Obesity and Bone Mineral Density Protection Paradox in Chronic Kidney Disease: Secreted Protein Acidic and Rich in Cysteine as a Piece of the Puzzle?

Obesity is a health condition that represents a risk factor for numerous diseases and complications. However, obesity might also have-to some extent-some "benefits" in certain situations. This includes potential bone protection in patients suffering from chronic kidney disease. In an attempt to explain such a paradox, we highlight secreted protein acidic and rich in cysteine (SPARC) as a hypothetical mediator of this protection. Indeed, SPARC properties provide a logical rationale to describe such bone protection via its overexpression combined with its calcium-binding and collagen-binding properties. We believe that exploring such hypotheses could open new doors to elucidate unknown pathways towards developing a new generation of molecular therapies.

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.

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.

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.

Cellulases: From Bioactivity to a Variety of Industrial Applications.

Utilization of microbial enzymes has been widely reported for centuries, but the commercial use of enzymes has been recently adopted. Particularly, cellulases have been utilized in various commercial sectors including agriculture, brewing, laundry, pulp and paper and textile industry. Cellulases of microbial origin have shown their potential application in various commercial sectors including textile, pulp and paper, laundry, brewing, agriculture and biofuel. Cellulases have diversified applications in the food industry, food service, food supply and its preservation. Indeed, cellulases can tenderize fruits, clarify the fruit juices, reduce roughage in dough, hydrolyze the roasted coffee, extract tea polyphenols and essential oils from olives and can increase aroma and taste in food items. However, their role in food industries has by and large remained neglected. The use of immobilized cellulases has further expanded their application in fruit and vegetable processing as it potentiates the catalytic power and reduces the cost of process. Technological and scientific developments will further expand their potential usage in the food industry.

Secreted Protein Acidic and Rich in Cysteine as A Regeneration Factor: Beyond the Tissue Repair.

Diverse pathologies (inflammation, tissues injuries, cancer, etc.) and physiological conditions (obesity, physical activity, etc.) induce the expression/secretion of the matricellular protein, secrete protein acidic and rich in cysteine (SPARC). SPARC contributes to the creation of an environment that is suitable for tissue regeneration through a variety of roles, including metabolic homeostasis, inflammation reduction, extracellular matrix remodeling and collagen maturation. Such a homeostatic environment optimizes tissue regeneration and improves tissues' repair ability. These properties that SPARC has within the regeneration contexts could have a variety of applications, such as in obesity, cancer, sarcopenia, diabetes and bioengineering.

Regeneration during Obesity: An Impaired Homeostasis.

Obesity is a health problem that, in addition to the known morbidities, induces the generation of a biological environment with negative impacts on regeneration. Indeed, factors like DNA damages, oxidative stress and inflammation would impair the stem cell functions, in addition to some metabolic and development patterns. At the cellular and tissulaire levels, this has consequences on growth, renewal and restoration which results into an impaired regeneration. This impaired homeostasis concerns also key metabolic tissues including muscles and liver which would worsen the energy balance outcome towards further development of obesity. Such impacts of obesity on regeneration shows the need of a specific care given to obese patients recovering from diseases or conditions requiring regeneration such as burns, radiotherapy and leukemia. On the other hand, since stem cells are suggested to manage obesity, this impaired regeneration homeostasis needs to be considered towards more optimized stem cells-based obesity therapies within the context of precision medicine.

Secreted protein acidic and rich in cysteine and bioenergetics: Extracellular matrix, adipocytes remodeling and skeletal muscle metabolism.

The extracellular matrix (ECM) remodeling plays important roles in both adipocytes shape/expansion remodeling and the skeletal muscle (SM) metabolism. Secreted protein acidic and rich in cysteine (SPARC) is expressed in divers tissues including adipose tissue (AT) and SM where it impacts a variety of remodeling as well as metabolic functions. SPARC, also known as osteonectin or BM-40, is a glycoprotein associated with the ECM. Numerous researches attempted to elucidate the implications of SPARC in these two key metabolic tissues under different conditions. Whereas SPARC deficiency tends to shape the remodeling of the adipocytes and the fat distribution, this deficiency decreases SM metabolic properties. On the other hand, SPARC seems to be an enhancer of the metabolism and a mediator of the exercise-induced adaptation in the SM and as well as an adipogenesis inhibitor. Some findings about the SPARC effects on AT and SM seem "contradictory" in terms of tissue development and energy profile therefore highlighting the mechanistic role of SPARC in both is a priority. Yet, within this review, we expose selected researches and compare the results. We conclude with explanations to "reconcile" the different observations, hypothesize the feedback and regulatory character of SPARC and put its roles within the energetic and structural maps of both adipocytes and myocytes in homeostasis and in situations such as obesity or exercise. These properties explain the modifications and the remodeling seen in AT and SM undergoing adaptive changes (obesity, exercise, etc.) and represent a starting point for precise therapeutic targeting of SPARC-related pathways is conditions such as obesity, sarcopenia and diabetes.

Interleukin-6 as a "metabolic hormone".

Interleukin 6 (IL-6) is a cytokine that is involved in divers immune responses and implicated in a number of diseases. However, this cytokine has other non-immune functions. Within this review, we highlight selected effects on metabolic pathways, which are mediated, controlled or modified by the IL-6. Importantly, putting spotlight on such concepts could allow us to classify IL-6 among the metabolic hormones and further study it to both deepen our knowledge on disorders involving metabolic or energy imbalances such as obesity and develop novel therapeutic strategies. Furthermore, potential explanations related to IL-6 roles in both physiology and pathology as well as relevant implications and applications on both research and therapeutic fields are also pointed as consequences of the involvement of IL-6 in the energy and metabolic homeostasis via its "endocrine" roles.

Neurons Differentiated from Transplanted Stem Cells Respond Functionally to Acoustic Stimuli in the Awake Monkey Brain.

Here, we examine whether neurons differentiated from transplanted stem cells can integrate into the host neural network and function in awake animals, a goal of transplanted stem cell therapy in the brain. We have developed a technique in which a small "hole" is created in the inferior colliculus (IC) of rhesus monkeys, then stem cells are transplanted in situ to allow for investigation of their integration into the auditory neural network. We found that some transplanted cells differentiated into mature neurons and formed synaptic input/output connections with the host neurons. In addition, c-Fos expression increased significantly in the cells after acoustic stimulation, and multichannel recordings indicated IC specific tuning activities in response to auditory stimulation. These results suggest that the transplanted cells have the potential to functionally integrate into the host neural network.