Comparison of mitochondrial transplantation by using a stamp-type multineedle injector and platelet-rich plasma therapy for hair aging in naturally aging mice.

The mechanism of hair loss caused by aging is related to mitochondrial dysfunction. Pep-1-mediated mitochondrial transplantation is a potential therapeutic application for mitochondrial disorders, but its efficacy against hair aging remains unknown. This study compared platelet-rich plasma (PRP) therapy with mitochondrial transplantation for hair restoration and examined the related regulation in naturally aging mice. After dorsal hair removal, 100-week-old mice received weekly unilateral injections of 200 µg of allogeneic mitochondria-labeled 5-bromo-2'-deoxyuridine with (P-Mito) or without Pep-1 conjugation (Mito) or human PRP with a stamp-type electric injector for 1 month. The contralateral sides were used as corresponding sham controls. Compared with the control and corresponding sham groups, all treatments stimulated hair regrowth, and the effectiveness of P-Mito was equal to that of PRP. However, histology revealed that only P-Mito maintained hair length until day 28 and yielded more anagen follicles with abundant dermal collagen equivalent to that of the PRP group. Mitochondrial transplantation increased the thickness of subcutaneous fat compared with the control and PRP groups, and only P-Mito consistently increased mitochondria in the subcutaneous muscle and mitochondrial DNA copies in the skin layer. Therefore, P-Mito had a higher penetrating capacity than Mito did. Moreover, P-Mito treatment was as effective as PRP treatment in comprehensively reducing the expression of aging-associated gene markers, such as IGF1R and MRPS5, and increasing antiaging Klotho gene expression. This study validated the efficacy of mitochondrial therapy in the restoration of aging-related hair loss and demonstrated the distinct effects of PRP treatment.

Radical Scavenging and Antiproliferative Effects of Cordycepin-Rich Ethanol Extract from Brown Rice-Cultivated Cordyceps militaris (Ascomycetes) Mycelium on Breast Cancer Cell Lines.

The yield and efficacy of bioactive compounds from Cordyceps militaris fruiting bodies and its fermented grains usually vary with the strain used. In this study, we compared the antiproliferative, apoptotic, and antioxidative properties of ethanolic extracts of fruiting bodies and solid-stated fermented rice (FRE) from two wild-type strains of C. militaris applied to human breast cancer cell lines. We observed that FRE of the Zhangzhou strain (FRE-Z) produced a high level of cordycepin and exhibited comprehensive in vitro antioxidant activity against the oxidation of 2,2-diphenyl-1-picrylhydrazyl, superoxide, and hydroxyl radicals and low-density lipoprotein. Only FRE-Z exhibited dose-dependent inhibition of cell proliferation in MCF-7 (0.7 mg/mL) and MDA-MB-231 cells (1 mg/mL) after culturing for 24 h. The antiproliferative effects of FRE-Z were associated with an early stage of apoptosis induction at 4 h of treatment with 0.5 mg/mL FRE-Z in MCF-7 cells. The antiproliferative effect was determined to occur through p53 activation but not through the release of mitochondrial apoptosis-inducing factor or caspase-9 activation for an initial culture period of 16 h. In addition to a transient increase in cellular antioxidant enzyme, Cu/Zn superoxide dismutase was identified in MCF-7 cells after 2 h of treatment with FRE-Z. Therefore, FRE-Z, which exhibits various dose- and exposure time-dependent activities, has potential application in breast cancer chemoprevention.

Functional properties of the major outer membrane protein in Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is an opportunistic pathogen that is closely associated with high morbidity and mortality in debilitated and immunocompromised individuals. Therefore, to investigate the pathogenesis mechanism is urgently required. However, there are very few studies to evaluate the functional properties of outer membrane protein, which may contribute to the pathogenesis in S. maltophilia. In this study, three abundant proteins in the outer membrane fraction of S. maltophilia were identified by liquid chromatography-tandem mass spectrometry as OmpW1, MopB, and a hypothetical protein. MopB, a member of the OmpA family, was firstly chosen for functional investigation in this study because many OmpA-family proteins are known to be involved in pathogenesis and offer potential as vaccines. Membrane fractionation analyses demonstrated that MopB was indeed the most abundant outer membrane protein (OMP) in S. maltophilia. For functional studies, the mopB mutant of S. maltophilia (SmMopB) was constructed by insertional mutation. MopB deficiency resulted in a change in the protein composition of OMPs and altered the architecture of the outer membrane. The SmMopB strain exhibited reduced cytotoxicity toward L929 fibroblasts and was more sensitive to numerous stresses, including human serum, sodium dodecyl sulfate, and hydrogen peroxide compared with wildtype S. maltophilia. These results suggest that MopB may be a good candidate for the design of vaccines or anti-MopB drugs for controlling serious nosocomial infections of multidrug-resistant S. maltophilia, especially in immunosuppressed patients.

Influence of auditory deprivation upon the tonopic organization in the inferior colliculus: a Fos immunocytochemical study in the rat.

The frequency organization in the inferior colliculus of neonatally-deafened rats was investigated using electrical stimulation of the cochlea and immunoreactivity for Fos as a marker of neuronal activity. An electrode implanted either at the base or at the apex of the right cochlea delivered a unique 45-min stimulation at two different level intensities and at two time points, i.e. either at 4 weeks or at 4 months. In 4-week-old rats stimulated at 5x threshold, a site-for-site organization was observed since basal or apical stimulation induced a strong labelling in the ventro-medial or in the dorsolateral part of the left inferior colliculus, respectively. In 4-month-old rats, stimulation of the base induced an extremely weak Fos labelling without any specific location in the left inferior colliculus while stimulation of the apex induced a diffuse labelling with two discrete bands being distinguishable in the left inferior colliculus. In 4-week-old rats stimulated at 15x threshold, basal stimulation elicited a diffuse Fos-like immunoreactivity in the left inferior colliculus while apical stimulation yielded a response restricted to the dorsal part of the left inferior colliculus. In 4-month-old rats, no response was detected in the left inferior colliculus after stimulation of the basal part of the cochlea. Stimulation of the apex could still induce a labelling in the dorsolateral left inferior colliculus. Thus, the inferior colliculus exhibits an adult-like tonotopic organization early on independently of any acoustic stimulation. Prolonged absence of auditory input dramatically alters this organization in the inferior colliculus, especially for high frequencies. From a clinical standpoint, these results could argue for early implantation in deaf children.