Injectable pH and Thermo-Responsive Hydrogel Scaffold with Enhanced Osteogenic Differentiation of Preosteoblasts for Bone Regeneration
Creator:
King, Jasmine L., Shrivastava, Roopali, Benhabbour, Soumya Rahima, Shah, Pooja D., and Maturavongsadit, Panita
Date of publication:
2023
Abstract Tesim:
Bone fractures are common in the geriatric population and pose a great economic burden worldwide. While traditional methods for repairing bone defects have primarily been autografts, there are several drawbacks limiting its use. Bone graft substitutes have been used as alternative strategies to improve bone healing. However, there remain several impediments to achieving the desired healing outcomes. Injectable hydrogels have become attractive scaffold materials for bone regeneration, given their high performance in filling irregularly sized bone defects and their ability to encapsulate cells and bioactive molecules and mimic the native ECM of bone. We investigated the use of an injectable chitosan-based hydrogel scaffold to promote the differentiation of preosteoblasts in vitro. The hydrogels were characterized by evaluating cell homogeneity, cell viability, rheological and mechanical properties, and differentiation ability of preosteoblasts in hydrogel scaffolds. Cell-laden hydrogel scaffolds exhibited shear thinning behavior and the ability to maintain shape fidelity after injection. The CNC-CS hydrogels exhibited higher mechanical strength and significantly upregulated the osteogenic activity and differentiation of preosteoblasts, as shown by ALP activity assays and histological analysis of hydrogel scaffolds. These results suggest that this injectable hydrogel is suitable for cell survival, can promote osteogenic differentiation of preosteoblasts, and structurally support new bone growth.
Resource type:
Article
Affiliation Label Tesim:
Division of Pharmacoengineering and Molecular Pharmaceutics and Joint Department of Biomedical Engineering
DOI:
https://doi.org/10.17615/97zg-0b45
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/pharmaceutics15092270
ISSN:
1999-4923
Journal Issue:
9
Journal Title:
Pharmaceutics
Journal Volume:
15
Keyword:
bone regeneration, cellulose nanocrystals, chitosan-based hydrogel, osteogenic differentiation, osteogenesis, and injectable hydrogels
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
Page Start:
2270
Person:
King, Jasmine L., Shrivastava, Roopali, Benhabbour, Soumya Rahima, Shah, Pooja D., and Maturavongsadit, Panita
Publisher:
Multidisciplinary Digital Publishing Institute (MDPI)
In-Clinic versus Hybrid Cancer Rehabilitation Service Delivery during the COVID-19 Pandemic: An Outcome Comparison Study
Creator:
Giri, Smith, Pergolotti, Mackenzi, Wood, Kelley C., and Kendig, Tiffany D.
Date of publication:
2023
Abstract Tesim:
Diminished health-related quality of life (HRQOL) is common among cancer survivors but often amendable to rehabilitation. However, few access real-world rehabilitation services. Hybrid delivery modes (using a combination of in-clinic and synchronous telehealth visits) became popular during the COVID-19 pandemic and offer a promising solution to improve access beyond the pandemic. However, it is unclear if hybrid delivery has the same impact on patient-reported outcomes and experiences as standard, in-clinic-only delivery. To fill this gap, we performed a retrospective, observational, comparative outcomes study of real-world electronic medical record (EMR) data collected by a national outpatient rehabilitation provider in 2020–2021. Of the cases meeting the inclusion criteria (N = 2611), 60 were seen to via hybrid delivery. The outcomes evaluated pre and post-rehabilitation included PROMIS® global physical health (GPH), global mental health (GMH), physical function (PF), and the ability to participate in social roles and activities (SRA). The patient experience outcomes included the Net Promoter Survey (NPS®) and the Select Medical Patient-Reported Experience Measure (SM-PREM). A linear and logistic regression was used to examine the between-group differences in the PROMIS and SM-PREM scores while controlling for covariates. The hybrid and in-clinic-only cases improved similarly in all PROMIS outcomes (all p < 0.05). The association between the delivery mode and the likelihood of achieving the minimal important change in the PROMIS outcomes was non-significant (all p > 0.05). No between-group differences were observed in the NPS or SM-PREM scores (all p > 0.05). Although more research is needed, this real-world evidence suggests that hybrid rehabilitation care may be equally beneficial for and acceptable to cancer survivors and supports calls to expand access to and reimbursement for telerehabilitation.
Resource type:
Article
Affiliation Label Tesim:
School of Medicine
DOI:
https://doi.org/10.17615/jqp4-aj94
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/curroncol30100644
ISSN:
1718-7729
Journal Issue:
10
Journal Title:
Current Oncology
Journal Volume:
30
Keyword:
outpatients, access and evaluation, cancer survivors, quality of life, telerehabilitation, neoplasms, patient-reported outcome measures, health care quality, rehabilitation, physical therapy specialty, and occupational therapy
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
University of Alabama at Birmingham, , and ReVital Cancer Rehabilitation
Page End:
8927
Page Start:
8916
Person:
Giri, Smith, Pergolotti, Mackenzi, Wood, Kelley C., and Kendig, Tiffany D.
Publisher:
Multidisciplinary Digital Publishing Institute (MDPI)
Implication of the Autophagy-Related Protein Beclin1 in the Regulation of EcoHIV Replication and Inflammatory Responses
Creator:
Owens, Florida, Zhao, Yuling, Rodriguez, Myosotys, Soler, Yemmy, Almohtadi, Rianna, El-Hage, Nazira, Perry, Marissa, Batrakova, Elena V., and Stone, Nicole
Date of publication:
2023
Abstract Tesim:
The protein Beclin1 (BECN1, a mammalian homologue of ATG6 in yeast) plays an important role in the initiation and the normal process of autophagy in cells. Moreover, we and others have shown that Beclin1 plays an important role in viral replication and the innate immune signaling pathways. We previously used the cationic polymer polyethyleneimine (PEI) conjugated to mannose (Man) as a non-viral tool for the delivery of a small interfering (si) Beclin1-PEI-Man nanoplex, which specifically targets mannose receptor-expressing glia (microglia and astrocytes) in the brain when administered intranasally to conventional mice. To expand our previous reports, first we used C57BL/6J mice infected with EcoHIV and exposed them to combined antiretroviral therapy (cART). We show that EcoHIV enters the mouse brain, while intranasal delivery of the nanocomplex significantly reduces the secretion of HIV-induced inflammatory molecules and downregulates the expression of the transcription factor nuclear factor (NF)-kB. Since a spectrum of neurocognitive and motor problems can develop in people living with HIV (PLWH) despite suppressive antiretroviral therapy, we subsequently measured the role of Beclin1 in locomotor activities using EcoHIV-infected BECN1 knockout mice exposed to cART. Viral replication and cytokine secretion were reduced in the postmortem brains recovered from EcoHIV-infected Becn1+/− mice when compared to EcoHIV-infected Becn1+/+ mice, although the impairment in locomotor activities based on muscle strength were comparable. This further highlights the importance of Beclin1 in the regulation of HIV replication and in viral-induced cytokine secretion but not in HIV-induced locomotor impairments. Moreover, the cause of HIV-induced locomotor impairments remains speculative, as we show that this may not be entirely due to viral load and/or HIV-induced inflammatory cytokines.
Resource type:
Article
Affiliation Label Tesim:
Eshelman School of Pharmacy
DOI:
https://doi.org/10.17615/mtg1-h469
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/v15091923
ISSN:
1999-4915
Journal Issue:
9
Journal Title:
Viruses
Journal Volume:
15
Keyword:
mannosylated polyethyleneimine, autophagy, intranasal delivery, Beclin1, and EcoHIV
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
Florida International University and
Page Start:
1923
Person:
Owens, Florida, Zhao, Yuling, Rodriguez, Myosotys, Soler, Yemmy, Almohtadi, Rianna, El-Hage, Nazira, Perry, Marissa, Batrakova, Elena V., and Stone, Nicole
Publisher:
Multidisciplinary Digital Publishing Institute (MDPI)
HIV-1 Infection Results in Sphingosine-1-Phosphate Receptor 1 Dysregulation in the Human Thymus
Creator:
Kim, Shawn J., Salvatore, Bradley, Vatakis, Dimitrios N., Uittenbogaart, Christel H., Gordon, Brent R., Blom, Bianca, and Resop, Rachel S.
Date of publication:
2023
Abstract Tesim:
Regeneration of functional naïve T lymphocytes following the onset of human immunodeficiency virus (HIV) infection remains a crucial issue for people living with HIV (PLWH), even when adhering to antiretroviral therapy (ART). Thus far, reports on the impact of HIV-1 infection on the entry of thymic precursors and the egress of functional naïve T lymphocytes to and from the thymus are limited. We examined the impact of HIV-1 on Sphingosine-1-phosphate (S1P) signaling, which governs the egress of functional naïve thymocytes from the thymus to the periphery. Using in vitro experiments with primary human thymocytes and in vivo and ex vivo studies with humanized mice, we show that HIV-1 infection results in upregulation of the expression of S1P receptor 1 (S1PR1) in the human thymus. Intriguingly, this upregulation occurs during intrathymic infection (direct infection of the human thymic implant) as well as systemic infection in humanized mice. Moreover, considering the dysregulation of pro- and anti-inflammatory cytokines in infected thymi, the increased expression of S1PR1 in response to in vitro exposure to Interferon-Beta (IFN-β) and Tumor Necrosis Factor-Alpha (TNF-α) indicates that cytokine dysregulation following HIV infection may contribute to upregulation of S1PR1. Finally, an increased presence of CD3hiCD69− (fully mature) as well as CD3hiCD69+ (less mature) T cells in the spleen during HIV infection in humanized mice, combined with earlier expression of S1PR1 during thymocyte development, suggests that upregulation of S1PR1 may translate to increased or accelerated egress from the thymus. The egress of thymocytes that are not functionally mature from the thymus to peripheral blood and lymphoid organs may have implications for the immune function of PLWH.
Resource type:
Article
Affiliation Label Tesim:
University of North Carolina at Chapel Hill
DOI:
https://doi.org/10.17615/6x4j-rs62
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/ijms241813865
ISSN:
1422-0067
Journal Issue:
18
Journal Title:
International Journal of Molecular Sciences
Journal Volume:
24
Keyword:
thymus, humanized mice, HIV, sphingosine-1-phosphate, and sphingosine-1-phosphate receptor
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
University of California, Los Angeles and University of Amsterdam
Page Start:
13865
Person:
Kim, Shawn J., Salvatore, Bradley, Vatakis, Dimitrios N., Uittenbogaart, Christel H., Gordon, Brent R., Blom, Bianca, and Resop, Rachel S.
Monitoring genetic diversity and recent HIV infections (RHIs) is critical for understanding HIV epidemiology. Here, we report HIV-1 genetic diversity and RHIs in blood samples from 190 HIV-positive MMSCs in Zhuhai, China. MMSCs with newly reported HIV were enrolled from January 2020 to June 2022. A nested PCR was performed to amplify the HIV polymerase gene fragments at HXB2 positions 2604–3606. We constructed genetic transmission network at both 0.5% and 1.5% distance thresholds using the Tamura-Nei93 model. RHIs were identified using a recent infection testing algorithm (RITA) combining limiting antigen avidity enzyme immunoassay (LAg-EIA) assay with clinical data. The results revealed that 19.5% (37/190) were RHIs and 48.4% (92/190) were CRF07_BC. Two clusters were identified at a 0.5% distance threshold. Among them, one was infected with CRF07_BC for the long term, and the other was infected with CRF55_01B recently. We identified a total of 15 clusters at a 1.5% distance threshold. Among them, nine were infected with CRF07_BC subtype, and RHIs were found in 38.8% (19/49) distributed in eight genetic clusters. We identified a large active transmission cluster (n = 10) infected with a genetic variant, CRF79_0107. The multivariable logistic regression model showed that clusters were more likely to be RHIs (adjusted OR: 3.64, 95% CI: 1.51~9.01). The RHI algorithm can help to identify recent or ongoing transmission clusters where the prevention tools are mostly needed. Prompt public health measures are needed to contain the further spread of active transmission clusters.
Resource type:
Article
Affiliation Label Tesim:
UNC Lineberger Comprehensive Cancer Center
DOI:
https://doi.org/10.17615/msx7-0a73
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/v15091947
ISSN:
1999-4915
Journal Issue:
9
Journal Title:
Viruses
Journal Volume:
15
Keyword:
human immunodeficiency virus, recent HIV infection, phylogenetic analysis, recent infection testing algorithms, and transmission network
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
Hong Kong University of Science and Technology, Sun Yat-sen University, Zhuhai Center for Disease Control and Prevention, Shenzhen Campus of Sun Yat-sen University, Southern Medical University, , and Macau University of Science and Technology
Herbal Remedies for Constipation-Predominant Irritable Bowel Syndrome: A Systematic Review of Randomized Controlled Trials
Creator:
Popa, Stefan Lucian, Dumitrascu, Dinu Iuliu, Ismaiel, Abdulrahman, Duse, Traian Adrian, Surdea-Blaga, Teodora, Brata, Vlad Dumitru, Pop, Cristina, Incze, Victor, and Chiarioni, Giuseppe
Date of publication:
2023
Abstract Tesim:
Background: Constipation-predominant irritable bowel syndrome (IBS-C) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Conventional treatments for IBS-C often provide limited efficiency, leading to an increasing interest in exploring herbal remedies. This systematic review aims to evaluate the efficacy and safety of herbal remedies in the management of IBS-C. Materials and Methods: A comprehensive search of PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library was conducted to identify relevant studies published up to July 2023 and data extraction was performed independently by two reviewers. Results: Overall, the included studies demonstrated some evidence of the beneficial effects of herbal remedies on IBS-C symptoms, including improvements in bowel frequency, stool consistency, abdominal pain, and quality of life. However, the heterogeneity of the interventions and outcome measures limited the ability to perform a meta-analysis. Conclusion: This systematic review suggests that herbal remedies may have potential benefits in the management of IBS-C. However, the quality of evidence is limited, and further well-designed, large-scale RCTs are needed to establish the efficacy and safety of specific herbal remedies for IBS-C. Clinicians should exercise caution when recommending herbal remedies and consider individual patient characteristics and preferences.
Resource type:
Article
Affiliation Label Tesim:
Division of Gastroenterology and Hepatology
DOI:
https://doi.org/10.17615/2ahf-t093
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/nu15194216
ISSN:
2072-6643
Journal Issue:
19
Journal Title:
Nutrients
Journal Volume:
15
Keyword:
herbal remedy, non-pharmacological therapy, and constipation-predominant irritable bowel syndrome
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
“Iuliu Hatieganu” University of Medicine and Pharmacy and
Page Start:
4216
Person:
Popa, Stefan Lucian, Dumitrascu, Dinu Iuliu, Ismaiel, Abdulrahman, Duse, Traian Adrian, Surdea-Blaga, Teodora, Brata, Vlad Dumitru, Pop, Cristina, Incze, Victor, and Chiarioni, Giuseppe
G1 Dynamics at the Crossroads of Pluripotency and Cancer
Creator:
Fleifel, Dalia and Cook, Jeanette Gowen
Date of publication:
2023
Abstract Tesim:
G1 cell cycle phase dynamics are regulated by intricate networks involving cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors, which control G1 progression and ensure proper cell cycle transitions. Moreover, adequate origin licensing in G1 phase, the first committed step of DNA replication in the subsequent S phase, is essential to maintain genome integrity. In this review, we highlight the intriguing parallels and disparities in G1 dynamics between stem cells and cancer cells, focusing on their regulatory mechanisms and functional outcomes. Notably, SOX2, OCT4, KLF4, and the pluripotency reprogramming facilitator c-MYC, known for their role in establishing and maintaining stem cell pluripotency, are also aberrantly expressed in certain cancer cells. In this review, we discuss recent advances in understanding the regulatory role of these pluripotency factors in G1 dynamics in the context of stem cells and cancer cells, which may offer new insights into the interconnections between pluripotency and tumorigenesis.
Resource type:
Article
Affiliation Label Tesim:
Department of Biochemistry and Biophysics
DOI:
https://doi.org/10.17615/h70g-5397
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/cancers15184559
ISSN:
2072-6694
Journal Issue:
18
Journal Title:
Cancers
Journal Volume:
15
Keyword:
cyclin-dependent kinase (CDK), cell cycle, pluripotent stem cells (PSCs), minichromosome maintenance (MCM), origin licensing, genome instability, and DNA replication
Complications of Mandibular Distraction Osteogenesis in Infants with Isolated Robin Sequence
Creator:
Mao, Zhe, Ye, Liang, Zhou, Jiawei, Tian, Gabriel, and Shrivastava, Mayank
Date of publication:
2023
Abstract Tesim:
Mandibular Distraction Osteogenesis (MDO) is now the preferred procedure to alleviate airway obstruction in infants with severe Robin Sequence (RS). However, there have been very few studies investigating complications related to MDO surgery performed on patients affected by isolated RS. In this study, age at distraction, weight at distraction, preoperative intubation, repeat MDO and complications associated with MDO were included as variables. Minor, moderate and major problems were evaluated and recorded as surgical site infections (SSI), injuries to the facial nerve, self-extinction hypertrophic scars, temporomandibular joint ankylosis, device failures, early ossification and fibrous non-union. One hundred and fifty one patients with isolated RS were included. At distraction, the mean age was 72 days (12–540 days) and the mean weight was 4.05 kg (2.4–12.2 kg). Only one patient needed tracheostomy after MDO, and none required further distraction. Ultimately, the complication rate was 15.23%, and there was a total of 7.95% minor, 9.27% moderate and 0% major complications. Minor incidents included surgical site infection (SSI) managed with antibiotics taken orally (n = 8), neuropraxia in the VII cranial nerve (CN) (n = 1), and hypertrophic scarring (n = 3). Incidents reported as moderate were SSIs managed with intravenous antibiotics (n = 9), incision and drainage (n = 3) and self-extubation (n = 2). There was no case of TMJ ankylosis. There were no cases of early or premature ossification, fibrous non-union and device fracture. In conclusion, MDO is an effective and appropriate management technique for infants with isolated RS and severe airway obstruction. Infections at the surgery site accounted for the vast majority of the complications. Further investigations may be needed to determine the long-term consequences of MDO.
Resource type:
Article
Affiliation Label Tesim:
School of Dentistry
DOI:
https://doi.org/10.17615/j630-1358
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/children10101591
ISSN:
2227-9067
Journal Issue:
10
Journal Title:
Children
Journal Volume:
10
Keyword:
complication, MDO, infant, and Robin Sequence
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
Guangzhou Women and Children’s Medical Center, University of Minnesota, and
Person:
Mao, Zhe, Ye, Liang, Zhou, Jiawei, Tian, Gabriel, and Shrivastava, Mayank
Publisher:
Multidisciplinary Digital Publishing Institute (MDPI)
ATM/Chk2 and ATR/Chk1 Pathways Respond to DNA Damage Induced by Movento® 240SC and Envidor® 240SC Keto-Enol Insecticides in the Germarium of Drosophila melanogaster
Creator:
Sekelsky J., González-Marín B., and Calderón-Segura M.E.
Date of publication:
2023
Abstract Tesim:
DNA damage response (DDR) pathways in keto-enol genotoxicity have not been characterized, and few studies have reported genotoxic effects in non-target organisms. The present study shows that concentrations of 11.2, 22.4, 37.3 mg/L of Movento® 240SC and 12.3, 24.6, 41.1 mg/L of Envidor® 240SC for 72 h oral exposure induced DSBs by significantly increasing the percentage of γH2AV expression in regions 2b and 3 from the germarium of wild type females of Drosophila melanogaster Oregon R, compared to the control group (0.0 mg/L of insecticides), via confocal immunofluorescence microscopy. The comparison between both insecticides’ reveals that only the Envidor® 240SC induces concentration-dependent DNA damage, as well as structural changes in the germarium. We determined that the DDR induced by Movento® 240SC depends on the activation of the ATMtefu, Chk1grp and Chk2lok kinases by significantly increasing the percentage of expression of γH2AV in regions 2b and 3 of the germarium, and that ATRmei−29D and p53dp53 kinases only respond at the highest concentration of 37.3 mg/L of Movento® 240SC. With the Envidor® 240SC insecticide, we determined that the DDR depends on the activation of the ATRmei−29D/Chk1grp and ATMtefu/Chk2lok kinases, and p53dp53 by significantly increasing the percentage of expression of γH2AV in the germarium.
Resource type:
Article
Affiliation Label Tesim:
Department of Biology
DOI:
https://doi.org/10.17615/3hz0-fs66
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/toxics11090754
ISSN:
2305-6304
Journal Issue:
9
Journal Title:
Toxics
Journal Volume:
11
Keyword:
keto-enol insecticides, DNA damage response, and Drosophila germarium
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
and Universidad Nacional Autónoma de México
Person:
Sekelsky J., González-Marín B., and Calderón-Segura M.E.
Publisher:
Multidisciplinary Digital Publishing Institute (MDPI)
A Portable Nanoporous Gold Modified Screen-Printed Sensor for Reliable and Simultaneous Multi-Vitamins Analysis
Creator:
Gao X., Liu H., Chen S., and Wang X.
Date of publication:
2023
Abstract Tesim:
Despite being present in minimal amounts, vitamin B2 (VB2), vitamin C (VC), and vitamin B6 (VB6) each play indispensable roles in human metabolisms. Given that VB2, VC, and VB6 cannot be synthesized by the human body, detections of these three vitamins both in fermentation liquid where vitamins are industrially manufactured and in human serum where vitamin concentrations could be clinically controlled are of significant importance. Here, a nanoporous gold (NPAu) modified screen-printed electrode (NPAu/SPE) was fabricated to detect VB2, VC, and VB6 based on NPAu’s electro-oxidation towards vitamins. Owing to the wide separation of peak potentials among VB2, VC, and VB6, the simultaneous detection of these three vitamins was achieved by the NPAu/SPE within a potential range from −0.8 V to 0.8 V. The achieved limits of detection (LOD) for VB2, VC, and VB6 were 0.46, 6.44, and 1.92 μM, with sensitivities of 68.58, 4.77, and 15.94 μA/μM, respectively. Subsequent reliability experiments suggested that the NPAu/SPE exhibited solid anti-interference capability and repeatability. Additionally, the real-sample detection of the NPAu/SPE towards VB2, VC, and VB6 was achieved both in human serum and in fermentation liquid with comparable accuracy (the recovery rates were from 89.8% to 111.7%) as high-performance liquid chromatography (HPLC). Moreover, the portable NPAu/SPE showed comparable performance in terms of the LOD and linear dynamic range when compared to glassy carbon electrodes (GCE) limited to laboratory detection. The proposed NPAu/SPE possesses various advantageous properties including portability, easy fabrication, high sensitivity, and cost-efficiency, making it a potential candidate for clinical and industrial multi-vitamins analysis.