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  • Publication
    Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis
    (nternational Association for Dental Research and American Association for Dental, Oral, and Craniofacial Research, 2023-01-11) A. Miroshnychenko; S. Ibrahim; M. Azab; Y. Roldan; J.P.D. Martinez; D. Tamilselvan; L. He; J.W. Little; O. Urquhart; M. Tampi; D.E. Polk; P.A. Moore; E.V. Hersh; B. Claytor; A. Carrasco-Labra; R. Brignardello-Petersen
    This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400mg plus acetaminophen 500 to 1,000mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06–2.31), acetaminophen 650mg plus oxycodone 10mg (MDp, 1.19; 95% CI, 0.85–1.54), ibuprofen 400mg (MDp, 1.31; 95% CI, 1.17–1.45), and naproxen 400–440mg (MDp, 1.44; 95% CI, 1.07–1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5mg, codeine 60mg, and tramadol 37.5mg plus acetaminophen 325mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650mg plus oxycodone 10mg) or placebo.
  • Publication
    Activation of Functional Somatic Stem Cells Promotes Endogenous Tissue Regeneration
    (International Association for Dental Research; American Association for Dental, Oral, and Craniofacial Research, 2022-02-03) W. Li; X. Huang; W. Yu; Y. Xu; R. Huang1, J. Park; A. Moshaverinia; P. Arora; C. Chen
    Periodontal ligament derived stem cells (PDLSCs) are capable of differentiating into multiple cell types and inducing a promising immunomodulation for tissue regeneration and disease treatment. However, it is still challenging to develop a practical approach to activate endogenous stem cells for tissue self-healing and regeneration. In this study, transcriptome analysis reveals that resveratrol promotes PDLSC stemness through activation of stem cell, osteoprogenitor, and chondroprogenitor markers. Self-renewal and multipotent differentiation abilities are also improved in resveratrol-treated PDLSCs. In addition, immunomodulation of PDLSCs is dramatically increased after resveratrol treatment. Mechanistically, we show that resveratrol activates ERK/WNT crosstalk through elevation of olfactory and growth factor signaling pathways to upregulate the expression levels of RUNX2 and FASL for osteogenesis and immunomodulation, respectively. By using a periodontitis animal model, administration of resveratrol partially rescues bone loss through activation of endogenous somatic stem cells and inhibition of inflammatory T-cell infiltration. Taken together, our findings identify a novel pharmacological approach to achieve autotherapies for endogenous tissue regeneration.
  • Publication
    Accurate gingival segmentation from 3D images with artifcial intelligence: an animal pilot study
    (BioMed Central Ltd, 2023-05-01) Min Yang; Chenshuang Li; Wen Yang; Chider Chen; Chun‑Hsi Chung; Nipul Tanna; Zhong Zheng
    Background Gingival phenotype plays an important role in dental diagnosis and treatment planning. Traditionally, determining the gingival phenotype is done by manual probing of the gingival soft tissues, an invasive and time-consuming procedure. This study aims to evaluate the feasibility and accuracy of an alternatively novel, non-invasive technology based on the precise 3-dimension (3D) soft tissue reconstruction from intraoral scanning and cone beam computed tomography (CBCT) to predict the gingival biotype. Methods As a proof-of-concept, Yorkshire pig mandibles were scanned, and the CBCT data were fed into a deep-learning model to reconstruct the teeth and surrounding bone structure in 3D. By overlaying the CBCT scan with the intraoral scans, an accurate superposition was created and used for virtual measurements of the soft tissue thickness. Meanwhile, gingival thicknesses were also measured by a periodontal probe and digital caliper on the buccal and lingual sides at 3 mm apical to the gingival margin of the posterior teeth and compared with the virtual assessment at the same location. The data obtained from virtual and clinical measurements were compared by Wilcoxon matched-pairs signed-rank analysis, while their correlation was determined by Pearson’s r value. The Mann–Whitney U test was used for intergroup comparisons of the amount of difference. Results Among 108 investigated locations, the clinical and virtual measurements are strongly positively correlated (r = 0.9656, P < 0.0001), and only clinically insignificant differences (0.066 ± 0.223 mm) were observed between the two assessments. There is no difference in the agreement between the virtual and clinical measurements on sexually matured samples (0.087 ± 0.240 mm) and pre-pubertal samples (0.033 ± 0.195 mm). Noticeably, there is a greater agreement between the virtual and clinical measurements at the buccal sites (0.019 ± 0.233 mm) than at the lingual sites (0.116 ± 0.215 mm). Conclusion In summary, the artificial intelligence-based virtual measurement proposed in this work provides an innovative technique potentially for accurately measuring soft tissue thickness using clinical routine 3D imaging systems, which will aid clinicians in generating a more comprehensive diagnosis with less invasive procedures and, in turn, optimize the treatment plans with more predictable outcomes.
  • Publication
    Abatement of microfibre pollution and detoxification of textile dye – Indigo by engineered plant enzymes
    (Society for Experimental Biology; the Association of Applied Biologists; John Wiley & sons Ltd., 2022-10-06) Geetanjali Wakade; Shina Lin; Prasenjit Saha; Uma Kumari; Henry Daniell
    Microfibres (diameter <5 mm) and textile dyes released from textile industries are ubiquitous, cause environmental pollution, and harm aquatic flora, fauna, animals and human life. Therefore, enzymatic abatement of microfibre pollution and textile dye detoxification is essential. Microbial enzymes for such application present major challenges of scale and affordability to clean up large scale pollution. Therefore, enzymes required for the biodegradation of microfibres and indigo dye were expressed in transplastomic tobacco plants through chloroplast genetic engineering. Integration of laccase and lignin peroxidase genes into the tobacco chloroplast genomes and homoplasmy was confirmed by Southern blots. Decolorization (up to 86%) of samples containing indigo dye (100 mg/L) was obtained using cp-laccase (0.5% plant enzyme powder). Significant (8-fold) reduction in commercial microbial cellulase cocktail was achieved in pretreated cotton fibre hydrolysis by supplementing cost effective cellulases (endoglucanases, ß glucosidases) and accessory enzymes (swollenin, xylanase, lipase) and ligninases (laccase lignin peroxidase) expressed in chloroplasts. Microfibre hydrolysis using cocktail of Cp-cellulases and Cp-accessory enzymes along with minimal dose (0.25% and 0.5%) of commercial cellulase blend (Ctec2) showed 88%–89% of sugar release from pretreated cotton and microfibres. Cp ligninases, Cp-cellulases and Cp-accessory enzymes were stable in freeze dried leaves up to 15 and 36 months respectively at room temperature, when protected from light. Use of plant powder for decolorization or hydrolysis eliminated the need for preservatives, purification or concentration or cold chain. Evidently, abatement of microfibre pollution and textile dye detoxification using Cp-enzymes is a novel and cost-effective approach to prevent their environmental pollution.
  • Publication
    A small molecule that targets the processivity factor of molluscum contagiosum virus has therapeutic potential
    (Elsevier, 2023-01-02) Hancheng Guan; Manunya Nuth; Stuart N. Isaacs; Yuhong Xiao; Richard W. Scott; Michael H. Parker; Eric D. Strobel; John L. Kulp III; Thomas R. Bailey; Allen B. Reitz; Robert P. Ricciardi
    Molluscum contagiosum (MC) is an infectious disease that occurs only in humans with a tropism that is narrowly restricted to the outermost epidermal layer of the skin. Molluscum contagiosum virus (MCV) is the causative agent of MC which produces skin lesions that can persist for months to several years. MCV is efficiently transmitted by direct physical contact or by indirect contact with fomites. MC is most prevalent in children and immune compromised patients. The failure to develop a drug that targets MCV replication has been hampered for decades by the inability to propagate MCV in cell culture. To address this dilemma, we recently engineered a surrogate poxvirus expressing the MCV processivity factor (mD4) as the drug target. The mD4 protein is essential for viral replication by keeping the viral polymerase tethered to the DNA template. In this study we have designed and synthesized a lead compound (7269) that is able to prevent mD4 dependent processive DNA synthesis in vitro (IC50 = 6.8 μM) and effectively inhibit propagation of the mD4-VV surrogate virus in BSC-1 cells (EC50 = 13.2 μM) with negligible cytotoxicity. In human liver microsomes, 7269 was shown to be stable for almost 2 h. When tested for penetration into human cadaver skin in a formulated gel, the level of 7269 in the epidermal layer was nearly 100 times the concentration (EC50) needed to inhibit propagation of the mD4-VV surrogate virus in BSC-1 cells. The gel formulated 7269 was scored as a non-irritant on skin and shown to have a shelf-life that was completely stable after several months. In summary, 7269 is a potential Lead for becoming the first MCV anti-viral compound to treat MC and thereby, addresses this unmet medical need that has persisted for many decades.