Project description:Alopecia is a challenging condition for both physicians and patients. Several topical, intralesional, oral, and surgical treatments have been developed in recent decades, but some of those therapies only provide partial improvement. Advanced medical therapies are medical products based on genes, cells, and/or tissue engineering products that have properties in regenerating, repairing, or replacing human tissue. In recent years, numerous applications have been described for advanced medical therapies. With this background, those therapies may have a role in the treatment of various types of alopecia such as alopecia areata and androgenic alopecia. The aim of this review is to provide dermatologists an overview of the different advanced medical therapies that have been applied in the treatment of alopecia, by reviewing clinical and basic research studies as well as ongoing clinical trials.
Project description:Matrix metalloproteinase-9 (MMP-9) deletion attenuates collagen accumulation and dilation of the left ventricle (LV) post-myocardial infarction (MI); however the biomechanical mechanisms underlying the improved outcome are poorly understood. The aim of this study was to determine the mechanisms whereby MMP-9 deletion alters collagen network composition and assembly in the LV post-MI to modulate the mechanical properties of myocardial scar tissue. Adult C57BL/6J wild-type (WT; n=88) and MMP-9 null (MMP-9(-/-); n=92) mice of both sexes underwent permanent coronary artery ligation and were compared to day 0 controls (n=42). At day 7 post-MI, WT LVs displayed a 3-fold increase in end-diastolic volume, while MMP-9(-/-) showed only a 2-fold increase (p<0.05). Biaxial mechanical testing revealed that MMP-9(-/-) infarcts were stiffer than WT infarcts, as indicated by a 1.3-fold reduction in predicted in vivo circumferential stretch (p<0.05). Paradoxically, MMP-9(-/-) infarcts had a 1.8-fold reduction in collagen deposition (p<0.05). This apparent contradiction was explained by a 3.1-fold increase in lysyl oxidase (p<0.05) in MMP-9(-/-) infarcts, indicating that MMP-9 deletion increased collagen cross-linking activity. Furthermore, MMP-9 deletion led to a 3.0-fold increase in bone morphogenetic protein-1, the metalloproteinase that cleaves pro-collagen and pro-lysyl oxidase (p<0.05) and reduced fibronectin fragmentation by 49% (p<0.05) to enhance lysyl oxidase activity. We conclude that MMP-9 deletion increases infarct stiffness and prevents LV dilation by reducing collagen degradation and facilitating collagen assembly and cross-linking through preservation of the fibronectin network and activation of lysyl oxidase.
Project description:Phosphorylcholine monoclonal immunoglobulin G antibody attenuates the immediate post-ischemic inflammatory response by reducing the proinflammatory chemokine (C-C motif) ligand 2 chemokine and circulating Ly-6Chi monocytes. This subsequently enhances the post-ischemic repair process, resulting in limited adverse cardiac remodeling and preservation of cardiac function. Therefore, phosphorylcholine monoclonal immunoglobulin G antibody therapy may be a valid therapeutic approach against myocardial ischemia-reperfusion injury.
Project description:BackgroundOxidative stress is an important factor involved in the progress of heart failure. The current study was performed to investigate whether pinocembrin was able to ameliorate post-infarct heart failure (PIHF) and the underlying mechanisms.MethodsRats were carried out left anterior descending artery ligation to induce myocardial infarction and subsequently raised for 6 weeks to produce chronic heart failure. Then pinocembrin was administrated every other day for 2 weeks. The effects were evaluated by echocardiography, western blot, Masson's staining, biochemical examinations, immunohistochemistry, and fluorescence. In vitro we also cultured H9c2 cardiomyocytes and cardiac myofibroblasts to further testify the mechanisms.ResultsWe found that PIHF-induced deteriorations of cardiac functions were significantly ameliorated by administrating pinocembrin. In addition, the pinocembrin treatment also attenuated collagen deposition and augmented vascular endothelial growth factor receptor 2 in infarct border zone along with an attenuated apoptosis, which were related to an amelioration of oxidative stress evidenced by reduction of reactive oxygen species (ROS) in heart tissue and malondialdehyde (MDA) in serum, and increase of superoxide dismutase (SOD). This were accompanied by upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway. In vitro experiments we found that specific Nrf2 inhibitor significantly reversed the effects resulted from pinocembrin including antioxidant, anti-apoptosis, anti-fibrosis and neovascularization, which further indicated the amelioration of PIHF by pinocembrin was in a Nrf2/HO-1 pathway-dependent manner.ConclusionPinocembrin ameliorated cardiac functions and remodeling resulted from PIHF by ROS scavenging and Nrf2/HO-1 pathway activation which further attenuated collagen fibers deposition and apoptosis, and facilitated angiogenesis.
Project description:Breast cancer has become the most prevalent cancer globally, predominantly affecting women, with mastectomy surgery a frequent treatment. Women often experience a discrepancy between their post-mastectomy body, and their former sense of self, affecting negatively on wellbeing. The narratives of eight women who chose to artistically tattoo over their mastectomy scars were explored in this study, through semi-structured interviews and Interpretative Phenomenological Analysis (IPA). Seven master themes are presented. These themes follow the women from a state of disruption (of body image and gender identity) and surgical scarring as the first marking of the body, to the second marking of the body through artistic tattooing, bringing with it transformation, acceptance, feeling heard and connection with the artist, closure and control and the creation of significance and meaning. Viewed through Self-Discrepancy Theory, the findings of this study has implications for psycho-oncology and wellbeing support for women following mastectomy surgery.
Project description:Wound healing (WH) is a complex multistep process in which a failure could lead to a chronic wound (CW). CW is a major health problem and includes leg venous ulcers, diabetic foot ulcers, and pressure ulcers. CW is difficult to treat and affects vulnerable and pluripathological patients. On the other hand, excessive scarring leads to keloids and hypertrophic scars causing disfiguration and sometimes itchiness and pain. Treatment of WH includes the cleaning and careful handling of injured tissue, early treatment and prevention of infection, and promotion of healing. Treatment of underlying conditions and the use of special dressings promote healing. The patient at risk and risk areas should avoid injury as much as possible. This review aims to summarize the role of physical therapies as complementary treatments in WH and scarring. The article proposes a translational view, opening the opportunity to develop these therapies in an optimal way in clinical management, as many of them are emerging. The role of laser, photobiomodulation, photodynamic therapy, electrical stimulation, ultrasound therapy, and others are highlighted in a practical and comprehensive approach.
Project description:Purpose of reviewTo examine the use of positron emission tomography (PET) for imaging post-infarct myocardial inflammation and repair.Recent findingsDysregulated immune responses after myocardial infarction are associated with adverse cardiac remodelling and an increased likelihood of ischaemic heart failure. PET imaging utilising novel tracers can be applied to visualise different components of the post-infarction inflammatory and repair processes. This approach could offer unique pathophysiological insights that could prove useful for the identification and risk-stratification of individuals who would ultimately benefit most from emerging immune-modulating therapies. PET imaging could also bridge the clinical translational gap as a surrogate measure of drug efficacy in early-stage clinical trials in patients with myocardial infarction. The use of hybrid PET/MR imaging, in particular, offers the additional advantage of simultaneous in vivo molecular imaging and detailed assessment of myocardial function, viability and tissue characterisation. Further research is needed to realise the true clinical translational value of PET imaging after myocardial infarction.
Project description:Post-stroke seizure (PSS) can have a strong negative impact on functional recovery after stroke. Researchers have identified numerous risk factors of PSS; however, the relationship between infarction location and PSS remains unclear. We recruited patients who presented with an acute cerebral infarction between 2012 and 2017 and suffered from seizures within 1 year after stroke (PSS group). PSS group was subgrouped into early-PSS and late-PSS groups based on the interval between seizure and stroke. We also recruited an equal number of acute cerebral infarction patients without post-stroke seizures during the follow-up period (Non-PSS group). All brain MRIs from the two groups were processed, whereupon normalized infarct maps from the PSS and Non-PSS groups were compared via voxel- and volumetric-based analyses. A total of 132 subjects were enrolled in the study, including PSS (n = 66, consisting of 31 early-PSS and 35 late-PSS) and Non-PSS (n = 66) patients. No significant differences were observed between the two groups in terms of stroke lateralization or severity. Image analysis revealed that the volume of infarction was larger in the PSS group than in the Non-PSS group; however, the difference did not reach the level of significance. Unlike the Non-PSS group, the PSS group presented hot spots over the left central region, left superior parietal lobule, and right frontal operculum. We observed differences between the distribution of hot spots among patients with early-PSS and those with late-PSS. We found that some brain regions were significantly associated with the development of PSS after ischemic stroke, and these regions differed between cases of early and late PSS. It appears that the location of infarction could help clinicians assess the risk of PSS in specific post-stroke stages.
Project description:During wound healing, excessive inflammation, angiogenesis, and differentiated human dermal fibroblast (HDF ) function contribute to scarring, whereas hyperpigmentation negatively affects scar quality. Over 100 million patients heal with a scar every year. To investigate the role of the beta 2 adrenergic receptor (β2AR) in wound scarring, the ability of beta 2 adrenergic receptor agonist (β2ARag) to alter HDF differentiation and function, wound inflammation, angiogenesis, and wound scarring was explored in HDFs, zebrafish, chick chorioallantoic membrane assay (CAM), and a porcine skin wound model, respectively. Here we identify a β2AR-mediated mechanism for scar reduction. β2ARag significantly reduced HDF differentiation, via multiple cAMP and/or fibroblast growth factor 2 or basic FGF (FGF2)-dependent mechanisms, in the presence of transforming growth factor betaβ1, reduced contractile function, and inhibited mRNA expression of a number of profibrotic markers. β2ARag also reduced inflammation and angiogenesis in zebrafish and CAMs in vivo, respectively. In Red Duroc pig full-thickness wounds, β2ARag reduced both scar area and hyperpigmentation by almost 50% and significantly improved scar quality. Indeed, mechanisms delineated in vitro and in other in vivo models were evident in the β2ARag-treated porcine scars in vivo. Both macrophage infiltration and angiogenesis were initially decreased, whereas DF function was impaired in the β2ARag-treated porcine wound bed. These data collectively reveal the potential of β2ARag to improve skin scarring.
Project description:The management of locally advanced rectal cancer has undergone significant transformations over the decades and optimal treatment approaches continue to evolve. There have been numerous advances in surgery, chemotherapy, and radiation therapy from the first description of the abdominoperineal resection in 1908, timing of chemotherapy and radiation therapy in the late 20th and early 21st century, and most recently, the introduction of organ preservation or nonoperative management in 2004. Alongside these advancements, the concept of shared decision making in medicine has evolved, prompting a focus on patient-centered care. This evolution in practice has been fueled by a growing recognition of the importance of patient autonomy and the alignment of treatment options with patients' values and preferences. With the growing number of possible treatment options, variability in patient counseling exists, highlighting the need for a standardized approach to shared decision making in locally advanced rectal cancer. This narrative review will describe the evolution of treatment options of locally advanced rectal cancer as well as the concept of shared decision making and decision aids, and will introduce a decision aid for patients with locally advanced rectal cancer who have achieved a complete clinical response and are eligible for watch and wait.