Air Pollution and Obesity?

It has been shown that the risk of developing obesity, a serious modern health problem, increases with air pollution. However, the molecular links are yet to be fully elucidated. Herein, we propose a hypothesis via which air pollution-induced DNA damage would be the mechanistic link between air pollution and the enhanced risk of obesity and overweight. Indeed, whereas air pollution leads to DNA damage, DNA damage results in inflammation, oxidative stress and metabolic impairments that could be behind energy balance changes contributing to obesity. Such thoughts, worth exploring, seems an important starting point to better understand the impact of air pollution on obesity development independently from the two main energy balance pillars that are diet and physical activity. This could possibly lead to new applications both for therapies as well as for policies and regulations.

Ageing and Obesity Shared Patterns: From Molecular Pathogenesis to Epigenetics.

In modern societies, ageing and obesity represent medical challenges for healthcare professionals and caregivers. Obesity and ageing share common features including the related cellular and molecular pathways as well as the impacts they have as risk factors for a variety of diseases and health problems. Both of these health problems also share exercise and a healthy lifestyle as the best therapeutic options. Importantly, ageing and obesity also have common epigenetic changes (histone modification, DNA methylation, noncoding RNAs, and chromatin remodeling) that are also impacted by exercise. This suggests that epigenetic pathways are among the mechanisms via which exercise induces its benefits, including ageing and obesity improvements. Exploring these interrelations and based on the fact that both ageing and obesity represent risk factors for each other, would lead to optimizing the available therapeutic approaches towards improved obesity management and healthy ageing.

Diet Impact on Obesity beyond Calories and Trefoil Factor Family 2 (TFF2) as an Illustration: Metabolic Implications and Potential Applications.

Obesity is a health problem with increasing impacts on public health, economy and even social life. In order to reestablish the energy balance, obesity management focuses mainly on two pillars; exercise and diet. Beyond the contribution to the caloric intake, the diet nutrients and composition govern a variety of properties. This includes the energy balance-independent properties and the indirect metabolic effects. Whereas the energy balance-independent properties are close to "pharmacological" effects and include effects such as antioxidant and anti-inflammatory, the indirect metabolic effects represent the contribution a diet can have on energy metabolism beyond the caloric contribution itself, which include the food intake control and metabolic changes. As an illustration, we also described the metabolic implication and hypothetical pathways of the high-fat diet-induced gene Trefoil Factor Family 2. The properties the diet has can have a variety of applications mainly in pharmacology and nutrition and further explore the "pharmacologically" active food towards potential therapeutic applications.

Post-Coronavirus Disease-2019 (COVID-19): Toward a Severe Multi-Level Health Crisis?

There were already numerous challenges facing the healthcare system prior to the ongoing coronavirus disease-2019 (COVID-19) pandemic. Although we look forward to ending this pandemic, it is still expected that the healthcare system will face further challenges leading to a multi-level health crisis. Indeed, after the COVID-19 pandemic, there will still be COVID-19 active cases and those left with health problems following COVID-19 infection who will be of a particular impact. In addition, we also have the health problems that either emerged or worsened during COVID-19, especially with the reduced ability of the healthcare system to take care of many non COVID-19 patients during the COVID-19 pandemic. Such expected evolution of the situation highlights the necessity for the decision-makers to consider applying serious reforms and take quick measures to prevent a post-COVID-19 health crisis.

Measuring Exercise-Induced Secreted Protein Acidic and Rich in Cysteine Expression as a Molecular Tool to Optimize Personalized Medicine.

The numerous exercise benefits for health as well as applications for diseases has lead to exercise being prescribed in many pathological conditions. Secreted protein acidic and rich in cysteine (SPARC) gene expression is stimulated by exercise and SPARC has been suggested as a molecular mediator of exercise. Therefore, we suggest using this property for personalized medicine. This can be achieved by prescribing the exercise with a pattern (duration, intensity, etc.) that corresponds to the optimum SPARC/Sparc expression. We expect this approach to optimize the exercise therapy in both the preventive and curative contexts. In the research field, measuring exercise -dependent expression of Sparc would represent a molecular tool to further optimize the selection of exercise animal models as well.

Secreted Protein Acidic and Rich in Cysteine as a Molecular Physiological and Pathological Biomarker.

Secreted protein acidic and rich in cysteine (SPARC) is expressed in diverse tissues and plays roles in various biological functions and processes. Increased serum levels of SPARC or its gene overexpression have been reported following numerous physiological and pathological changes including injuries, exercise, regeneration, obesity, cancer, and inflammation. Such expression pattern interrelation between these biological changes and the SPARC expression/secretion points to it as a biomarker. This property could lead to a variety of potential applications ranging from mechanistic studies and animal model validation to the clinical and therapeutic evaluation of both disease prognosis and pharmacological agents.

Trefoil Factor Family Member 2 Expression as an Indicator of the Severity of the High-Fat Diet-Induced Obesity.

Trefoil Factor Family Member 2 (TFF2) belongs to TFF family peptides that includes TFF1, TFF2, TFF3. TFF2 is mainly known for its roles in the mucosal protection. In the context of obesity and high fat diet (HFD), Tff2 has been characterized as a HFD-induced gene. The knock-out of Tff2 in mice lead to the protection from HFD-induced obesity with a metabolic profile towards a negative energy balance. Such HFD-specific expression gives Tff2 a pattern worth exploring in biomedical research. Indeed, measuring TFF2/TFF2/Tff2 expression in biological samples following the ingestion of high-fat diet reflects the biological "responsiveness" to the lipids ingestion and would reflect the severity of obesity establishment afterwards. Such property could be explored for instance to screen animal models, evaluate the predisposition to HFD-induced obesity as well as in biomedical and clinical applications. Results might advance obesity research especially in terms of understanding lipid-induced signals, appetite control and adiposity storage.

Impact of Adiposity and Fat Distribution, Rather Than Obesity, on Antibodies as an Illustration of Weight-Loss-Independent Exercise Benefits.

Obesity represents a risk factor for a variety of diseases because of its inflammatory component, among other biological patterns. Recently, with the ongoing COVID-19 crisis, a special focus has been put on obesity as a status in which antibody production, among other immune functions, is impaired, which would impact both disease pathogenesis and vaccine efficacy. Within this piece of writing, we illustrate that such patterns would be due to the increased adiposity and fat distribution pattern rather than obesity (as defined by the body mass index) itself. Within this context, we also highlight the importance of the weight-loss-independent effects of exercise.

Coronavirus Disease 2019 (COVID-19) Crisis Measures: Health Protective Properties?

The ongoing 2019 coronavirus disease (COVID-19) crisis has led governments to impose measures including mask wearing, physical distancing, and increased hygiene and disinfection, combined with home confinement and economic shutdown. Such measures have heavy negative consequences both on public health and the economy. However, these same measures have positive outcomes as "side effects" that are worth mentioning since they contribute to the improvement of some aspects of the population health. For instance, mask wearing helps to reduce allergies as well as the transmission of other airborne disease-causing pathogens. Physical distancing and social contact limitation help limit the spread of communicable diseases, and economic shutdown can reduce pollution and the health problems related to it. Decision makers could get inspired by these positive "side effects" to tackle and prevent diseases like allergies, infectious diseases and noncommunicable diseases, and improve health care and pathology management. Indeed, the effectiveness of such measures in tackling certain health problems encourages inspiration from COVID-19 measures towards managing selected health problems. However, with the massive damage COVID-19-related measures have caused to countries' economies and people's lives, the question of how to balance the advantages and disadvantages of these measures in order to further optimize them needs to be debated among health care professionals and decision makers.

Trefoil Factor Family Member 2: From a High-Fat-Induced Gene to a Potential Obesity Therapy Target.

Obesity has its epidemiological patterns continuously increasing. With controlling both diet and exercise being the main approaches to manage the energy metabolism balance, a high-fat (HF) diet is of particular importance. Indeed, lipids have a low satiety potential but a high caloric density. Thus, focusing on pharmacologically targetable pathways remains an approach with promising therapeutic potential. Within this context, trefoil factor family member 2 (Tff2) has been characterized as specifically induced by HF diet rather than low-fat diet. TFF2 has also been linked to diverse neurological mechanisms and metabolic patterns suggesting its role in energy balance. The hypothesis is that TFF2 would be a HF diet-induced signal that regulates metabolism with a focus on lipids. Within this review, we put the spotlight on key findings highlighting this line of thought. Importantly, the hypothetical mechanisms pointed highlight TFF2 as an important contributor to obesity development via increasing lipids intestinal absorption and anabolism. Therefore, an outlook for future experimental activities and evaluation of the therapeutic potential of TFF2 inhibition is given. Indeed, its knockdown or downregulation would contribute to an antiobesity phenotype. We believe this work represents an addition to our understanding of the lipidic molecular implications in obesity, which will contribute to develop therapies aiming to manage the lipidic metabolic pathways including the absorption, storage and metabolism via targeting TFF2-related pathways. We briefly discuss important relevant concepts for both basic and clinical researchers.

Coronavirus Disease 2019 (COVID-19) Crisis: Losing Our Immunity When We Need It the Most.

The ongoing coronavirus disease 2019 (COVID-19) crisis has led to a new socioeconomic reality with the acquisition of novel habits. Measures imposed by governments and health authorities such as confinement and lockdown have had important consequences, including mental health problems, economic crisis, and social isolation. Combined with newly acquired habits such as hand washing, sanitization, and face masks, these have all directly and indirectly led to reduced immunity. Such effects on the immune system not only impact the epidemiological profile with respect to COVID-19 and other infectious diseases but also limit the efficacy of the ongoing anti-COVID-19 vaccination campaign. Therefore, there is a need to review these approaches and optimize measures towards better population immunity, which is much needed during such an epidemic.