Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization

Regenerative medicine is a novel approach for treating conditions in which enhanced bone regeneration is required. We identified transgelin (TAGLN), a transforming growth factor beta (TGFβ)-inducible gene, as an upregulated gene during in vitro osteoblastic and adipocytic differentiation of human bone marrow-derived stromal (skeletal) stem cells (hMSC). siRNA-mediated gene silencing of TAGLN impaired lineage differentiation into osteoblasts and adipocytes but enhanced cell proliferation. Additional functional studies revealed that TAGLN deficiency impaired hMSC cell motility and in vitro transwell cell migration. On the other hand, TAGLN overexpression reduced hMSC cell proliferation, but enhanced cell migration, osteoblastic and adipocytic differentiation, and in vivo bone formation. In addition, deficiency or overexpression of TAGLN in hMSC was associated with significant changes in cellular and nuclear morphology and cytoplasmic organelle composition as demonstrated by high content imaging and transmission electron microscopy that revealed pronounced alterations in the distribution of the actin filament and changes in cytoskeletal organization. Molecular signature of TAGLN-deficient hMSC showed that several genes and genetic pathways associated with cell differentiation, including regulation of actin cytoskeleton and focal adhesion pathways, were downregulated. Our data demonstrate that TAGLN has a role in generating committed progenitor cells from undifferentiated hMSC by regulating cytoskeleton organization. Targeting TAGLN is a plausible approach to enrich for committed hMSC cells needed for regenerative medicine application

Anoctamin1 and c-Kit immunohistochemical study of interstitial cells of Cajal in the muscularis externa of human gastrointestinal tract

Background: Interstitial cells of Cajal )ICC) are widely distributed in human gastrointestinal (GI) tract  specially in the layer of muscularis externa between neurons and smooth muscles. They play a very important role of coordination of GI tract motility. The aims of this research were to study the morphology and distribution of ICC in the muscularis externa of the GI tract, using immunohistochemistry staining methods, to determine the distribution of immune reactivity of Anoctamin1 (Ano1) compared with c-Kit, and to determine if Ano1 is a reliable marker for ICC in human GI tract. Materials and methods: Specimens from the wall of stomach, small intestine, and colon were taken from human cadavers and processed for histological and immunohistochemical study using c-Kit and Ano1 primary antibodies. Results: ICC appeared as bipolar cells, not forming network, in both the circular and longitudinal muscle layers, while in the myenteric area they appeared as multipolar interconnected cells. They were unevenly distributed in and between the muscle layers of the muscularis externa of human GI tract. They were more numerous in the stomach followed by the colon then the small intestine, and more numerous in the myenteric area followed by the circular muscle layer then the longitudinal muscle layer, in the three organs. Our results also showed that Ano1 is a more reliable marker for human ICC than c-kit. Conclusions: ICC differed in morphology and were unevenly distributed between muscle layers of muscularis externa and between different parts of human GI tract

Is high soleus muscle activity during the stance phase of the running cycle a potential risk factor for the development of medial tibial stress syndrome? A prospective study

© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group. To assess the impact of lower-leg muscle activity during the stance phase of running on the development of medial tibial stress syndrome (MTSS), in 123 healthy participants (18.2 ± 0.8 years), dynamic and static foot posture, and soleus and tibialis anterior muscle activity during the stance phase of running were measured before a 17-week track- and field-course. After the course, MTSS was identified in 20.5% of the participants. MTSS participants had a higher body mass (ES = 1.13), body mass index (BMI) (ES = 1.31), lower previous vigorous physical activity level (ES = 0.84) and VO2max (ES = 0.61), greater dynamic foot pronation (ES = 0.66), higher soleus peak EMG amplitude during the absorption (ES = 0.60) and propulsion phases (ES = 0.56) of running, and a history of MTSS (OR = 6.38) (p < 0.05). Stepwise logistic regression showed BMI, dynamic foot index, soleus peak EMG amplitude during propulsion, MTSS history and previous vigorous physical activity were predictors of MTSS. The model predicted 96.6% of the healthy participants and 56.5% of the MTSS participants and correctly classified 88.4% of overall cases. Coaches and sports-medicine professionals that screen for injury risk should consider adopting a comprehensive evaluation that includes these parameters

Antiparasitic and cytotoxic activity of bokkosin, a novel diterpene-substituted chromanyl benzoquinone from Calliandra portoricensis

Calliandra portoricensis is a medicinal plant growing freely in Nigeria. It is used traditionally to treat tuberculosis, as an anthelmintic and an abortifacient. Phytochemical fractionation and screening of its root extracts has yielded a novel (5-hydroxy-7-methoxy-4-oxo-1-chromanyl)-4-methoxy-p-benzoquinone (breverin)-substituted cassane diterpene, which was designated bokkosin. It was obtained from column chromatography of the ethyl acetate extract of the roots. The compound was characterized using IR, NMR (1D and 2D) and mass spectral data. Promising antiparasitic activity was observed against the kinetoplastid parasite Trypanosoma brucei brucei, as well as moderate activity against Trypanosoma congolense and Leishmania mexicana and low toxicity in mammalian cells, with the best in vitro EC50 values against T. b. brucei (0.69µg/mL against a standard laboratory strain, and its multi-drug resistant clone (0.33µg/mL). The effect on T. b. brucei in culture was rapid and dose-dependent, leading to apparently irreversible growth arrest and cell death after an exposure of just 2 h at 2 × or 4 × EC50. The identification of bokkosin constitutes the first isolation of this class of compound from any natural source and establishes the compound as a potential trypanocide that, considering its novelty, should now be tested for activity against other microorganisms as well

Research barriers in Saudi pharmacy residency training programs

Background: The aim of this study is to identify potential barriers to conducting and publishing pharmacy residency research. Methods: A cross-sectional study surveyed pharmacy residents in Saudi Arabia from August to September 2020. The online survey assesses residents’ characteristics, residency research experience, barriers to completion, and challenges in publishing. A Likert scale assessed factors and barriers to conducting and publishing research during residency. Descriptive statistics were performed for binary variables, with Likert scale responses visualized using Gannt charts. Results: A total of 69 residents completed the survey, of whom 63.5 percent were female, and the median age was 28 years. More than half of the residents were in R2 (56.5 %), followed by R1 (24.6 %) and R3 (4.4 %). Half of residents had prior research experience, while 84.1 % had prior research training in workshops or courses. Cohort study design was the most common type of residency research project conducted. According to residents, the main barriers to conducting research were a lack of allocated time for research during rotations (81.7 %) and a lack of a realistic timeline determined by the SCFHS to finish the research project (66.2 %). Regarding barriers to publishing research, the majority of residents reported lack of time to work on the publication process (78.6 %), lack of previous publication experience (60 %), and lack of guidance from mentors (55.7 %) as the most important barriers. Conclusion: Pharmacy residents face barriers to conducting research during their residency program, including limited allocated time during rotations, a lack of realistic timelines, and data collection limitations. Additionally, they face challenges in publishing their research due to a lack of experience, mentorship, and guidance. Future research should consider seeking the perspective of residency program directors and preceptors on research barriers and evaluating the publication rate of residents’ projects

Appropriateness of proton pump inhibitors use in noncritically ill hospitalized children in a tertiary hospital in Saudi Arabia

Background: Studies assessing the appropriate use of proton pump inhibitors (PPIs) for hospitalized noncritically ill pediatric patients are lacking. Therefore, this study aimed to assess the suitability of PPI prescriptions in noncritically ill pediatric patients. Methods: This cross sectional retrospective study was conducted at a maternity hospital in Qassim, Saudi Arabia from November 2020 to January 2021. All noncritically ill hospitalized children aged 14 years and below who received PPIs were included. The endpoints included the number and percentage of patients who appropriately received PPIs in general and in each age category. The collected data were analyzed using Microsoft Excel (version 2208, Microsoft Corp., Redmond, WA, USA). Results: In total, 332 medical records were screened, of which 246 were included. Of all patients, 49.2% were children and 50.8% were infants, with the average age at admission being 5.39 ± 5.4 years years. More than half of the patients were female, and the average weight of patients was 19.8 kg. Omeprazole was appropriately used in 95 (38.5%) patients. Based on age groups, omeprazole was appropriately used in 66.3% of children and 38.4% of infants. Conclusion: The use of omeprazole in noncritically ill pediatrics was only deemed appropriate in 38.6% of the study population. This result indicates that this medication was overused in the institution. Additional research is required to confirm this on a nationwide scale

Esculeogenin A, a Glycan from Tomato, Alleviates Nonalcoholic Fatty Liver Disease in Rats through Hypolipidemic, Antioxidant, and Anti-Inflammatory Effects

This study examined the preventative effects of esculeogenin A (ESGA), a newly discovered glycan from tomato, on liver damage and hepatic steatosis in high-fat-diet (HFD)-fed male rats. The animals were divided into six groups (each of eight rats): a control group fed a normal diet, control + ESGA (200 mg/kg), HFD, and HFD + ESAG in 3 doses (50, 100, and 200 mg/kg). Feeding and treatments were conducted for 12 weeks. Treatment with ESGA did not affect gains in the body or fat weight nor increases in fasting glucose, insulin, and HOMA-IR or serum levels of free fatty acids (FFAs), tumor-necrosis factor-α, and interleukin-6 (IL-6). On the contrary, it significantly reduced the serum levels of gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-c) in the HFD-fed rats. In addition, it improved the liver structure, attenuating the increase in fat vacuoles; reduced levels of TGs and CHOL, and the mRNA levels of SREBP1 and acetyl CoA carboxylase (ACC); and upregulated the mRNA levels of proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase I (CPT I) in HFD-fed rats. These effects were concomitant with increases in the mRNA, cytoplasmic, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO); a reduction in the nuclear activity of nuclear factor-kappa beta (NF-κB); and inhibition of the activity of nuclear factor kappa B kinase subunit beta (IKKβ). All of these effects were dose-dependent effects in which a normal liver structure and normal levels of all measured parameters were seen in HFD + ESGA (200 mg/kg)-treated rats. In conclusion, ESGA prevents NAFLD in HFD-fed rats by attenuating hyperlipidemia, hepatic steatosis, oxidative stress, and inflammation by acting locally on Nrf2, NF-κB, SREBP1, and PPARα transcription factors