Ratiometric Fluorescent Probe Promotes Trans-differentiation of Human Mesenchymal Stem Cells to Neurons.

Development of multifunctional theranostics is challenging and crucial for deciphering complex biological phenomena and subsequently treating critical disease. In particular, development of theranostics for traumatic brain injury (TBI) and understanding its repair mechanism are challenging and highly complex areas of research. Recently, there have been interesting pieces of research work demonstrated that a small molecule-based neuroregenerative approach using stem cells has potential for future therapeutic lead development for TBI. However, these works demonstrated the application of a mixture of multiple molecules as a "chemical cocktail", which may have serious toxic effects in the differentiated cells. Therefore, development of a single-molecule-based potential differentiating agent for human mesenchymal stem cells (hMSCs) into functional neurons is vital for the upcoming neuro-regenerative therapeutics. This lead could be further extraploted for the design of theranostics for TBI. In this study, we have developed a multifunctional single-molecule-based fluorescent probe, which can image the transdifferentiated neurons as well as promote the differentiation process. We demonstrated a promising class of fluorescent probes (CP-4) that can be employed to convert hMSCs into neurons in the presence of fibroblast growth factor (FGF). This fluorescent probe was used in cellular imaging as its fluorescence intensity remained unaltered for up to 7 days of trans-differentiation. We envision that this imaging probe can have an important application in the study of neuropathological and neurodegenerative studies.

Cell-Derived Exosome Therapy: A Novel Approach to Treat Post-traumatic Brain Injury Mediated Neural Injury.

Traumatic brain injury (TBI) causes serious neuronal injury that often leads to death. To date there is no clinically successful treatment strategy that has been reported which offers repair of the brain injury or neural injury. Significant attempts have been made to develop effective therapies for TBI, and one of the most promising approaches is a stem cell based therapeutic approach with mesenchymal stem cells (MSCs). This approach is regarded as having the most potential in regenerative medicine. Toward this venture, the generation and release of exosomes can be attributed to the therapeutic effects of MSCs. Exosomes are nanosized vesicles, carry proteins, lipids, mRNA, and miRNA, and assist in cell-cell communication. Exosomes can interact with brain parenchyma cells and with the neurogenic niche, which can help in neurogenesis and brain remodeling. Exosomes derived from MSCs and human-induced pluripotent stem cells (hiPSCs) can be a promising approach in neuronal injury healing. In this Viewpoint, we discussed the most recent knowledge for exosome therapies for neural injuries and highlighted the major advantages of this therapy.

Extracapsular excision of hepatic hemangioma: A single centre experience.

BACKGROUNDS/AIMS: Hepatic hemangioma is a common non-epithelial neoplasm of the liver. Presence of symptoms and uncertainty in diagnosis are the most common indications for surgery. METHODS: Eighteen patients with hepatic hemangioma, operated on from January 2011 to December 2016 at the Hepato-pancreato-biliary surgical unit of Tata Memorial Hospital, were retrospectively analyzed. RESULTS: Main indications for operation were presence of symptoms, the most common being pain and diagnostic uncertainty. The median size of hemangioma was 9.9 cm (range 3.2 to 24 cm). All patients underwent extra-capsular excision of hemangioma. The median operating time was 180 minutes (range 75 to 460 minutes) and median blood loss was 950 ml (range 100 to 3,500 ml). Median post-operative stay was 5.5 days (range 3 to 10 days). One (5.6%) patient required re-exploration for post-operative hemorrhage, Clavien Dindo (CD) grade IIIb, and one (5.6%) had postoperative purulent intra-abdominal collection requiring percutaneous cutaneous drainage CD grade IIIa. There was no postoperative mortality. Postoperative day 3 liver function tests were within normal limits. Size of the tumor did not correlate significantly with postoperative complications (p=0.135). CONCLUSIONS: Surgical treatment of hemangioma should be guided by presence of symptoms or by the presence of diagnostic uncertainty, not by size alone. The size had no correlation with perioperative complications. The technique of extra-capsular excision is safe and technically feasible in most of the hemangiomas. This technique preserves maximum liver parenchyma, resulting in early postoperative recovery with minimal morbidity.

Aurora kinase-induced phosphorylation excludes transcription factor RUNX from the chromatin to facilitate proper mitotic progression.

The Runt-related transcription factors (RUNX) are master regulators of development and major players in tumorigenesis. Interestingly, unlike most transcription factors, RUNX proteins are detected on the mitotic chromatin and apparatus, suggesting that they are functionally active in mitosis. Here, we identify key sites of RUNX phosphorylation in mitosis. We show that the phosphorylation of threonine 173 (T173) residue within the Runt domain of RUNX3 disrupts RUNX DNA binding activity during mitotic entry to facilitate the recruitment of RUNX proteins to mitotic structures. Moreover, knockdown of RUNX3 delays mitotic entry. RUNX3 phosphorylation is therefore a regulatory mechanism for mitotic entry. Cancer-associated mutations of RUNX3 T173 and its equivalent in RUNX1 further corroborate the role of RUNX phosphorylation in regulating proper mitotic progression and genomic integrity.

Calculating prevalence of hepatitis B in India: using population weights to look for publication bias in conventional meta-analysis.

Publication bias can result from the propensity of researchers to document what is unusual. This can distort the inferences drawn in systematic reviews. To measure the distortion, it has been suggested that a second analysis be done; using weights proportional to the size of the population from which the samples are drawn. We re-evaluate data from a published meta-analysis on prevalence of hepatitis B in India, to see how this approach alters the results. Prevalence of hepatitis B among tribal and non-tribal populations in different States was analyzed. Weights were then assigned according to population of the State. The overall country prevalence was then calculated. Using population-weights it is estimated that the point-prevalence of hepatitis B among non-tribal populations is 3.07% [95% CI: 2.5-3.64]. Among tribal populations it is 11.85% (CI 10.76-12.93). Overall prevalence was 3.70 (CI: 3.17-4.24) (corresponding to a chronic carrier rate of 2.96%). The present analysis using population-weights has resulted in the estimated prevalence among non tribal populations increasing by 24% and that among tribal populations decreasing by 25.5% when compared to figures of the meta-analysis published earlier. The advantages and drawbacks of this procedure are discussed.