Migration of bone marrow-derived very small embryonic-like stem cells toward an injured spinal cord

Abstract Objective: Bone marrow (BM) is one of the major hematopoietic organs in postnatal life that consists of a heterogeneous population of stem cells which have been previously described. Recently, a rare population of stem cells that are called very small embryonic-like (VSEL) stem cells has been found in the BM. These cells express several developmental markers of pluripotent stem cells and can be mobilized into peripheral blood (PB) in response to tissue injury. In this study we have attempted to investigate the ability of these cells to migrate toward an injured spinal cord after transplantation through the tail vein in a rat model. Materials and Methods: In this experimental study, VSELs were isolated from total BM cells using a fluorescent activated cell sorting (FACS) system and sca1 and stage specific embryonic antigen (SSEA-1) antibodies. After isolation, VSELs were cultured for 7 days on C2C12 as the feeder layer. Then, VSELs were labeled with 1,1´-dioctadecyl-3,3,3´,3´- tetramethylindocarbocyanine perchlorate (DiI) and transplanted into the rat spinal cord injury (SCI) model via the tail vein. Finally, we sought to determine the presence of VSELs in the lesion site. Results: We isolated a high number of VSELs from the BM. After cultivation, the VSELs colonies were positive for SSEA-1, Oct4 and Sca1. At one month after transplantation, real-time polymerase chain reaction analysis confirmed a significantly increased expression level of Oct4 and SSEA-1 positive cells at the injury site. Conclusion: VSELs have the capability to migrate and localize in an injured spinal cord after transplantation

Pessimistic Off-Policy Multi-Objective Optimization

Multi-objective optimization is a type of decision making problems where multiple conflicting objectives are optimized. We study offline optimization of multi-objective policies from data collected by an existing policy. We propose a pessimistic estimator for the multi-objective policy values that can be easily plugged into existing formulas for hypervolume computation and optimized. The estimator is based on inverse propensity scores (IPS), and improves upon a naive IPS estimator in both theory and experiments. Our analysis is general, and applies beyond our IPS estimators and methods for optimizing them. The pessimistic estimator can be optimized by policy gradients and performs well in all of our experiments

Learning Physical Models that Can Respect Conservation Laws

Recent work in scientific machine learning (SciML) has focused on incorporating partial differential equation (PDE) information into the learning process. Much of this work has focused on relatively ``easy'' PDE operators (e.g., elliptic and parabolic), with less emphasis on relatively ``hard'' PDE operators (e.g., hyperbolic). Within numerical PDEs, the latter problem class requires control of a type of volume element or conservation constraint, which is known to be challenging. Delivering on the promise of SciML requires seamlessly incorporating both types of problems into the learning process. To address this issue, we propose ProbConserv, a framework for incorporating conservation constraints into a generic SciML architecture. To do so, ProbConserv combines the integral form of a conservation law with a Bayesian update. We provide a detailed analysis of ProbConserv on learning with the Generalized Porous Medium Equation (GPME), a widely-applicable parameterized family of PDEs that illustrates the qualitative properties of both easier and harder PDEs. ProbConserv is effective for easy GPME variants, performing well with state-of-the-art competitors; and for harder GPME variants it outperforms other approaches that do not guarantee volume conservation. ProbConserv seamlessly enforces physical conservation constraints, maintains probabilistic uncertainty quantification (UQ), and deals well with shocks and heteroscedasticities. In each case, it achieves superior predictive performance on downstream tasks

Nuclear Factor Kappa-B Protein Levels in Sperm of Obese Men with and without Diabetes; Cellular Approach in Male Infertility

Objective: Although the role of obesity and diabetes mellitus (DM) in male infertility is well established, little informationabout the underlying cellular mechanisms in infertility is available. In this sense, nuclear factor kappa-B (NF-kB) hasbeen recognized as an important regulator in obesity and DM; However, its function in the pathogenesis of maleinfertility has never been studied in obese or men who suffer from diabetes. Therefore, the main goal of current researchis assessing NF-kB existence and activity in ejaculated human spermatozoa considering the obesity and diabeticscondition of males. Materials and Methods: In an experimental study, the ELISA technique was applied to analyze NF-kB levels in spermof four experimental groups: non-obese none-diabetic men (body mass index (BMI) 30 kg/m2; OB group; n=30), non-obese diabetic men (BMI 30 kg/m2; OB-DM group; n=30) who were presented to Royan Institute Infertility Center.In addition, protein localization was shown by Immunocytofluorescent assay. Sperm features were also evaluated usingCASA. Results: The diabetic men were older than non-diabetic men regardless of obesity status (P=0.0002). Sperm progressivemotility was affected by obesity (P=0.035) and type A sperm progressive motility was affected by DM (P=0.034). Theconcentration of sperm (P=0.013), motility (P=0.025) and morphology (P<0.0001) were altered by obesity × diabetesinteraction effects. The NF-kB activity was negatively influenced by the main impact of diabetics (P=0.019). Obesitydid not affect (P=0.248) NF-kB activity. Uniquely, NF-kB localized to the midpiece of sperm and post-acrosomal areas. Conclusion: The current study indicated a lower concentration of NF-kB in diabetic men, no effect of obesity on NF-kBwas observed yet. Additionally, we revealed the main obesity and diabetes effects, and their interaction effect adverselyinfluenced sperm characteristics

The Effect of Mesenchymal Stem Cells Derived-Conditioned Media in Combination with Oral Anti-Androgenic Drugs on Male Pattern Baldness: An Animal Study

Objective: Androgenetic alopecia (AGA) is a prevalent form of hair loss, mainly caused by follicular sensitivity toandrogens. Despite developing different anti-androgen treatment options, the success rate of these treatments hasbeen limited. Using animal models, this study evaluated the therapeutic effects of umbilical cord (UC) stem cellconditioned media (CM) combined with oral anti-androgens for hair regeneration.Materials and Methods: In this experimental study, Poloxamer 407 (P407) was used as a drug carrier forsubcutaneous testosterone injection. AGA models were treated with oral finasteride, oral flutamide, and CMinjections. Samples were thoroughly evaluated and compared using histological, stereological, and molecularanalyses.Results: Injecting CM-loaded hydrogel alone or combined with oral intake of anti-androgens improved hair regeneration.These treatments could promote hair growth by inducing hair follicles in the anagen stage and shortening the telogenand catagen phases. Furthermore, the combination treatment led to an upregulation of hair induction gene expressionwith a downregulation of inflammation genes.Conclusion: Through a reduction in inflammation, injection of CM-loaded hydrogel alone or combined with oral intakeof anti-androgens induces the hair cell cycle with regeneration in damaged follicles. Hence, this could be a promisingtherapeutic method for AGA patients

Evaluating The Association Between Serum Hsp27 Antibody and Hypertension in Patients without Underlying Cardiovascular Disease

Introduction: An association between heat shock protein 27 (Hsp27) antigen with cardiovascular risk factors has been shown previously. Furthermore, higher levels of serum anti-HSP27 antibodies are also related to higher cardiovascular morbidity and mortality. In the current study, we looked at the relationship between serum Hsp27 antibodies and hypertension, as an important cardiovascular risk factor, in individuals without evidence of cardiovascular disease (CVD).Methods: A sub-population of hypertensive patients (HTN+) without underlying CVD were recruited from the Mashhad stroke and atherosclerosis heart disease (MASHAD) study to assess the association between serum Hsp27 antibodies and hypertension; independent of other cardiovascular risk factors. A total of 1599 people were studied of whom 288 individuals had hypertension and 1311 were used as controls (HTN-).Results: Mean serum Hsp27 antibody titers were 0.20 (0.27) OD in the whole population sample and was not significantly different in the normotensive (HTN-) compared to HTN+ individuals with different degrees of hypertension.Conclusion: There were no significant associations between serum anti-Hsp27 concentrations and either the presence or severity of hypertension. Future studies are warranted to explore the association of anti-Hsp27 antibody and antigen levels and other cardiovascular risk factors

More Than Smell—COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis

Correction: Chemical Senses, Volume 46, 2021, bjab050, https://doi.org/10.1093/chemse/bjab050 Published: 08 December 2021Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change +/- 100) revealed a mean reduction of smell (-79.7 +/- 28.7, mean +/- standard deviation), taste (-69.0 +/- 32.6), and chemesthetic (-37.3 +/- 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis.The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.Peer reviewe