Despite recent advances in targeted cancer therapies, drug resistance remains an important setback in tumor control. Understanding the complex mechanisms involved in both innate and acquired drug resistance represents the first step in discovering novel therapeutic agents. Because of its importance in tumorigenesis, progression, and metastasis, lipid metabolism is increasingly garnering attention. CD36 is a membrane receptor at the top of the signaling cascade that transports lipids. Its expression has been repeatedly presented as an unfavorable prognostic factor for various tumor types, raising the question: could CD36 be a critical factor in cancer treatment resistance? In our review, we set out to explore the most prominent studies on the implication of CD36 in resistance to platinum-based drugs and other adjuvant cancer therapies in solid and haematological neoplasia. Moreover, we provide an overview of the latest anti-CD36 cancer therapies, thus opening new perspectives for future personalized medicine.

Parkinson’s Disease (PD) is a prevalent and escalating neurodegenerative disorder with significant societal implications. Despite being considered a proteinopathy, in which the aggregation of α-synuclein is the main pathological change, the intricacies of PD initiation remain elusive. Recent evidence suggests a potential link between gut microbiota and PD initiation, emphasizing the need to explore the effects of microbiota-derived molecules on neuronal cells. In this study, we exposed dopaminergic-differentiated SH-SY5Y cells to microbial molecules such as lipopolysaccharide (LPS), rhamnolipid, curli CsgA and phenol soluble modulin α-1 (PSMα1). We assessed cellular viability, cytotoxicity, growth curves and α-synuclein levels by performing MTS, LDH, real-time impedance readings, qRT-PCR and Western Blot assays respectively. Statistical analysis revealed that rhamnolipid exhibited concentration-dependent effects, reducing viability and inducing cytotoxicity at higher concentrations, increasing α-synuclein mRNA and protein levels with negative effects on cell morphology and adhesion. Furthermore, LPS exposure also increased α-synuclein levels. Curli CsgA and PSMα-1 showed minimal or no changes. Our findings suggest that microbiota-derived molecules, particularly rhamnolipid and LPS, impact dopaminergic neurons by increasing α-synuclein levels. This study highlights the potential involvement of gut microbiota in initiating the upregulation of α-synuclein that may further initiate PD, indicating the complex interplay between microbiota and neuronal cells.

For more than 40 years, autologous platelet concentrates have been used in clinical medicine. Since the first formula used, namely platelet-rich plasma (PRP), other platelet concentrates have been experimented with, including platelet-rich fibrin and concentrated growth factor. Platelet concentrates have three standard characteristics: they act as scaffolds, they serve as a source of growth factors and cytokines, and they contain live cells. PRP has become extensively used in regenerative medicine for the successful treatment of a variety of clinical (non-)dermatological conditions like alopecies, acne scars, skin burns, skin ulcers, muscle, cartilage, and bone repair, and as an adjuvant in post-surgery wound healing, with obvious benefits in terms of functionality and aesthetic recovery of affected tissues/organs. These indications were well documented, and a large amount of evidence has already been published supporting the efficacy of this method. The primordial principle behind minimally invasive PRP treatments is the usage of the patient’s own platelets. The benefits of the autologous transplantation of thrombocytes are significant, representing a fast and economic method that requires only basic equipment and training, and it is biocompatible, thus being a low risk for the patient (infection and immunological reactions can be virtually disregarded). Usually, the structural benefits of applying PRP are attributed to fibroblasts only, as they are considered the most numerous cell population within the interstitium. However, this apparent simplistic explanation is still eluding those different types of interstitial cells (distinct from fibroblasts) that are residing within stromal tissue, e.g., telocytes (TCs). Moreover, dermal TCs have an already documented potential in angiogenesis (extra-cutaneous, but also within skin), and their implication in skin recovery in a few dermatological conditions was attested and described ultrastructurally and immunophenotypically. Interestingly, PRP biochemically consists of a series of growth factors, cytokines, and other molecules, to which TCs have also proven to have a positive expression. Thus, it is attractive to hypothesize and to document any tissular collaboration between cutaneous administered PRP and local dermal TCs in skin recovery/repair/regeneration. Therefore, TCs could be perceived as the missing link necessary to provide a solid explanation of the good results achieved by administering PRP in skin-repairing processes.

Muscular dystrophies (MDs) are a complex group of rare neuromuscular disorders caused by genetic mutations that progressively weaken the muscles, resulting in an increasing level of disability. The underlying cause of these conditions consists of mutations in the genes in charge of a person’s muscle composition and functionality. MD has no cure, but medications and therapy can help control symptoms and slow the disease’s progression. Effective treatments have yet to be developed, despite the identification of the genetic origins and a thorough knowledge of the pathophysiological alterations that these illnesses induce. In this scenario, there is an urgent need for novel therapeutic options for these severe illnesses, and drug repositioning might be one feasible answer. In other words, drug repositioning/repurposing is an accelerated method of developing novel pharmaceuticals since the new indication is based on previously accessible safety, pharmacokinetic, and manufacturing data. This is particularly crucial for individuals with life-threatening illnesses such as MDs, who cannot wait for a conventional medication development cycle. This chapter aims to review the challenges and opportunities of drug-repositioning in a variety of MDs to establish novel treatment approaches for these incurable diseases.

Muscular dystrophies (MDs) are a complex group of rare neuromuscular disorders caused by genetic mutations that progressively weaken the muscles, resulting in an increasing level of disability. The underlying cause of these conditions consists of mutations in the genes in charge of a person’s muscle composition and functionality. MD has no cure, but medications and therapy can help control symptoms and slow the disease’s progression. Effective treatments have yet to be developed, despite the identification of the genetic origins and a thorough knowledge of the pathophysiological alterations that these illnesses induce. In this scenario, there is an urgent need for novel therapeutic options for these severe illnesses, and drug repositioning might be one feasible answer. In other words, drug repositioning/repurposing is an accelerated method of developing novel pharmaceuticals since the new indication is based on previously accessible safety, pharmacokinetic, and manufacturing data. This is particularly crucial for individuals with life-threatening illnesses such as MDs, who cannot wait for a conventional medication development cycle. This chapter aims to review the challenges and opportunities of drug-repositioning in a variety of MDs to establish novel treatment approaches for these incurable diseases.

The skin's recognised functions may undergo physiological alterations due to ageing, manifesting as varying degrees of facial wrinkles, diminished tautness, density, and volume. Additionally, these functions can be disrupted (patho)physiologically through various physical and chemical injuries, including surgical trauma, accidents, or chronic conditions like ulcers associated with diabetes mellitus, venous insufficiency, or obesity. Advancements in therapeutic interventions that boost the skin's innate regenerative abilities could significantly enhance patient care protocols. The application of Platelet-Rich Plasma (PRP) is widely recognized for its aesthetic and functional benefits to the skin. Yet, the endorsement of PRP's advantages often borders on the dogmatic, with its efficacy commonly ascribed solely to the activation of fibroblasts by the factors contained within platelet granules. PRP therapy is a cornerstone of regenerative medicine which involves the autologous delivery of conditioned plasma enriched by platelets. This is achieved by centrifugation, removing erythrocytes while retaining platelets and their granules. Despite its widespread use, the precise sequences of cellular activation, the specific cellular players, and the molecular machinery that drive PRP-facilitated healing are still enigmatic. There is still a paucity of definitive and robust studies elucidating these mechanisms. In recent years, telocytes (TCs)-a unique dermal cell population-have shown promising potential for tissue regeneration in various organs, including the dermis. TCs' participation in neo-angiogenesis, akin to that attributed to PRP, and their role in tissue remodelling and repair processes within the interstitia of several organs (including the dermis), offer intriguing insights. Their potential to contribute to, or possibly orchestrate, the skin regeneration process following PRP treatment has elicited considerable interest. Therefore, pursuing a comprehensive understanding of the cellular and molecular mechanisms at work, particularly those involving TCs, their temporal involvement in structural recovery following injury, and the interconnected biological events in skin wound healing and regeneration represents a compelling field of study.

The SH-SY5Y cell line is a simple and inexpensive in vitro experimental model for studying Parkinson disease (PD). This experimental model is a useful tool for elucidating pathophysiological mechanisms of PD and in the development of new pharmacological therapies. In this review, we aim to summarize current protocols for SH-SY5Y cell culturing and differentiation and PD experimental designs derived from the SH-SY5Y cell line. The most efficient protocol for differentiation of the SH-SY5Y cell line into dopaminergic neurons seems to be the addition of retinoic acid to the growth medium, followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) addition in a low concentration of fetal bovine serum. PD pathological changes, such as neuronal apoptosis and the intraneuronal alpha-synuclein aggregation, can be reproduced in the SH-SY5Y cell line either by the use of neurotoxic agents [such as rotenone, 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine] or by genetic modification (transfection of the alpha-synuclein wild-type or mutant gene, genetic manipulation of other genes involved in PD). In addition, compounds with a potential neuroprotective role may be tested on neurotoxicity-induced SH-SY5Y models. The cell line can also be used for testing PD pathophysiological mechanisms such as the prion-like neuronal transmission of alpha-synuclein or the microbiota influence in PD. In conclusion, the use of the SH-SY5Y cell line represents a basic but consistent first step in experiments related to PD, but which must be followed by the confirmation of the results through more complex in vitro and in vivo experimental models.

Fifteen years after their discovery, telocytes (TCs) are yet perceived as a new stromal cell type. Their presence was initially documented peri-digestively, and gradually throughout the interstitia of many (non-)cavitary mammalian, human, and avian organs, including skin. Each time, TCs proved to be involved in diverse spatial relations with elements of interstitial (ultra)structure (blood vessels, nerves, immune cells, etc.). To date, transmission electron microscopy (TEM) remained the single main microscopic technique able to correctly and certainly attest TCs by their well-acknowledged (ultra)structure. In skin, dermal TCs reiterate almost all (ultra)structural features ascribed to TCs in other locations, with apparent direct implications in skin physiology and/or pathology. TCs' uneven distribution within skin, mainly located in stem cell niches, suggests involvement in either skin homeostasis or dermatological pathologies. On the other hand, different skin diseases involve different patterns of disruption of TCs' structure and ultrastructure. TCs' cellular cooperation with other interstitial elements, their immunological profile, and their changes during remission of diseases suggest their role(s) in tissue regeneration/repair processes. Thus, expanding the knowledge on dermal TCs could offer new insights into the natural skin capacity of self-repairing. Moreover, it would become attractive to consider that augmenting dermal TCs' presence/density could become an attractive therapeutic alternative for treating various skin defects.

The reprogramming of lipid metabolism has been highlighted in colorectal cancer (CRC) studies, suggesting a critical role for the scavenger receptor CD36 and fatty acid synthase (FASN) in this malignancy. In this study, we analyzed the gene expression levels of CD36, FASN, the cell surface glypican 4 (GPC4), and the two transporters SLC27A3 and SLC27A4 in 39 paired tumoral and peritumoral tissues from patients with CRC compared with 18 normal colonic mucosae. Moreover, the levels of seven miRNAs targeting CD36 and most of the analyzed genes were evaluated. We found a significant impairment of the expression of all the analyzed genes except GPC4 as well as the differential expression of miR-16-5p, miR-26b-5p, miR-107, miR-195-5p, and miR-27a-3p in the colonic mucosa of CRC patients. Interestingly, CD36 and miR-27a-3p were downregulated and upregulated, respectively, in tumoral tissues compared to peritumoral and control tissues, with a significant negative correlation in the group of patients developing lymph node metastasis. Our results sustain the relationship between CRC and fatty acid metabolism and emphasize the importance of related miRNAs in developing new therapeutic strategies.

In aged muscle, satellite cells’ symmetric and asymmetric divisions are impaired, and intrinsic and extrinsic complex mechanisms govern these processes. This review presents many updated aspects regarding muscle stem cells’ fate in normal and aging conditions. The balance between self-renewal and commitment divisions contributes to muscle regeneration, muscle homeostasis, aging, and disease. Stimulating muscle regeneration in aging could be a therapeutic target, but there is still a need to understand the many mechanisms that influence each other in satellite cells and their niche. We highlight here the general outlines regarding satellite cell divisions, the primary markers present in muscle stem cells, the aging aspects concerning signaling pathways involved in symmetric/asymmetric divisions, the regenerative capacity of satellite cells and their niche alteration in senescent muscle, genetics and epigenetics mechanisms implied in satellite cells aging and exercise effect on muscle regeneration in the elderly.

The metastatic potential does not rely on the accumulation of new driver mutations by the cancer cells. Metastasis inception depends on the metabolic reprogramming of the metastasis-initiating cells (MICs), thus making it the limiting factor in the process of colonization of distant locations with different tissue environments, oxygen, and nutrient availabilities. Recent studies showed that the most significant correlation with cancer progression and prognosis in metastatic tumors is an increased copy number alterations and expression profile for the genes responsible for fatty acid uptake and metabolism, thus showing distinctive lipid metabolism starting with lipid uptake, fatty acid beta-oxidation, lipid biosynthesis, and storage. Fatty acid translocase/CD36 is the most prominent lipid transporter expressed by MICs. Its expression has been reported to be correlated with an increased metastatic potential and a poor prognosis in some tumors. Targeting various sides of the lipid metabolism appears to be a promising therapeutic in preventing metastatic dissemination and tumor growth.

Background: Anesthetic preconditioning (AP) is known to mimic ischemic preconditioning. The purpose of this study was to investigate the effects of an interrupted sevoflurane administration protocol on myocardial ischemia/reperfusion (I/R) injury. Methods: Male Wistar rats (n = 60) were ventilated for 30 min with room air (control group, CG) or with a mixture of air and sevoflurane (1 minimum alveolar concentration—MAC) in 5-min cycles, alternating with 5-min wash-out periods (preconditioned groups). Cytokines implicated in the AP response were measured. An (I/R) lesion was produced immediately after the sham intervention (CG) and preconditioning protocol (early AP group, EAPG) or 24 h after the intervention (late AP group, LAPG). The area of fibrosis, the degree of apoptosis and the number of c-kit+ cells was estimated for each group. Results: Cytokine levels were increased post AP. The area of fibrosis decreased in both EAPG and LAPG compared to the CG (p < 0.0001). When compared to the CG, the degree of apoptosis was reduced in both LAPG (p = 0.006) and EAPG (p = 0.007) and the number of c-kit+ cells was the greatest for the LAPG (p < 0.0001). Conclusions: Sevoflurane preconditioning, using an interrupted anesthesia protocol, is efficient in myocardial protection and could be beneficial to reduce perioperative or periprocedural ischemia in patients with increased cardiovascular risk.

Although they are considered rare disorders, muscular dystrophies have a strong impact on people’s health. Increased disease severity with age, frequently accompanied by the loss of ability to walk in some people, and the lack of treatment, have directed the researchers towards the development of more effective therapeutic strategies aimed to improve the quality of life and life expectancy, slow down the progression, and delay the onset or convert a severe phenotype into a milder one. Improved understanding of the complex pathology of these diseases together with the tremendous advances in molecular biology technologies has led to personalized therapeutic procedures. Different approaches that are currently under extensive investigation require more efficient, sensitive, and less invasive methods. Due to its remarkable analytical sensitivity, droplet digital PCR has become a promising tool for accurate measurement of biomarkers that monitor disease progression and quantification of various therapeutic efficiency and can be considered a tool for non-invasive prenatal diagnosis and newborn screening. Here, we summarize the recent applications of droplet digital PCR in muscular dystrophy research and discuss the factors that should be considered to get the best performance with this technology.

Molecular diagnostics for the detection and characterization of genetic variants is based in the majority of cases on PCR technology. Since the primers and probes are designed according to the nucleotide sequence of the DNA region for the specific mutation, PCR technology can only be applied if the mutation is well known. In cases where the mutated region of a gene may have variable sequences, different between patients, a set of primers for each sequence variant is necessary, which involves a large volume of work. The nucleophosmin (NPM1) gene mutation is also included in this category where more than 24 variants of the gene are known of which 6 are more common. The aim of our study was to establish a qPCR assay and a molecular kit (a set of primers) for detection and quantification of NPM1 gene mutations regardless of its sequence by using RNase H-dependent PCR (rhPCR). Several sets of rh-primers that show point mismatches in relation to some mutations have been designated and tested. The rh-primers carried a removable PCR blocker at the 3′ end. Only after the removal of this blocker by the RNaseH2 enzyme, the primers are expandable by DNA polymerase. qPCR was used to determine the extent to which the presence of these sequence mismatches could affect the H2-endonuclease activity of ribose digestion and PCR activation. The evaluation was carried out in a preclinical context, using synthetic fragments of NPM1 carrying mutations (AML mutation type A, B, D, I, K). After establishing the optimal combination for the primer sets as well as the reaction conditions, the sensitivity limit was tested in samples with the number of target copies that varied decreasingly: 1000000, 100000, 10000, 1000, 100, 10. It was observed that regardless of the nature of the mutation, the same set of primers can detect 10 copies of mutant NPM1. The main advantage of this assay is that different sequence-variable NPM1 mutations can be detected and quantified with high specificity through a single rhPCR reaction. It is no longer necessary to design, synthesize and optimize primers and probes for each individual mutation. Our study demonstrates the potential use of rhPCR for monitoring patients with AML for minimum residual disease and recurrence risk.

Macrophages (MCs) are present in all tissues, not only supporting homeostasis, but also playing an important role in organogenesis, post-injury regeneration, and diseases. They are a heterogeneous cell population due to their origin, tissue specificity, and polarization in response to aggression factors, depending on environmental cues. Thus, as pro-inflammatory M1 phagocytic MCs, they contribute to tissue damage and even fibrosis, but the anti-inflammatory M2 phenotype participates in repairing processes and wound healing through a molecular interplay with most cells in adult stem cell niches. In this review, we emphasize MC phenotypic heterogeneity in health and disease, highlighting their systemic and systematic contribution to tissue homeostasis and repair. Unraveling the intervention of both resident and migrated MCs on the behavior of stem cells and the regulation of the stem cell niche is crucial for opening new perspectives for novel therapeutic strategies in different diseases.

Past decades demonstrate an increasing interest in herbal remedies in the public eye, with as many as 80% of people worldwide using these remedies as healthcare products, including those for skin health. Sea buckthorn and its derived products (oil; alcoholic extracts), rich in flavonoids and essential fatty acids, are among these healthcare products. Specifically, sea buckthorn and its derivatives are reported to have antioxidant and antitumor activity in dysplastic skin cells. On the other hand, evidence suggests that the alteration of lipid metabolism is related to increased malignant behavior. Given the paradoxical involvement of lipids in health and disease, we investigated how sea-buckthorn seed oil, rich in long-chain fatty acids, modifies the proliferation of normal and dysplastic skin cells in basal conditions, as well as under ultraviolet A (UVA) radiation. Using real-time analysis of normal and dysplastic human keratinocytes, we showed that sea-buckthorn seed oil stimulated the proliferation of dysplastic cells, while it also impaired the ability of both normal and dysplastic cells to migrate over a denuded area. Furthermore, UVA exposure increased the expression of CD36/SR-B2, a long-chain fatty acid translocator that is related to the metastatic behavior of tumor cells.

An increasing number of studies provide evidence for the existence of a microbiota-gut-brain axis and its potential involvement in the development of sporadic Parkinson's disease and other neurodegenerative conditions. The neuropathologic hallmark of Parkinson's disease is the presence of brain intraneuronal aggregates of misfolded alpha-synuclein, known as Lewy bodies. Some gut microbiota products may trigger alpha-synuclein conformational changes in the neurons of the enteric nervous system, which can then spread to the brain in a prion-like fashion through the vagus nerve. Others may interfere with neuroinflammatory pathways and susceptibility to neurodegeneration. In this review, we assess the potential role of putative gut microbiota products in the etiopathogeny of Parkinson's disease, with a special emphasis on functional bacterial amyloid proteins, bacterial biosurfactants, endotoxins and short-chain fatty acids. The possible roles of molecular hydrogen, a common byproduct of bacterial fermentation, are also addressed.