bluuebunny/crossref_metadata_2025 huggingface dataset:
Fucoidan Extracted From Sporophyll of Undaria pinnatifida Grown in Weihai, China – Chemical Composition and Comparison of Antioxidant Activity of Different Molecular Weight Fractions
Authors: Yu Jing , Li Qianqian , Wu Jun , Yang Xiaotong , Yang Shiping , Zhu Wei , Liu Yang , Tang Wei , Nie Shaoping , Hassouna Amira , White William Lindsey , Zhao Yu , Lu Jun
Published: May 2021

Fucoidan is a multifunctional marine carbohydrate polymer that differs in its chemical composition and bioactivity both between seaweed species and within species from different locations across the globe. In this study, fucoidan was extracted from the sporophyll of Undaria pinnatifida grown in Weihai, Shandong Province, China. Fucoidan fractions with molecular weight cutoffs (MWCO) of >300 kDa and <10 kDa were obtained via dialysis. The fucoidan standard from Sigma (Fstd, ≥95, CAS: 9072-19-9), fucoidan crude extract (WH), >300 kDa fraction (300k) and <10 kDa fraction (10k) were compared in terms of chemical composition and antioxidant capacity. Based on Fourier transform infrared spectroscopy (FT-IR) analysis, Fstd, WH, and 300k all showed strong bands around 830 cm−1, corresponding to the sulfate substituent in the molecule. The results showed that compared with WH and 300 k, the degree of sulfation at 10k was the lowest. From Nuclear magnetic resonance spectroscopy (NMR) result, the four fucoidan samples all contain α-L-fucose. The primary antioxidant ability of the 10k is significantly higher than that of the 300k, WH, and Fstd, but the secondary antioxidant capabilities of the 10k and 300k were similar, and both were higher than that of the butylated hydroxyanisole (BHA). The ferric reducing antioxidant ability was higher in the 300k and WH fractions. This demonstrates that fucoidan extracted from U. pinnatifida grown in Weihai, China should be a useful nutraceutical resource.
Supplementation of Diets With Spirulina Influences Immune and Gut Function in Dogs
Authors: Satyaraj Ebenezer , Reynolds Arleigh , Engler Robyn , Labuda Jeff , Sun Peichuan
Published: May 2021

Spirulina refers to two species of blue green algae (Arthrospira platensis, and A. maxima) consumed by humans as food for centuries. While, Spirulina has been shown to have immune enhancing properties in several animal and human studies, there are no systematic studies in dogs. The aim of this study was to evaluate the immunomodulatory effect of dietary supplementation with Spirulina in dogs. The study was conducted in two phases: Pre-test (8 wks.) and Test (42 wks.). Thirty adult dogs (mean 2.9 yrs.) were randomized into two groups and fed a nutritionally complete diet in the “Pre-test” phase. At the end of “Pre-test” phase all dogs received a rabies vaccine, and dogs in “test group” were switched to diet supplemented with dried Arthrospira platensis (Spirulina). Response to rabies vaccine was evaluated by Rapid Fluorescent Focus Inhibition Test (RFFIT). Gut immune response was assessed by measuring fecal IgA. Gut microbiota was evaluated by Temporal Temperature Gel Electrophoresis (TTGE) methodology. Repeated measures ANOVA was used to test for differences between groups and statistical significance considered to be p < 0.05. Dogs fed diets supplemented with Spirulina demonstrated enhanced immune status by showing significantly higher vaccine response and higher levels of fecal IgA as compared to the control group. Supplementing diets with Spirulina also resulted in significantly increased gut microbiota stability in the test group. In conclusion, diets supplemented with Spirulina significantly enhanced immune response and gut health in dogs.
Wheat ATIs: Characteristics and Role in Human Disease
Authors: Geisslitz Sabrina , Shewry Peter , Brouns Fred , America Antoine H. P. , Caio Giacomo Pietro Ismaele , Daly Matthew , D'Amico Stefano , De Giorgio Roberto , Gilissen Luud , Grausgruber Heinrich , Huang Xin , Jonkers Daisy , Keszthelyi Daniel , Larré Colette , Masci Stefania , Mills Clare , Møller Marie Sofie , Sorrells Mark E. , Svensson Birte , Zevallos Victor F. , Weegels Peter Louis
Published: May 2021

Amylase/trypsin-inhibitors (ATIs) comprise about 2–4% of the total wheat grain proteins and may contribute to natural defense against pests and pathogens. However, they are currently among the most widely studied wheat components because of their proposed role in adverse reactions to wheat consumption in humans. ATIs have long been known to contribute to IgE-mediated allergy (notably Bakers' asthma), but interest has increased since 2012 when they were shown to be able to trigger the innate immune system, with attention focused on their role in coeliac disease which affects about 1% of the population and, more recently, in non-coeliac wheat sensitivity which may affect up to 10% of the population. This has led to studies of their structure, inhibitory properties, genetics, control of expression, behavior during processing, effects on human adverse reactions to wheat and, most recently, strategies to modify their expression in the plant using gene editing. We therefore present an integrated account of this range of research, identifying inconsistencies, and gaps in our knowledge and identifying future research needs.

Note 

This paper is the outcome of an invited international ATI expert meeting held in Amsterdam, February 3-5 2020
Optimizing the Management of Cancer Patients Treated With Systemic Therapies During the COVID-19 Pandemic: The New Role of PCR and CT Scan
Authors: Viansone Alessandro A. , Ammari Samy , Dercle Laurent , Arnedos Monica
Published: May 2021

In late 2019 and early 2020, the world witnessed the outbreak of the SARS-CoV-2 (also referred as COVID-19) in Wuhan, China. Its rapid expansion worldwide and its contagiousness rate have forced the activation of several measures to contain the pandemic, mostly through confinement and identification of infected patients and potential contacts by testing.
Beneficial Diets and Pancreatic Cancer: Molecular Mechanisms and Clinical Practice
Authors: Zhang Yang , Zhang Tao , Yang Wenbo , Chen Hongze , Geng Xinglong , Li Guanqun , Chen Hua , Wang Yongwei , Li Le , Sun Bei
Published: May 2021

Pancreatic cancer (PC) is a malignant tumor with high invasiveness, easy metastatic ability, and chemoresistance. Patients with PC have an extremely low survival rate due to the difficulty in early diagnosis. It is estimated that nearly 90% of PC cases are caused by environmental risk factors. Approximately 50% of PC cases are induced by an unhealthy diet, which can be avoided. Given this large attribution to diet, numerous studies have assessed the relationship between various dietary factors and PC. This article reviews three beneficial diets: a ketogenic diet (KD), a Mediterranean diet (MD), and a low-sugar diet. Their composition and impact mechanism are summarized and discussed. The associations between these three diets and PC were analyzed, and we aimed to provide more help and new insights for the prevention and treatment of PC.
Cutaneous Melanoma Classification: The Importance of High-Throughput Genomic Technologies
Authors: Scatena Cristian , Murtas Daniela , Tomei Sara
Published: May 2021

Cutaneous melanoma is an aggressive tumor responsible for 90% of mortality related to skin cancer. In the recent years, the discovery of driving mutations in melanoma has led to better treatment approaches. The last decade has seen a genomic revolution in the field of cancer. Such genomic revolution has led to the production of an unprecedented mole of data. High-throughput genomic technologies have facilitated the genomic, transcriptomic and epigenomic profiling of several cancers, including melanoma. Nevertheless, there are a number of newer genomic technologies that have not yet been employed in large studies. In this article we describe the current classification of cutaneous melanoma, we review the current knowledge of the main genetic alterations of cutaneous melanoma and their related impact on targeted therapies, and we describe the most recent high-throughput genomic technologies, highlighting their advantages and disadvantages. We hope that the current review will also help scientists to identify the most suitable technology to address melanoma-related relevant questions. The translation of this knowledge and all actual advancements into the clinical practice will be helpful in better defining the different molecular subsets of melanoma patients and provide new tools to address relevant questions on disease management. Genomic technologies might indeed allow to better predict the biological - and, subsequently, clinical - behavior for each subset of melanoma patients as well as to even identify all molecular changes in tumor cell populations during disease evolution toward a real achievement of a personalized medicine.
Advanced Renal-Cell Carcinoma Pseudoprogression After Combined Immunotherapy: Case Report and Literature Review
Authors: Zhang Xiaojie , Huang Hao , Han Lu , Li Tiepeng , Wang Zibing , Gao Quanli
Published: May 2021

Treatment with a combination of programmed cell death-1 (PD-1) blocker and cytokine-induced killer (CIK) cells has improved outcome in cancer patients but is also associated with various patterns of responses. Pseudoprogression is a unique and uncommon phenomenon with no clear criteria for rapid diagnosis. Although some reports of pseudoprogression during immunotherapy exist, there are few reports of pseudoprogression occurring twice in the same patient. Here, we report the case of 51-year-old female patient with advanced renal cell carcinoma, who received a combination treatment of PD-1 blocker and CIK cells, and where pseudoprogression of lung and brain tumors occurred successively during treatment.
Construction and Identification of New Molecular Markers of Triple-Negative Breast Cancer Stem Cells
Authors: Liu Tingting , Wang Hongyue , Liu Zhiyong , Zhang Jing , Liu Yan , Zhang Lin , Zheng Chunhui , Liu Fei , Hou Chuanqiang , Li Baojiang
Published: May 2021

Objective: We screened the TNBC stem cells using phage display (PD) and acquired the specific binding clones; and then the positive phage DNAs were amplified and extracted, synthesized with specific polypeptides, and labeled with fluorescein isothiocyanate (FITC). Finally, we identified the specificity of the polypeptides in vitro and in vivo.

Methods: Human breast cancer cell line MDA-MB-231 and human mammary gland cell line hs578bst were chosen in our study, and MDA-MB-231 breast cancer stem cells (BCSCs) were cultured and identified by flow cytometry. The phage peptide library was screened using MDA-MB-231 BCSCs, the positive phage clones were identified by ELISA, and the DNA of the positive phages was extracted and sent to a biotechnology company for sequencing. According to the sequencing results, a specific polypeptide was synthesized and labeled with FITC. In the end, the specificity of a polypeptide to BCSCs was identified in vivo and in vitro.

Results: The MDA-MB-231 BCSCs were cultured and enriched with the “serum and serum-free alternate” method. The BCSCs were found to have characteristics of CD44+/CD24−/low epithelial surface antigen (ESA) and ALDH+ with flow cytometry. The phage was enriched to 200-fold after three rounds of screening for MDA-MB-231 BCSCs. The positive phages were sequenced; then a polypeptide named M58 was synthesized according to sequencing results. Polypeptide M58 has a specific affinity to MDA-MB-231 BCSCs in vivo and in vitro.

Conclusion: Specific polypeptides binding to MDA-MB-231 BCSCs were screened out by PD screening method, which laid a theoretical foundation for the targeted therapy and further research of BCSCs.
Naples Prognostic Score: A Novel Prognostic Score in Predicting Cancer-Specific Survival in Patients With Resected Esophageal Squamous Cell Carcinoma
Authors: Feng Ji-Feng , Zhao Jian-Ming , Chen Sheng , Chen Qi-Xun
Published: May 2021

Background

Naples prognostic score (NPS) serves as a new prognostic index based on nutritional and inflammatory status in recent years. The aim of the current study was to explore the prognostic effect of NPS and to develop and validate a reliable nomogram based on NPS for individual cancer-specific survival (CSS) prediction in patients with resected ESCC without neoadjuvant therapy.

Methods

The clinical data for 287 (Jan. 2010 to Jun. 2012, Training sets) and 118 (Jan. 2015 to Dec 2015, Validation sets) consecutive resected ESCC cases were retrospectively analyzed. Two NPS models based on the different cut-off values of parameters were compared. Cut-off values in model 1 were derived from previous published studies, while cut-off values in model 2 were obtained in this study based on receiver operating characteristic (ROC) curves. The relationships between NPS and clinical characteristics and CSS were analyzed. The prediction model of nomogram was developed with independent prognostic factors in the training sets and was validated in the validation sets.

Results

The 5-year CSS for NPS 0, 1 and 2 were 61.9%, 34.6% and 13.4% in model 1 and 75.0%, 42.4% and 13.0% in model 2, respectively (P<0.001). Subgroup analyses revealed that NPS was also significantly associated with CSS in both model 1 and model 2 in different TNM stages. Multivariate analyses revealed that NPS was an independent prognostic marker regarding CSS in patients with resected ESCC (P<0.001). A predictive nomogram based on NPS was established and validated. The C-indexes of the nomogram in the training sets and validation sets were 0.68 and 0.72 in model 1 and 0.69 and 0.73 in model 2, respectively. These results confirmed that NPS-based nomogram was a more accurate and effective tool for predicting CSS in patients with resected ESCC.

Conclusion

The current study confirmed that NPS was still a useful independent prognostic score in patients with resected ESCC. The NPS-based nomogram was successfully developed and validated, which may contribute to individual CSS prediction for resected ESCC patients.
Cost-Effectiveness of Lorlatinib as a First-Line Therapy for Untreated Advanced Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer
Authors: Li SiNi , Li JianHe , Peng LiuBao , Li YaMin , Wan XiaoMin
Published: May 2021

Introduction

Recently, a phase III CROWN trial compared the efficacy of two anaplastic lymphoma kinase (ALK) inhibitors and demonstrated that lorlatinib displayed clinical improvement over crizotinib for advanced non-small cell lung cancer (NSCLC) patients. Therefore, the aim of this study was to estimate the cost-effectiveness of lorlatinib as a first-line therapy for patients with advanced ALK-positive (+) NSCLC.

Materials and Methods

A cost-effectiveness analysis was performed using a microsimulation model from the US payer perspective and a lifetime horizon (30 years) in patients with previous untreated advanced ALK+ NSCLC. Based on the CROWN trial, patient characteristics were obtained, and the transition probabilities were estimated. All direct costs were derived from official sources and published literature. The main outcomes of the model were total costs, incremental cost-effectiveness ratio (ICER), quality-adjusted life years (QALYs), and life years (LYs). One-way and probabilistic sensitivity analyses and multiple scenario analyses were conducted to test the robustness of the model outcomes.

Results

In the base case analysis, in which 1 million patients were simulated, treatment with lorlatinib or crizotinib as the first-line treatment was related to a mean cost of $909,758 and $616,230 (incremental cost: $293,528) and a mean survival of 4.81 QALYs and 4.09 QALYs (incremental QALY: 0.72) per patient, respectively. The main drivers of cost effectiveness were drug price and subsequent cost. PAS indicated that lorlatinib has 90% cost-effectiveness when compared to crizotinib when the willingness-to-pay (WTP) threshold in increased to $448,000/QALY. Scenario analysis demonstrated that lorlatinib has 100% cost-effectiveness at a WTP threshold of 200,000/QALY compared to crizotinib treatment when the price of lorlatinib is decreased to 75% ($424.5) of its original price.

Conclusions

In this study, lorlatinib was unlikely to be cost effective compared with crizotinib for patients with previously untreated advanced ALK+ NSCLC at a WTP threshold of 200,000/QALY.
Pilot Study of Telehealth Delivered Rehabilitative Exercise for Youth With Concussion: The Mobile Subthreshold Exercise Program (MSTEP)
Authors: Chrisman Sara P. D. , Mendoza Jason A. , Zhou Chuan , Palermo Tonya M. , Gogue-Garcia Tierra , Janz Kathleen F. , Rivara Frederick P.
Published: May 2021

Background: Concussion is common, and up to 30% of youth develop persistent symptoms. Preliminary data suggests treatment with rehabilitative exercise is beneficial, but most programs require frequent in-person visits, which is challenging for youth in rural areas, and has been made more difficult for all youth during the COVID-19 pandemic. We have adapted an exercise intervention to be delivered via telehealth using Zoom and personal fitness devices, which could ensure access to this type of treatment.

Objective: The goal of this study was to assess feasibility and acceptability of a telehealth delivered exercise intervention for concussion, the Mobile Subthreshold Exercise Program (MSTEP), and collect pilot data regarding efficacy.

Materials and Methods: All youth received the 6-week MSTEP intervention which included wearing a Fitbit and setting exercise heartrate and duration goals weekly over Zoom with the research assistant. Youth completed standardized measures of concussive symptoms (Health Behavior Inventory, HBI), fear-avoidance (Fear of Pain Questionnaire, FOPQ) and health-related quality of life (Pediatric Quality of life Assessment, PedsQL), as well as a structured qualitative exit interview. We examined change in measures over time using mixed effects modeling, controlling for age, sex, prior concussion and duration of symptoms. We coded qualitative interviews using Thematic analysis.

Results: We recruited 19 subjects, 79% female with average age 14.3 (SD 2.2) and mean duration of symptoms 75.6 days (SD 33.7). Participants wore the Fitbit on 80% of days, and completed 94% of surveys and 96% of Zoom calls. Concussive symptoms (HBI) decreased significantly over the 6 week intervention (−10.6, 95%CI: −16.0 to −5.1) as did fear-avoidance (−21.6, 95%CI: −29.8 to −13.5). PedsQL improved significantly during the same time period (+15.1, 95%CI: 8.6–21.6). Approximately three-quarters (76%) of youth rated their care as “excellent.” Participants appreciated the structure of the guided exercise program and the support of the RA. They also enjoyed being able to track their progress with the Fitbit.

Conclusion: This study provides evidence for the feasibility and acceptability of a telehealth delivered rehabilitative exercise intervention for youth with concussion. Further research utilizing a randomized controlled trial is needed to assess efficacy.

Clinical Trial Registration:https://clinicaltrials.gov, identifier: NCT03691363. https://clinicaltrials.gov/ct2/show/NCT03691363
Transfusion Reactions in Pediatric Patients: An Analysis of 5 Years of Hemovigilance Data From a National Center for Children's Health in China
Authors: Guo Kai , Wang Xiaohuan , Zhang Huimin , Wang Mengjian , Song Shanshan , Ma Shuxuan
Published: May 2021

Objective: This study aimed to describe transfusion reactions of pediatric patients from a National Center for Children's Health in China and to examine reaction incidents, reaction types by blood transfusion, and the associated blood products resulting in transfusion reactions.

Methods: We compared transfusion reaction rates, among platelets, plasma, and red blood cells (RBCs) using a retrospective analysis of pediatric patients treated with blood transfusion based on data from the National Center for Children's Health (Beijing, China) by a hemovigilance reporting system from January 2015 to December 2019.

Results: Over the past 5 years, 165 reactions were reported, and the overall incidence was 1.35‰ (95% CI: 1.14–1.55‰; 165/122,652); for each separate year, the incidences were 1.25‰ (95% CI: 0.76–1.74‰; 25/20,035; 2015), 1.09‰ (95% CI: 0.65–1.52‰; 24/22,084; 2016), 1.66‰ (95% CI: 1.14–2.18‰; 39/23,483; 2017), 1.36‰ (95% CI: 0.92–1.81‰; 36/26,440; 2018) and 1.34‰ (95% CI: 0.93–1.75‰; 41/30,610; 2019). Transfusion reaction incidents by person included 0.37‰ (95% CI: 0.21–0.53‰; 21/56,815) RBCs, 2.98‰ (95% CI: 2.33–3.64‰; 79/26,496) platelets and 1.65‰ (95% CI: 1.25–2.05‰; 65/39,341) frozen plasma. According to the analysis by blood products, the incidence of transfusion was 0.34‰ (95% CI: 0.20–0.48‰; 23/66,958) for RBCs, 3.21‰ (95% CI: 2.50–3.92‰; 78/24,318.5) for platelets, and 0.94‰ (95% CI: 0.71–1.17‰; 64/67,912) for frozen plasma. Transfusion reactions were most commonly associated with platelets, followed by plasma and RBC transfusions. The types of blood transfusion reactions were mainly allergic reactions (86.67%) and febrile non-hemolytic transfusion reactions (FNHTRs, 4.24%). The disease types of pediatric patients with transfusion reactions were concentrated among those with blood system diseases. A total of 80.61% of children with transfusion reactions had a previous blood transfusion history.

Conclusions: Transfusion reactions are still relatively common in pediatric patients, and additional studies are necessary to address the differences in reaction rates, especially allergic and FNHTRs. Robust hemovigilance systems do include a special section dedicated to children will further the understanding of these reactions and trends, and prospective randomized clinical controlled trials may need to be conducted to perform preventive and corrective measures.
Cetuximab Can Be an Effective and Low-Toxicity Maintenance Treatment Drug in Patients With Metastatic Colorectal Cancer: A Real-World Study of Zhejiang Cancer Hospital
Authors: Yuan Meiqin , Wang Zeng , Zhao Yazhen , Feng Tingting , Lv Wangxia , Zhong Haijun
Published: May 2021

After initial treatment, maintenance therapy is now commonly used in mCRC patients, which can help patients live longer, have lower side effects, and higher quality of life. The maintenance treatment may include chemotherapy, targeted therapy, or combined with chemotherapy and targeted therapy. But the evidence of cetuximab maintenance is still scant.

Methods: We collected real-world data of wild-type RAS unresectable mCRC patients who were treated with cetuximab-based chemotherapy as the first-line therapy between January 2013 and December 2018 at the Zhejiang Cancer Hospital (Hangzhou, China).

Results: A total of 177 patients were ultimately included in the study, and 107 patients had progression information in medical records; all patients had survival data. The median OS was 40.9 ms, ORR was 14.7%, and DCR was 73.5%. The subgroup analysis showed that the mOS was better in maintenance patients than in non-maintenance patients (47.1 vs. 28.6 ms, p = 0.001), patients with primary tumor resection had better mOS than who did not (47.1 vs. 35.4 ms, p = 0.038). In those 107 patients who had progression information, the median PFS was 9 ms, the median OS was 42.6 ms, ORR was 18.7%, and DCR was 84.1%. The subgroup analysis showed that the mPFS and mOS were 11.6 and 47.1 ms, respectively, in the maintenance group, which were significantly better than 6.1 ms and 28.7 ms in the non-maintenance group (p = 0.025 and 0.017, respectively). The mPFS and mOS in patients with efficacy evaluation of CR + PR + SD were 10.3 and 47.1 ms, respectively, which is significantly better than 2.8 and 13.5 ms in the PD patients (p = 0.012 and <0.001, respectively). The mOS was best in only lung metastases patients (60.9 ms), then only liver metastases patients (47.1 ms), and then in both liver and lung metastases (42.6 ms); the mOS in patients with other organs metastases was the worst (22.4 ms), p = 0.022. The mOS in male individuals is better than that in female individuals, 60.99 vs. 29.1 ms, respectively, p = 0.042. The primary tumor site and primary tumor resection also affect the OS, primary tumor resection better than did not (not reach the end vs. 35.7 ms, p = 0.048), left side better than right side (47.1 vs. 16.6 ms, p < 0.001), which is consistent with the literature report. There was no statistical difference in other subgroups.

Conclusion: For patients with all RAS wild-type and initially unresectable mCRC who experienced standard first-line cetuximab-based treatment and maintenance treatment that contained cetuximab can significantly improve the mPFS and mOS, and the observed toxicity was mostly mild too. So, we consider that cetuximab can be an effective and safety maintenance drug in mCRC patients.
Selective Wnt/β-Catenin Pathway Activation Concomitant With Sustained Overexpression of miR-21 is Responsible for Aristolochic Acid-Induced AKI-to-CKD Transition
Authors: Kuang Qing , Wu Sheng , Xue Ning , Wang Xiaoyan , Ding Xiaoqianq , Fang Yi
Published: May 2021

Acute kidney injury (AKI) is increasingly recognized as a cumulative risk factor for chronic kidney disease (CKD) progression. However, the underlying mechanisms remain unclear. Using an aristolochic acid (AA)-induced mouse model of AKI-to-CKD transition, we found that the development of tubulointerstitial fibrosis following AKI was accompanied with a strong activation of miR-21 and canonical Wnt signaling, whereas inhibition of miR-21 or selective silencing of Wnt ligands partially attenuated AKI-to-CKD transition. To explore the interaction between miR-21 and Wnt/β-catenin signaling, we examined the effects of genetic absence or pharmacologic inhibition of miR-21 on Wnt/β-catenin pathway expression. In miR-21−/− mice and in wild-type mice treated with anti-miR21 oligos, Wnt1 and Wnt4 canonical signaling in the renal tissue was significantly reduced, with partial reversal of renal interstitial fibrosis. Although the renal abundance of miR-21 remained unchanged after inhibition or activation of Wnt/β-catenin signaling, early intervention with ICG-001, a β-catenin inhibitor, significantly attenuated renal interstitial fibrosis. Moreover, early (within 24 h), but not late β-catenin inhibition after AA administration attenuated AA-induced apoptosis and inflammation. In conclusion, inhibition of miR-21 or β-catenin signaling may be an effective approach to prevent AKI-to-CKD progression.
Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial
Authors: Pawar Kirti S , Mastud Rahul N , Pawar Satheesh K , Pawar Samragni S , Bhoite Rahul R , Bhoite Ramesh R , Kulkarni Meenal V , Deshpande Aditi R
Published: May 2021

Background: Coronavirus disease-2019 (COVID-19) has a wide range of pathophysiological effects. Curcumin, an active constituent of Curcuma longa (turmeric), has several properties, including anti-inflammatory, antioxidant, antiviral, anti-thrombotic, and anti-proliferative effects, which make it a promising candidate for the symptomatic treatment of COVID-19.

Objective: We aimed to determine the effects of curcumin administered with piperine (to optimize absorption) on symptoms in patients with COVID-19 in a double-blind, randomized, controlled trial at a 30-bed dedicated COVID Health Center (DCHC) in Maharashtra, India.

Methods: In addition to conventional COVID-19 treatment, patients in the control group received a dose of probiotics twice a day, and patients in the study group received curcumin (525 mg) with piperine (2.5 mg) in tablet form twice a day. The effects of curcumin/piperine treatment on primary and secondary outcomes were assessed for the duration of hospitalization.

Results: Patients with mild, moderate, and severe symptoms who received curcumin/piperine treatment showed early symptomatic recovery (fever, cough, sore throat, and breathlessness), less deterioration, fewer red flag signs, better ability to maintain oxygen saturation above 94% on room air, and better clinical outcomes compared to patients of the control group. Furthermore, curcumin/piperine treatment appeared to reduce the duration of hospitalization in patients with moderate to severe symptoms, and fewer deaths were observed in the curcumin/piperine treatment group.

Conclusions: Administration of oral curcumin with piperine as an adjuvant symptomatic therapy in COVID-19 treatment could substantially reduce morbidity and mortality, and ease the logistical and supply-related burdens on the healthcare system. Curcumin could be a safe and natural therapeutic option to prevent Post-Covid thromboembolic events.

Clinicaltrials.gov identifier:CTRI/2020/05/025482
The Anti-Neuroinflammatory Effect of Fuzi and Ganjiang Extraction on LPS-Induced BV2 Microglia and Its Intervention Function on Depression-Like Behavior of Cancer-Related Fatigue Model Mice
Authors: Yang Songwei , Yang Yantao , Chen Cong , Wang Huiqin , Ai Qidi , Lin Meiyu , Zeng Qi , Zhang Yi , Gao Yan , Li Xun , Chen Naihong
Published: May 2021

The Chinese herb couple Fuzi and Ganjiang (FG) has been a classic combination of traditional Chinese medicine that is commonly used clinically in China for nearly 2000 years. Traditional Chinese medicine suggests that FG can treat various ailments, including heart failure, fatigue, gastrointestinal upset, and depression. Neuroinflammation is one of the main pathogenesis of many neurodegenerative diseases in which microglia cells play a critical role in the occurrence and development of neuroinflammation. FG has been clinically proven to have an efficient therapeutic effect on depression and other neurological disorders, but its mechanism remains unknown. Cancer-related fatigue (CRF) is a serious threat to the quality of life of cancer patients and is characterized by both physical and psychological fatigue. Recent studies have found that neuroinflammation is a key inducement leading to the occurrence and development of CRF. Traditional Chinese medicine theory believes that extreme fatigue and depressive symptoms of CRF are related to Yang deficiency, and the application of Yang tonic drugs such as Fuzi and Ganjiang can relieve CRF symptoms, but the underlying mechanisms remain unknown. In order to define whether FG can inhibit CRF depression-like behavior by suppressing neuroinflammation, we conducted a series of experimental studies in vitro and in vivo. According to the UPLC-Q-TOF/MSE results, we speculated that there were 49 compounds in the FG extraction, among which 30 compounds were derived from Fuzi and 19 compounds were derived from Ganjiang. Our research data showed that FG can effectively reduce the production of pro-inflammatory mediators IL-6, TNF-α, ROS, NO, and PGE2 and suppress the expression of iNOS and COX2, which were related to the inhibition of NF-κB/activation of Nrf2/HO-1 signaling pathways. In addition, our research results revealed that FG can improve the depression-like behavior performance of CRF model mice in the tail suspension test, open field test, elevated plus maze test, and forced swimming test, which were associated with the inhibition of the expression of inflammatory mediators iNOS and COX2 in the prefrontal cortex and hippocampus of CRF model mice. Those research results suggested that FG has a satisfactory effect on depression-like behavior of CRF, which was related to the inhibition of neuroinflammation.
The Therapeutic Landscape of Rheumatoid Arthritis: Current State and Future Directions
Authors: Shams Shahin , Martinez Joseph M. , Dawson John R. D. , Flores Juan , Gabriel Marina , Garcia Gustavo , Guevara Amanda , Murray Kaitlin , Pacifici Noah , Vargas Maxemiliano V. , Voelker Taylor , Hell Johannes W. , Ashouri Judith F.
Published: May 2021

Rheumatoid arthritis (RA) is a debilitating autoimmune disease with grave physical, emotional and socioeconomic consequences. Despite advances in targeted biologic and pharmacologic interventions that have recently come to market, many patients with RA continue to have inadequate response to therapies, or intolerable side effects, with resultant progression of their disease. In this review, we detail multiple biomolecular pathways involved in RA disease pathogenesis to elucidate and highlight pathways that have been therapeutic targets in managing this systemic autoimmune disease. Here we present an up-to-date accounting of both emerging and approved pharmacological treatments for RA, detailing their discovery, mechanisms of action, efficacy, and limitations. Finally, we turn to the emerging fields of bioengineering and cell therapy to illuminate possible future targeted therapeutic options that combine material and biological sciences for localized therapeutic action with the potential to greatly reduce side effects seen in systemically applied treatment modalities.
Anti-Rheumatoid Arthritic Effects of Paris Saponin VII in Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Adjuvant-Induced Arthritis in Rats
Authors: Meng Mei , Yue Zhenggang , Chang Lu , Liu Yanru , Hu Jinhang , Song Zhongxing , Tang Zhishu , Zhou Rui , Wang Changli
Published: May 2021

In the pathogenesis of rheumatoid arthritis (RA), rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) have tumor-like characteristics, mainly manifested by hyperproliferation and resistance to apoptosis and then it will erode the bone and cartilage, eventually leading to joint destruction. Paris saponin VII (PS VII) is an active compound derived from a traditional herbal medicine named Trillium tschonoskii Maxim, which has anti-tumor, analgesic, and immunomodulatory effects. However, its anti-RA effect has not yet been reported. This study was to investigate the effect of PS VII on two rheumatoid arthritis fibroblast-like synoviocytes lines (RA-FLS and MH7A) and adjuvant-induced arthritis (AIA) in rats. In vitro, the effects of PS VII on the proliferation, cell cycle, and apoptosis of RA-FLS and MH7A cells were detected by MTT, flow cytometry, and western blot analysis. In vivo, the effect of PS VII on the weight of the rat, paw swelling, ankle joint diameter, arthritis index, serum inflammatory cytokines (TNF-α, IL-6, and IL-1β), histopathological assessment and apoptosis proteins in the synovial tissues were evaluated in AIA rats. The in vitro studies showed that PS VII inhibited the proliferation of RA-FLS and MH7A cells, induced S phase arrest and triggered cell apoptosis mainly through the mitochondrial apoptotic pathway and the regulation of JNK and p38 MAPK pathways. The in vivo studies revealed that PS VII could improve ameliorate body weight, paw swelling, ankle joint diameter, reduce the spleen and thymus index, suppress the production of TNF-α, IL-6 and IL-1β, improve histopathological changes and regulate the expressions of apoptosis proteins in AIA Rats. In conclusion, PS VII could inhibit the proliferation and trigger apoptosis of RA-FLS and MH7A cells by regulating the mitochondrial apoptosis pathway and the JNK and p38 MAPK pathways, and alleviate the symptoms of RA, signifying it to be one of the potential anti-RA therapeutics.
Quark Structure of the X (4500), X (4700) and χc(4P,5P) States
Authors: Ferretti J. , Santopinto E.
Published: May 2021

We study some of the main properties (masses and open-flavor strong decay widths) of 4P and 5P charmonia. While there are two candidates for the χc0(4P,5P) states, the X(4500) and X(4700), the properties of the other members of the χc(4P,5P) multiplets are still completely unknown. With this in mind, we start to explore the charmonium interpretation for these mesons. Our second goal is to investigate if the apparent mismatch between the Quark Model (QM) predictions for χc0(4P,5P) states and the properties of the X(4500) and X(4700) mesons can be overcome by introducing threshold corrections in the QM formalism. According to our coupled-channel model results for the threshold mass shifts, the χc0(5P)→X(4700) assignment is unacceptable, while the χc0(4P)→X(4500) or X(4700) assignments cannot be completely ruled out.
Using Monte Carlo to Simulate Complex Polymer Systems: Recent Progress and Outlook
Authors: Mavrantzas Vlasis G.
Published: May 2021

Metropolis Monte Carlo has been employed with remarkable success over the years to simulate the dense phases of polymer systems. Owing, in particular, to the freedom it provides to accelerate sampling in phase space through the clever design and proper implementation of even unphysical moves that take the system completely away from its natural trajectory, and despite that it cannot provide any direct information about dynamics, it has turned to a powerful simulation tool today, often viewed as an excellent alternative to the other, most popular method of Molecular Dynamics. In the last years, Monte Carlo has advanced considerably thanks to the design of new moves or to the efficient implementation of existing ones to considerably more complex systems than those for which these were originally proposed. In this short review, we highlight recent progress in the field (with a clear emphasis in the last 10 years or so) by presenting examples from applications of the method to several systems in Soft Matter, such as polymer nanocomposites, soft nanostructured materials, confined polymers, polymer rings and knots, hydrogels and networks, crystalline polymers, and many others. We highlight, in particular, extensions of the method to non-equilibrium systems (e.g., polymers under steady shear flow) guided by non-equilibrium thermodynamics and emphasize the importance of hybrid modeling schemes (e.g., coupled Monte Carlo simulations with field theoretic calculations). We also include a short section discussing some key remaining challenges plus interesting future opportunities.
A Bi-Axial Quantum State That Controls Molecular Collisions Like a Double-Slit Interferometer
Authors: Perreault William E. , Zhou Haowen , Mukherjee Nandini , Zare Richard N.
Published: May 2021

To control molecular scattering, we consider hydrogen molecules prepared in a coherent superposition of m states within a single rovibrational (v, j) energy eigenstate using Stark-induced adiabatic Raman passage (SARP). Specifically, SARP can prepare a bi-axial state of the HD molecule in which the HD bond axis exists simultaneously in two possible alignments at right angles to one another with a well-defined relative phase. We show that scattering from this biaxial state will interfere, resulting in a φ -dependent scattering intensity distribution, where φ is the azimuthal angle about the collision velocity direction. Using the scattering matrix extracted from our experiments on the rotationally inelastic collisions of quantum state prepared HD at low temperatures, we calculate the differential scattering cross-section dσ/dΩ, which shows an interference pattern as function of θ and φ in the image plane perpendicular to the collision velocity. The calculated scattering image shows that scattering from the bi-axial state directs molecules along well-defined angles, corresponding to interference maxima. Thus, the bi-axial state behaves like a double slit for molecular scattering. Moreover, by rotating the polarizations of the SARP preparation lasers, we can control the interference thereby altering the scattering angular distribution. This molecular interferometer, which experimentally measures the relative phases of the scattering matrix elements, allows a direct test of theoretical calculations on important, fundamental collision processes.
Advances in High-Speed Structured Illumination Microscopy
Authors: Zhao Tianyu , Wang Zhaojun , Chen Tongsheng , Lei Ming , Yao Baoli , Bianco Piero R.
Published: May 2021

Super-resolution microscopy surpasses the diffraction limit to enable the observation of the fine details in sub-cellular structures and their dynamics in diverse biological processes within living cells. Structured illumination microscopy (SIM) uses a relatively low illumination light power compared with other super-resolution microscopies and has great potential to meet the demands of live-cell imaging. However, the imaging acquisition and reconstruction speeds limit its further applications. In this article, recent developments all targeted at improving the overall speed of SIM are reviewed. These comprise both hardware and software improvements, which include a reduction in the number of raw images, GPU acceleration, deep learning and the spatial domain reconstruction. We also discuss the application of these developments in live-cell imaging.
Chemomechanical Simulation of Microtubule Dynamics With Explicit Lateral Bond Dynamics
Authors: Schmidt Matthias , Kierfeld Jan
Published: May 2021

We introduce and parameterize a chemomechanical model of microtubule dynamics on the dimer level, which is based on the allosteric tubulin model and includes attachment, detachment and hydrolysis of tubulin dimers as well as stretching of lateral bonds, bending at longitudinal junctions, and the possibility of lateral bond rupture and formation. The model is computationally efficient such that we reach sufficiently long simulation times to observe repeated catastrophe and rescue events at realistic tubulin concentrations and hydrolysis rates, which allows us to deduce catastrophe and rescue rates. The chemomechanical model also allows us to gain insight into microscopic features of the GTP-tubulin cap structure and microscopic structural features triggering microtubule catastrophes and rescues. Dilution simulations show qualitative agreement with experiments. We also explore the consequences of a possible feedback of mechanical forces onto the hydrolysis process and the GTP-tubulin cap structure.
Effects of Ursolic Acid on Intestinal Health and Gut Bacteria Antibiotic Resistance in Mice
Authors: Peng Fang , Zhang Haihan , He Xi , Song Zehe
Published: May 2021

Ursolic acid (UA), a natural pentacyclic triterpenoid, has been widely reported to exert anti-oxidant and anti-inflammatory properties. However, the effects of UA on the intestinal homeostasis and gut microbiota were rarely explored. The aim of the present study was to investigate the effects of UA on intestinal health and gut microflora antibiotic-resistance in antibiotic-exposed mice. Kunming mice (n = 80) were randomly allocated into three groups and fed with one of the following diets, respectively: Cont group (n = 20), the basal diet; UA group (n = 20), the basal diet supplemented with 150 mg/kg UA; Tet group (n = 40), the basal diet supplemented with 659 mg/kg chlortetracycline. After 14 days, 10 mice in each group were euthanatized and the remaining 30 mice in the Tet group were randomly allocated into three sub-groups (n = 10 per group) as follows: the Tet group which were kept feeding a Tet diet for 14 days; the Natural Restoration (NatR) group which received a basal diet for 14 days; and the UA therapy (UaT) group which fed a basal diet supplemented with 150 mg/kg UA for 14 days. Throughout the experiment, the weight and the food intake of each mouse were recorded once weekly. Serum LPS and diamine oxidase (DAO), jejunal morphology, jejunal tight junction proteins and nutrient transporters, colonic inflammatory cytokines, gut microbiota and its antibiotic resistance gene (ARG) were examined at euthanasia. The results showed that UA treatment significantly increased average daily food intake (ADFI) of mice. Notably, UA increased the jejunal villi height, decreased the jejunal crypt depth and promoted the expression of jejunum nutrient transporters. UaT group had higher villi height, lower crypt depth and higher nutrient transporter mRNA expression in jejunum than NatR group. Besides, UA decreased serum DAO content, upregulated mRNA expression of ZO-1, claudin-1 and occludin and downregulated TNF-α and IL-6. The mRNA abundances of ZO-1, claudin-1 and occludin and TNF-α and IL-6 in UaT group were, respectively upregulated and downregulated than NatR group. Furthermore, an analysis of 16S rDNA sequences demonstrated that UA increased the abundance of beneficial bacteria in the gut. And the results of ARG test showed that UA downregulated the expression of antibiotic-induced resistance genes. The UaT group inhibited the increase of harmful bacteria abundance and suppressed the mRNA abundances of ARG compared to the NatR group. In conclusion, considering the positive effects of UA on the growth performance and intestinal mucosal barrier, we anticipate that these findings could be a stepping stone for developing UA as a novel substitute of antibiotics.
Chinese Soft-Shelled Turtle Oil in Combination With Swimming Training Improves Spatial Memory and Sports Performance of Aging Rats
Authors: Yang Chia-En , Yeh Tsung-Ming , Chang Ching-Dong , Shih Wen-Ling
Published: May 2021

In this study, waste fat from the Chinese soft-shelled turtle (Pelodiscus sinensis) was used as the raw material, and soft-shelled turtle oil (SSTO) was extracted by water heating. Analysis of the fatty acid composition of SSTO revealed that unsaturated fatty acids (UFAs) comprised more than 70% of the oil, of which more than 20% were omega-3 poly-UFAs. DPPH radical scavenging and cellular ROS assays confirmed the reduction of oxidative stress by SSTO. In D-galactose-induced aging rats, SSTO feeding alone or in combination with swimming training resulted in improved memory and physical strength. In addition, SSTO feeding with swimming intervention significantly increased the SOD level and maintained better blood pressure in the aged rats. The serum DHEAS and soleus muscle glycogen level were also highly correlated with SSTO feeding and swimming training. In conclusion, the results of this study demonstrated that SSTO has the potential to be developed into a health food that exerts anti-aging effects, and those effects are stronger when combined with daily swimming exercise.
Identifying Anti-Oxidant Biosynthesis Genes in Pearl Millet [Pennisetum glaucum (L.) R. Br.] Using Genome—Wide Association Analysis
Authors: Yadav Chandra Bhan , Tokas Jayanti , Yadav Devvart , Winters Ana , Singh Ram B. , Yadav Rama , Gangashetty Prakash I. , Srivastava Rakesh K. , Yadav Rattan S.
Published: May 2021

Pearl millet [Pennisetum glaucum (L.) R Br.] is an important staple food crop in the semi-arid tropics of Asia and Africa. It is a cereal grain that has the prospect to be used as a substitute for wheat flour for celiac patients. It is an important antioxidant food resource present with a wide range of phenolic compounds that are good sources of natural antioxidants. The present study aimed to identify the total antioxidant content of pearl millet flour and apply it to evaluate the antioxidant activity of its 222 genotypes drawn randomly from the pearl millet inbred germplasm association panel (PMiGAP), a world diversity panel of this crop. The total phenolic content (TPC) significantly correlated with DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity (% inhibition), which ranged from 2.32 to 112.45% and ferric-reducing antioxidant power (FRAP) activity ranging from 21.68 to 179.66 (mg ascorbic acid eq./100 g). Genome-wide association studies (GWAS) were conducted using 222 diverse accessions and 67 K SNPs distributed across all the seven pearl millet chromosomes. Approximately, 218 SNPs were found to be strongly associated with DPPH and FRAP activity at high confidence [–log (p) > 3.0–7.4]. Furthermore, flanking regions of significantly associated SNPs were explored for candidate gene harvesting. This identified 18 candidate genes related to antioxidant pathway genes (flavanone 7-O-beta-glycosyltransferase, GDSL esterase/lipase, glutathione S-transferase) residing within or near the association signal that can be selected for further functional characterization. Patterns of genetic variability and the associated genes reported in this study are useful findings, which would need further validation before their utilization in molecular breeding for high antioxidant-containing pearl millet cultivars.