Spontaneous Regeneration of Plantlets Derived from Hairy Root Cultures of Lopezia racemosa and the Cytotoxic Activity of Their Organic Extracts

A histological analysis was performed with the aim of elucidating the spontaneous regeneration process of the hairy root lines LRT 2.3 and LRT 6.4, derived from Lopezia racemosa leaf explants and genetically transformed with the Agrobacterium rhizogenes strain ATCC15834/pTDT. The analysis showed both lines regenerate via indirect somatic embryogenesis; LRT 6.4 also regenerated by direct organogenesis. The morphogenic characteristics of the regenerated plantlets from both lines showed the typical characteristics, described previously, including a higher number of axillary shoot formation, short internodes, and plagiotropic roots compared with wild-type seedlings. The regeneration process occurred without the addition of plant growth regulators and was linked to the sucrose concentration in the culture medium. Reducing the sucrose concentration from 3% to 2%, 1%, and 0.5% increased the regeneration rate in LRT 6.4; the effect was less pronounced in LRT 2.3. The cytotoxic activity of different organic extracts obtained from roots and shoots were evaluated in the cancer cell lines HeLa (cervical carcinoma), HCT-15 (colon adenocarcinoma), and OVCAR (ovary carcinoma). The hexane and dichloromethane extracts from roots of both lines showed cytotoxic activity against the HeLa cell line. Only the dichloromethane extract from the roots of PLRT 2.3 showed cytotoxic activity against the OVCAR cell line. None of the methanol extracts showed cytotoxic activity, nor the shoot extracts from any solvent.

A Funhouse Mirror: Muscular Co-Contractions as a Reflection of a Spontaneous Aberrant Regeneration of the Brachial Plexus Injury in the Adults: Anatomical Background, an Attempt to Classify and their Clinical Relevance within the Reconstruction Strategies

A certain number of spontaneously recovering birth injuries to the brachial (BPI) plexus are known to be accompanied by muscle co-contractions (Co-Cs). The process of aberrant spontaneous regeneration contributes to the appearance of this phenomenon. Treatment strategies are mostly narrowed down to temporarily “switching off” the antagonist, allowing the agonist to perform. Less is known about the incidence of BPI-associated Co-Cs in adults (a-BPI), the control of which mainly presumes the extrapolation of a treatment strategy that has been shown to be effective in infants. Nowadays, surgical reconstruction of independent elbow flexion at BPIs relies heavily on redirection (transfer) of nerves that produce their own Co-Cs. These induced Co-Cs could potentially be reduced. Selecting the appropriate nerve transfer strategy (when the donor pool is narrowing), with its potential impact on the already complex and intricate global and segmental biomechanics of the upper extremity, becomes challenging. The chapter presents the anatomical background for the occurrence of muscular Co-Cs, a work on clinical classification of both regeneration associated and induced Co-Cs, possible surgical strategies, their benefits and limitations, in the presence of regeneration-associated muscle Co-Cs at a-BPI and clinical examples.

Neural Stem Cells: Promoting Axonal Regeneration and Spinal Cord Connectivity

Spinal cord injury (SCI) leads to irreversible functional impairment caused by neuronal loss and the disruption of neuronal connections across the injury site. While several experimental strategies have been used to minimize tissue damage and to enhance axonal growth and regeneration, the corticospinal projection, which is the most important voluntary motor system in humans, remains largely refractory to regenerative therapeutic interventions. To date, one of the most promising pre-clinical therapeutic strategies has been neural stem cell (NSC) therapy for SCI. Over the last decade we have found that host axons regenerate into spinal NSC grafts placed into sites of SCI. These regenerating axons form synapses with the graft, and the graft in turn extends very large numbers of new axons from the injury site over long distances into the distal spinal cord. Here we discuss the pathophysiology of SCI that makes the spinal cord refractory to spontaneous regeneration, the most recent findings of neural stem cell therapy for SCI, how it has impacted motor systems including the corticospinal tract and the implications for sensory feedback.

Autophagy Regulates the Survival of Hair Cells and Spiral Ganglion Neurons in Cases of Noise, Ototoxic Drug, and Age-Induced Sensorineural Hearing Loss

Inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) are the core components of the auditory system. However, they are vulnerable to genetic defects, noise exposure, ototoxic drugs and aging, and loss or damage of HCs and SGNs results in permanent hearing loss due to their limited capacity for spontaneous regeneration in mammals. Many efforts have been made to combat hearing loss including cochlear implants, HC regeneration, gene therapy, and antioxidant drugs. Here we review the role of autophagy in sensorineural hearing loss and the potential targets related to autophagy for the treatment of hearing loss.

Epidermal-Derived Hedgehog Signaling Drives Mesenchymal Proliferation during Digit Tip Regeneration

Hand injuries often result in significant functional impairments and are rarely completely restored. The spontaneous regeneration of injured appendages, which occurs in salamanders and newts, for example, has been reported in human fingertips after distal amputation, but this type of regeneration is rare in mammals and is incompletely understood. Here, we study fingertip regeneration by amputating murine digit tips, either distally to initiate regeneration, or proximally, causing fibrosis. Using an unbiased microarray analysis, we found that digit tip regeneration is significantly associated with hair follicle differentiation, Wnt, and sonic hedgehog (SHH) signaling pathways. Viral over-expression and genetic knockouts showed the functional significance of these pathways during regeneration. Using transgenic reporter mice, we demonstrated that, while both canonical Wnt and HH signaling were limited to epidermal tissues, downstream hedgehog signaling (through Gli) occurred in mesenchymal tissues. These findings reveal a mechanism for epidermal/mesenchyme interactions, governed by canonical hedgehog signaling, during digit regeneration. Further research into these pathways could lead to improved therapeutic outcomes after hand injuries in humans.

Efficacy Treatment of Osteoarthritis with Combine Chondroitin and Glucosamine

Osteoarthritis led to the articular cartilage damage and cause different kind of problems – from social to biological. The analysis of existing research unfortunately subjected questioned the reliability of spontaneous regeneration of damaged cartilage, which makes it necessary to focus on the possibilities of protection of the tissue from further its degradation. Treatment of osteoarthritis require to use many drugs, which would lead to slowdown the this process. The aim of below publication is to analyse the practical, clinical biological possibilities of articular cartilage protection with a usage of SYSADOA – (symptomatic slow acting drugs of OA). Osteoarthritis is most frequent disease of the joints and prescription of the SYSADOA should be main principle of that treatment.

Forest regeneration and seed rain in the conversion of a stand of Pinus sp. into native forest

In Southern Brazil, the National Forests (NF) are protected areas of sustainable use; however, most of them present a significant cover with old plantations of Pinus spp. established to foster commercial forestry. Nowadays, the NF management plans propose the conversion of Pinus stands into native forests. Pinus spp. are worrisome invasive plants whose spontaneous recruitment is a challenge to forest restoration. This paper aims to analyze seed rain and woody community composition in a stand where Pinus trees were eliminated to drive spontaneous regeneration (REG) in an NF in the Southern Atlantic Forest. The seed rain was measured in the restoring area and inside an adjacent Pinus stand (PIN). The tree community structure was analyzed comparatively in REG, PIN, and in a Native Araucaria Forest (NAT). One year after Pinus cutting, the seed rain of woody species was 1,802 and 1,502 seeds m-2.year-1 in REG and PIN, respectively. REG’s seed rain had higher diversity than PIN and absence of Pinus seeds. REG and NAT presented higher diversity of tree species than PIN, although REG had the lowest basal area and tree density. Nevertheless, 188 Pinus seedlings.ha-1 were observed in REG, which indicates that complementary restoration actions are needed.

Overturning the paradigm that IL6 signaling drives liver regrowth while shining light on a new therapeutic target for regenerative medicine

It is accepted that IL6 signaling in hepatocytes, mediated via glycoprotein 130 (gp130), is beneficial and that HyperIL6 promotes liver regeneration by activating STAT3. Recently, autocrine IL11 activity, which also signals via gp130 and ERK, was found to be hepatotoxic. Here we examined whether the beneficial effects of HyperIL6 could reflect unappreciated competitive inhibition of IL11 signaling. In hepatocytes, HyperIL6 inhibited N-acetyl-p-aminophenol (APAP)-induced cell death that mimicked inhibition of IL11 signaling and was unrelated to STAT3 phosphorylation. In mice, expression of HyperIL6 reduced liver damage due to IL11 dosing or APAP and promoted hepatic regeneration in a STAT3-independent manner. Following APAP, mice deleted for Il11 were protected from liver failure and exhibited spontaneous regeneration. Despite robustly activating STAT3, HyperIL6 had no beneficial effect in Il11 null mice. These data overturn the premise that IL6 promotes liver regeneration, show STAT3 activation to be redundant and suggest IL11 as a focus for regenerative medicine.

Oligodendrocyte Dysfunction in Amyotrophic Lateral Sclerosis: Mechanisms and Therapeutic Perspectives

Myelin is the lipid-rich structure formed by oligodendrocytes (OLs) that wraps the axons in multilayered sheaths, assuring protection, efficient saltatory signal conduction and metabolic support to neurons. In the last few years, the impact of OL dysfunction and myelin damage has progressively received more attention and is now considered to be a major contributing factor to neurodegeneration in several neurological diseases, including amyotrophic lateral sclerosis (ALS). Upon OL injury, oligodendrocyte precursor cells (OPCs) of adult nervous tissue sustain the generation of new OLs for myelin reconstitution, but this spontaneous regeneration process fails to successfully counteract myelin damage. Of note, the functions of OPCs exceed the formation and repair of myelin, and also involve the trophic support to axons and the capability to exert an immunomodulatory role, which are particularly relevant in the context of neurodegeneration. In this review, we deeply analyze the impact of dysfunctional OLs in ALS pathogenesis. The possible mechanisms underlying OL degeneration, defective OPC maturation, and impairment in energy supply to motor neurons (MNs) have also been examined to provide insights on future therapeutic interventions. On this basis, we discuss the potential therapeutic utility in ALS of several molecules, based on their remyelinating potential or capability to enhance energy metabolism.