scholarly journals Hymecromone: A Clinical Prescription Hyaluronan Inhibitor for Efficiently Blocking COVID-19 Progression

2021 ◽  
Author(s):  
Shuai Yang ◽  
Yun Ling ◽  
Fang Zhao ◽  
Wei Li ◽  
Zhigang Song ◽  
...  
Keyword(s):  
Standard Care ◽  
Cultured Cells ◽  
Action Plan ◽  
Science And Technology ◽  
Pulmonary Lesion ◽  
Control Group ◽  
Therapeutic Effects ◽  
Clinical Parameters ◽  
Pulmonary Lesions ◽  
D Dimer

Summary Background We previously found that human identical sequences (HIS) of SARS-CoV-2 promote the clinical progression of COVID-19 by upregulating hyaluronan (HA). As one of the drugs for hyaluronan inhibition, hymecromone was chosen for evaluating its therapeutic effects on COVID-19. Methods ELISA was performed to detect the level of HA in COVID-19 patients. We first analyzed the correlation between the level of plasma HA and clinical parameters (lymphocytes, C-reactive protein, D-dimer, and fibrinogen). We then assessed the correlation between the plasma HA level and pulmonary lesions, which were quantified by using artificial intelligence based on chest CT scans, including ground-glass opacity (GGO) and consolidation. Furthermore, we assessed the effect of hyaluronan treatment on the formation of pulmonary lesions in mice and evaluated the role of hymecromone on hyaluronan production in cultured cells. Finally, 94 of the 144 confirmed COVID-19 patients received oral hymecromone in addition to standard care, whereas the others with only standard care were treated as control. Abnormal serological markers in two groups were selected to determine the efficacy of hymecromone. Findings Plasma HA was closely relevant to clinical parameters, including lymphocytes (n = 158; r = -0.50; P＜0.0001), CRP (n = 156; r = 0.55; P＜0.0001), D-dimer (n = 154; r = 0.38; P＜0.0001), and fibrinogen (n = 152; r = 0.37; P＜0.0001), as well as the mass (n = 120; r = 0.30; P = 0.0008) and volume (n = 120; r = 0.30; P = 0.0009) of GGO, the mass (n = 120; r = 0.34; P = 0.0002) and volume (n = 120; r = 0.35; P＜0.0001) of consolidation. Mice experiment further verified that hyaluronan could cause pulmonary lesions directly. Hymecromone remarkably reduced HA via downregulating HAS2/HAS3 expression. Accordingly, the number of lymphocytes recovered more quickly as the fold change of lymphocytes per day was higher in hymecromone-treated patients (n=8) than the control group (n=5) (P ＜0.01). Moreover, 89% patients with hymecromone treatment had pulmonary lesion absorption while only 42% patients in control group had pulmonary lesion absorption (P＜0.0001). Interpretation Hyaluronan is closely correlated with COVID-19 progression and can serve as a plasma biomarker. As a promising treatment for COVID-19, hymecromone deserves our further efforts to determine its effect in a larger cohort of COVID-19 patients. Funding National Key R&D Program of China, Major Special Projects of Basic Research of Shanghai Science and Technology Commission, and Shanghai Science and Technology Innovation Action Plan, Medical Innovation Research Special Project, Research of early identification and warning of acute respiratory infectious diseases.

Assessment of healing of dental implant surgical site following Low-Level Laser Therapy using Bio-Clinical parameters: An Exploratory Study

2020 ◽  
Author(s):  
VARSHA PALLED ◽  
DR. JITENDRA RAO ◽  
DR. RAGHUWAR DAYAL SINGH ◽  
DR. SHUCHI TRIPATHI ◽  
DR. KALPANA SINGH ◽  
...  
Keyword(s):  
Laser Therapy ◽  
Test Group ◽  
Low Level Laser Therapy ◽  
Control Group ◽  
Clinical Parameters ◽  
Implant Stability ◽  
Low Level ◽  
Implant Stability Quotient ◽  
Low Level Laser ◽  
Level Laser

The purpose of this study was to evaluate whether Low-Level Laser Therapy (LLLT) improves the healing of the implant surgical site with clinical and biochemical parameters.Thirty patients with an edentulous space spanning a single tooth were selected. The patients were randomly allocated to two groups - the control group and the test group. The test group received laser energy at a power of 2J/cm 2 with a total of 4-6J energy over each implant. Clinical parameters (Implant Stability Quotient, probing index, modified sulcus bleeding index)and osteoprotegerin (OPG) were assessed at baseline and follow-up intervals (2 weeks, 6 weeks, and 3 months).The test group showed significantly higher implant stability quotient compared to thecontrol group at 2 weeks(57.93±3.95 and 35.67±3.08; p<0.01) and 3months(58.86±3.75 and 67.06±3.78; p<0.01). A significant rise in OPG levels of the test group(686.30±125.36pg/ml at baseline and 784.25±108.30pg/ml at 3months;p<0.01) was seen contrary to significant decline in the control group (839.50±249.08pg/ml at baseline,415.30±78.39pg/ml at 3months;p<0.01). Within the limitations of the study, the study suggests that the healing of peri-implant hard and soft tissues may be enhanced with the use of LLLT as an explicit modality during the post-operative period.

Optimization of the terms of supportive periodontal therapy using photoactivated disinfection

2019 ◽  
Vol 24 (2) ◽  
pp. 121-126 ◽  
Author(s):  
V. G. Atrushkevich ◽  
L. Yu. Orekhova ◽  
O. O. Yanushevich ◽  
E. Yu. Sokolova ◽  
E. S. Loboda
Keyword(s):  
Chronic Periodontitis ◽  
Adjunctive Treatment ◽  
Control Group ◽  
Clinical Parameters ◽  
Ozone Therapy ◽  
Pocket Depth ◽  
Clinical Attachment Loss ◽  
Supportive Periodontal Therapy ◽  
Tannerella Forsythensis ◽  
Observation Period

Relevance: to indentify if periodontal treatment which is presented by photoactivated disinfection (PAD) adjunctively to scaling and root planing (SRP) yield better outcomes than ozone therapy as an adjunct to SRP in periodontitis.Materials and methods: we examined 57 (mean age 49,3 ± 1,02) patients with chronic periodontitis, divided into groups, SRP + PAD, SRP + ozone therapy and SRP alone. Subgingival plaque samples were subjected to DNA extraction and real time PCR amplifcation for detection Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythensis (Tf), Treponema denticola (Td), Aggregatibacter actinomycetemcomitans (Aa). The amount of periodontopathogens and clinical parameters including plaque index, clinical attachment loss, pocket depth, bleeding on probing were measured at baseline, after 40, 90 and 180 days.Results: the results in groups of PAD+SRP and ozone therapy+SRP showed an improvement in all clinical parameters PI, BOP, PD, CAL and the quantity of Pg, Td and Tf compared to the control group during an observation period.Conclusion: the results showed additional benefts from PAD and ozone therapy as an adjunctive treatment to SRP for patients of chronic periodontitis.

Assessment of biochemical determinants in Multiple Sclerosis patients following the oral administration of β-D-Mannuronic acid [M2000]

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohamad Reza Nikouei Moghaddam ◽  
Monireh Movahedi ◽  
Maryam Bananej ◽  
Soheil Najafi ◽  
Nahid Beladi Moghadam ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Uric Acid ◽  
Vitamin D3 ◽  
Chronic Inflammatory Disease ◽  
Toxic Effects ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
Multiple Sclerosis Patients

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely, and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid [M2000] have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of Urea, Creatinine, GGT, and non-significant changes in Uric acid and AntiPhospholipids levels, besides a significant rise in Vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

PP455 Cost-effectiveness Of Ixazomib-Based Regimen Compared With Bortezomib-Based Regimen In Chinese Patients With Relapsed/Refractory Multiple Myeloma: A Retrospective Study

2020 ◽  
Vol 36 (S1) ◽  
pp. 36-37
Author(s):  
Pei Wang ◽  
Jing Li ◽  
Yang Yang ◽  
Peng Liu
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Staging System ◽  
Chinese Patients ◽  
Disease Stage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lower Grade ◽  
Refractory Multiple Myeloma ◽  
Grade 3

IntroductionThe treatment of relapsed/refractory multiple myeloma (RRMM), a common hematological malignancy, remains a great challenge in China, partially due to the limited accessibility to novel agents and inadequate public health insurance coverage. Ixazomib, a novel oral proteasome inhibitor (PI), was approved by the China Food and Drug Administration (CFDA) for RRMM in 2018. While bortezomib, a traditional PI, is the recommended agent in the clinical guideline for MM. Here, we compared their costs and effectiveness.MethodsRRMM patients who has received an ixazomib-based regimen (at least 2 cycles) were analyzed. Using a propensity score matching method, we generated a control group of RRMM patients who received the bortezomib-based regimen. The criteria included the number of treatment lines, age, and the revised international staging system stage (R-ISS) which representing the disease stage for myeloma, and paired at a ratio of 1:2 (allowing one control to match multiples). The difference in hospitalization stay, grade 3/4 adverse events rates, overall response rate (ORR), mortality during treatment, and treatment costs was then compared.ResultsNineteen patients received ixazomib and twenty-seven that received bortezomib were included. The ixazomib-group demonstrated a shorter hospital stay (9 days versus 27 days, p < 0.001), lower grade 3–4 adverse events rates (42.1% versus 55.6%, p < 0.001), higher ORR (63.2% versus 48.1%, p = 0.228), and lower mortality rate during treatment (0% versus 7.4%, p = 0.169) than that of bortezomib-group. The ixazomib group had lower total costs (127,620CNY versus 156,424CNY [18,033USD versus 22,103USD], p > 0.05), lower drug costs (98,376CNY versus 103,307CNY [13,901USD versus 14,598USD], p > 0.05), and the lower costs of supportive treatment (5,507CNY versus 14,701 CNY [778USD versus 2,077USD], p < 0.001). Only in terms of self-funded costs, the bortezomib-based regimen was significantly lower (37,127CNY versus 11,521CNY [5,246USD versus 1,628USD], p < 0.001).ConclusionsCompared with the bortezomib-based regimen, the ixazomib-based regimen has better therapeutic effects on MM patients while saving costs. Hence, it may be preferable for use in the treatment of RRMM in China.

scholarly journals Therapeutic effects of coronary granulocyte colony-stimulating factor on rats with chronic ischemic heart disease

2020 ◽  
Vol 15 (1) ◽  
pp. 742-752
Author(s):  
Pengcheng Ren ◽  
Ming Zhang ◽  
Shuren Dai
Keyword(s):  
Heart Disease ◽  
Myocardial Perfusion ◽  
Ischemic Heart Disease ◽  
Left Ventricular ◽  
Control Group ◽  
Therapeutic Effects ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Chronic Ischemic Heart Disease ◽  
Stimulating Factor

AbstractBackgroundThe aim of this study was to evaluate the therapeutic effects of coronary granulocyte colony-stimulating factor (G-CSF) on rats with chronic ischemic heart disease (CIHD).MethodsThirty healthy rats were randomly divided into control, subcutaneous and intracoronary G-CSF injection groups (n = 10) after the CIHD model was established. Left ventricular ejection fraction (LVEF), myocardial injury area, myocardial perfusion area and viable myocardium were observed by coronary angiography, dual-isotopic myocardial imaging and first-pass delayed myocardial perfusion magnetic resonance imaging (MRI) before modeling as well as 2 and 4 weeks after surgery.ResultsThe peak times of peripheral blood and subcutaneous G-CSF levels were 3 and 5 days after mobilization, respectively. The peripheral blood CD34+/CD133+ cell ratio of subcutaneous or intracoronary G-CSF injection group significantly exceeded that of the control group (P < 0.05). The distal stenosis degrees of target lesions in subcutaneous and intracoronary G-CSF injection groups were significantly lower than that of the control group (P < 0.05). Compared with the situation before mobilization, LVEF was significantly improved after 2 weeks in intracoronary and subcutaneous G-CSF injection groups (P < 0.01). Their infarcted myocardial areas were reduced, the left ventricular remodeling was relieved, the percentage of viable myocardium was increased, angiogenesis was promoted and cardiomyocyte apoptosis was inhibited.ConclusionIntracoronary G-CSF injection is safe and effective as subcutaneous injection, improving the cardiac function of CIHD rats.

scholarly journals Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Li-Yao Duan ◽  
Yan Liang ◽  
Wen-Ping Gong ◽  
Yong Xue ◽  
Jie Mi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
Treatment Group ◽  
Mechanism Of Action ◽  
Cell Damage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Model Group ◽  
Lung Histopathology ◽  
Th17 Cytokines

Abstract Background The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. Methods BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. Results After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P < 0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P < 0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P < 0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model. Conclusions NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.

scholarly journals Antifungal Effect of Long Noncoding RNA 9708-1 in the Vulvovaginal Candidiasis Murine Model

2021 ◽  
Vol 186 (2) ◽  
pp. 177-188
Author(s):  
Ying Wu ◽  
Lisha Jiang ◽  
Lingling Zhang ◽  
Xia Liu ◽  
Lina Yan ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Basal Layer ◽  
Vulvovaginal Candidiasis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Blank Control Group ◽  
Candida Spp ◽  
Expression Levels ◽  
Gene And Protein Expression

AbstractVulvovaginal candidiasis (VVC) caused by Candida spp. affects 70–75% of women at least once during their lives. We aim to elucidate the potential mechanism of VVC and investigate the therapeutic effects of long noncoding RNA 9708-1. Female BALB/c mice were randomized to four treatment groups, including the blank control group, VVC control group, vehicle control group and lncRNA 9708-1-overexpressed group. Mice were euthanized on Day 4, Day 7 and Day 14 after treatment. Colony-forming unit (CFU) was measured, and the inflammation was detected by hematoxylin and eosin (H&E). Gene and protein expression levels of lncRNA 9708-1 and FAK were determined by real-time PCR, Western blot and immunohistochemistry. The overexpression of lncRNA 9708-1 significantly decreased the fungal load from Day 4 to 7. H&E staining indicated that the impaired histological profiles were improved in lncRNA 9708-1-overexpressed group. LncRNA 9708-1 led to a significant increase in FAK level of vagina tissue which is expressed mainly in epithelial basal layer. This study suggests that lncRNA 9708-1 played a protective role on murine experimental VVC by upregulating the expression levels of FAK.

scholarly journals Mobile Health to Improve Adherence and Patient Experience in Heart Transplantation Recipients: The mHeart Trial

Healthcare ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 463
Author(s):  
Mar Gomis-Pastor ◽  
Sonia Mirabet Perez ◽  
Eulalia Roig Minguell ◽  
Vicenç Brossa Loidi ◽  
Laura Lopez Lopez ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Patient Experience ◽  
Mobile Application ◽  
Standard Care ◽  
Controlled Trial ◽  
Intervention Group ◽  
Group Versus ◽  
Control Group ◽  
P Value ◽  
Adherence Score

Non-adherence after heart transplantation (HTx) is a significant problem. The main objective of this study was to evaluate if a mHealth strategy is more effective than standard care in improving adherence and patients’ experience in heart transplant recipients. Methods: This was a single-center, randomized controlled trial (RCT) in adult recipients >1.5 years post-HTx. Participants were randomized to standard care (control group) or to the mHeart Strategy (intervention group). For patients randomized to the mHeart strategy, multifaceted theory-based interventions were provided during the study period to optimize therapy management using the mHeart mobile application. Patient experience regarding their medication regimens were evaluated in a face-to-face interview. Medication adherence was assessed by performing self-reported questionnaires. A composite adherence score that included the SMAQ questionnaire, the coefficient of variation of drug levels and missing visits was also reported. Results: A total of 134 HTx recipients were randomized (intervention N = 71; control N = 63). Mean follow-up was 1.6 (SD 0.6) years. Improvement in adherence from baseline was significantly higher in the intervention group versus the control group according to the SMAQ questionnaire (85% vs. 46%, OR = 6.7 (2.9; 15.8), p-value < 0.001) and the composite score (51% vs. 23%, OR = 0.3 (0.1; 0.6), p-value = 0.001). Patients’ experiences with their drug therapy including knowledge of their medication timing intakes (p-value = 0.019) and the drug indications or uses that they remembered (p-value = 0.003) significantly improved in the intervention versus the control group. Conclusions: In our study, the mHealth-based strategy significantly improved adherence and patient beliefs regarding their medication regimens among the HTx population. The mHeart mobile application was used as a feasible tool for providing long-term, tailor-made interventions to HTx recipients to improve the goals assessed.

Topical Lidocaine Patch for Postthoracotomy and Poststernotomy Pain in Cardiothoracic Intensive Care Unit Adult Patients

2019 ◽  
Vol 39 (5) ◽  
pp. 51-57 ◽  
Author(s):  
Michael Liu ◽  
Mabel Wai ◽  
James Nunez
Keyword(s):  
Intensive Care Unit ◽  
Cardiac Surgery ◽  
Intensive Care ◽  
Standard Care ◽  
Academic Medical Center ◽  
Adult Patients ◽  
Control Group ◽  
Lidocaine Group ◽  
Lengths Of Stay ◽  
Topical Lidocaine

Background Transdermal lidocaine patches have few systemic toxicities and may be useful analgesics in cardiac surgery patients. However, few studies have evaluated their efficacy in the perioperative setting. Objective To compare the efficacy of topical lidocaine 5% patch plus standard care (opioid and nonopioid analgesics) with standard care alone for postthoracotomy or poststernotomy pain in adult patients in a cardiothoracic intensive care unit. Methods A single-center, retrospective cohort evaluation was conducted from January 2015 through December 2015 in the adult cardiothoracic intensive care unit at a tertiary academic medical center. Cardiac surgery patients with new sternotomies or thoracotomies were included. Patients in the lidocaine group received 1 to 3 topical lidocaine 5% patches near sternotomy and/or thoracotomy sites daily. Patches remained in place for 12 hours daily. Patients in the control group received standard care alone. Results The primary outcome was numeric pain rating for sternotomy/thoracotomy sites. Secondary outcomes were cardiothoracic intensive care unit and hospital lengths of stay and total doses of analgesics received. Forty-seven patients were included in the lidocaine group; 44 were included in the control group. Mean visual analogue scores for pain did not differ between groups (lidocaine, 2; control, 1.9; P = .58). Lengths of stay were similar for both groups (cardiothoracic intensive care unit: lidocaine, 3.06 days; control, 3.11 days; P = .86; hospital: lidocaine, 8.26 days; control, 7.61 days; P = .47). Conclusions Adjunctive lidocaine 5% patches did not reduce acute pain in postthoracotomy and post-sternotomy patients in the cardiothoracic intensive care unit.

scholarly journals AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Sipin Zhu ◽  
Yibo Ying ◽  
Jiahui Ye ◽  
Min Chen ◽  
Qiuji Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Control Group ◽  
Therapeutic Effects ◽  
Hypoxia Response Element ◽  
Neurofilament Protein ◽  
Response Element ◽  
Hypoxia Response ◽  
Cord Injury

AbstractNeural stem cell (NSCs) transplantation has been one of the hot topics in the repair of spinal cord injury (SCI). Fibroblast growth factor (FGF) is considered a promising nerve injury therapy after SCI. However, owing to a hostile hypoxia condition in SCI, there remains a challenging issue in implementing these tactics to repair SCI. In this report, we used adeno-associated virus 2 (AAV2), a prototype AAV used in clinical trials for human neuron disorders, basic FGF (bFGF) gene under the regulation of hypoxia response element (HRE) was constructed and transduced into NSCs to yield AAV2-5HRE-bFGF-NSCs. Our results showed that its treatment yielded temporally increased expression of bFGF in SCI, and improved scores of functional recovery after SCI compared to vehicle control (AAV2-5HRE-NSCs) based on the analyses of the inclined plane test, Basso–Beattie–Bresnahan (BBB) scale and footprint analysis. Mechanistic studies showed that AAV2-5HRE-bFGF-NSCs treatment increased the expression of neuron-specific neuronal nuclei protein (NeuN), neuromodulin GAP43, and neurofilament protein NF200 while decreased the expression of glial fibrillary acidic protein (GFAP) as compared to the control group. Further, the expressions of autophagy-associated proteins LC3-II and Beclin 1 were decreased, whereas the expression of P62 protein was increased in AAV2-5HRE-bFGF-NSCs treatment group. Taken together, our data indicate that AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy. Thus, this study represents a step forward towards the potential use of AAV2-5HRE-bFGF-NSCs for future clinical trials of SCI repair.

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