Modifications in the microbiota caused by environmental and genetic reasons can unbalance the intestinal homeostasis, deregulating the host’s metabolism and immune system, intensifying the risk factors for the development and aggravation of non-alcoholic fat liver disease (NAFLD). The use of probiotics, prebiotics and synbiotics have been considered a potential and promising strategy to regulate the gut microbiota and produce beneficial effects in patients with liver conditions. For this reason, this review aimed to evaluate the effectiveness of probiotics, prebiotics, and symbiotics in patients with NAFLD and NASH. Pubmed, Embase, and Cochrane databases were consulted, and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. The clinical trials used in this study demonstrated that gut microbiota interventions could improve a wide range of markers of inflammation, glycemia, insulin resistance, dyslipidemia, obesity, liver injury (decrease of hepatic enzymes and steatosis and fibrosis). Although microbiota modulators do not play a healing role, they can work as an important adjunct therapy in pathological processes involving NAFLD and its spectrums, either by improving the intestinal barrier or by preventing the formation of toxic metabolites for the liver or by acting on the immune system.

Flavonoids are natural phytochemicals that have therapeutic effects and act in the prevention of several pathologies. These phytochemicals can be found in seeds, grains, tea, coffee, wine, chocolate, cocoa, vegetables and, mainly, in citrus fruits. Neohesperidin, hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory and antioxidant potential. Neohesperidin, in the form of neohesperidin dihydrochalcone (NHDC), also has dietary properties as a sweetener. In general, these flavanones have been investigated as a strategy to control bone diseases, such as osteoporosis and osteoarthritis. In this literature review, we compiled studies that investigated the effects of neohesperidin, hesperidin and its aglycone, hesperetin, on bone health. In vitro studies showed that these flavanones exerted an antiosteoclastic and anti- inflammatory effects, inhibiting the expression of osteoclastic markers and reducing the levels of reactive oxygen species, proinflammatory cytokines and matrix metalloproteinase levels. Similarly, such studies favored the osteogenic potential of preosteoblastic cells and induced the overexpression of osteogenic markers. In vivo, these flavanones favored the regeneration of bone defects and minimized inflammation in arthritis- and periodontitis-induced models. Additionally, they exerted a significant anticatabolic effect in ovariectomy models, reducing trabecular bone loss and increasing bone mineral density. Although research should advance to the clinical field, these flavanones may have therapeutic potential for controlling the progression of metabolic, autoimmune or inflammatory bone diseases.

Quercetin is a dietary flavonoid present in vegetables, fruits, and beverages, such as onions, apples, broccoli, berries, citrus fruits, tea, and red wine. Flavonoids have antioxidant and anti-inflammatory effects, acting in the prevention of several diseases. Quercetin also has neuroprotective properties and may exert a beneficial effect on nervous tissue. In this literature review, we compiled in vivo studies that investigated the effect of quercetin on regeneration and functional recovery of the central and peripheral nervous system. In spinal cord injuries (SCI), quercetin administration favored axonal regeneration and recovery of locomotor capacity, significantly improving electrophysiological parameters. Quercetin reduced edema, neutrophil infiltration, cystic cavity formation, reactive oxygen species production, and pro-inflammatory cytokine synthesis, while favoring an increase in levels of anti-inflammatory cytokines, minimizing tissue damage in SCI models. In addition, the association of quercetin with mesenchymal stromal cells transplantation had a synergistic neuroprotective effect on spinal cord injury. Similarly, in sciatic nerve injuries, quercetin favored and accelerated sensory and motor recovery, reducing muscle atrophy. In these models, quercetin significantly inhibited oxidative stress and cell apoptosis, favoring Schwann cell proliferation and nerve fiber remyelination, thus promoting a significant increase in the number and diameter of myelinated fibers. Although there is still a lack of clinical research, in vivo studies have shown that quercetin contributed to the recovery of neurological functions, exerting a beneficial effect on the regeneration of the central and peripheral nervous system.

Background/Objectives: Major depressive disorder (MDD) is a major global health concern that is intimately linked to neuroinflammation, oxidative stress, mitochondrial dysfunction, and complicated metabolic abnormalities. Traditional antidepressants frequently fall short, highlighting the urgent need for new, safer, and more acceptable therapeutic techniques. Phytochemicals, i.e., natural antidepressants derived from plants, are emerging as powerful plant-based therapies capable of targeting many pathogenic pathways at the same time. Summary: This narrative review synthesizes evidence from preclinical and clinical studies on the efficacy of phytochemicals such as curcumin, polyphenols, flavonoids, and alkaloids in lowering depressed symptoms. Consistent data show that these substances have neuroprotective, anti-inflammatory, and antioxidant properties, altering neuroimmune interactions, reducing oxidative damage, and improving mitochondrial resilience. Particularly, polyphenols and flavonoids have great therapeutic potential because of their capacity to penetrate the blood–brain barrier, inhibit cytokine activity, and encourage neuroplasticity mediated by brain-derived neurotrophic factor (BDNF). Despite promising results, the heterogeneity in study designs, phytochemical formulations, and patient demographics highlights the importance of thorough, standardized clinical studies. Conclusions: This review identifies phytochemicals as compelling adjuvant or independent therapies in depression treatment, providing multimodal mechanisms and enhanced tolerability. Additional research into improved dosage, pharmacokinetics, long-term safety, and integrative therapy approaches is essential. Using phytotherapeutics could considerably improve holistic and customized depression care, encouraging new research routes in integrative neuroscience and clinical psychiatry.

Cell therapy strategies using mesenchymal stem cells (MSCs) carried in fibrin glue have shown promising results in regenerative medicine. MSCs are crucial for tissue healing because they have angiogenic, anti-apoptotic and immunomodulatory properties, in addition to the ability to differentiate into several specialized cell lines. Fibrin sealant or fibrin glue is a natural polymer involved in the coagulation process. Fibrin glue provides a temporary structure that favors angiogenesis, extracellular matrix deposition and cell-matrix interactions. Additionally, fibrin glue maintains the local and paracrine functions of MSCs, providing tissue regeneration through less invasive clinical procedures. Thus, the objective of this systematic review was to assess the potential of fibrin glue combined with MSCs in bone or cartilage regeneration. The bibliographic search was performed in the PubMed/MEDLINE, LILACS and Embase databases, using the descriptors (“fibrin sealant” OR “fibrin glue”) AND “stem cells” AND “bone regeneration”, considering articles published until 2021. In this case, 12 preclinical and five clinical studies were selected to compose this review, according to the eligibility criteria. In preclinical studies, fibrin glue loaded with MSCs, alone or associated with bone substitute, significantly favored bone defects regeneration compared to scaffold without cells. Similarly, fibrin glue loaded with MSCs presented considerable potential to regenerate joint cartilage injuries and multiple bone fractures, with significant improvement in clinical parameters and absence of postoperative complications. Therefore, there is clear evidence in the literature that fibrin glue loaded with MSCs, alone or combined with bone substitute, is a promising strategy for treating lesions in bone or cartilaginous tissue.

Fibrin, derived from proteins involved in blood clotting (fibrinogen and thrombin), is a biopolymer with different applications in the health area since it has hemostasis, biocompatible and three-dimensional physical structure properties, and can be used as scaffolds in tissue regeneration or drug delivery system for cells and/or growth factors. Fibrin alone or together with other biomaterials, has been indicated for use as a biological support to promote the regeneration of stem cells, bone, peripheral nerves, and other injured tissues. In its diversity of forms of application and constitution, there are platelet-rich fibrin (PRF), Leukocyte- and platelet-rich fibrin (L-PRF), fibrin glue or fibrin sealant, and hydrogels. In order to increase fibrin properties, adjuvant therapies can be combined to favor tissue repair, such as photobiomodulation (PBM), by low-level laser therapy (LLLT) or LEDs (Light Emitting Diode). Therefore, this systematic review aimed to evaluate the relationship between PBM and the use of fibrin compounds, referring to the results of previous studies published in PubMed/MEDLINE, Scopus and Web of Science databases. The descriptors “fibrin AND low-level laser therapy” and “fibrin AND photobiomodulation” were used, without restriction on publication time. The bibliographic search found 44 articles in PubMed/MEDLINE, of which 26 were excluded due to duplicity or being outside the eligibility criteria. We also found 40 articles in Web of Science and selected 1 article, 152 articles in Scopus and no article selected, totaling 19 articles for qualitative analysis. The fibrin type most used in combination with PBM was fibrin sealant, mainly heterologous, followed by PRF or L-PRF. In PBM, the gallium-aluminum-arsenide (GaAlAs) laser prevailed, with a wavelength of 830 nm, followed by 810 nm. Among the preclinical studies, the most researched association of fibrin and PBM was the use of fibrin sealants in bone or nerve injuries; in clinical studies, the association of PBM with medication-related treatments osteonecrosis of the jaw (MRONJ). Therefore, there is scientific evidence of the contribution of PBM on fibrin composites, constituting a supporting therapy that acts by stimulating cell activity, angiogenesis, osteoblast activation, axonal growth, anti-inflammatory and anti-edema action, increased collagen synthesis and its maturation, as well as biomolecules.