bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytoplasmic APE1 promotes lung cancer aggressiveness and cisplatin resistance via the COX-2/Akt/β-catenin pathway
Authors: Lian Xiaojuan , Yue Hongxu , Xiang Debing , Zhang Zhimin
Published: June 2022

Background
Cisplatin is commonly used in lung cancer therapy, but cisplatin resistance in lung cancer cells remains an unsolved problem. Here, we report that cytoplasmic APE1 contributes to cisplatin resistance, cell proliferation and migration in lung cancer cells.
Methods
Immunofluorescence, western blot analysis, lentivirus transfection and scratch assays, and transwell migration and invasion assays were carried out on the cell lines A549 and Calu-1. A total of 124 samples of lung cancer tissues were evaluated to determine the clinical effects of cytoplasmic APE1 and COX-2.
Results
We found that cytoplasmic APE1 expression was lower in cisplatin sensitive cells than in cisplatin-resistant cells, and the upregulation of cytoplasmic APE1 significantly reduced cisplatin sensitivity in lung cancer cells. Gain-of-function studies demonstrated that cytoplasmic APE1 promoted lung cancer cell proliferation, migration and invasion in vitro and tumor growth in vivo, which were inhibited after cisplatin treatment. In patient samples, cytoplasmic APE1 in lung cancer tissues was an independent indicator of overall survive (OS) for lung cancer patients (P < 0.001). Mechanistic studies revealed that cytoplasmic APE1 promotes lung cancer malignancy by activating the COX-2/Akt/β-catenin pathway, and that APE1-C65 site mutations can increase cytoplasmic APE1 expression and resistance to cisplatin in lung cancer cells.
Conclusion
We suggest that modulating cytoplasmic APE1 in lung cancer is a promising novel strategy for overcoming cisplatin resistance.
Analysis of metabolites of fungal balls in the paranasal sinuses
Authors: ZHANG Xiaoqing , ZHANG Na , HUANG Qian , CUI Shunjiu , LIU Lingyan , ZHOU Bing
Published: June 2022

Fungal ball sinusitis is characterized by complex fungus infections with non-invasive inflammation. But no research reported fungal ball composition and metabolic-related product types currently. 12 patients with chronic rhinosinusitis who underwent surgery and 9 healthy control were enrolled in this study. Samples from both groups were analyzed for high-throughput metabolites by UPLC-MS. OsiriX software was applied to perform imaging measurements on sinus CT. 2138 and 394 metabolites were screened from cationic and anionic modes. There was a significant difference in the abundance of glycerophospholipid metabolism and sphingolipid metabolism between the two groups, with the experimental group showing an increased trend related to the sphingolipid metabolic pathway, including sphingosine 1-phosphate (S1P) and related products, diacylglycerol (DG), sphingomyelin (SM), suggesting that its metabolites are associated with mucosal and bony inflammation. Imaging measurements showed a median sinus CT value (median (P25, P75) of 351(261.4, 385.8) HU and a median sinus wall thickness (median (P25, P75) of 2.31(1.695, 3.718) mm, which correlated with the levels of glycerophospholipid metabolites and sphingolipid metabolites (P < 0.03). Dysfunctional glycerophospholipid and sphingolipid metabolism is present in the lesion of fungal ball sinusitis. Glycerophospholipid and sphingolipid metabolism plays a significant role in the progression of mucosal and osteitis produced by fungal ball sinusitis.
Molecular characterization, expression and localization analysis of a pedal like peptide in cuttlefish Sepiella japonica
Authors: Li Gong , Qiu Jiayin , Cao Huimin , Li Shuang , Zheng Libing , Chi Changfeng
Published: June 2022

BackgroundNeuropeptide pedal peptide (PP) and orcokinin (OK) are related active peptides that have been widely discovered in invertebrates. They have complex structures, and play key roles in various physiological process. Till now, there were no any reports in cephalopods with highly differentiated multi-lobular brain.MethodsThe partial cDNA sequence of neuropeptide PP in Sepiella japonica (termed as Sj-PP) was identified from a transcriptome, the full-length cDNA was obtained by rapid amplification cDNA ends (RACE) method. The bioinformatic analysis was performed through associated softwares. The tissue distribution profile and spatio-temporal expression were detected out by semi-quantitative RT-PCR and quantative Real-time PCR (qRT-PCR) assay, respectively. The tissue location was carried out with in situ hybridization (ISH).ResultsThe putative precursor of Sj-PP encodes 22 mature peptides, of which, only tridecapeptides could be post-translationally amidated at C-terminus. Each tridecapeptide owns the most conserved and frequent N-terminus DSI. The sequence analysis showed PPs shared low identity, and Sj-PP might be a PP3 member. The quantitative data showed Sj-PP widely distributed in various tissues, and the content in brain, optic lobe, liver and nidamental gland continuously increased till gonad maturation during the whole growth and development stages. In situ hybridization (ISH) detected Sj-PP positive signals in almost all regions of optic lobe except plexiform zone, all functional lobes in brain, epithelial cells and outer membrane layer of accessary nidamental gland, which hinted it is likely to be involved in the regulation of reproduction, such as vitellogenin synthesis, restoration, and ova encapsulation.ConclusionsThe results declared Sj-PP was involved in the neuroendocrine regulation in cephalapod, and provided a basic theoretical data for further studying regulatory role in the reproduction.
STIM1-mediated SOCE Promotes Autophagy through AKT/mTOR Pathway in Hippocampal Neurons after Ischemic Stroke
Authors: Zhang Hongchen , Xie Wenyu , Feng Yuan , Wei Jialiang , Yang Changbin , Luo Peng , Yang Yuefan , Zhao Peng , Jiang Xiaofan , Liang Wenbin , Dai Shuhui , Li Xia
Published: June 2022

Disturbance of calcium homeostasis and autophagy are two major pathogenesis in cerebral ischemic-induced neuronal injury. However, the interconnection of these two pathways and downstream target during injury remains unclear. Stromal interaction molecule 1 (STIM1) acts as a calcium sensor and activates Orai1 calcium channels, triggering store-operated Ca2+ entry (SOCE). Recently, STIM1 has also been shown to promote autophagy in multiple cell lines. Previously we have discovered that, under hypoxia condition, the AKT/mTOR signaling pathway plays a protective role in oxygen and glucose deprivation (OGD)-induced neuronal damage by reducing autophagic activity. In the present study, we provide preclinical studies supporting that inhibition of autophagy through the STIM1/SOCE/mTOR pathway can achieve neuronal protection during ischemic stroke. Using a mouse model of transient middle cerebral artery occlusion (tMCAO) and an in vitro culture of primary neurons, we found that STIM1 depletion reduced autophagic activity by inhibiting STIM1-induced SOCE, thereby attenuating neuron damage under hypoxia conditions. The inhibitory effect could be reversed by AZD5363, an AKT/mTOR pathway inhibitor, demonstrating that AKT/mTOR regulates STIM1/SOCE-induced autophagy. This work supports the potential STIM1 inhibition to protect neuronal damage during ischemic stroke.
Early contact with anesthesiologists at anesthesiology consulting clinic and preoperative anxiety remission in the parturients scheduled for cesarean section: A case control study
Authors: Zheng Lanlan , Li Jun , Xue Hang , Zhang Xinping , Ni Fanshu , Wu Qijun , Zhang Hehua , Zhao Ping
Published: June 2022

Background: Surgery and anesthesia can be traumatic for parturients scheduled for cesarean section, leading to anxiety, and anxiety may accumulate during preoperative period. We conducted this study to determine if early contact with anesthesiologists could contribute to relieving preoperative anxiety of parturients scheduled for cesarean section.Method: This is a single center case control study. From June 1, 2021, to August 30, 2021, parturients scheduled for cesarean section surgery with intraspinal anesthesia, ASAⅠ~Ⅲ, without preoperative psychiatric disorder. The State Anxiety Inventory was used to estimate the participants’ preoperative anxiety symptoms one day preoperative. Participants who sought to communicate with anesthesiologists at the anesthesiology consulting clinic were categorized as having early contact with anesthesiologists. Multiple logistic regression analysis was used to explore the association between early contact with anesthetists and preoperative anxiety symptoms. The odds ratio (95% confidence interval [CI]) of early contact with anesthesiologists in relation to the preoperative anxiety of the parturients (measured by State Anxiety Inventory). Multiple linear regression and stratified analysis using the Edinburgh Postnatal Depression Scale (EPDS) score were used for sensitivity analysis. Results: A total of 226 participants completed the study; 83 (36.7%) experienced moderate-to-severe preoperative anxiety, with 45.37 ± 5.31 State Anxiety Inventory points. Early contact with anesthesiologists was associated with a lower risk of moderate-to-severe preoperative anxiety (odds ratio = 0.23; 95% confidence interval: 0.10, 0.52) and lower anxiety score (β = -4.18, 95% CI: -6.32, -2.05). The results of the stratified analysis by depression level (measured by Edinburgh Postnatal Depression Scale) showed that this association was also statistically significant among parturients with lower (depression score <10) and higher (depression score ≥10) depression levels. Conclusion: Early contact with anesthesiologists is associated with lower risk of preoperative anxiety for parturients scheduled for cesarean section. It suggested that anesthesia consulting clinic is clinical significant and could routinely serve parturients.Registration: This study was registered in chictr.org.cn, on 28/05/2021; identifier ChiCTR2100046798)
A Pan-Cancer Analysis of the Oncogenic Role of Insulin-Like Growth Factor2 mRNA -Binding Protein 2 (IGF2BP2) in Human Tumors
Authors: Zeng Yu , Liu Yu , Zhuang Gaojian , Hao Weijing , Li Lijuan , Ma Weike , Gu Pengfei , Xie Wenjun , Zheng Xiangqian , Ruan Xianhui , Gao Ming
Published: June 2022

N6-methyladenosine (m6A) is one of the most common post-transcriptional modifications of eukaryotic mRNA, accounting for approximately 80% of RNA methylation modifications. Increasing studies have demonstrated that m6A modification has an important role in the development of a variety of tumors. Insulin-like growth factor 2 (IGF2BP2), as an important methylation recognition proteins in the process of m6A modification, is similarly involved in the progression of human cancers. Therefore, based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we first explored the potential oncogenic role of IGF2BP2 in thirty-three tumors and found that IGF2BP2 was highly expressed in most cancers, and it is also strongly associated with poor prognosis in some tumor patients. We performed the first pan-cancer analysis of the m6A methylation recognition protein IGF2BP2with the main goal of gaining a more comprehensive understanding of the oncogenic role of IGF2BP2 in different tumors.
Rare Benign Liver Tumors That Require Differentiation from Hepatocellular Carcinoma: Focus on Diagnosis and Treatment
Authors: Luo Laihui , Wang Tao , Cheng Mengting , Ge Xian , Song Shengjiang , Zhu Guoqing , Xiao Yongqiang , Deng Wei , Xie Jin , Shan Ren Feng
Published: June 2022

Background/Aim: Recently, an increase in the number of asymptomatic rare benign liver tumors (BLTs) has been reported during health check-ups. It is difficult to determine the nature of partial rare BLTs and not easy to distinguish from malignant liver tumors. This study aimed to analysis clinical features, diagnosis, and treatment of rare BLTs to reduce misdiagnosis and provide reference for clinical practice.Methods: From January 2012 to January 2021, we treated 112 rare BLTs by hepatectomy, including 54 focal nodular hyperplasia, 14 hepatocellular adenoma, 28 hepatic angiomyolipoma, 3 hepatic granuloma, 2 inflammatory pseudotumor of the liver, 2 nodular regenerative hyperplasia, 2 hepatic lipoma, 1 solitary fibrous tumor of the liver, 1 hepatic schwannoma and 1 hepatic myelolipoma.Results: The majority of patients were middle-aged female and asymptomatic. Single tumors were dominant. The diagnostic accuracies of computed tomography (CT) and magnetic resonance imaging (MRI) were 32.5% and 44.2%, respectively. The majority of tumors were likely to be misdiagnosed as hepatocellular carcinoma (HCC) or difficult to distinguish from HCC. All patients underwent surgical treatment. Postoperative pathological and immunohistochemical examination can confirm the diagnosis. No patients without tumor recurrence or metastasis during follow up period.Conclusion: Altogether, the clinical symptoms of rare BLTs lack specificity, and their preoperative diagnosis largely depends on imaging examination, with a low diagnostic accuracy rate and high chances of misdiagnosis as HCC. Diagnosis is confirmed by pathological and immunohistochemical examination. Surgical resection for rare BLT is safe and effective, regular postoperative follow-up is necessary.
Long-term Cardiovascular Outcomes after Acute Coronary Syndrome: Incidence and Predictors During Long-term Follow-up in a Population-based Cohort Study
Authors: Ulvenstam Anders , Graipe Anna , Irevall Anna-Lotta , Söderström Lars , Mooe Thomas
Published: June 2022

IntroductionThere is limited data on long-term outcomes after hospitalization for ACS. We aimed to estimate the rate of recurrent cardiovascular events in the long-term, in a population-based, unselected cohort of ACS patients.Methods and resultsWe included 1379 patients with ACS hospitalized at Östersund hospital 2010-2014 and followed them from the day after discharge to 31 December 2017. The primary endpoint was the unadjusted rate of the composite of CV death, AMI and ischemic stroke. Risk factors for the primary endpoint were assessed in a multivariable Cox proportional hazards regression model. During a median follow-up of 4.7 years, the unadjusted rate of the primary endpoint was 10.3% at 1 year and 28.6% at the end of follow-up. Predictors of increased risk for subsequent events were congestive heart failure, diabetes mellitus, angina pectoris, prior revascularization with PCI or CABG and treatment with diuretics at discharge. Lipid-lowering therapy at discharge and revascularization with PCI or CABG were associated with a lower risk of recurrent events.ConclusionThe risk of recurrent cardiovascular was high at 1 year and continued to be so during the following almost three years of median follow-up. Established predictors of cardiovascular risk were confirmed.
Proteomic analysis of cardiometabolic biomarkers and predictive modeling of severe outcomes in patients hospitalized with COVID-19
Authors: Schroeder Philip , Brenner Laura , Kaur Varinderpal , Cromer Sara , Armstrong Katrina , LaRocque Regina , Ryan Edward , Meigs James , Florez Jose , Charles Richelle , Mercader Josep , Leong Aaron
Published: June 2022

Background: The high heterogeneity in the symptoms and severity of COVID-19 makes it challenging to identify high-risk patients early in the disease. Cardiometabolic comorbidities have shown strong associations with COVID-19 severity in epidemiologic studies. Cardiometabolic protein biomarkers, therefore, may provide predictive insight regarding which patients are most susceptible to severe illness from COVID-19.Methods: In plasma samples collected from 343 patients hospitalized with COVID-19 during the first wave of the pandemic, we measured 92 circulating protein biomarkers previously implicated in cardiometabolic disease. We performed proteomic analysis and developed predictive models for severe outcomes. We then used these models to predict the outcomes of out-of-sample patients hospitalized with COVID-19 later in the surge (N=194).Results: We identified a set of seven biomarkers predictive of admission to the intensive care unit and/or death (ICU/death) within 28 days of presentation to care. Two of the biomarkers, ADAMTS13 and VEGFD, were associated with a lower risk of ICU/death. The remaining biomarkers, ACE2, IL-1RA, IL6, KIM1, and CTSL1, were associated with higher risk. When used to predict the outcomes of the future, out-of-sample patients, the predictive models built with these biomarkers outperformed all models built from standard clinical data, including known COVID-19 risk factors. Conclusions: These findings suggest that proteomic profiling can inform the early clinical impression of a patient’s likelihood of developing severe COVID-19 outcomes and, ultimately, accelerate the recognition and treatment of high-risk patients.
Low Water Pollution of Valley Bottom Irrigated Rice in West Africa Case of the Boulbi in Burkina Faso
Authors: KEITA Amadou , MANTORO Maanou Rosella Axiane , NIANG Dial , BAMA Delphine Aissata
Published: June 2022

Agricultural inputs are considered as important source of water pollution. This study investigates the situation in the case of the 85 ha Boulbi valley bottom irrigated rice scheme in Burkina Faso, West Africa. Soil hydraulic conductivities and texture were obtained using double-ring infiltrometer and Harmonized World Soil Database. Groundwater recharge was assessed by Thornthwaite's equation. The DRASTIC, GOD and SI methods were applied to map the valley’s vulnerability. Fertilizers and phytochemicals were also recorded by individual surveys. A sampling of surface and groundwater was done in 32 locations and the chemical characteristics (pH, EC, NO3-, SO42-, PO42- and K+) confronted with the vulnerability indices. The soils are predominantly clay (41%), silt (37%) and silty-sand (22%). Twenty types of phytochemicals are used, among which 35% are composed of the controversial glyphosate (denounced as carcinogenic) and 30% made with paraquat chloride also accused of being responsible for magnesium and potassium depletion in soils. All the three methods pointed to a low vulnerability risk, partly because of the epuration role of clay. The SI values (57.5 to 60.0) agreed with the laboratory analysis of NO3- concentration in the groundwater for the 11 locations for which all values were below 50 mg/l, the maximum defined by WHO. The average pH value is 8.2 ± 0.4. This may partly explain the low rice yield (less than 4.0 tons/ha) observed in Boulbi, in spite of fertilizers’ application. Although the risk assessment rendered non-alarming situation, preventive measures about health and environmental threats are necessary for raising awareness among the population.
Open-System Behaviour at the Campi Flegrei Caldera: from Evidence of Magma Mixing to pre-Eruptive Timescales
Authors: Petrelli Maurizio , López Mónica Ágreda , Pisello Alessandro , Perugini Diego
Published: June 2022

We review the evidence of open-system behavior in the volcanic plumbing system of the Campi Flegrei Caldera. Also, we highlight the estimates of magma residence time, magma ascent, and mixing-to-eruption timescales. In detail, we concentrate on the Campanian Ignimbrite ~ 40ka, the Neapolitan Yellow Tuff (~ 15ka), and the recent activity within the Phlegrean area. We start highlighting the evidence of magma mixing on the pyroclastic rocks deriving from different sources (e.g., crystal disequilibria, vertical zonings, and isotopic records). Then we describe geophysical and geochemical data of the magma feeding system with a focus on magma residence times and mixing to eruption timescales. Also, we link the timescales of magma ascent reported in the literature with a physically constrained model based on the magma-driven ascending dyke theory. Results show that considerably fast ascent velocities (i.e., units to tens m/s) can be easily achieved for eruptions fed by both shallow (i.e., 3–4 km) and deep (i.e., ~ 9 Km) reservoirs when characterized by large enough overpressures (i.e., > 25 MPa). Finally, we highlight the volcanological implications of timescale estimates for residence time and ascent in both open- and closed-system behavior of the volcanic plumbing system. The main aim is to provide constraints to the volcanic hazard definition of the area.
Sodium butyrate alleviates deoxynivalenol-induced hepatic cholesterol metabolic dysfunction via RORγ-mediated histone acetylation modification in weaning piglets
Authors: Zong Qiufang , Qu Huan , Zhao Yahui , Liu Hao-yu , Wu Shenglong , Wang Shuai , Bao Wenbin , Cai Demin
Published: June 2022

Background
Cholesterol is an essential component of lipid rafts in cell plasma membrane, which exerts a hepatoprotective role against mycotoxin exposure in pigs, and cholesterol metabolism is vulnerable to epigenetic histone acetylation. Therefore, our present study aimed to investigate whether a histone deacetylase inhibitor (sodium butyrate [NaBu]) could protect porcine liver from deoxynivalenol (DON) exposure by modulating cholesterol metabolism. Herein, we randomly divided 28 pigs into four groups, which were fed an uncontaminated basal diet, 4 mg/kg DON-contaminated diet, basal diet supplemented with 0.2% NaBu or 4 mg/kg DON + 0.2% NaBu for 28 days.
Results
We found that the serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were all increased in pigs exposed to DON, indicative of significant liver injury. Furthermore, the cholesterol content in the serum of DON-exposed pigs was significantly reduced, compared to healthy control pigs. Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure. In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated. Importantly, NaBu effectively restored parameters associated with liver injury, along with the cholesterol content and the expression of key genes involved in cholesterol biosynthesis pathway. Mechanistically, we performed ChIP-seq analysis of H3K27ac, and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment. We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu, as determined by ChIP-qPCR analysis. Notably, nuclear receptor RORγ, a novel regulator of cholesterol biosynthesis, was found in the hyperacetylated regions. Again, a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers were drastically reduced by NaBu. Consistent with RORγ expression, NaBu also hindered RORγ transcriptional binding enrichments on these activated cholesterol biosynthesis genes like HMGCR, SQLE and DHCR24. Furthermore, we conducted an in vitro luciferase reporter assay to verify that porcine RORγ directly bond to the promoters of above target genes.
Conclusions
Collectively, our results demonstrate the utility of the natural product NaBu as a potential anti-mycotoxin nutritional strategy for regulating cholesterol metabolism via RORγ-mediated histone acetylation modification.
PER3 rs772027021 SNP induce pigmentation phenotypes of dyschromatosis universalis hereditaria
Authors: Chen Hongyu , Yang Pingping , Yang Dan , Wang Dongsheng , Lu Mao , Li Yadong , Zhong Zhiqiang , Zhang Jing , Zeng Zhen , Liu Zhi , Jia Xu , Xing Qinghe , Zhou Ding'an
Published: June 2022

Dyschromatosis universalis hereditaria (DUH) is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body. Although Sterile Alpha motifs- and SH3 domain-containing protein 1 (SASH1) and ATP-binding cassette subfamily B, member 6(ABCB6) have been identified as the causative genes for this disorder, there are still some cases with unknown pathogenic genes. In this study, whole exome sequencing, data analysis and sanger sequencing were utilized in a four-generations extended Chinese family with DUH. A single nucleotide polymorphism (SNP) (c. 517C > T (p.P173S, rs772027021) variant in the exon 5 of Period Circadian Regulator 3 (PER3) (NM_001289861), was found in each affected individuals of the DUH family and the c. 517C > T SNP of PER3( PER3 rs772027021 SNP) and a novel c. 1574C > G (p.T525R) mutation in exon 14 of SASH1 were both found in the proband. Increased melanin syntheses were induced by the PER3 rs772027021 SNP in melanocytes of the affected epithelial tissues. Mutated SASH1 or PER3 rs772027021 SNP alone, or mutated SASH1 and PER3 rs772027021 SNP synergistically caused more synthesized melanin, respectively in vitro. We also phenotypically characterized a commercially available zebrafish mutant line that harbored PER3 rs772027021 SNP to induce proliferative melanocytes in vivo. Our studies firstly revealed the PER3 SNP may be as the pathogenic gene for a novel DUH subtype which was of delayed dominance and mutation of SASH1 and PER3 cooperatively promote hyperpigmentation phenotypes.
Do Physiognomically Designated Protected Areas Match Well with Ecological Data based upon Diversity Indices and Ordination? Implications for Urban Forest Conservation
Authors: Jeong Sung Chan , Pi DaeMin , Lee IL Won , Lee Jeong Yeon , Kim Kee Dae
Published: June 2022

We surveyed the vegetation of an ecological landscape preservation area (legally protected conservation areas or national parks) and surrounding areas in Mt. Cheonggye, Republic of Korea to explore conservation implications for preservation areas and surrounding transition areas. We calculated diversity indices to identify properties of the preservation areas and the surrounding areas that are relevant to conservation efforts. We then compared the plant community composition between areas using field and quadrat surveys in the preservation area and surrounding areas. The covers of dominant species in all tree and herb layers were markedly higher in the preservation area than in the peripheral zones. Additionally, species richness indices were significantly higher in the preservation area than in the peripheral zones. Ordination by detrended canonical correspondence analyses showed that the covers of dominant tree species and rock could explain the distributions of plant species in the Cartesian space of the ordination. Our results demonstrate that physiognomically designated protected areas match well with ecological data based upon diversity indices and ordination analyses and disturbances in the areas surrounding ecological landscape of the preservation areas can have considerable impacts on plant diversity indices. Hence, the preservation and management of surrounding areas are essential conservation elements for protecting the entire ecological landscape of the preservation areas.
Disaster Management System in Himachal Pradesh
Authors: KUMAR VINOD
Published: June 2022

The state of Himachal Pradesh has been facing widespread and extensive damages almost every year because of natural calamities, unprecedented droughts situation, excessive rains, snow and flash flood due to cloud burst etc. which have been taking its toll of human lives, cattle heads, destruction of public utilities, roads, bridges, footpaths, culverts, landslides and washing away of drinking water supply and irrigation schemes and damage to public and private properties making a dependent into the already fragile economy of the state. The losses sustained are so serve that relief and restoration operations without adequate financial resources are not possible despite best efforts of the state to cope up with the emergent situation out of the available scanty resources. Disaster Management can be defined as the body of policy and administrative decisions and operational activities which pertain to the various stages of a disaster at all levels. This paper focuses on analyzing natural and man-made disasters in Himachal Pradesh and also discusses Disaster Management system in Himachal Pradesh. In the present paper the data was collected through primary and secondary sources. The primary data has been collected by observation and field survey method. The Secondary data was collected from records, reports, relief manual, action plan and memorandum of the state revenue department and other department which are concerned with disaster management. Newspapers, magazines, journals, books, articles and website have been utilized.
Scaling-up community-based rehabilitation programs in rural Thailand: the development of a capacity building program
Authors: Tongsiri Sirinart
Published: June 2022

Background: Approximately 15% of the world population have some forms of disability and their quality of life is compromised. According to Thailand Persons with Disabilities (PWDs) Empowerment Act, B.E. 2550 (2007), PWDs are entitled for benefits ranging from medical care to social support services. The CBR framework and the International Classification of Functioning, Disability and Health (ICF) can be used to promote the interdisciplinary approach across staff from different organizations. This study aimed to demonstrate the capacity building strategy for user organizations and resource teams, the key components in environment of scale-up as described in “WHO/ExpandNet Scaling-up Framework” to promote the implementation process of CBR interventions in Thailand. Methods: The study were conducted with a network of representative from five sub-districts in Thailand. A set of capacity building training courses was designed. Fieldworkers were trained to administer the ICF questionnaire to collect data of PWDs in community. A qualitative interview was conducted to investigate the changes of the interdisciplinary teams.Results: The total of 1,783 PWDs data were collected during 1 April 2018-30 December 2019. All of them have, at least, one type of impairments and one type of difficulties in activity of daily living (ADL). Needs of assistive devices and home modifications were also recognized. Individual ICF profile can also developed to monitor change of their functioning after receiving services. After the discussions in the qualitative interviews, it is indicated that their perceptions towards work with PWDs were changed. The six steps in capacity building include: dialogue, team building, disability role-play; ICF data collection and analysis; developing individual care plans for PWDs; home and environmental modifications for PWDs; training to promote employment opportunities; and evaluation of the care plan. Conclusions: The study highlighted the innovative training methodology for building up the capacity of staff to work as a team and to become agents of change to set up a strategic plan for delivering CBR interventions in their own settings.
A new proof of evidence of cysteamine quantification for therapeutic drug monitoring in patients with cystinosis
Authors: Franzin Martina , Rossetto Silvia , Ruoso Rachele , Savio Rossella Del , Stocco Gabriele , Decorti Giuliana , Addobbati Riccardo
Published: June 2022

Background: To date, measurement of intracellular cystine is used for the therapeutic monitoring of patients affected by cystinosis in treatment with cysteamine. Since this method is time and sample consuming, development of a faster method to quantify cysteamine would be extremely useful in order to help clinicians to adjust dosages of cysteamine and to define better the pharmacokinetic profile of this drug. The aim of the study was to develop a liquid chromatography tandem mass spectrometry method for the quantification of cysteamine in plasma samples and to test its applicability on plasma samples derived from patients with nephropathic infantile cystinosis in treatment with cysteamine.Results: The percentage of accuracy of the developed method varied between 97.80 and 106.00% and CV% between 0.90 and 6.93%. There was no carry over. The calibration curves were built from 2.5 to 50 µM. The limit of detection and the lower limit of quantification occurred at 0.25 and 1.25 µM respectively. Cysteamine was stable up to 2 months at -20 °C. Concentrations of cysteamine and intracellular cystine of 4 patients were in line with data previously reported.Conclusions: The proposed method showed an appropriate selectivity, specificity, linearity, sensibility, accuracy, precision and good applicability to samples.
The influence of transarterial chemoembolization on serum levels of soluble programed cell death protein-1 in advanced hepatocellular carcinoma patients
Authors: Ma Xiaochen , Song Huishu , Xie Fubo , Jian Wencheng , Wang Qingliang , Sun Xiangyang , Xie Yang , Li Caixia , Zhang Kai
Published: June 2022

Aims
To investigate the implications of soluble programmed cell death protein 1 (sPD-1) in hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE) and to evaluate the potential value of sPD-1 to guide selection of the optimal time to begin combination therapy of TACE and immune checkpoint inhibitors (ICIs).
Materials and methods
Forty-four HCC patients suitable for TACE and fifty-five healthy volunteers were enrolled in this study. Three milliliters of peripheral venous blood of patients were collected on 1 day before TACE and 3, 7, and 30 days after TACE respectively for assay of sPD-1 using enzyme-linked immunosorbent assay. The associations of the sPD-1 level with the clinical features, outcomes, and the fluctuation of sPD-1 during the treatment were analyzed.
Results
The initial sPD-1 level of patients was significantly higher than that of the control group. Although the initial level of sPD-1 showed a decreasing trend with the increase of BCLC stage, there were no significant differences among patients with different BCLC stages. The sPD-1 level of 3 and 7 days after TACE was significantly lower than the initial level. The sPD-1 level of 30 days after TACE was significantly higher than that of 7 days after TACE and nearly elevated to the initial level before TACE. The level of sPD-1 of CR and PD patients was lower than that of PR, SD patients, but the differences were not significant.
Conclusion
The level of sPD-1 was significantly elevated in patients with HCC but further research is necessary to better understand the value of sPD-1 in onset, development, and prognosis of HCC as a potential biomarker. The decreases in sPD-1 after TACE suggested that TACE could probably reduce immune effector cells as well as weaken immune function, which indicated that the ICIs shouldn’t be administered shortly after TACE.
TLR2 genetic diversity and the risk of Schizophrenia
Authors: Ayari fayza , Chaaben Arij Ben , Abbaza Hajer , Mihoub Ons , Ouni Nesrine , Mankai Amani , Boukouaci Wahid , kharat Maher , Leboyer Marion , Tamouza Ryad
Published: June 2022

Objectives: Schizophrenia (SZ) is a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction plays a key etiopathogenic role. In order to explore the control of innate immune responses in SZ, we aimed to investigate the potential association of two TLR2 polymorphisms (rs3804099T>C and rs3804100T>C) with susceptibility to SZ in a Tunisian population. Methods: TLR2 genotyping was done using a TaqMan 5’-nuclease assay for 150 SZ patients and 201 healthy controls (HC) with no history of psychiatric illness.Results: we did not observe any significant differences in genotypes and alleles frequencies between the SZ patient and control groups (p>0.05).Conclusion: The results indicate that rs3804099T>C and rs3804100T>C in TLR 2 polymorphisms are unlikely to have a significant impact on the genetic predisposition to SZ in the presently studied population-group.
Three-dimensional Network of Nitrogen-doped Carbon Matrix-encapsulated Si Nanoparticles/Carbon Nanofibers Hybrids for Lithium Ion Battery Anodes with Excellent Capability
Authors: Lee Chang-Seop , Cong Ruye , Jo Minsang , Martino Angelica , Park Hyun-Ho , Lee Hochun
Published: June 2022

Three-dimensionally structured silicon (Si)-carbon (C) nanocomposites have great potential as anodes in lithium-ion batteries (LIBs). Here, we report a Nitrogen-doped graphene/carbon-encapsulated Si nanoparticle/carbon nanofiber composite (NG/C@Si/CNF) prepared by methods of surface modification, electrostatic self-assembly, cross-linking with heat treatment, and further carbonization as a potential high-performance anode for LIBs. The N-doped C matrix wrapped around Si nanoparticles improved the electrical conductivity of the composites and buffered the volume change of Si nanoparticles during lithiation/delithiation. Uniformly dispersed CNF in composites acted as conductive networks for the fast transport of ions and electrons. The entire tightly connected organic material of NG/C@Si and CNF prevented the crushing and shedding of particles and maintained the integrity of the electrode structure. The NG/C@Si/CNF composite exhibited better rate capability and cycling performance compared with the other electrode materials. After 100 cycles, the electrode maintained a high reversible specific capacity of 1,371.4 mAh/g.
TIPE2 reverses TGF-β1-induced migration and invasion by targeting the Smad2-EMT signal pathway in ovarian cancer cells
Authors: Tang Zhongyun , Zhang Derui , Yao Chenchen , Jiang Mengmeng , Wang Chongli , Jia Mingyue , Yu Huayun , Xue Chenyue , Liu Yuqiu , Shi Yongyu , Zhang Lining , Wang Xiaoyan , Wei Zengtao
Published: June 2022

Ovarian cancer is the deadliest among all the gynecologic malignancies, and it is also a kind of highly metastatic disease. Transforming growth factor-β1 (TGF-β1) is a dominant driver of epithelial-mesenchymal transformation (EMT) and promotes the metastasis of tumor cells and therapy resistance. Tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) is a negative regulator of innate and adaptive immunity. It also involves the occurrence and development of different tumors. However, the roles of TIPE2 in ovarian cancer and whether TIPE2 reverses TGF-β1-induced EMT in ovarian cancer cells remain unclear. The present study demonstrated that TIPE2 protein was significantly down-regulated in ovarian cancer tissues and related to tumor pathological types, patients’age, tumor differentiation degree, and FIGO stage of tumor. TIPE2 inhibited the metastasis and EMT of ovarian cancer cells by combining with Smad2 in vitro and intraperitoneal metastasis model and reversed TGF-β1-induced migration, invasion of ovarian cancer cells by targeting the Smad2-EMT signaling pathway. Moreover, we found that TIPE2 decreased the expression of TGF-β1 and TGF-β1 down-regulated the levels of TIPE2 in ovarian cancer cells. There is a negative relationship between TIPE2 and TGF-β1. In summary, our results suggest TIPE2 plays an important inhibitory role in the metastasis of ovarian cancer by affecting TGF-β1/Smad2/EMT signal pathway and acts as a potential target in the diagnosis and treatment of ovarian cancer.
Cardiovascular Screening of Athletes: Implications in Reducing the Risk of Sudden Cardiac Deaths
Authors: Vaňova Natalia , fatima Ghizal , Zenuch Pavol , Fedacko Jan
Published: June 2022

Sudden cardiac death (SCD) in sports is defined as unexpected death during exercise or shortly after physical exertion (within 24 hours of exercise cessation) in athletes who appeared perfectly healthy otherwise. To highlight the importance of cardiovascular screening in athletes for reducing incidences of SCD, we performed a prospective study and analysed 280 athletes who were recruited and followed up between 2016 to 2021 at the Agel Košice-Šaca Hospital (city and country) for cardiovascular screening using electrocardiography (ECG) and other imaging modalities such as echocardiography (ECHO). During the screening, arrhythmias were diagnosed in thirteen athletes and higher degrees of AV block and ventricular extrasystoles were diagnosed in four athletes. These athletes subsequently underwent interventional procedures. At the end of the follow up period and interventional procedures, three athletes were diagnosed with sever cardiovascular disease (CVD), which led to early termination of their sports career. Our findings suggest that endurance athletes in particular are at risk for arrhythmias and chronic myocardial remodelling and that most of the diseases that are associated with an increased risk of SCD could be identified by changes in resting ECG. We also confirmed that endurance athlete, both professional and recreational, are at higher risk of developing atrial fibrillation later in life. In addition, we emphasize on the benefit of an automated ECG module and echocardiographic examination, and suggest that SCD prevention in athletes lies in improving and expanding cardiovascular screening.
Evaluation of lung adverse events with trastuzumab using the Japanese pharmacovigilance database
Authors: Kanbayashi Yuko , Uchida Mayako , Kashiwagi Misui , Akiba Hitomi , Shimizu Tadashi
Published: June 2022

The present study aimed to determine the risk of trastuzumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analysed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analysed 1,772,494 reports and identified 4,362 reports of AEs caused by trastuzumab. Of these, 693 lung toxicities were reportedly associated with trastuzumab. Signals were detected for seven lung toxicities: interstitial lung disease, pulmonary oedema, pleural effusion, lung disorder, acute pulmonary oedema, pulmonary fibrosis, and radiation pneumonitis. Among these, interstitial lung disease was the most frequently reported (61.8%). A histogram of times to onset showed occurrence from 1 to 105 days, but some cases of interstitial lung disease occurred even more than one year after the start of administration. The AEs showing the highest fatality rates were interstitial lung disease, pulmonary fibrosis, and radiation pneumonitis. This study focused on lung toxicities caused by trastuzumab as post-marketing AEs. Some cases could potentially involve serious outcomes; therefore, patients should be monitored for signs of the onset of these AEs not only at the start of administration, but also over an extended period, especially for interstitial lung disease.
Association between Abnormal Glucose Regulation at Different Time Point and Fetal Congenital Heart Diseases during Pregnancy: a Cohort Study of 72236 Births
Authors: Zhang Yulong , Zhang Qian , Ye Xu , Wu Yi , Lin Tinghua , Yan Jianying , Zheng Xiangqin , Huang Huiyun , Zhang Wenhui , Lin Hai , Lai Shuhua
Published: June 2022

BACKGROUND: GDM or prepregnancy diabetes mellitus during pregnancy will lead to an increased risk of fetal congenital malformations16-18. However, the influence of different time periods on blood glucose level is not clear, the object of this study was to explore the association between abnormal glucose regulation at different time point and congenital heart diseases during pregnancyMETHODS: This retrospective and consecutive cohort study were conducted on singleton pregnancies carried to 20 completed weeks of gestation or beyond, from the Fujian Provincial Maternity and Children’s Hospital, China, between January 1, 2014 and December 31, 2020. A diagnosis of gestational diabetes was defined according to Fasting blood glucose level and 75-g OGTT. Maternal and infant characteristics and outcomes were compared between neonates born to mothers with and without Abnormal blood glucose at different time of OGTT. Descriptive statistics are shown as mean ± standard deviation or median (range interquartile) for continuous variables and tested with ANOVA or Kruskal-Wallis rank-sum test, whereas frequency (percentage) and χ2 test were used for categorical variables. All analyses were conducted using R version 4.1.0.RESULTS: A total of 71703 normal subjects and 533 subjects with fetal cardiovascular malformations were included in this study. Pregnant women who deliver a normal fetus tend to older and have higher rate of gestational hypertension and abnormal glucose during pregnancy than those who deliver a newborn with CHD (P < 0.05). Compared to the corresponding normal group, GDM, OGTT 0 hour≥5.1mmol/L, OGTT 1 hour≥10mmol/L, and OGTT 2 hour≥8.5mmol/L confer to 55%, 48%, 54%, and 59% increase in risk of CHD, respectively. Compared to group 1 (OGTT 0h and OGTT 1h and 2h are both normal), group 3 (OGTT 0h is normal, while OGTT 1h or 2h is abnormal) and group 4 (OGTT 0h and OGTT 1h or 2h are both abnormal) exhibit higher risk of CHD (OR= 1.53 and 2.21, respectively, all P<0.05). However, group 2 (OGTT 0h is abnormal, while OGTT 1h and 2h is normal) did not demonstrate a statistically significant elevated risk.CONCLUSION: Gestational diabetes is an identified hazard factor for neonatal CHD. The effect of GDM on CHD is more reflected in impaired tolerance of glucose regulation than in elevated fasting blood glucose levels. Pregnant women with normal fasting glucose but abnormal OGTT 1 hour or 2 hour may be overlooked as an implicit risk population, and should be given adequate attention.
The Inhibitory Effect of Betulinic Acid on Epithelial-Mesenchymal Transition Pathway in Renal Cell Carcinoma
Authors: Ataş Merve Nur , Ertuğrul Barış , İplik Elif Sinem , Çakmakoğlu Bedia , Ergen Arzu
Published: June 2022

Renal cancer is the most lethal urological cancer and characterized by high metastasis rate at initial diagnosis and drug resistance to current chemotherapeutics. Betulinic acid is a pentacyclic triterpene with broad biological activity that occurs naturally in variety of plants. Even though the anti-cancer efficacy of betulinic acid have been reported by many studies, the information about the pathways and the molecules which are affected by betulinic acid in renal cancer are limited. Epithelial-mesenchymal transition (EMT) is considered as the initial step of metastasis and contributes to drug resistance of cancer cells. Depending on the role of EMT in cancer progression and drug resistance, targeting EMT may represent an effective strategy in this context. Therefore, we aimed to investigate the anti-metastatic effects of betulinic acid on renal cell carcinoma cells by evaluating two EMT markers, SNAIL-1, and SDC-2. Following the treatment of betulinic acid at determined doses by WST-1 cytotoxicity assay in our previous study, SDC-2 expression level was decreased in both cell lines. Additionally, in correlation with this result, we also found a reduction in SDC-2 and SNAIL-1 protein levels which are measured by ELISA. Furthermore, the migration and invasion capacities were suppressed by betulinic acid treatment in metastatic renal adenocarcinoma ACHN cells. Taken together, our findings indicate that betulinic acid may constitute a potential treatment approach for renal cancer with further investigations.