Research Spotlight

Jing, D., Li, C., Yao, K., Xie, X., Wang, P., Zhao, H., Feng, J.Q., Zhao, Z., Wu, Y. and Wang, J. (2021). “The vital role of Gli1(+) mesenchymal stem cells in tissue development and homeostasis.” J Cell Physiol.

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The hedgehog (Hh) signaling pathway plays an essential role in both tissue development and homeostasis. Glioma-associated oncogene homolog 1 (Gli1) is one of the vital transcriptional factors as well as the direct target gene in the Hh signaling pathway. The cells expressing the Gli1 gene (Gli1(+) cells) have been identified as mesenchymal stem cells (MSCs) that are responsible for various tissue developments, homeostasis, and injury repair. This review outlines some recent discoveries on the crucial roles of Gli1(+) MSCs in the development and homeostasis of varieties of hard and soft tissues.

George, S.M., Campbell, P.M., Tadlock, L.P., Schneiderman, E. and Buschang, P.H. (2021). “Keys to Class II correction: A comparison of 2 extraction protocols.” Am J Orthod Dentofacial Orthop 159(3): 333-342.

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INTRODUCTION: The purpose of this study was to evaluate the effects of 2 extraction patterns on incisor and molar movements in patients with growing Class II Division 1. METHODS: The sample included 54 patients 10-17 years of age treated by 2 private practice orthodontists using Tweed directional force mechanics, 4 premolar extractions, J-hook headgears, and Class II elastics or Saif springs. The sample was divided on the basis of having maxillary and mandibular first premolars (4/4) or maxillary first and mandibular second premolars (4/5) extracted. Each group included 27 patients. Treatment lasted 2.8 ± 0.60 years and 2.6 ± 0.54 years for the 4/4 and 4/5 groups, respectively. Pretreatment (T1) and posttreatment lateral cephalograms and dental casts were evaluated. Cranial base, mandibular, and maxillary superimpositions were performed to quantify tooth movements and displacements. RESULTS: There were no statistically significant T1 between-group differences in crowding or in the SNA, SNB, ANB, and MPA angles. Analyses of covariance, controlling for statistically significant (P <0.05) differences in T1 mandibular incisor position, showed that mandibular first premolars extractions produced greater (1.6 mm) mandibular incisor retraction than second premolar extractions. The mandibular first molars were protracted significantly more (0.7 mm) after the second premolar than the first premolar extractions. Within-group changes of the MPA, between-group differences in the changes in MPA, and the amount of vertical eruption of the maxillary and mandibular molars were not significantly different between the 2 extraction patterns. CONCLUSIONS: Extraction of mandibular second premolars enhances Class II molar correction, with greater mesial first molar movement and less distal incisor movement. Neither extraction pattern has an effect on the MPA or the vertical dimension (ie, there was no "wedge effect").

Yun, H.C., Cable, C.T., Pizzimenti, D., Desai, S.S., Muchmore, E.A., Vasilias, J., Thomas, C., Nasca, T.J. and Lieh-Lai, M.W. (2020). “Internal Medicine 2035: Preparing the Future Generation of Internists.” J Grad Med Educ 12(6): 797-800

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Residency education should prepare physicians for practice. While no one would intentionally design a residency program otherwise, planning program requirements to meet this aim is difficult. Substantial changes in program requirements take years to establish. With the rapid changes in health care, program requirements that are appropriate in 2020 will be out of date by the time that the residents trained entirely under those requirements graduate. [No abstract; excerpt from article].

Walters, D.C., Jansen, E.E.W., Salomons, G.S., Arning, E., Ashcraft, P., Bottiglieri, T., Roullet, J.B. and Gibson, K.M. (2020). “Preferential accumulation of the active S-(+) isomer in murine retina highlights novel mechanisms of vigabatrin-associated retinal toxicity.” Epilepsy Res Dec 29;170:106536. [Epub ahead of print].

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((S)-(+)/(R)-(-)) vigabatrin (Sabril(R); γ-vinyl GABA), an antiepileptic irreversibly inactivating GABA-transaminase, was administered to male C57Bl6 J mice via continuous infusion (0, 40, 80 mg/kg/d) for 12 days. Our study design pooled retina, eye (minus retina), whole brain and plasma from n = 24 animals for each dose to provide n = 8 triplicates per treatment group. Hypothesizing that (S)-(+) VGB (active isomer) would preferentially accumulate in retina, we determined VGB isomers, comprehensive amino acids, and pharmacokinetic parameters. In brain, eye and plasma, the ((S)-(+)/(R)-(-)) ratio varied from 0.73 to 1.29 and 13.3 in retina, accompanied by a partition coefficient (tissue/plasma, ((S)-(+);(R)-(-))) of 5.8;0.34, 0.63;0.49, and 0.51;0.34 in retina, eye and brain, respectively. Racemic VGB (nmol/g; plasma, nmol/mL, range of means for dose) content was: retina, 25-36; eye (minus retina), 4.8-8.0; brain, 3.1-6.8 and plasma, 8.7-14.9. GABA tissue content (nmol/g) was 1246-3335, 18-64 and 2615-3200 as a function of VGB dose for retina, eye (minus retina) and brain, respectively. The retinal glial cell toxin 2-aminoadipic acid also increased with VGB dose (76-96 nmol/g). Partitioning of active (S)-(+) VGB to retina suggests the involvement of a stereospecific transporter, the identification of which could reveal new therapeutic paradigms that might mitigate VGB’s well-known retinal toxicity and expand its clinical utility.

Toden, S., Zumwalt, T.J. and Goel, A. (2020). “Non-coding RNAs and potential therapeutic targeting in cancer.” Biochim Biophys Acta Rev Cancer 1875(1): 188491.

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Recent advances have begun to clarify the physiological and pathological roles of non-coding RNAs (ncRNAs) in various diseases, including cancer. Among these, microRNAs (miRNAs) have been the most studied and have emerged as key players that are involved in the regulation of important growth regulatory pathways in cancer pathogenesis. The ability of a single ncRNA to modulate the expression of multiple downstream gene targets and associated pathways, have provided a rationale to pursue them for therapeutic drug development in cancer. In this context, early data from pre-clinical studies have demonstrated that synthetic miRNA-based therapeutic molecules, along with various protective coating approaches, has allowed for their efficient delivery and anti-tumor activity. In fact, some of the miRNA-based cancer therapeutic strategies have shown promising results even in early-phase human clinical trials. While the enthusiasm for ncRNA-based cancer therapeutics continue to evolve, the field is still in the midst of unraveling a more precise understanding of the molecular mechanisms and specific downstream therapeutic targets of other lesser studied ncRNAs such as the long-non-coding RNAs, transfer RNAs, circular RNAs, small nucleolar RNAs, and piwi-interacting RNAs. This review article provides the current state of knowledge and the evolving principles for ncRNA-based therapeutic approaches in cancer, and specifically highlights the importance of data to date and the approaches that are being developed to overcome the challenges associated with their delivery and mitigating the off-target effects in human cancers.