Biofeedback-Based Proprioceptive Training to Improve Functional Prerequisites of Dragon Boating in Breast Cancer Survivors.

Breast cancer (BC)-related sequelae drastically impact the psychophysical functioning and quality of life of affected women. Adapted physical activity (APA) has proved to effectively counteract these impairments in a non-medicalized framework. In particular, dragon boats are able to promote body functionality, social interaction, and quality of life in BC survivors, but the literature on specific motor gestures is scarce and practice is still based more on a re-educative perspective than a performative one. In this context, the present longitudinal study investigated the benefits of an adapted biofeedback-based sensorimotor training intervention on upper body functionality in a team of dragon ladies. The 8-week intervention was conceived as integrated dry workout sessions led by an APA kinesiologist and applied a novel sensorized proprioceptive device, such as a Libra board. Post-protocol evaluation revealed a significant improvement in bilateral upper limb mobility, core endurance, and trunk stability along with a distress decrease and quality of life enhancement through validated assessment tools. Our findings suggest that integrating biofeedback-based workout sessions can effectively promote upper body functionality in BC survivors practicing dragon boating. Furthermore, our innovative approach could help spread methodological hints able to boost exercise adherence in this target population, thus counteracting cancer recurrence while promoting overall well-being.

Pharmacological Stimulation of Soluble Guanylate Cyclase Counteracts the Profibrotic Activation of Human Conjunctival Fibroblasts.

Conjunctival fibrosis is a serious clinical concern implicated in a wide spectrum of eye diseases, including outcomes of surgery for pterygium and glaucoma. It is mainly driven by chronic inflammation that stimulates conjunctival fibroblasts to differentiate into myofibroblasts over time, leading to abnormal wound healing and scar formation. Soluble guanylate cyclase (sGC) stimulation was found to suppress transforming growth factor ß (TGFß)-induced myofibroblastic differentiation in various stromal cells such as skin and pulmonary fibroblasts, as well as corneal keratocytes. Here, we evaluated the in vitro effects of stimulation of the sGC enzyme with the cell-permeable pyrazolopyridinylpyrimidine compound BAY 41-2272 in modulating the TGFß1-mediated profibrotic activation of human conjunctival fibroblasts. Cells were pretreated with the sGC stimulator before challenging with recombinant human TGFß1, and subsequently assayed for viability, proliferation, migration, invasiveness, myofibroblast marker expression, and contractile properties. Stimulation of sGC significantly counteracted TGFß1-induced cell proliferation, migration, invasiveness, and acquisition of a myofibroblast-like phenotype, as shown by a significant downregulation of FAP, ACTA2, COL1A1, COL1A2, FN1, MMP2, TIMP1, and TIMP2 mRNA levels, as well as by a significant reduction in α-smooth muscle actin, N-cadherin, COL1A1, and FN-EDA protein expression. In addition, pretreatment with the sGC stimulator was capable of significantly dampening TGFß1-induced acquisition of a contractile phenotype by conjunctival fibroblasts, as well as phosphorylation of Smad3 and release of the proinflammatory cytokines IL-1ß and IL-6. Taken together, our findings are the first to demonstrate the effectiveness of pharmacological sGC stimulation in counteracting conjunctival fibroblast-to-myofibroblast transition, thus providing a promising scientific background to further explore the feasibility of sGC stimulators as potential new adjuvant therapeutic compounds to treat conjunctival fibrotic conditions.

Adapted Physical Activity Protocol for Lower Limb Functional and Strength Recovery in a Young Athlete with Cutaneous Melanoma: Feasibility and Efficacy during COVID-19 Pandemic.

Adapted physical activity (APA) can improve psychophysical wellbeing and quality of life (QoL) in cancer survivors, a vulnerable population requiring a global management, especially during the recent pandemic. On this basis, we investigated for the first time the impact of a tailored APA intervention on a melanoma-affected 18-year-old female athlete to counteract treatment sequelae and promote lower limb functional and strength recovery. Patient was evaluated at baseline and post-protocol by a test battery focusing on mobility, muscle strength measured by dynamometry, and lower limb girths assessed at specific anatomical points. Moreover, health-related QoL, depression/anxiety, psychological distress and pain intensity were evaluated by Functional Assessment of Cancer Therapy-Melanoma (FACT-M), Hospital Anxiety and Depression Scale (HADS), distress thermometer, and numerical rating scale (NRS) questionnaires, respectively. An almost doubled up increase in lower limb strength, along with hip mobility improvement, and post-surgical edema and pain reduction were observed following the protocol. Concerning the QoL assessment, a moderate post-intervention improvement in physical and emotional wellbeing was detected, while depression state worsened though remaining within the normality range. Our findings show that a specialist-supervised structured APA protocol based on a patient-centered multidisciplinary approach may represent an effective strategy to recover functional and psychophysical efficiency, thus promoting a quick return to daily life activities and offering a concrete chance of resuming competitive sport practice.

Quality of life improvement in breast cancer survivors affected by upper limb lymphedema through a novel multiperspective physical activity methodology: a monocentric pilot study.

PURPOSE: Chronic lymphedema causes psychophysical sequelae jeopardizing quality of life (QoL) of breast cancer (BC) survivors, and lack of effective therapies represents a major challenge for healthcare professionals. Structured adapted physical activity (APA) may represent an effective strategy to attenuate cancer treatment-related impairments and improve QoL. Here, we describe the effects of a specific APA intervention based on a novel multiperspective methodology in counteracting lymphedema-related morphofunctional alterations and improving QoL of BC survivors. METHODS: BC survivors with chronic moderate/severe lymphedema attending the Cancer Rehabilitation Center in Florence were assessed before and after 8-week APA. The protocol consisted of both APA specialist-supervised and self-leaded sessions using a tailor-designed proprioceptive board. Body mass index, bioimpedance parameters, indirect upper limb volume measurement, and ultrasonography were performed. Wrist flexion/extension and hand strength functional tests were also executed. QoL, depression/anxiety and pain intensity were evaluated by ULL27, HADS, distress thermometer and NRS questionnaires, respectively. RESULTS: Although bioimpedance, ultrasound and volumetric measures remained mostly unchanged, wrist mobility, pain perception, depression, and QoL were all significantly ameliorated after APA. CONCLUSIONS: Our findings suggest that a multidisciplinary treatment approach involving APA professionals should be employed in the management of BC-related lymphedema to improve patient psychophysical outcomes and QoL.

Manual DALK in Keratoconus: An Ex Vivo Light and Transmission Electron Microscopy Analysis 2 Years After Surgery.

PURPOSE: The aim of this study was to evaluate the microscopic structure of a human cornea 2 years after manual deep anterior lamellar keratoplasty (DALK) for keratoconus with a recipient residual stromal bed thickness of 100 µm, using light and transmission electron microscopy. METHODS: A human cornea treated with manual DALK for keratoconus 2 years before was removed during penetrating keratoplasty because of stromal opacity of unknown origin, involving about half of the sample. The transparent half of the specimen was processed for light and transmission electron microscopy. RESULTS: Light microscopy examination performed with different staining techniques (hematoxylin and eosin, Picrosirius red, and Masson trichrome) revealed a homogeneous stroma. No interface was detected. Electron microscopy confirmed these findings. CONCLUSIONS: This study confirmed the available clinical and confocal studies that show progressive stromal remodeling after manual DALK. Two years after surgery, no posterior stromal interface was detected.

Co-expression of the SARS-CoV-2 entry receptors ACE2 and TMPRSS2 in healthy human conjunctiva.

The purpose of this study was to evaluate the expression of the SARS-CoV-2 receptors ACE2 and TMPRSS2 in an immortalized human conjunctival epithelial cell line and in healthy human conjunctiva excised during ocular surgery, using Western blot, confocal microscopy and immunohistochemistry. The Western blot showed that ACE2 and TMPRSS2 proteins were expressed in human immortalized conjunctival cells, and this was confirmed by confocal microscopy images, that demonstrated a marked cellular expression of the viral receptors and their co-localization on the cell membranes. Healthy conjunctival samples from 11 adult patients were excised during retinal detachment surgery. We found the expression of ACE2 and TMPRSS2 in all the conjunctival surgical specimens analyzed and their co-localization in the superficial conjunctival epithelium. The ACE2 Western blot levels and immunofluorescence staining for ACE2 were variable among specimens. These results suggest the susceptibility of the conjunctival epithelium to SARS-CoV-2 infection, even though with a possible interindividual variability.

Effectiveness of an Adapted Physical Activity Protocol for Upper Extremity Recovery and Quality of Life Improvement in a Case of Seroma after Breast Cancer Treatment.

Growing evidence indicates that physical activity (PA) interventions may reduce upper limb function-limiting side effects of treatments and improve quality of life (QoL) of breast cancer (BC) survivors. However, the possible effectiveness of PA in cases developing seroma after BC treatment has yet to be demonstrated. Here, we describe for the first time the impact of a structured PA pathway (i.e., two cycles of eight-week adapted PA followed by eight-week adapted fitness) on upper limb disability and QoL in a peculiar case of chronic seroma as complication of reconstructive plastic surgery after left breast mastectomy and lymphadenectomy. A 56-year-old female BC survivor underwent a functional test battery (i.e., shoulder-arm mobility, range of motion, back flexibility and indirect assessment of pectoralis minor muscle) at baseline, during and after ending the structured PA pathway. Upper limb and back pain intensity and QoL were evaluated by numerical rating scale and Short Form-12 questionnaire, respectively. A relevant seroma reduction, an improvement in upper limb mobility and pain perception, and an overall increase in QoL were achieved after the structured PA intervention. Our findings suggest that an adapted PA intervention may represent an effective strategy for seroma treatment in BC survivors.

Tailored Sailing Experience to Reduce Psychological Distress and Improve the Quality of Life of Breast Cancer Survivors: A Survey-Based Pilot Study.

Background: Growing evidence indicates that physical/sporting activities may improve the health outcomes and quality of life (QoL) of breast cancer (BC) survivors. Since recent reports have suggested that sailing can improve the psychophysical well-being and QoL of people with disabilities, this pilot study evaluated the effectiveness of a tailored sailing experience on the QoL and psychological distress (PD) of BC survivors. Methods: A group of 19 breast cancer survivors, who were attending the Cancer Rehabilitation Center in Florence, were invited to participate in a sailing school and completed a survey based on a structured online questionnaire assessing QoL and PD both on departure (baseline) and one week after returning (follow-up). The survey comprised a first part (i.e., sociodemographic characteristics and the practice of physical/sporting activities at baseline; sailing experience satisfaction at follow-up) and a second part (i.e., Short Form-12 (SF-12), State/Trait-Anxiety Inventory form Y (STAI-Y), distress thermometer questionnaires). A paired Student's t-test was used to compare the baseline versus follow-up QoL and PD scores. Results: A statistically significant improvement in SF-12 mental component scores and a reduction in both STAI-Y state/trait components and distress thermometer scores were found after the sailing experience. Conclusions: We conclude that sailing practice could be a feasible intervention to increase the psychophysical well-being of BC survivors.

Characterization and distribution of sialic acids in human testicular seminoma.

Aberrant content of sialic acids (Sias) has been observed in various human cancer types in different organs. Sias have been implicated in cancerous transformation, invasiveness and metastasis, and in the escaping of cancer cells from immune surveillance. Indeed, Sias are commonly regarded as important biomarkers to distinguish cancer cells from their healthy counterparts. However, scarce and not exhaustive investigations have been performed on Sia content in testicular cancers and, in particular, in seminoma, one of the most common malignant testicular tumors. Hence, the aim of this study was to investigate the content and distribution of Sias with different glycosidic linkage, namely α2,3 and α2,6 galactose- or N-acetyl-galactosamine-linked Sias and polymeric Sia (polySia), in the germinal and stromal components of human testes affected by seminoma compared to normal testicular tissue. Structural changes in seminoma tissue were examined using hematoxylin-eosin staining. α2,3 and α2,6 linked Sias were evaluated by lectin histochemistry (Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA)), while confocal immunofluorescence was used for polySia detection. Histopathological findings in seminoma tissue included loss of seminiferous tubules replaced by clusters of uniform polygonal cells with a clear cytoplasm, bundles of fibrotic tissue, numerous microvessels and some atrophic tubules. The content of α2,3 and α2,6 linked Sias was lost in almost all seminoma components respect to normal tissue, with the exception of microvessels in which it was higher. On the contrary, polySia level was increased in all the seminoma components compared to normal testicular tissue. Our findings suggest that an aberrant content of different Sias might have important and differential roles in seminoma development and progression. In particular, polySia might be implicated in seminoma progression by promoting cancer invasiveness and regulating the cross-talk between cancer cells, reactive stroma and vessels. Thus, the possibility that polySia might represent an important biomarker for seminoma deserves further investigation.

Changes in the telocyte/CD34+ stromal cell and α-SMA+ myoid cell networks in human testicular seminoma.

Telocytes (TCs), also known as CD34+ stromal/interstitial cells, have recently been identified within the connective tissue of a variety of organs including the normal human testis. Testicular TCs appear to constitute a widespread reticular network distributed either in the peritubular or in the intertubular stromal spaces where they have been suggested to play different roles, such as participation to testis morphogenesis, postnatal preservation of the normal tissue/organ three-dimensional structure, and regulation of spermatogenesis and androgen hormone secretion and release. Although increasing evidence indicates that TCs may be involved in the pathophysiology of various diseases, no study has yet reported possible changes in these cells within the stromal compartment of seminoma, one of the most frequent malignant testicular cancers in humans. Therefore, here we carried out the first investigation of the presence and tissue distribution of TCs/CD34+ stromal cells in human testicular seminoma in comparison with normal human testis using either CD34 immunohistochemistry or CD34/CD31 and CD34/α-smooth muscle actin (α-SMA) double immunofluorescence analyses. In seminoma tissue sections, we observed an overall loss of TCs (CD34+/CD31- stromal cells) accompanying a severe degeneration of the normal architecture of seminiferous tubules and stromal tissue associated with dense cellularity increase and presence of interstitial fibrosis. Noteworthy, in the seminoma tissue the disappearance of TCs was paralleled by an expansion of α-SMA+ myoid cells. Moreover, the CD34+/CD31+ blood vessel network was greatly expanded, while steroidogenic Leydig cells were undetectable in seminoma specimens. Since TCs are emerging as important regulators of tissue and organ homeostasis, collectively the present findings indicate that the possible pathophysiologic implications of the loss of TCs in human testicular seminoma should not be further overlooked.

Telocytes constitute a widespread interstitial meshwork in the lamina propria and underlying striated muscle of human tongue.

Telocytes have recently emerged as unique interstitial cells defined by their extremely long, thin and moniliform prolongations termed telopodes. Despite growing evidence that these cells consistently reside in the stromal compartment of various organs from human beings, studies dealing with telocytes in structures of the oral cavity are scarce. Hence, the present morphologic study was undertaken to explore for the first time the presence and specific localization of telocytes within tissues of the normal human tongue, a complex muscular organ whose main functions include taste, speech, and food manipulation in the oral cavity. Telocytes were initially identified by CD34 immunostaining and confirmed by CD34/PDGFRα double immunofluorescence and transmission electron microscopy. CD34+/PDGFRα+ telocytes were organized in interstitial meshworks either in the tongue lamina propria or in the underlying striated muscle. Lingual telocytes were immunonegative for CD31, c-kit and α-SMA. Telopodes were finely distributed throughout the stromal space and concentrated beneath the lingual epithelium and around CD31+ vessels, skeletal muscle bundles/fibers, and intramuscular nerves and ganglia. They also enveloped salivary gland units outside the α-SMA+ myoepithelial cells and delimited lymphoid aggregates. These findings establish telocytes as a previously overlooked interstitial cell population worth investigating further in the setting of human tongue pathophysiology.

Role of a Structured Physical Activity Pathway in Improving Functional Disability, Pain and Quality of Life in a Case of Breast and Gynecological Cancer Survivorship.

Physical activity (PA) interventions can improve physical functioning, treatment-related symptoms and quality of life (QoL) in cancer survivors. Most investigations have been conducted in breast cancer survivors, while studies on PA interventions in gynecological cancer survivors are scant. Here, we report for the first time the possible benefits of a structured PA pathway (i.e., eight weeks of adapted PA followed by twelve weeks of adapted fitness) on physical side effects, pain and QoL in an uncommon case of survivorship of both primary breast and gynecological cancers. For this purpose, a 69-year-old woman was assessed by functional test battery (shoulder-arm mobility, range of motion, back flexibility) at baseline and after the structured PA pathway. QoL and surgical shoulder, back and lower limb pain intensity were evaluated by Short Form-12 (SF-12) and numerical rating scale questionnaires, respectively. Lower limb circumference was also assessed. Improvement in upper limb function, reduction of lower limb edema and pain perception, as well as an increase in overall QoL were achieved after the completion of structured PA intervention. Our findings suggest that a PA intervention tailored to individual characteristics may represent an effective countermeasure to reduce post-treatment functional disability and pain, and thus to improve QoL in breast and gynecologic cancer survivors.

Immunolocalization of VEGF/VEGFR system in human fetal vomeronasal organ during early development.

The vomeronasal system (VNS) is an accessory olfactory structure present in most mammals adhibited to the detection of specific chemosignals implied in social and reproductive behavior. The VNS comprises the vomeronasal organ (VNO), vomeronasal nerve and accessory olfactory bulb. VNO is characterized by a neuroepithelium constituted by bipolar neurons and supporting and stem/progenitor cells. In humans, VNO is present during fetal life and is supposed to possess chemoreceptor activity and participate in gonadotropin-releasing hormone neuronal precursor migration toward the hypothalamus. Instead, the existence and functions of VNO in postnatal life is debated. Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) have been demonstrated to play fundamental roles in various neurogenic events. However, there are no data regarding the localization and possible function of VEGF/VEGFRs in human fetal VNO. Therefore, this study was conceived to investigate the expression of VEGF/VEGFRs in human VNO in an early developmental period (9-12 weeks of gestation), when this organ appears well structured. Coronal sections of maxillofacial specimens were subjected to peroxidase-based immunohistochemistry for VEGF, VEGFR-1 and VEGFR-2. Double immunofluorescence for VEGF, VEGFR-1 or VEGFR-2 and the neuronal marker protein gene product 9.5 (PGP 9.5) was also performed. VEGF expression was evident in the entire VNO epithelium, with particularly strong reactivity in the middle layer. Strongly VEGF-immunostained cells with aspect similar to bipolar neurons and/or their presumable precursors were detected in the middle and basal layers. Cells detaching from the basal epithelial layer and detached cell groups in the surrounding lamina propria showed moderate/strong VEGF expression. The strongest VEGFR-1 and VEGFR-2 expression was detected in the apical epithelial layer. Cells with aspect similar to bipolar neurons and/or their presumable precursors located in the middle and basal layers and the detaching/detached cells displayed a VEGFR-1 and VEGFR-2 reactivity similar to that of VEGF. The basal epithelial layer exhibited stronger staining for VEGFRs than for VEGF. Cells with morphology and VEGF/VEGFR expression similar to those of the detaching/detached cells were also detected in the middle and basal VNO epithelial layers. Double immunofluorescence using anti-PGP 9.5 antibodies demonstrated that most of the VEGF/VEGFR-immunoreactive cells were neuronal cells. Collectively, our findings suggest that during early fetal development the VEGF/VEGFR system might be involved in the presumptive VNO chemoreceptor activity and neuronal precursor migration.

Longitudinal assessment of the impact of adapted physical activity on upper limb disability and quality of life in breast cancer survivors from an Italian cohort.

PURPOSE: The purpose of this study was to evaluate the effectiveness of a specific adapted physical activity (APA) protocol on upper limb disability and quality of life in breast cancer survivors and to assess longitudinally the possible role of APA on long-term benefits. METHODS: Breast cancer survivors from an Italian cohort were assessed by fitness tests (shoulder-arm mobility, range of motion, and back flexibility) before and after 8-week APA. Quality of life and back and surgical shoulder pain intensity were evaluated by Short Form-12 and numerical rating scale questionnaires, respectively. At 1.5-year post-APA follow-up, survivors were evaluated as at baseline/post-APA to assess long-term effects. RESULTS: A statistically significant improvement in shoulder-arm mobility, pain perception, and quality of life was observed in breast cancer survivors after APA intervention. Longitudinal analyses indicated an overall decrease in the achieved benefits at 1.5-year post-APA. CONCLUSIONS: The survivorship phase of breast cancer requires a multidisciplinary collaboration involving either the cancer-care medical team or APA professionals to manage psychophysical outcomes. A specific APA protocol may represent an effective countermeasure to reduce post-treatment upper limb disability and improve the quality of life in breast cancer survivors. Participation in structured APA protocols should be maintained over time to preserve the achieved benefits.

Cardiac Telocyte-Derived Exosomes and Their Possible Implications in Cardiovascular Pathophysiology.

Among cardiac interstitial cells, the recently described telocytes (TCs) display the unique ability to build a supportive three-dimensional network formed by their very long and thin prolongations named telopodes. Cardiac TCs are increasingly regarded as pivotal regulators in intercellular signaling with multiple cell types, such as cardiomyocytes, stem/progenitor cells, microvessels, nerve endings, fibroblasts and immune cells, thus converting the cardiac stromal compartment into an integrated system that may drive either heart development or maintenance of cardiac homeostasis in post-natal life. Besides direct intercellular communications between TCs and neighboring cells, different types of TC-released extracellular vesicles (EVs), namely exosomes, ectosomes and multivesicular cargos, may act as shuttles for paracrine molecular signal exchange between cardiac TCs and cardiomyocytes or putative cardiomyocyte progenitors. In this review, we summarize the recent research findings on cardiac TCs and their EVs. We first provide an overview of the general features of TCs, including their peculiar morphological traits and immunophenotypes, intercellular signaling mechanisms and possible functional roles. Thereafter, we describe the distribution of TCs in normal and diseased hearts, as well as their role as intercellular communicators via the release of exosomes and other types of EVs. Finally, the involvement of cardiac TCs in cardiovascular diseases and the potential utility of TC transplantation and TC-derived exosomes in cardiac regeneration and repair are discussed.

Telocytes in normal and keratoconic human cornea: an immunohistochemical and transmission electron microscopy study.

Telocytes (TC) are typically defined as cells with telopodes by their ultrastructural features. Their presence was reported in the interstitium of various organs in vertebrates, including humans. However, no study has yet described the presence of TC in the human eye and in particular, within the stromal compartment of the cornea. To address this issue, samples of normal and pathologic (keratoconic) human corneas were tested by immunohistochemistry for CD34, platelet-derived growth factor receptor α (PDGFRα) and c-kit/CD117 or examined by transmission electron microscopy. We found that TC coexpressing CD34 and PDGFRα were distributed throughout the whole normal corneal stroma with different TC subtypes being distinguishable on the basis of the expression of the stemness marker c-kit (i.e. c-kit-positive and c-kit-negative TC subpopulations). Transmission electron microscopy examination confirmed the existence of spindle-shaped and bipolar TC typically displaying two long and thin moniliform telopodes establishing intercellular contacts formed by gap junctions. Keratoconic corneas were characterized by ultrastructural damages and patchy loss of TC with an almost complete depletion of the c-kit-positive TC subpopulation. We propose that TC may contribute to the maintenance of corneal stromal homoeostasis and that, in particular, the c-kit-positive TC subtype might have stemness capacity participating in corneal regeneration and repair processes. Further studies are needed to clarify the differential roles of corneal TC subtypes as well as the possible therapeutic applications of TC in degenerative corneal disorders such as keratoconus.

Sialic acid expression in human fetal skeletal muscle during limb early myogenesis.

Investigations on animal models demonstrated that changes of sialic acid (SA) expression, particularly the polymeric form, in the skeletal muscle during embryonic and post-natal development seem to be related to muscle differentiation and functionality onset. The aim of this study was to evaluate the monomeric and polymeric SA expression in human skeletal muscle during early stages of fetal development, when important morphofunctional events occur. Specimens of fetal skeletal muscle from limb, between 9 and 12 weeks of gestation (wg), were obtained from 19 pregnant women. To investigate some morphofunctional features occurring during this development period, haematoxylin-eosin staining, tunel assay and immunohistochemistry for connexin-43 (Cx43) and parvalbumin were performed. SA expression and characterization was evaluated using lectin histochemistry (MAA, SNA, PNA, SBA, DBA), associated with enzymatic and chemical treatments. Polysialic acid (PSA) expression was also evaluated using immunohistochemistry. The results showed apoptotic myotubes between 9 and 10.5 wg, disappearing from 11 wg; Cx43 was more abundant in myotubes/myoblasts between 9 and 9.5 wg, decreasing and/or disappearing from 10 wg and parvalbumin was present in myotubes between 10 and 10.5 wg. PSA was revealed in myotubes/myoblasts from 9 to 10.5 wg; from 11 wg it was reduced or disappeared. Monomeric SA appeared in myotubes/myoblasts from 10 wg, increasing successively; acetylated SA was present from 11 wg. These findings demonstrated that changes in expression of various types of SA, occurring in human fetal skeletal muscle during early development, seem to be related to some morphofunctional aspects distinctive of this organogenesis crucial period.

A case of mandible hypoplasia treated with autologous bone graft from mandibular symphysis: Expression of VEGF and receptors in bone regeneration.

The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) system plays an important role in angiogenesis and osteogenesis during both skeletal development and postnatal bone growth and repair. Indeed, protein expression changes of this system could contribute to craniofacial defects commonly associated with a variety of congenital syndromes. Similarly to other craniofacial bones, mandible arises from neural crest cells of the neuroectodermal germ layer, and undergoes membranous ossification. Here, we report a case of left mandibular hypoplasia in a 42-year-old man treated with autologous bone graft from mandibular symphysis. After 3 months from surgical reconstruction, the protein expression of VEGF and receptors (VEGFR-1, -2 and -3) in regenerated bone tissue was evaluated by immunohistochemistry. At variance with the mandibular symphysis bone harvested for graft surgery, we observed de novo expression of VEGF and VEGFRs in osteoblasts and osteocytes from post-graft regenerating mandible bone tissue. In particular, while VEGFR-1 and VEGFR-3 immunopositivity was widespread in osteoblasts, that of VEGFR-2 was scattered. Among the three receptors, VEGFR-3 was the more intensively expressed both in osteoblasts and osteocytes. These findings suggest that VEGFR-2 might be produced during the early period of regeneration, while VEGFR-1 might participate in bone cell maintenance during the middle or late consolidation period. VEGFR-3 might, instead, represent a specific signal for ectomesenchymal lineage differentiation during bone regeneration. Modulation of VEGF/VEGFR signaling could contribute to graft integration and new bone formation during mandibular regeneration.

Differential expression of vascular endothelial growth factor in human fetal skeletal site-specific tissues: Mandible versus femur.

Vascular endothelial growth factor (VEGF) is a well-known mediator that signals through pathways in angiogenesis and osteogenesis. Angiogenesis and bone formation are coupled during either skeletal development or bone remodeling and repair occurring in postnatal life. In this study, we examined for the first time the expression of VEGF in human fetal mandibular and femoral bone in comparison with the respective adult tissues. Similarly to other craniofacial bones, but at variance with the axial and appendicular skeleton, during development mandible does not arise from mesoderm but neural crest cells of the neuroectoderm germ layer, and undergoes intramembranous instead of endochondral ossification. By quantitative real-time PCR technique, we could show that VEGF gene expression levels were significantly higher in fetal than in adult samples, especially in femoral tissue. Western blotting analysis confirmed higher protein expression of VEGF in the fetal femur respect to the mandible. Moreover, immunohistochemistry revealed that in both fetal tissues VEGF expression was mainly localized in pre- and osteoblasts. Differential expression of VEGF in femoral and mandibular bone tissues could be related to their different structure, function and development during organogenesis.

Human striatum remodelling after neurotransplantation in Huntington's disease.

BACKGROUND: Restoration of functions in Huntington's disease (HD) by neurotransplantation stems from the formation of a striatum-like structure capable of establishing host connections as a result of grafted striatal neuroblast maturation. For the first time, we demonstrated some developmental steps accomplished by progenitor cells in the brain of an HD patient and analysed the molecular asset of the human primordium. CASE REPORT: Surgery involved bilateral (two sessions) stereotactic, caudate-putaminal transplantation of whole ganglionic eminence fragments from single legally aborted fetuses. MRI showed that the tissue deposits of the left hemisphere grew and joined to constitute a single tissue mass that remodelled basal ganglia anatomy and remained stable in size over time. No evidence of graft growth was observed contralaterally. PET demonstrated increased striatal and stable cortical metabolism. Unified Huntington's Disease Rating Scale assessments demonstrated improvement of motor performances, which faded over the 36-month follow-up. Cognitive performance tended to decrease at a lower rate than before transplantation. CONCLUSION: The striatal primordium grew into the host brain and this process was associated with metabolic change and some clinical benefit. The study suggests the plasticity and reparative potential of un-manipulated primordium in an era where promising cell-based therapies are still in their infancy.