bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive association between physical outcomes and patient-reported outcomes in late-onset Pompe disease: a cross sectional study
Authors: Yuan Meng , Andrinopoulou Eleni-Rosalina , Kruijshaar Michelle E. , Lika Aglina , Harlaar Laurike , Ploeg Ans T Van Der , Rizopoulos Dimitris , Beek Nadine A.M.E. van der
Published: May 2020

Background Pompe disease is a rare, progressive metabolic myopathy. The aim of this study is to investigate the associations of physical outcomes with patient-reported outcome measures (PROMs) in late-onset Pompe disease. Methods We included 121 Dutch adult patients with Pompe disease. Physical outcomes comprised muscle strength (manual muscle testing using Medical Research Council [MRC] grading, hand-held dynamometry [HHD]), walking ability (6-minute walk test [6MWT]), and pulmonary function (forced vital capacity [FVC] in upright and supine positions). PROMs comprised quality of life (Short Form 36 health survey [SF-36]), participation (Rotterdam Handicap Scale [RHS]) and daily-life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale). Analyses were cross-sectional: the time-point before, and closest to, start of Enzyme Replacement Therapy was chosen. Associations between PROMs and physical outcomes were investigated using linear regression models. Results RHS and R-PAct scores were better in patients with higher FVC supine and upright, HHD, MRC and 6MWT scores, accounting for the effect of sex, disease duration, use of wheelchair and ventilator support. While the SF-36 Physical Component Summary (PCS) was correlated positively with FVC upright, HHD, MRC and 6MWT scores, there was no significant relationship between the SF-36 Mental Component Summary (MCS) and any of the physical outcomes. Conclusions Participation, daily-life activities, and the physical component of quality of life of adult Pompe patients are positively correlated to physical outcomes. This work serves as a first step towards assessing how changes over time in physical outcomes are related to changes in PROMs, and to define the minimal change in physical outcomes required to make an important difference for the patient.
Two novel heterozygote mutations of ATM in a Chinese family with dystonia-dominant ataxia telangiectasia and literatures review
Authors: Liu Zhi-Jun , Wang Ya-Ling , xu yan
Published: May 2020

Background Ataxia-telangiectasia (A-T) is an autosomal recessive disorder with high clinical heterogeneity. A-T may present in complicated variable forms, mainly including classic A-T and milder forms. Contrary to the classic A-T, the milder form does not present the cardinal features of A-T, including ataxia and telangiectasia. A few ATM mutations have been reported in variant A-T cases manifested as isolated dystonia without any signs of classical A-T. To date, more than 400 disease-related ATM mutations have been identified in patients with A-T. Methods A pedigree with A-T and predominant dystonia were collected. Genetic testing of the proband were performed by target exome-sequencing of a panel designed to cover 101 genes associated with movement disorders. The candidate variants were further confirmed by Sanger sequencing.Results Two novel ATM variants (p.I2683T and p.S2860P) with probable pathogenicity were identified in the family. The proband presented obviously isolated segmental dystonia without any signs of ataxia and telangiectasias. We then reviewed previously published literatures of genetically confirmed A-T cases with predominant dystonia and summarized the clinical characteristics of dystonia-dominant A-T. Conclusion This is the first report of A-T patient with predominant dystonia in China. Dystonia may appear as one of the predominant manifestations or initial symptom of A-T. ATM genetic testing should be early considered for those patients with predominant dystonia, despite without accompanying ataxia or telangiectasia.
Caspase-3 Silencing Attenuates Tumor Repopulation Via Impairing Radiation-Induced DNA Damage Response and Downstream Pathway in Non-Small-Cell Lung Cancer
Authors: Zhao Minghui , Wang Yiwei , Zhao Yucui , He Sijia , Zhao Ruyi , Song Yanwei , Cheng Jin , Gong Yanping , Xie Jianzhu , Wang Yulan , Hu Binjie , Tian Ling , Huang Qian
Published: May 2020

Background: Radiotherapy is an effective treatment on non-small-cell lung cancer (NSCLC). However, radiation-induced dying tumor cells are postulated to generate potent growth signals to stimulate the repopulation of adjacent surviving tumor cells, which may promote tumor recurrence. We investigated the role of caspase-3-centered molecular mechanism in NSCLC repopulation after radiotherapy.Methods: The stable caspase-3 knockout (Casp3 KO) NSCLC cells were compared with wild-type cells for growth-promoting effect after radiotherapy using in vitro repopulation model. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay and luciferase reporter assay were used to identify the possible molecules and pathway. To elucidate the function of caspase-3 in tumor repopulation, a series of in vitro assays were performed with Casp3 KO NSCLC cells. Finally, tumor cell growth rate of Casp3 KO and wild-type tumor cells in vivo was tested using xenograft tumor assay and key proteins were further confirmed in tumor tissues with or without radiotherapy.Results: We found that radiation induced DNA damage response (DDR) and caspase-3 activation, as well as promoted tumor repopulation in NSCLC cells. Unexpectedly, depleting caspase-3 significantly attenuated ataxia-telangiectasia mutated kinase (ATM)/p53-mediated DDR via attenuating endonuclease G (EndoG) nuclear migration, thus decreasing the growth-promoting effect of irradiated dying cells. Moreover, we identified p53 as a regulator of the Cox-2/PGE2 axis, which was probably involved in caspase-3-centered tumor repopulation after radiotherapy. Additionally, depleting caspase-3 in NSCLC cells showed impaired tumor growth in nude mice model.Conclusions: Our findings demonstrated that caspase-3 was implicated in tumor repopulation and that was accompanied by promoting DDR and downstream Cox-2/PGE2 axis activation in NSCLC cells. This hitherto undescribed signaling pathway mediated by caspase-3 may deepen insight into the radiobiology and provide therapeutic targets to reduce NSCLC recurrence after radiotherapy.
IFN-γ Enhances the Therapeutic Effect of Mscs on Experimental Renal Fibrosis
Authors: Kanai Ryo , Nakashima Ayumu , Doi Shigehiro , Kimura Tomoe , Yoshida Ken , Maeda Satoshi , Ishiuchi Naoki , Yamada Yumi , Ike Takeshi , Doi Toshiki , Kato Yukio , Masaki Takao
Published: May 2020

Background:Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes may require a substantial period of time, leading to a delayed onset of MSCs therapeutic effects. Here, we investigatedwhetherpretreatment with IFN-γ potentiates the anti-fibrotic and anti-inflammatory activities of MSCs in an injured kidney. Methods:MSCs with or without IFN-γ treatment were injected into rats after ischemia-reperfusion injury (IRI) or unilateral ureter obstruction (UUO) to evaluate the therapeutic effect of IFN-γ-treated MSCs. In addition, we used conditioned medium obtained from IFN-γ-treated MSCs to investigate fibrotic change in cultured cells induced by transforming growth factor-β1 and phenotypic change of macrophages using THP-1 monocytes.Results:Administration of MSCs treated with IFN-γ strongly ameliorated renal fibrosis and inflammation in rat IRI and UUO models compared with that of untreated MSCs. In vitro experiments demonstrated that IFN-γ treatment enhanced the anti-fibrotic effects of MSCs by inhibiting the transforming growth factor-β1/Smad signaling pathway. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 induced polarization of immunosuppressive CD163-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ.Conclusions:Administration of MSCs treated with IFN-γ may represent a promising therapy to prevent the progression of renal fibrosis.
A strain affiliated to Bacillus amyloliquefaciens alleviates high-carbohydrate diet- induced metabolic syndrome by restoration of acetate-producing bacteria in fish intestines
Authors: Xu Rong , Li Miao , Wang Tong , Zhao Yi-Wei , Shan Cheng-Jie , Qiao Fang , Chen Li-Qiao , Du Zhen-Yu , Zhang Mei-Ling
Published: May 2020

Background: Increasing the utilization efficiency of high-carbohydrate diet has the potential to promote “protein sparing effects” in farmed fish; however, many fish utilize carbohydrates poorly. The intestinal microbiota plays an important role in carbohydrate degradation. Whether the addition of functional bacteria could increase the carbohydrate utilization efficiency and alleviate high-carbohydrate diet-induced adverse effects is unknown.Results: A bacterial strain that could degrade starch in vitro was isolated from the intestines of Nile tilapia (Oreochromis niloticus). The bacterium was affiliated to Bacillus amyloliquefaciens (designated as B. amy SS1) based on 16S rRNA gene sequencing. Three diets, including control diet (CON), high-carbohydrate diet (HCD), and high-carbohydrate diet supplemented with B. amy SS1 (HCB), were used to feed Nile tilapia for 10 weeks. The beneficial effects of B. amy SS1 on weight gain and protein accumulation were observed. The HCB decreased blood glucose levels and reduced lipid deposition compared with the HCD group. To detect the possible mechanism, the intestinal microbiota composition was characterized using high-throughput sequencing. The HCB increased the abundance of short-chain fatty acid-producing bacteria. Gas chromatographic analysis indicated that theconcentration of acetate increased dramatically in the HCB group compared with that in the HCD group. Glucagon-like peptide-1 (GLP-1) levels increased in the intestine and serum of the HCB group. Different concentrations of sodium acetate (low (HLA), 900 mg/kg; medium (HMA), 1800 mg/kg, and high (HHA), 3600 mg/kg) were added to the HCD to feed the fish for eight weeks. The HMA and HHA groups mirrored the effects of the HCD supplemented with B. amy SS1 by increasing serum GLP-1 levels. Increased acetate concentrations stimulated GLP-1 production, which might account for the effects caused by the addition of B. amy SS1 to the HCD.Conclusions: This study systematically analyzed the influence of B. amy SS1 on fish metabolism, suggesting that B. amy SS1 treatment alleviates the metabolic syndrome caused by HCD by enriching acetate-producing bacteria in fish intestines. Regulating the intestinal microbiota and their metabolites might represent a powerful strategy for fish nutrition modulation and health maintenance in future.
Cancer in Moroccan Elderly: The first Multicenter Transverse Study Exploring the Sociodemographic Characteristics, Clinical Profile and Quality of Life of Elderly Moroccan Cancer Patients
Authors: Amzerin Mounia , Laayachi Mohamed , Bazine Aziz , Aassab Rachid , Arifi Samia , Benbrahim Zineb , Khmamouche Mohamed Reda , Kairouani Mouna , Raiss Hanan , Majid Noura , Ouaouch Saloua , Ichou Mohammed , Afqir Said , Mellas Nawfal , Fetohi Mohamed , Razine Rachid , Errihani Hassan
Published: May 2020

Background Moroccan incidence of cancer is increasing with the lengthening of life expectancy. Data regarding elderly Moroccan cancer patients are lacking. In the context of our project aiming to develop an adapted version of the Comprehensive Geriatric Assessment CGA to the Moroccan population, we launched the first Moroccan multicenter transverse study to explore the characteristics of elderly Moroccan cancer patients.Methods The study was conducted in nine Moroccan medical oncology departments. Patients were enrolled over 4 months. Inclusion criteria were patients aged 65 years or over with verified solid cancer. The questionnaire included four sections: socio-demographic and economic data, clinical data, vulnerability and EORTC-QLQ C30. We explored the entire included population. Then, we compared the results according to age (65–70 years old and ≥ 71 years old) and sex. We also explored the correlation between G8 scores and the ability to practice religion as an indicator of fitness level.Results In total, 164 patients were enrolled. The mean age was 73.18 ± 6.01 years. The majority of patients were married, lived with their children and received their financial income from them. Fifteen percent of families asked to hide the diagnosis from the patient. Breast (23%), colorectal (15.9%) and lung (14%) cancers were the most frequent, and 83.5% had an abnormal G8. The majority of the patients were independent for basic daily activities. Female patients had poorer social and economic conditions. Abnormal G8 was correlated with religious practice and quality of life scores.Conclusion This is the first multicenter prospective study designed to collect data on the lifestyle and clinical profiles of elderly Moroccan cancer patients as an Arab and Muslim population. Our study shows that it is a well-cared-for population with strong social ties. However, there is deep economic vulnerability, especially among women, requiring urgent care. Religious practice is an important daily activity for our elderly patients and should be included in the Moroccan CGA.
Elevated Troponin T and enlarged left atrium predict the incidence of atrial fibrillation in patients with chronic kidney disease stage 4-5
Authors: Hakamäki Markus , Hellman Tapio , Lankinen Roosa , Koivuviita Niina , Pärkkä Jussi , Kallio Petri , Kiviniemi Tuomas , Airaksinen Juhani KE , Järvisalo Mikko J , Metsärinne Kaj
Published: May 2020

Background

Atrial fibrillation (AF) and chronic kidney disease (CKD) are commonly co-existing conditions. However, data on epidemiology of AF in patients with CKD stage 4–5 is scarce.
Methods

We prospectively enrolled 210 consecutive non-dialysis patients with CKD stage 4–5 between 2013 and 2017. Follow-up data on AF incidence along with medical history, laboratory tests and echocardiography at baseline were gathered.
Results

At baseline, mean age was 62 years, estimated glomerular filtration rate 12.8 ml/min and 73/210 (34.8%) of the participants were female. Altogether 41/210 (19.5%) patients had a previous diagnosis of AF. After median follow-up of 46 [IQR 27] months, new-onset AF occurred in 33/169 (19.5%) patients (69.9 events/1000 person-years). Overall, 22/33 (66.7%) of patients with new-onset AF were identified with a triggering condition and 21/33 (63.6%) were receiving renal replacement therapy (dialysis or acquired kidney transplant) at the time of AF detection, respectively. In Cox proportional hazard model age > 60 years (HR 4.27, CI95% 1.57–11.64, p < 0.01), elevated troponin T (TnT) > 50 ng/l (HR 3.61, CI95% 1.55–8.37, p < 0.01) and left atrial volume index (LAVI) > 30 ml/m2 (HR 4.82, CI95% 1.11-21.00, p = 0.04) independently predicted the incidence of new-onset AF.
Conclusions

The prevalence and incidence of AF was markedly high in this prospective study on patients with CKD stage 4–5. Elevated TnT and increased LAVI were identified as independent predictors for new-onset AF in patients with severe CKD.
Effects of mouth breathing on facial skeletal development and malocclusion in children: A systematic review and meta-analysis.
Authors: Zhao Ziyi , Zheng Leilei , Huang Xiaoya , Li Caiyu , Liu Jing , Hu Yun
Published: May 2020

BACKGROUND: Mouth breathing is closely related to the facial skeletal development and malocclusion. The purpose of this systematic review and meta-analysis was to assess the effect of mouth breathing on facial skeletal development and malocclusion in children. METHODS: An electronic search in PubMed, the Cochrane Library, Medline, Web of Science, EMBASE and Sigle through February 23rd, 2020, was conducted. Methodological quality assessments of the selected articles were performed using the Newcastle-Ottawa Scale. Review Manager 5.3, was used to synthesize various parameters associated with the impact of mouth breathing on facial skeletal development and malocclusion. RESULTS: Following full-text evaluations for eligibility, 7 studies (387 mouth-breathing subjects and 433 nasal-breathing controls) were included in the final quantitative synthesis; they were all high-quality. The included indicators were SNA (p>0.050), ANS-PNS (p>0.050), 1.NB (p>0.050), MP-H (p>0.050), FMA (p>0.050), SNB (MD: -1.99, P <0.0001), ANB (MD: 0.95, P = 0.0005), SN-OP (MD: 3.20, P < 0.0001), SNGoGn (MD: 4.34, P < 0.0001), 1-NA (MD: 0.72, P = 0.004), 1. NA (MD: 1.98, P = 0.020), 1-NB (MD: 1.06, P < 0.0001), SPAS (MD: -5.23, P < 0.0001), PAS (MD: -2.11, P < 0.0001), and C3-H (MD: -1.34, P < 0.0001). CONCLUSIONS: The results showed that mouth breathing can cause underdevelopment of the mandible. The mandible rotated backward and downward, and the occlusal plane was steep. However, there was little effect on the maxilla. In addition, mouth breathing presented a tendency of lip inclination of the upper and lower anterior teeth. Airway stenosis was common in mouth-breathing children. TRIAL REGISTRATION: crd-register@york.ac.uk; registration number CRD42019129198 KEYWORDS: Mouth breathing; Facial skeletal development; Children; Systematic review, Meta-analysis.
Liver Injury in patients with COVID-19: Clinical Profiles, CT findings and their Correlation with the Severity
Authors: Lei Ping , Zhang Lan , Han Ping , Zheng Chuansheng , Tong Qiaoxia , Shang Haitao , Yang Fan , Hu Yu , Li Xin , Song Yuhu
Published: May 2020

BACKGROUND & AIMS: Liver injury is found in some of patients with COVID-19. Liver injury of patients based on severity grading and abdominal radiological signs have not been reported until now. The aim of our study is to determine clinical profiles of the patients based on severity grading, describe abdominal radiological signs, and investigate the correlations of the severity with clinical profiles and radiological signs.METHODS: This retrospective cohort study included 115 patients with COVID-19 from Jan 2020 to Feb 2020. Medical records of the patients were collected and CT images were reviewed.RESULTS: Common clinical manifestations of the patients with COVID-19 were fever (68.70%), cough (56.52%), fatigue (31.30%); some of them had gastrointestinal symptoms (diarrhea,12.17%; nausea or vomiting 7.83%; inappetence, 7.83%). Abnormal liver function was observed in some of the patients with COVID-19. Significant differences in the levels of AST, albumin,CRP were observed among different groups classified by the severity. Common findings of upper abdominal CT scan were liver hypodensity (26.09%) and pericholecystic fat stranding (21.27%); liver hypodensity were more frequently found in critical cases (58.82%). The semi-quantitative CT score of pulmonary lesions, CT-quantified liver/spleen attenuation ratio correlated with severity grading in patients with COVID-19.CONCLUSIONS: Some of patients with COVID-19 displayed liver damage revealed by liver functional tests and upper abdominal CT imaging, and some of liver functional tests and CT signs correlate with severity grading; thus, it will allow an earlier identification of high-risk patients for early effective intervention.
Purple Nutsedge Management in Florida Strawberry with Herbicides and a Modified Florida 3-Way Fumigation Program
Authors: Khatri Kshitij , Peres Natalia , Noling Joseph , Boyd Nathan
Published: May 2020

The “Florida 3-way” consists of chloropicrin 35% + 1,3-dichloropropene 65% followed by minicoulter application of metam potassium. We evaluated the efficacy of a modified version of the Florida 3-way in which chloropicrin 35% + 1,3-dichloropropene 65% was used as primary bed fumigant and consisted of different drip tape application timings (at the time of bed formation and 2 weeks after bed formation) of metam potassium or the use of herbicides (sulfentrazone and s-ethyl dipropylthiocarbamate) as the supplemental application for the control of purple nutsedge (Cyperus rotundus) in strawberry (Fragaria ×ananassa) fields. Efficacy of modified Florida 3-way was not significantly different from standard Florida 3-way; however, supplemental herbicide such as s-ethyl dipropylthiocarbamate and sulfentrazone provided better purple nutsedge control than supplemental metam potassium application in one of two experimental growing seasons. Addition of metam potassium to the chloropicrin 35% + 1,3-dichloropropene 65% did not result in additional purple nutsedge control in Florida 3-way, which indicates the limitations of this approach.
Novel Targets of Metformin in Cardioprotection: Beyond the Effects Mediated by AMPK
Authors: Bolívar Samir , Noriega Laura , Ortega Stefany , Osorio Estefanie , Rosales Wendy , Mendoza Xilene , Mendoza-Torres Evelyn
Published: May 2020

Ischemic heart disease is the main cause of death globally. In the heart, the ischemia/reperfusion injury
gives rise to a complex cascade of molecular signals, called cardiac remodeling, which generates harmful
consequences for the contractile function of the myocardium and consequently heart failure. Metformin is the
drug of choice in the treatment of type 2 diabetes mellitus. Clinical data suggest the direct effects of this drug
on cardiac metabolism and studies in animal models showed that metformin activates the classical pathway of
AMP-activated protein kinase (AMPK), generating cardioprotective effects during cardiac remodeling, hypertrophy
and fibrosis. Furthermore, new studies have emerged about other targets of metformin with a potential
role in cardioprotection. This state of the art review shows the available scientific evidence of the cardioprotective
potential of metformin and its possible effects beyond AMPK. Targeting of autophagy, mitochondrial function
and miRNAs are also explored as cardioprotective approaches along with a therapeutic potential. Further
advances related to the biological effects of metformin and cardioprotective approaches may provide new
therapies to protect the heart and prevent cardiac remodeling and heart failure.
Pharmaceutical Approaches for Treatment of Hepatitis C virus
Authors: Milani Alireza , Basimi Parya , Agi Elnaz , Bolhassani Azam
Published: May 2020

Many studies have been performed to develop an antiviral therapy against the hepatitis C virus (HCV)
infections. The usual treatment for HCV infection is a combination of PEGylated interferon and ribavirin which
offer restricted efficiency and major side effects. Thus, recent development in molecular biology of HCV and its
life cycle led to the design of many drugs that target viral proteins and host factors required for viral replication.
These drugs were named as direct-acting antivirals (DAAs) that were specifically designed for inhibition of viral
life cycle, promising tolerability, short duration of treatment, higher barrier to resistance, and fewer drug interactions.
The use of DAAs for the treatment of HCV infection resulted in high virological cure rates in patients.
However, the use of combined DAA regimens may present drug interactions especially in patients under treatment
for other co-morbidities. On the other hand, drug resistance against virus infection determines the success of
long-term therapy. High genetic diversity among HCV virions due to error-prone polymerase activity led to the
reduced susceptibility to DAA-therapy. Therefore, preclinical and clinical analysis of HCV resistance to novel
drugs is needed. In this review, we describe pharmaceutical approaches for HCV treatment, structural and functional
properties of DAAs, the principles of HCV drug-drug interaction, and finally HCV resistance to DAAs.
Targeted Photodynamic Therapy (PDT) of Lung Cancer with Biotinylated Silicon (IV) Phthalocyanine
Authors: Dong Wenyi , Li Ke , Wang Shijie , Qiu Ling , Liu Qingzhu , Xie Minhao , Lin Jianguo
Published: May 2020

Background:

Lung cancer is the leading cause of cancer-associated mortality in the world. Traditional cancer therapies prolong the life expectancy of patients but often suffer from adverse reactions. Photodynamic Therapy (PDT) has been recommended as a treatment option for lung cancer in several countries, due to its non-invasive procedures, high selectivity and weak side effects.

Objective:

We have designed and synthesized a biotin receptor-targeted silicon phthalocyanine (IV) (compound 1) which showed a good therapeutic effect on biotin receptor-positive tumors. Since the overexpression of Biotin Receptor (BR) is also present in human lung cancer cells (A549), we explored the therapeutic properties of compound 1 on A549 xenograft tumor models.

Methods:

The selectivity of compound 1 toward A549 cells was studied with a fluorescence microscope and IVIS Spectrum Imaging System. The cytotoxicity was measured using the MTT assay. In vivo anti-tumor activity was investigated on the nude mice bearing A549 xenografts.

Results:

In vitro assays proved that compound 1 could selectively accumulate in A549 cells via the BR-mediated internalization. In vivo imaging and distribution experiments showed that compound 1 could selectively accumulate in tumor tissues of tumor-bearing mice. After 16 days of the treatment, the volumes of tumor in the PDT group were obviously smaller than that in other groups.

Conclusion:

This study demonstrates that compound 1 is a promising photosensitizer and has broad application prospects in clinical PDT of lung cancers.
Bioactive Molecules from the Alpinia Genus: A Comprehensive Review
Authors: Dash Santwona , Panda Manasa K. , Singh Mayanglambam C. , Jit Bimal P. , Singh Yengkhom D. , Patra Jayanta K.
Published: May 2020

Background:

Floral has diversity and unique nature due to the complex structure and component.
Alpinia is an important genus of the Zingiberaceae family having complex taxonomical diversity.
The presence of many unique bioactive molecules makes this genus, a pharmaceutically important
genus. They provide a wide range of medicinal properties, including traditional remedies to modern
therapeutic applications.

Methods:

Extracts of Alpinia mostly contain bioactive molecules and secondary metabolites such as
polyphenolics, tannins, flavonoids and other therapeutically important compounds. These bioactive
molecules are biologically active, treating against inflammation, cancer, arterial hypertension, and other
deadly diseases.

Results:

These bioactive molecules can act as natural enzyme inhibitors for some of the deadly diseases
and can block the pathway for metabolic activities. In addition, these genera have played a major role in
multidisciplinary studies of phytochemistry, ethnobotany, and pharmacological aspects in day-to-day life.

Conclusion:

Therefore, this review highlights the fewer known facts of the genus Alpinia in terms of bioactive
molecules and its significant therapeutic applications to help in combating major diseases of humans.
Acetaminophen Oxidation and Inflammatory Markers – A Review of Hepatic Molecular Mechanisms and Preclinical Studies
Authors: Stefanello Silvio Terra , de Carvalho Nelson Rodrigues , Reis Simone Beder , Soares Felix Alexandre Antunes , Barcelos Rômulo Pillon
Published: May 2020

Acetaminophen is a widely used analgesic for pain management, especially useful in chronic
diseases, such as rheumatoid arthritis. However, easy access to this medicine has increased the occurrence
of episodes of poisoning. Patients often develop severe liver damage, which may quickly
lead to death. Consequently, numerous studies have been conducted to identify new biomarkers that
allow the prediction of the degree of acetaminophen intoxication and thus intervene in a timely manner
to save patients’ lives. This review highlights the main mechanisms of the induction and progression
of liver damage arising from acetaminophen poisoning. In addition, we have discussed the possibility
of using new clinical biomarkers for detecting acetaminophen poisoning.
PD-L1 Testing for Urothelial Carcinoma: Interchangeability, Reliability and Future Perspectives
Authors: Gevaert Thomas , Cimadamore Alessia , Montironi Rodolfo , Eckstein Markus
Published: May 2020

Five programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved
for the treatment of locally advanced or metastatic urothelial carcinoma of the bladder and the
upper urinary tract. Following the FDA and EMA restrictions of first-line treatment with Atezolizumab
and Pembrolizumab in platinum-ineligible patients, immunohistochemical PD-L1 testing is now required.
Several emerging issues on antibodies, test platforms and scoring algorithms have raised concerns
about the comparability and interchangeability between these assays. In this review, we have focused
on the interchangeability of the used algorithms and assays for PD-L1 testing in urothelial carcinoma,
on the predictive reliability of PD-L1 testing in urothelial carcinoma and the potential of other
new and upcoming biomarkers.
Nano-Strategies for Improving the Bioavailability of Inhaled Pharmaceutical Formulations
Authors: Xing Yue , Lu Peng , Xue Zhifeng , Liang Chunxia , Zhang Bing , Kebebe Dereje , Liu Hongfei , Liu Zhidong
Published: May 2020

Pulmonary pharmaceutical formulations are targeted for the treatment of respiratory diseases. However, their application is limited due to the physiological characteristics of the lungs, such as branching structure, mucociliary and macrophages, as well as certain properties of the drugs like particle size and solubility. Nano-formulations can ameliorate particle sizes and improve drug solubility to enhance bioavailability in the lungs. The nano-formulations for lungs reviewed in this article can be classified into nanocarriers, no-carrier-added nanosuspensions and polymer-drug conjugates. Compared with conventional inhalation preparations, these novel pulmonary pharmaceutical formulations have their own advantages, such as increasing drug solubility for better absorption and less inflammatory reaction caused by the aggregation of insoluble drugs; prolonging pulmonary retention time and reducing drug clearance; improving the patient compliance by avoiding multiple repeated administrations. This review will provide the reader with some background information for pulmonary drug delivery and give an overview of the existing literature about nano-formulations for pulmonary application to explore nano-strategies for improving the bioavailability of pulmonary pharmaceutical formulations.
Recent Developments of Target Based Coumarin Derivatives as Potential Anticancer Agents
Authors: Goud Nerella Sridhar , Kumar Pardeep , Bharath Rose Dawn
Published: May 2020

Cancer is the second life-threatening disease worldwide, and it resulted in around 9.6 million
deaths globally in 2018. The multidrug-resistant cancers and non-selectivity create an urge for the
development of novel anticancer drugs with a diverse mechanism of action. Coumarin is one of the
most widely used scaffolds for the development of highly effective anticancer agents. It has versatile
anticancer profiles with diverse mechanisms to inhibit tumor progression. The facile synthetic strategies
are also favoured for target-based coumarin derivatives. Structural Activity Relationship (SAR)
studies determine anticancer potentials with minimal side effects through the substitution pattern of
coumarin. A number of coumarin derivatives have been developed against the Galectin-1 (Gal-1), Carbonic
anhydrases (CAs), Tubulin protein, and other essential targets for the treatment in cancer therapy.
Therefore, in this review, we have mainly focused on different target based coumarin derivatives,
and synthetic strategies.
The Protective Roles and Molecular Mechanisms of Troxerutin (Vitamin P4) for the Treatment of Chronic Diseases: A Mechanistic Review
Authors: Zamanian Mohammad , Bazmandegan Gholamreza , Sureda Antoni , Sobarzo-Sanchez Eduardo , Yousefi-Manesh Hasan , Shirooie Samira
Published: May 2020

:

Troxerutin (TRX), a semi-synthetic bioflavonoid derived from rutin, has been reported to
exert several pharmacological effects including antioxidant, anti-inflammatory, antihyperlipidemic,
and nephroprotective. However, the related molecular details and its mechanisms remain poorly
understood. In the present review, we presented evidences from the diversity in vitro and in vivo
studies on the therapeutic potential of TRX against neurodegenerative, diabetes, cancer and cardiovascular
diseases with the purpose to find molecular pathways related to the treatment efficacy.
TRX has a beneficial role in many diseases through multiple mechanisms including, increasing
antioxidant enzymes and reducing oxidative damage, decreasing in proapoptotic proteins (APAF-1,
BAX, caspases-9 and-3) and increasing the antiapoptotic BCL-2, increasing the nuclear translocation
of nuclear factor erythroid 2-related factor 2 (Nrf2) and downregulating the nuclear factor κB
(NFκ). TRX also reduces acetylcholinesterase activity and upregulates phosphoinositide 3-
kinase/Akt signaling pathway in Alzheimer’s disease models. Natural products such as TRX may
develop numerous and intracellular pathways at several steps in the treatment of many diseases.
Molecular mechanisms of action are revealing novel, possible combinational beneficial approaches
to treat multiple pathological conditions.
The Early Results of Vertebral Pathological Compression Fracture of Extra- nodal Lymphoma with HIV-positive Patients Treated by Percutaneous Kyphoplasty
Authors: Sun Sheng , Xu Biao , Zhang Qiang , Zhao Chang-song , Ma Rui , He Jie , Zhang Yao
Published: May 2020

Background:

Vertebral pathological compression fracture involving extra-nodal lymphoma impacts negatively on the quality of
life of HIV-positive patients. The choice of a safe and effective approach to palliative care in this condition remains a challenge.

Objective:

The purpose of this study was to investigate the safety and efficacy of percutaneous kyphoplasty (PKP) in the treatment of
vertebral pathological compression fracture of extra-nodal lymphoma in HIV-positive patients.

Methods:

A retrospective analysis, from January 2016 to August 2019, was performed on 7 HIV-positive patients, 3 males and 4 females,
with extra-nodal lymphoma with vertebral pathological compression fracture. The patients were treated using percutaneous kyphoplasty in
our hospital. Preoperative assessment of the patients was conducted regarding their hematological profile, biochemical indicators, liver and
kidney function, blood coagulation function, CD4+T lymphocyte count and viral load. Subsequently, the patients were placed on highly active
antiretroviral therapy (HAART) and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen. Besides,
antibiotics, nutritional support and immune-modulating drugs were also administered, rationally. Postoperative, the height of the anterior edge
of the injured vertebrae, Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) values were evaluated. Patients were also
monitored for any complications relating to the operation.

Results:

The average CD4+T cell count for the patients was 164 (range 114 ~247 / ul) while the viral load was 26,269 (range 5,765 ~82,321
copies/ul). All patients received nutritional and immune support and registered significant improvements in the levels of ALB and Hb
(P<0.05). In all cases, the operation was uneventful with neither cement leakage nor toxic reactions observed. Similarly, no opportunity
infections, other complications or deaths were reported. The height of the anterior vertebral body and the ODI score of the injured vertebrae
were significantly improved immediately after surgery (P<0.05). Compared to the preoperative VAS (7.71±1.11), postoperative values were
significantly reduced immediately after surgery (3.85±0.90) and at 2 weeks, 1 month and 6 months post-surgery: 2.71±0.76, 3.29±1.11,
4.00±0.82, respectively (P<0.01).

Conclusion:

Supported with appropriate perioperative treatment measures, PKP is safe and effective in the treatment of pathological vertebral
compression fracture due to extra-nodal lymphoma in HIV-positive patients.
Evaluation of the Properties of Encapsulated Stavudine Microparticulate Lipid-based Drug Delivery System in Immunocompromised Wistar Rats
Authors: Chime Salome A. , Onunkwo Godswill C. , Attama Anthony A.
Published: May 2020

Background:

Lipid based formulations have been confirmed to lower some side effects of drug and can be tailor made to offer sustained
drug release of drugs with short half-life like stavudine.

Aim:

To evaluate the immunomodulatory properties of stavudine-loaded solid lipid microparticles (SLMs) using immunocompromised Wistar rats.
Methods: The SLMs were formulated by homogenization method. The optimized batches were used for further in vivo studies. The effect of formulation
on the CD4 count and the haematological properties of immunocompromised Wistar rats were studied.

Results:

The particle size range of 4 -8 µm, EE range of 85-93 % and maximum drug release at 10 h. The CD4 cells increased from 115 ± 3.17 cell/mm3
at day zero to 495 ± 5.64 cell/mm3
at day 14 of treatment and 538 ± 6.31 cell/mm3
at day 21. The red blood cells increased from 2.64 ± 1.58 (x 106
/mm3
)
at day zero to 6.96 ± 3.47 (x 106
/mm3
) at day 14 and 7.85 ± 3.64 (x 106
/mm3
) at day 21. PCV increased significantly (p < 0.05) to about 42 – 50 % at
day 21 in the groups that received the SLMs formulations. The white blood cells (WBC) also were 12 x 103
/mm3
, for SLM formulations, while the rats
that received plain stavudine exhibited WBC of 9.6 x 103
/mm3
at day 21. The histopathological studies revealed that oral stavudine-loaded SLMs had
no significant damage to the kidney, liver, spleen and the brain of Wistar rats.

Conclusion:

Formulations exhibited significantly higher immunomodulatory properties than plain stavudine (p<0.05) and showed good properties for
once daily oral administration and could be a better alternative to plain stavudine tablets for the management of patients living with HIV.
Phyto-derived Products as Matrix Metalloproteinases Inhibitors in Cardiovascular Diseases
Authors: do Prado Alejandro F. , Bannwart Cahy M. , Shinkai Victoria M.T. , de Souza Lima Ildercílio M. , Meschiari César A.
Published: May 2020

:

Matrix metalloproteinases (MMPs) are enzymes that present a metallic element in their
structure. These enzymes are ubiquitously distributed and function as extracellular matrix (ECM)
remodelers. MMPs play a broad role in cardiovascular biology regulating processes such as cell
adhesion and function, cellular communication and differentiation, integration of mechanical force
and force transmission, tissue remodeling, modulation of damaged-tissue structural integrity, cellular
survival or apoptosis and regulation of inflammation-related cytokines and growth factors.
MMPs inhibition and downregulation are correlated with minimization of cardiac damage, i.e.,
Chinese herbal medicine has shown to stabilize abdominal aorta aneurysm due to its antiinflammatory,
antioxidant and MMP-2 and 9 inhibitory properties. Thus phyto-derived products
rise as promising sources for novel therapies focusing on MMPs inhibition and downregulation to
treat or prevent cardiovascular disorders.
A Sleeping rs-fMRI Study of Preschool Children with Autism Spectrum Disorders
Authors: Li Xiaomeng , Wang Longlun , Qin Bin , Zhang Yun , Zhou Zhiming , Qin Yong , Bao Guangcheng , Huang Jie , Cai Jinhua
Published: May 2020

Objectives:

The brain functional network of autism spectrum disorders (ASDs) in the
earlier stages of life has been almost unknown due to difficulties in obtaining a resting-state functional
magnetic resonance imaging (rs-fMRI). This study aimed to perform rs-MRI under a sedated
sleep state and reveal possible alterations in the brain functional network.

Methods:

Rs-fMRI was performed in a group of preschool children (aged 2–6 years, 53 with ASD,
63 as controls) under a sedated sleeping state. Based on graph theoretical analysis, global and local
topological metrics were calculated to investigate alterations in brain functional networks. Besides,
correlation analyses were conducted between the abnormal attribute values and the Childhood
Autism Rating Scale (CARS) scores.

Results:

The graph theoretical analysis showed that the nodal degree of the right medial frontal
gyrus and the nodal efficiency of the right lingual gyrus in the ASD group were higher than those
in the control group (P<0.05). There was a statistically significant positive correlation (R=0.318,
P<0.05) between the right midfrontal gyrus nodal degree values and CARS scores in the ASD patients.

Conclusion:

Alterations of some nodal attributes in the brain network occurred in preschool autistic
children which could serve as potential imaging biomarkers for evaluating ASD in earlier
stages.
3D Printing as a Significant Achievement for Application in Posttraumatic Surgeries - A Literature Review
Authors: Smoczok Michał , Starszak Krzysztof , Starszak Weronika
Published: May 2020

Background:

3D printing is increasingly used in many fields of medicine. The broadening
of knowledge in this field and the cooperation of doctors and engineers increase the interest in
this technology and results in attempts to implement it at every stage of the treatment.

Objective:

The review aims to summarize the current literature on the use of 3D printing technology
in the treatment of post-trauma patients.

Method:

A review of available scientific publications in PubMed regarding 3D printing and its application
in the context of posttraumatic procedures was carried out. Clinical Trials and Reviews
from the period 2014-2019 (6-year period) were taken into consideration. The database was
searched for “Printing”, “ThreeDimensional” [MAJR] [MeSH Term]. Finally, 48 studies have been
included in our review article.

Results:

3D printing technology has a number of applications in patients who have suffered injuries.
3D printing has found application in the preparation of procedures, accurate visualization of
occurring injuries and complications, education of doctors and patients, prototyping, creation of
synthetic scaffolding, production and implementation of target implants and rehabilitation.

Conclusion:

3D printing is increasingly used in providing for the posttraumatic patients. It is necessary to conduct further research in this area
and to provide development opportunities in regarding biopolymers and bioprinting. It is also necessary to improve cooperation between doctors
and engineers and to create new centres that can comprehensively use 3D printing - from imaging diagnostics to the production of implants and
their surgical use.
Synthesis and Cytotoxic Activity of Novel Mono- and Bis-Indole Derivatives: Analogues of Marine Alkaloid Nortopsentin
Authors: Kamel Mona Monir , Abdel-hameid Mohamed Kamal , El-Nassan Hala Bakr , El-Khouly Eman Adel
Published: May 2020

Background:

The oceans cover more than 70% of the earth’s surface, which represents
over 95% of the biosphere. Therefore, oceans provide a wealth of marine invertebrates, especially
sponges, ascidians, bryozoans and molluscs that produce structurally unique bioactive metabolites
such as alkaloids. The bioactive scaffolds of marine alkaloids exhibit cytotoxic activities against
human cancer cell lines.

Objective:

To prepare analogues of the marine alkaloid nortopsentin [having 2,4-bis(3'-
indolyl)imidazole scaffold] as cytotoxic agents via structural modification of the core imidazole
ring and one of the side indole rings.

Methods:

Four series of nortopsentin analogues were synthesized in which the imidazole ring was
replaced by pyrazole, pyrido[2,3-d]pyrimidinone and pyridine rings. Furthermore, one of the side
indole rings was replaced by substituted phenyl moiety. The target compounds were tested for
their in vitro cytotoxic activity against HCT-116 cell-line and the most potent compound was subjected
to further investigation on its effect on HCT-116 cell cycle progression.

Results:

The cytotoxic screening of the synthesized compounds revealed that bis-indolylpyridinedicarbonitriles
8a-d exhibited the most potent cytotoxic activity with IC50=2.6-8.8 μM. Compound
8c was further tested by flow cytometry analysis to explore its effect on HCT-116 cell cycle progression
that, in turn, indicated its anti-proliferative effect.

Conclusion:

Marine-derived bis-indole alkaloids (nortopsentins) have emerged as a new class of
indole-based antitumor agents. The design of new analogues involved several modifications in order
to obtain more selective and potent cytotoxic agents. Indole derivatives bearing a pyridine core
displayed more potent cytotoxic activity than those containing pyrido[2,3-d]pyrimidin-4(1H)-one
moiety.
α-Substituted Lactams and Acetamides: Ion Channel Modulators that Show Promise in Treating Drug-resistant Epilepsy
Authors: Krivoshein Arcadius V.
Published: May 2020

The two main problems in the pharmacotherapy of epilepsy are resistance to currently
available first-line medications (which occurs in about one third of patients) and the high incidence of
side effects. To address these two challenges, extensive efforts are being undertaken to design new,
structurally distinct antiepileptic drugs with a broad spectrum of anticonvulsant activity. Tests in animal
models of epilepsy indicate that α-substituted lactams and acetamides show a broad spectrum of
anticonvulsant activity (including very promising activity in drug-resistant models) as well as an excellent
safety profile. Limited clinical results confirm these preclinical findings. In the first part of this
review, pharmacology and toxicology of α-substituted lactams and acetamides and their putative protein
targets in the brain have been discussed. This is followed by a discussion of structure-activity relationships
among α-alkyl-, α-aryl-, and α-aryl-α-alkyl-substituted derivatives. The most promising
structures seem to be those related to 3-ethyl-3-phenylpyrrolidin-2-one, 2-phenylbutyramide, and 2-
sec-butylvaleramide. The information presented in this review is expected to facilitate rational drug
design and development efforts for α-substituted lactams and acetamides.
An In Silico Approach Towards Investigation of Possible Effects of Essential Oils Constituents on Receptors Involved in Cardiovascular Diseases (CVD) and Associated Risk Factors (Diabetes Mellitus and Hyperlipidemia)
Authors: Hamedi Azadeh , Sakhteman Amirhossein , Moheimani Seyed Mahmoud
Published: May 2020

Aim:

Aromatherapy products, hydrosol beverages and distillates containing essential oils
are widely used for cardiovascular conditions. Investigation of the possible activity of their major
constituents with the cardiovascular-related receptors may lead to developing new therapeutics. It
also may prevent unwanted side effects and drug-herb interactions.

Materials and Methods:

A list of 243 volatile molecules (mainly monoterpene and sesquiterpene)
was prepared from a literature survey in Scopus and PubMed (2000-2019) on hydrosols and essential
oils which are used for Cardiovascular Diseases (CVD) and its risk factors (diabetes mellitus and hyperlipidemia).
The PDB files of the receptors (229 native PDB files) included alpha-glucosidase, angiotensin-
converting enzymes, beta-2 adrenergic receptor, glucocorticoid, HMG-CoA reductase, insulin,
mineralocorticoid, potassium channel receptors and peroxisome proliferator-activated receptoralpha,
were downloaded from Protein Data Bank. An in silico study using AutoDock 4.2 and Vina in
parallel mode was performed to investigate possible interaction of the molecules with the receptors.
Drug likeliness of the most active molecules was investigated using DruLiTo software.

Results:

Spathulenol, bisabolol oxide A, bisabolone oxide, bergapten, bergamotene, dill apiole, pcymene,
methyl jasmonate, pinocarveol, intermedeol, α-muurolol, S-camphor, ficusin, selinen-4-ol,
iso-dihydrocarveol acetate, 3-thujanone, linanool oxide and cadinol isomers made a better interaction
with some of the named receptors. All of the named molecules had an acceptable dug likeliness except
for α-bergamotene. In addition, all of the named molecules had the ability to pass the bloodbrain
barrier and it is possible to produce unwanted side effects.

Conclusion:

Some ingredients of essential oils might be active on cardiovascular-related receptors.