Neural population dynamics reveals disruption of spinal circuits' responses to proprioceptive input during electrical stimulation of sensory afferents.

While neurostimulation technologies are rapidly approaching clinical applications for sensorimotor disorders, the impact of electrical stimulation on network dynamics is still unknown. Given the high degree of shared processing in neural structures, it is critical to understand if neurostimulation affects functions that are related to, but not targeted by, the intervention. Here, we approach this question by studying the effects of electrical stimulation of cutaneous afferents on unrelated processing of proprioceptive inputs. We recorded intraspinal neural activity in four monkeys while generating proprioceptive inputs from the radial nerve. We then applied continuous stimulation to the radial nerve cutaneous branch and quantified the impact of the stimulation on spinal processing of proprioceptive inputs via neural population dynamics. Proprioceptive pulses consistently produce neural trajectories that are disrupted by concurrent cutaneous stimulation. This disruption propagates to the somatosensory cortex, suggesting that electrical stimulation can perturb natural information processing across the neural axis.

Large-scale assessment of pros and cons of autopsy-derived or tumor-matched tissues as the norms for gene expression analysis in cancers.

Normal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived "healthy" normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 min - 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact "differential" expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice.

Autologous Bone Marrow-Derived Mononuclear Cells Combined With ß-TCP for Maxillary Bone Augmentation in Implantation Procedures.

Replacing missing bone or adding mass to existing bone is often essential to the success of a dental implant. A large variety of graft materials have been used for maxillary and mandibular atrophy. To date there has been no graft material, which can be regarded as completely satisfactory. Our experience with freshly isolated autologous bone marrow-derived mononuclear cells combined with ß-tricalcium phosphate for augmentation of the extremely atrophied maxilla is presented. These techniques are based on stimulation of natural events continuously present in living bone (ie, the process of bone remodeling). The property of the mixture material for bone augmentation to place dental implant was discussed.

Therapeutic Angiogenesis in Ischemic Tissues by Growth Factors and Bone Marrow Mononuclear Cells Administration: Biological Foundation and Clinical Prospects.

The processes of new vessels formation in tissues are supported by two definite mechanisms: de novo development of blood vessels (vasculogenesis) through the accumulation of progenitor cells during early prenatal stage, and extension of a pre-existing microcirculatory network by endothelial cell germination (angiogenesis), the essential mechanism of blood vessel formation in postnatal period. Angiogenesis is associated with a series of inductive, permissive and restrictive communications that result in the appearance, differentiation, and formation of new vessels. The goal of therapeutic angiogenesis is to improve blood circulation, relay survival factors and regenerative stem cell populations to sites of tissue repair, and ultimately recover function and form of the tissue. Growth factors and bone marrow mononuclear cells represent a very interesting research field for the realization of therapeutic angiogenesis in ischemic tissues. They provide a potential key component in the healing processes of ischemic injured tissues.

Autologous bone-marrow-derived-mononuclear-cells-enriched fat transplantation in breast augmentation: evaluation of clinical outcomes and aesthetic results in a 30-year-old female.

Autologous fat transfer (lipofilling) is becoming an invaluable tool for breast augmentation as well as for breast reconstruction. Autologous lipofilling has several advantages, including biocompatibility, versatility, natural appearance, and low donor site morbidity. The main limitation is unpredictable fat graft resorption, which ranges from 25% to 80%, probably as a result of ischaemia and lack of neoangiogenesis. To obviate these disadvantages, several studies have searched for new ways of increasing the viability of the transplanted fat tissue. One promising approach is to enrich the fat graft with autologous bone-marrow-derived mononuclear cells (BMMNCs) before transplantation. BMMNCs produce many angiogenic and antiapoptotic growth factors, and their secretion is significantly enhanced by hypoxia. All of these mechanisms of actions could be beneficial for the stimulation of angiogenesis in ischemic tissues by BMMNCs administration. In our aesthetic surgery practice, we use fat transplantation enriched with BMMNCs, which caused a significant improvement in survival of fat grafts, compared with that of traditional lipofilling. Our experience with freshly isolated autologous fat enriched with BMMNCs for breast augmentation procedures is presented. The concept of this surgical and tissue handling technique is based on ability of BMMNCs to stimulate blood vessel growth.

Autologous bone marrow derived mononuclear cells combined with ß-tricalcium phosphate and absorbable atelocollagen for a treatment of aneurysmal bone cyst of the humerus in child.

Aneurysmal bone cyst is a benign, locally destructive lesion of bone. Based on progressive cortical thinning pathological fractures are common, and are often the presenting feature. Despite the long experience of orthopaedists, radiologists and pathologists with aneurysmal bone cyst there is limited knowledge regarding the cause of the lesion and optimal treatment. Common methods of treatment vary considerably in the literature, particularly in children. A large variety of bone substitutes have been used to fill the cystic lesions. To date there has been no graft material which can be regarded as completely satisfactory. Our experience with freshly isolated autologous bone marrow derived mononuclear cells combined with ß-tricalcium phosphate and absorbable atelocollagen for bone formation is presented. The concept of this treatment is based on stimulation of natural events continuously present in living bone appear to be a reasonable and beneficial alternative to promote healing of bone cysts and offering both osteoinduction and osteoconductive features.

Autologous bone marrow-derived mononuclear cells combined with ß-TCP for maxillary bone augmentation in implantation procedures.

Replacing missing bone or adding mass to existing bone is often essential to the success of a dental implant. A large variety of graft materials have been used for maxillary and mandibular atrophy. To date, there has been no graft material which can be regarded as completely satisfactory. Our experience with freshly isolated autologous bone marrow-derived mononuclear cells combined with ß-tricalcium phosphate for augmentation of the extremely atrophied maxilla is presented. The techniques are based on stimulation of natural events continuously present in living bone, that is, the process of bone remodeling. The property of the mixture material for bone augmentation to place dental implant was discussed.

Advanced and prospective technologies for potential use in craniofacial tissues regeneration by stem cells and growth factors.

The processes of craniofacial tissues development and regeneration are largely dependent on sequential and reciprocal interactions between mesenchymal and epithelial components. These processes involve a series of inductive and permissive interactions that result in the determination, differentiation, and organization of craniofacial tissues. Stem cells and growth factors represent a very interesting research field for craniofacial tissues regeneration. They represent a potential key component in autologous graft for craniofacial tissues regeneration. An ideal goal of oral-craniofacial dental reconstructive therapy is to establish treatment modalities that predictably restore functional tissues. One major area of focus has been that of dental materials with marked improvements in the design of materials used to restore teeth/periodontium/bone lost as a consequence of disease or disorders. Interest in these technologies continues to increase in dental application as a substitute for traditional treatments and artificial components. Recent progress in the studies of molecular basis of tooth development, adult stem cell biology, and regeneration will provide fundamental knowledge for the realization of human craniofacial tissues regeneration in the near future.

Selective pharmacologic inhibition of c-Jun NH2-terminal kinase radiosensitizes thyroid anaplastic cancer cell lines via induction of terminal growth arrest.

CONTEXT: The high radioresistance of anaplastic thyroid cancer (ATC) and cultured ATC cells stipulates for the means of increasing their radiosensitivity. It has been shown that c-Jun NH(2)-terminal kinase (JNK) activation is one of the manifestations of radiation response in ATC cells. OBJECTIVE: Assessment of the effect of selective JNK inhibition on ATC cell radiosensitivity and clarification of the associated mechanisms. RESULTS: The JNK inhibitor markedly suppressed ATC cell growth in a reversible cytostatic manner. The combination treatment with JNK inhibitor plus ionizing radiation induced a significant decrease in clonogenic survival of irradiated cells as compared with either singular treatment. The effect was not due to apoptosis of exposed cells but to a profound senescence-like terminal growth arrest occurring irrespectively of cells' p53 mutational status. Postradiational DNA damage repair was also significantly compromised in the presence of SP600125. CONCLUSIONS: JNK signaling is an essential component of ATC cell proliferation and survival after radiation therapy. Hence, pharmacological interference with JNK pathway in combination with radiotherapy may be a promising treatment of ATC.