bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of endometrial carcinoma with obesity and diabetes mellitus
Authors: Begum Shirin Akter , Mahmud Tasfia , Amatullah Mehriban
Published: November 2020

Background: Endometrial cancer, previously referred to as carcinoma of the uterus. The incidence of endometrial cancer is raising, due to improved screening causing fewer hysterectomies in ageing population. Several studies are going on to find out the association and effects between DM and DM-related diseases, especially the cancer. Obesity and physical inactivity plays important role as modifiable determinants of insulin resistance, hyperinsulinaemia and diabetes. All these factors are also responsible for endometrial cancer.
Objectives: To find out the association between endometrial carcinoma with obesity and diabetes mellitus
Methods: This was a cross sectional and observational study, conducted among. 50 consecutive patients admitted as known case of endometrial carcinoma diagnosed by fractional curettage and endometrial biopsy and 50 consecutive patients having other common gynaecological problems in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from January 2015 to December 2017.
Results: Out of 50 women having endometrial carcinoma, only 4% (n=2) having healthy BMI, 36% (n=18) were overweight, 60% (n=30) were obese. Among 50 healthy women without endometrial carcinoma showed that 4% (n=2) having underweight, 70% (n=35) having healthy BMI, 14% (n=7) having overweight and only 12% (n=6) were obese. Regarding distribution of diabetes mellitus among study population, 50 women having endometrial carcinoma 26 % (n=13) were diabetic and 74% (n=37) were non diabetic.50 healthy women without endometrial carcinoma showed that 8% (n=4) diabetic and 92% (n=46) were non diabetic. Among total 17% (n=17) diabetic patients, 76.5% (n-13) having endometrial carcinoma and 23.5% (n=4) were healthy having no endometrial carcinoma. Among 83% (n=83) women having no diabetes 55.4% (n=46) were healthy having no endometrial carcinoma and 44.6% (n=37) having endometrial carcinoma. Association between Diabetes mellitus and endometrial carcinoma was statistically significant (p=0.017).  Having high BMI (overweight, obese) and diabetics had significant elevated risks of endometrial cancer, compared with non-overweight non-diabetic subjects.
Conclusion: Obesity, history of PCOS, physical inactivity and diabetes are the risk factors of endometrial carcinoma. So, it should be treated promptly these diseases to reduce risk factors. Moreover, strengthen public awareness to address these risk factors at earlier to reduce the cancer burden is recommended.
Bangladesh Med Res Counc Bull 2020; 46(2): 120-127
Tuberculosis notifications in Australia, 2015–2018
Authors: Bright Amy , Denholm Justin T , Coulter Chris , Waring Justin , Stapledon Rick ,   the National Tuberculosis Advisory Committee,   the Communicable Diseases Network Australia,   the Australian Mycobacterium Reference Laboratory Network
Published: November 2020

In 2018, the National Notifiable Diseases Surveillance System received 1,438 tuberculosis (TB) notifications, representing a rate of 5.8 per 100,000 population, consistent with the preceding three years. Australia has achieved and maintained good tuberculosis (TB) control since the mid-1980s, sustaining a low annual TB incidence rate of approximately five to six cases per 100,000 population. The number of multi-drug-resistant TB (MDR-TB) cases diagnosed in Australia is low by international standards, with approximately 2% of TB notifications per year classified as MDR-TB. Australia’s overseas-born population continue to represent the majority of TB notifications (between 86% to 89% across the four reporting years) and the Aboriginal and Torres Strait Islander population continues to record TB rates around four to five times higher than the Australian-born Non-Indigenous population. Whilst Australia has achieved and maintained excellent control of TB in Australia, sustained effort is required to reduce local rates further, especially among Aboriginal and Torres Strait Islander populations, and to contribute to the achievement of the World Health Organization’s goal to end the global TB epidemic by 2035.
Teknik Relaksasi dengan Alat Musik Tradisional Mandar Menurunkan Skala Nyeri pada Ibu Bersalin Kala I Fase Aktif
Authors: Satriani G Satriani G , Mahmud Abbas
Published: November 2020

The direct causes of maternal mortality rate are bleeding, eclampsia, abortion, infection, and prolonged labor. Maternal mortality rate can be minimized by safe, clean help, and prevent complications. Labor is a process that begins with uterine contractions causing progressive dilation of the cervix, birth of a baby, and labor of placenta and it is a natural process. This study aims to see the effectiveness of instrumental music relaxation techniques using traditional musical instruments on the labor process of inpartu mothers when phase I was active at Community Health Center in Tampa Padang, Mamuju. This study is an experimental study with a pre-experimental conception and use one group pretest-posttest conception with the population of maternal mothers at Tampa Padang Community Health Centre. The samples are pregnant women who entered the delivery room with inpartu diagnosis of the first stage/phase is active or the opening stage. The sampling technique was consecutive sampling which could be done by 31 people. The data then being analyzed with univariable analysis and bivariable analysis using the Wilcoxon Test with a significance level of 0.05 to see the interface relationship with the decrease in pain scale. The results showed a relationship in reducing pain scale of mothers who were given musical intervention with Mandar traditional musical instruments where p = 0.000. The conclusion of this study shows that by applying instrumental music relaxation techniques with traditional Mandar musical instruments, mothers can adjust to pain during labor so that it can reduce the pain scale in mothers in labor when phase 1 is active.
The role of nutrients in promoting a bloom of the nuisance raphidophyte species Gonyostomum semen in a subtropical reservoir
Authors: Burford MA , Faggotter SJ , Gibbes B , Neilen AD , Bartkow M
Published: November 2020

The nuisance raphidophyte Gonyostomum semen (Ehrenberg) Diesing blooms in lakes and is known to produce a mucilage which can cause human skin irritation. Parameters such as water temperature, iron and high dissolved organic matter loads are shown to be important drivers in temperate regions. However, the causes of blooms in warmer latitudes are less well understood. Over a 6 mo study period, we used field monitoring and a nutrient addition experiment within a water reservoir to examine the role of nutrients in promoting G. semen growth. Early in the study, an inflow event delivered nutrients which increased dissolved inorganic nitrogen (DIN) concentrations 2-fold and filterable reactive phosphorus (FRP = phosphate) 4-fold. This event shifted the phytoplankton community from a mixed community to one dominated by G. semen. Two months after the inflow event, the effect of nutrients in promoting G. semen was confirmed with a nutrient addition experiment. Total biovolumes of this species across the study were strongly predicted by FRP and nitrate + nitrite concentrations. G. semen biovolumes also decreased as ratios of total nitrogen (TN):total phosphorus (TP) and DIN:FRP increased, highlighting the importance of P inputs. The stable isotope tracer 15N-nitrate was also used to trace N through the G. semen-dominated phytoplankton community. The tracer rapidly cycled through the G. semen-dominated phytoplankton community in 1-2 d, settled and remineralized, providing an ongoing source of DIN for maintaining blooms. Overall, the results highlight the importance of FRP, and to a lesser extent nitrate, in promoting blooms of this nuisance species.
Sea lice infections on wild Atlantic salmon and sea trout in the River Tamar, UK: a temporal study
Authors: James J , Bradley HA , Hillman R , Elsmere P , Reading AJ , Williams CF
Published: November 2020

Sea lice are amongst the most ecologically and economically damaging parasites of farmed salmonids globally. Spill-over from aquaculture can increase parasite pressure on wild fish populations, but quantifying this effect is challenging due to the relative paucity of data available on ‘natural’ salmonid louse burdens in the absence of aquaculture, particularly for Atlantic salmon Salmo salar. Here, wild Atlantic salmon and sea trout S. trutta were screened at the tidal limit of the River Tamar (UK) for the presence of sea lice. During 2013 and 2015, the prevalence of sea lice ranged from 41 (n = 361) to 60% (n = 275) and 55 (n = 882) to 58% (n = 800) in Atlantic salmon and sea trout, respectively. All sea lice collected were identified as Lepeophtheirus salmonis. Mean L. salmonis infection intensity across the study period was 5.84 (range: 1-66) in Atlantic salmon and 6.45 (range: 1-37) in sea trout. Infection intensity was positively correlated with the amount of external damage present for both fish species. Given that the fish were examined when returning to freshwater, the lice burdens obtained may represent an underestimate. Nevertheless, these data provide important baseline information on ‘natural’ sea louse infections in South West England, which has been proposed as a potential region for aquaculture development.
Massive infection of Cystidicoloides ephemeridarum in brown trout Salmo trutta with skeletal deformities
Authors: Iaria C , Spanò N , Smeriglio A , Capparucci F , De Benedetto G , Lanteri G , Marino F , Macheda S , Macrì F , Belvedere A , D’Agostino M , Caridi F , Marguccio S , Salvo A , Acri G , Siclari A , Brundo MV , Trombetta D
Published: November 2020

We investigated the cause of skeletal deformities found in brown trout from the Aspromonte mountain area in Reggio Calabria, Italy. Toxicological, histopathological and parasitological analyses were carried out on 14 fish with evident macro-morphological alterations from 2 different locations in the same river, and 4 control fish without morphological alterations from a different river (far from the first river but still within the area under study). Histopathological and radiological observations confirmed severe skeletal deformities in the specimens investigated. Parasitological examinations highlighted the presence of the nematodeCystidicoloides ephemeridarum, found only within the gastrointestinal tract of specimens showing deformities. Moreover, a direct correlation between parasite number and fish size was found. Given the low heavy metal levels and the presence of a massive parasitosis in teleosts showing deformities, we postulate a correlation between skeletal deformities and nematode infestation: the parasites caused a serious vitamin and mineral deficiency in the fish, which led to a dysplastic vertebral column. The low calcium levels found in malformed specimens compared with negative controls effectively confirm this hypothesis.
Ichthyophonosis in Peruvian rainbow trout Oncorhynchus mykiss: identification of endemic areas using molecular and histopathological tools
Authors: Castro T , Mendoza L , Vilela R , Vilela C , Mateo EC
Published: November 2020

Ichthyophonus infection was first detected in Peruvian Oncorhynchus mykiss in 1986, but the occurrence of ichthyophonosis disease in the region is unknown. This study investigated the presence and distribution of Ichthyophonus sp. in Peruvian rainbow trout using traditional and DNA sequencing tools. Between 2007 and 2008, 205 rainbow trout from 13 hatcheries in the Mantaro river basin were examined for the presence of Ichthyophonus, and at that time only 3 farms were positive. This early study confirmed the presence of Ichthyophonus sp. in the Tranca Grande lagoon for the first time, at a prevalence of 50%. In 2012, examination of 240 trout from 24 fish farms in 2 Peruvian Departments found 9 infected farms. More recently, in 2018, Ichthyophonus sp. was found in Lake Titicaca, infecting a trout in the Ichu area (in the Department of Puno). Our molecular analysis of the infected trout showed that ichthyophonosis disease in the Peruvian trout was caused by Ichthyophonus sp. Clade C. The finding of this pathogen in Lake Titicaca should be an alert for nearby farms and entities dealing with fish of economic importance in the rivers of Peru.
Mechanisms leading to recruitment inhibition of giant kelp Macrocystis pyrifera by an understory alga
Authors: Beckley BA , Edwards MS
Published: November 2020

The forest-forming giant kelpMacrocystis pyriferaand the communities it supports have been decreasing across their native ranges in many parts of the world. The sudden removal of giant kelp canopies by storms increases space and light for the colonization by understory macroalgae, such asDesmarestia herbacea,which can inhibitM. pyriferarecovery and alter local community composition. Understanding the mechanisms by which algae such asD. herbaceainteract withM. pyriferacan provide insight into patterns of kelp forest recovery following these disturbances and can aid in predicting future community structure. This study experimentally tested the independent and combined effects of two likely competitive mechanisms by whichD. herbaceamight inhibit recovery ofM. pyriferain the Point Loma kelp forest in San Diego, California (USA). Specifically, we conducted field experiments to study the individual and combined effects of shade and scour byD. herbaceaon the survival ofM. pyriferamicroscopic life stages, and the recruitment, survival, and growth of its young sporophytes. Our results show that scour had the strongest negative effect on the survival ofM. pyriferamicroscopic life stages and recruitment, but shade and scour both adversely affected survival and growth of these sporophytes as they grew larger. Canopy-removing storms are increasing in frequency and intensity, and this change could facilitate the rise of understory species, likeD. herbacea, which might alter community succession and recovery of kelp forests.
Sex-biased dispersal depends on the spatial scale in a tube-building amphipod
Authors: Peres PA , Ferreira AP , Machado GBO , Azevedo-Silva M , Siqueira SGL , Leite FPP
Published: November 2020

Behavioral differences between males and females can lead to sex-biased dispersal (SBD), and tube-building amphipods are good model organisms to study this process. Depending on the species, males or females have a different affinity to their tubes, and one sex may be more mobile than the other. This distinct dispersal behavior and the scales at which it occurs are not fully understood. Here, we tested the SBD hypothesis at different spatial scales in Cymadusa filosa using direct and indirect approaches. We conducted laboratory (small scale) and field experiments (local scale), and molecular analyses (local and large scale). Laboratory experiments indicated male-biased dispersal over small scales (cm), whereas over local scales (m), field experiments showed similar colonization rates of previously cleaned fronds for both males and females, suggesting no SBD. A higher proportion of juveniles than expected had colonized these fronds, suggesting that juveniles have higher dispersal rates than adults. Also, neighboring individuals were not more genetically related than spatially distant individuals. Over large scales (km), molecular analyses did not indicate SBD, and there were no differences in genetic structure between sexes. Our results showed that SBD depends on the spatial scale. Combining different approaches, we showed that the dispersal of males and females over local and large scales is sufficient to cause a lack of genetic differentiation within each sex, despite small-scale SBD.
Comparative seascape genetics of co-distributed intertidal snails Monodonta spp. in the Japanese and Ryukyu archipelagoes
Authors: Yamazaki D , Miura O , Uchida S , Ikeda M , Chiba S
Published: November 2020

Recent molecular ecological studies have focused on how the relationships between physical and ecological factors influence marine biogeography. Comparative phylogeography using closely related species is a powerful approach to evaluate the role of ecological traits in the genetic variation of marine organisms. In the present study, we compared ecological traits and genetic variation in 3 species of the intertidal snail genusMonodontathat co-occur in the Japanese and Ryukyu archipelagoes. We found thatM. labiowas dominant in sheltered habitats andM. perplexawas dominant in wave-exposed habitats, whileM. confusashowed no habitat specificity. This indicates thatM. labioandM. perplexaarehabitat specialists regarding wave exposure, whileM. confusais a generalist.M. labioandM. perplexashowed lower genetic diversity and greater genetic differentiation among populations thanM. confusa. Our findings support the specialist-generalist variation hypothesis in a well-connected marine environment.
Słowiańskie osadnictwo w fazie plemiennej i wczesnopaństwowej (VII/VIII–XIII wiek) / Slavic settlement in the Tribal and Early State phase (7th/8th–13th centuries)
Authors: Szmoniewski Bartłomiej , Tunia Krzysztof
Published: November 2020

After the Early Slavic period a number of changes took place, which was manifested, among others, in the construction of strongholds – fortified seats of local power. This stage of Slavic development, lasting approximately 200 years from the turn of the 7th and 8th century on, is called the Tribal phase. At that time, the areas of western Lesser Poland belonged to the Vistulan tribe. Their central seat was the stronghold on Wawel Hill in Kraków. At the end of the 10th century the Piasts began to play an active military and political role in the Vistula River basin. Their successful expansion gave rise to the Early State phase. After 966, as Christianity progressed, inhumation replaced cremation as the burial rite. The oldest row-arranged cemeteries were founded on the upper Vistula from the turn of the 10th and 11th centuries. They were used until end of the 12th century, or longer. Two such cemeteries were examined in the study area, in Wawrzeńczyce and Stręgoborzyce. They were abandoned with the consolidation of the parish network and the establishment of church cemeteries in the 13th century. Material culture of the Tribal phase – besides native production – yielded artifacts indicating contacts with areas south of the Carpathians, with the nomadic Avars and, after their fall, with Hungarians.
“Mostri Marini”: Constantine S. Rafinesque's names for three of Antonino Mongitore's Sicilian whales
Authors: Woodman Neal , Mead James G. , McGowen Michael R.
Published: November 2020

In 1815, the naturalist Constantine Samuel Rafinesque (1783–1840) previewed three new species of cetaceans –  Delphinus dalippus, Physeter urganantus and Oxypterus mongitori – that he intended to describe from Sicily based on illustrations in Antonino Mongitore's published work Della Sicilia ricercata nelle cose più memorabili (1742–1743). Although formal descriptions of the three species were never published, Rafinesque's reference to Mongitore's illustrations made the names available by “indication”. The names, nonetheless, fell into obscurity, most likely a result of contemporary taxonomists' lack of access to Mongitore's work. Rafinesque's names remain relevant to the history of cetacean taxonomy, although they are no longer applicable. Moreover, the animals associated with these names add to the historical record of whale strandings in the Mediterranean. For these reasons, we studied the illustrations Rafinesque indicated for his cetaceans and reviewed Mongitore's accompanying text, which together provide sufficient distinctive characters that two of the three animals can be confidently identified with modern species, namely the sperm whale, Physeter catodon Linnaeus, 1758 , and the false killer whale, Pseudorca crassidens (Owen, 1846). Had Rafinesque's name D. dalippus been recognized for what it was, it would have had priority over P. crassidens as the earliest scientific name for the false killer whale.
Harry Pasley Higginson and his role in the re-discovery of the dodo (Raphus cucullatus)
Authors: Brown Clare M.
Published: November 2020

Harry Pasley Higginson, a railway engineer from Yorkshire, northeast England, is one of the people credited with the first discovery of mid-Holocene dodo ( Raphus cucullatus) bones at Mare aux Songes, Mauritius, in 1865. A question still hangs over who could rightfully claim to be the first discoverer of the bones. It could have been Higginson, George Clark (a local schoolteacher) or perhaps someone else. Higginson collected a number of bones and kindly sent three boxes of dodo remains to museums in York, Leeds and Liverpool. The bones he sent are still there. Higginson later set up residence in New Zealand, where he became established as a successful engineer. Two of his achievements, the Kawarau suspension bridge and a dodo, are commemorated in stained glass in the Wellington Cathedral of St Paul in the New Zealand capital.
Pazvantoğlu Osman ve Vidin’de Kurduğu Kütüphane
Authors: ALTAY Ahmet
Published: November 2020

Bu çalışmada; Pazvantoğlu Osman tarafından 19. yüzyılın başlarında Vidin’de kurulan ve onun ismini taşıyan Vidin Pazvantoğlu Kütüphanesi hakkında bilgiler verilmektedir. Kütüphane hem Osmanlı Devleti döneminde İstanbul dışında kurulan ilk müstakil kütüphanelerden biri olması; hem de zengin bir dermeyi barındırması özellikleriyle döneminin önemli kütüphanelerinden birisidir. 1877-1878 Osmanlı-Rus Savaşı’na kadar Vidin halkına hizmet veren kütüphane, savaş sonrasında yağma ve talan tehlikesi altında kalınca Vidin’den Sofya’ya taşınmıştır. Burada oluşturulan bir komisyon aracılığıyla kitapların yaklaşık üçte biri Sofya’da Bulgaristan Ulusal Kütüphanesi’nde bırakılırken, üçte ikisi İstanbul’daki Beyazıd Kütüphane-i Umumisi’ne nakledilmiştir. Bulgar alanyazınında Pazvantoğlu Kütüphanesi ile ilgili yapılan birçok çalışma bulunmaktadır. Ancak bu çalışmalarda kütüphanenin tarihsel gelişimi hakkında bazı eksik bilgiler ve yanlışlar bulunmaktadır. Türkiye’de ise Pazvantoğlu Kütüphanesi hakkında yapılmış kapsamlı bir çalışmaya rastlanmamıştır. Bu kapsamda, çalışma, hem Türkiye alanyazınında bu konuda var olan boşluğu doldurmayı, hem de Bulgar araştırmacılar tarafından yapılan çalışmalarda eksik kalan kısımları tamamlamayı ve hataların düzeltilmesini amaçlamaktadır. Çalışmada, belgesel tarama yöntemi kullanılarak arşiv belgeleri ve alanyazındaki kaynaklar ışığında kütüphanenin ve kütüphanedeki kitapların tarihsel gelişimi ele alınmıştır.
The Study Of Theological Sin And The Meaning Of Transformation Based On Romans 12:1-2
Authors: Andrean Tony , Ming David
Published: November 2020

"In the beginning He created the heavens and the earth, the earth was formless and empty; pitch darkness covered the great oceans, and the Spirit of God drifted over the surface of the earth '(Genesis 1: 1). chaotic "or" irregular. "(Warren Baker, Study OId Testament. AMG publisher, 1994: 2-3G.). Then in the process of creating humans for maintain the universe, but man falls into sin so that his mind or intellect is dominated by sin. What is produced by the mind ruled by sin? The Scriptures state the following: first, the human character is in vain (Romans 1:21). Second, it is not fair for anyone to be wise (Romans 3.11). Third, the human mind becomes evil (Ephesians 5: 4, the human mind is hostile to God and results in evil deeds 1.21) In further development, the universe is not getting better, it's actually getting more and more damaged. Natural disasters occur everywhere, economic conditions are chaotic, laws are violated by the leaders themselves, society is socially hostile to each other, crime is everywhere. With the chaotic event, humans crave a real change and share of activities carried out to realize these desires, among others, with the current plasticity, the transformation movement. The author conducted this research and the results are expected to provide information and additional insight for parties related to the problem of understanding the doctrine of existence and the meaning of sin, thus understanding the meaning of transformation based on the Bible to be changed to not sin anymore. The expected benefit is to provide correct knowledge to the congregation and God's servants regarding the effects of sin in their lives. Especially in service, how they anticipate sin and experience transformation changes in their lives. Thus it can remind every believer to remain faithful and abstain from every action that brings sin
27-Hydroxycholesterol Promotes the Transfer of Astrocyte-Derived Cholesterol to Neurons in Co-cultured SH-SY5Y Cells and C6 Cells
Authors: Wang Yushan , Zhang Xiaona , Wang Tao , Liu Wen , Wang Lijing , Hao Ling , Ju Mengwei , Xiao Rong
Published: November 2020

Abnormality in cholesterol homeostasis in the brain is a feature of Alzheimer’s disease (AD). 27-Hydroxycholesterol (27-OHC) has been identified as a possible biomarker of AD, but its effects on cholesterol metabolism have not been fully characterized. This study was aimed to investigate the impacts of 27-OHC on cholesterol metabolism in nerve cells. SH-SY5Y cells and C6 cells were co-cultured and treated with 5, 10, and 20 μM 27-OHC for 24 h. Results showed that 27-OHC decreased cholesterol levels and up-regulated the expression of transport-related proteins in C6 cells. In SH-SY5Y cells, 27-OHC increased cholesterol accumulation, especially on plasma membrane (PM), which was consistent with the up-regulation of expressions of cholesterol endocytosis receptors, lipid raft-related proteins, and cholesterol esterase. Simultaneously, accumulation of membrane cholesterol promoted cholesterol conversion to 24S-OHC by CYP46A1(24S-hydroxylase) transfer from the endoplasmic reticulum (ER) to PM. Besides, Aβ levels were elevated in SH-SY5Y cells after 27-OHC treatment. Our results suggest that 27-OHC motivates the transfer of astrocyte-derived cholesterol to neurons. Although there exists a feedback mechanism that excessive cholesterol promotes its conversion to 24S-OHC, the increased cholesterol induced by 27-OHC could not be wholly offset in neurons.
Potential of Soluble Decellularized Extracellular Matrix for Musculoskeletal Tissue Engineering – Comparison of Various Mesenchymal Tissues
Authors: Hanai Hiroto , Jacob George , Nakagawa Shinichi , Tuan Rocky S. , Nakamura Norimasa , Shimomura Kazunori
Published: November 2020

Background

It is well studied that preparations of decellularized extracellular matrix (ECM) obtained from mesenchymal tissues can function as biological scaffolds to regenerate injured musculoskeletal tissues. Previously, we reported that soluble decellularized ECMs derived from meniscal tissue demonstrated excellent biocompatibility and produced meniscal regenerate with native meniscal anatomy and biochemical characteristics. We therefore hypothesized that decellularized mesenchymal tissue ECMs from various mesenchymal tissues should exhibit tissue-specific bioactivity. The purpose of this study was to test this hypothesis using porcine tissues, for potential applications in musculoskeletal tissue engineering.

Methods

Nine types of porcine tissue, including cartilage, meniscus, ligament, tendon, muscle, synovium, fat pad, fat, and bone, were decellularized using established methods and solubilized. Although the current trend is to develop tissue specific decellularization protocols, we selected a simple standard protocol across all tissues using Triton X-100 and DNase/RNase after mincing to compare the outcome. The content of sulfated glycosaminoglycan (sGAG) and hydroxyproline were quantified to determine the biochemical composition of each tissue. Along with the concentration of several growth factors, known to be involved in tissue repair and/or maturation, including bFGF, IGF-1, VEGF, and TGF-β1. The effect of soluble ECMs on cell differentiation was explored by combining them with 3D collagen scaffold culturing human synovium derived mesenchymal stem cells (hSMSCs).

Results

The decellularization of each tissue was performed and confirmed both histologically [hematoxylin and eosin (H&E) and 4’,6-diamidino-2-phenylindole (DAPI) staining] and on the basis of dsDNA quantification. The content of hydroxyproline of each tissue was relatively unchanged during the decellularization process when comparing the native and decellularized tissue. Cartilage and meniscus exhibited a significant decrease in sGAG content. The content of hydroxyproline in meniscus-derived ECM was the highest when compared with other tissues, while sGAG content in cartilage was the highest. Interestingly, a tissue-specific composition of most of the growth factors was measured in each soluble decellularized ECM and specific differentiation potential was particularly evident in cartilage, ligament and bone derived ECMs.

Conclusion

In this study, soluble decellularized ECMs exhibited differences based on their tissue of origin and the present results are important going forward in the field of musculoskeletal regeneration therapy.
Effects of Erythropoietin in White Adipose Tissue and Bone Microenvironment
Authors: Suresh Sukanya , Lee Jeeyoung , Noguchi Constance Tom
Published: November 2020

Erythropoietin (EPO) is expressed primarily in fetal liver and adult kidney to stimulate red blood cell production. Erythropoietin receptor expression is not restricted to erythroid progenitor cells, and non-erythroid EPO activity includes immune response and bone remodeling. In bone fracture models, EPO administration promotes bone formation and accelerates bone healing. In contrast, in healthy adult mice, exogenous EPO-stimulated erythropoiesis has been concomitant with bone loss, particularly at high EPO, that may be accompanied by increased osteoclast activation. Other EPO-associated responses include reduced inflammation and loss of fat mass with high-fat diet feeding, especially in male mice. While EPO exhibited a sex-dimorphic response in regulation of fat mass and inflammation in obese mice, EPO-stimulated erythropoiesis as well as EPO-associated bone loss was comparable in males and females. EPO administration in young mice and in obese mice resulted in bone loss without increasing osteoclasts, suggesting an osteoclast-independent mechanism, while loss of endogenous EPO decreased bone development and maintenance. Ossicle formation of bone marrow stromal cell transplants showed that EPO directly regulates the balance between osteogenesis and adipogenesis. Therefore, during development, endogenous EPO contributes to normal bone development and in maintaining the balance between osteogenesis and adipogenesis in bone marrow stromal cells, while EPO treatment in mice increased erythropoiesis, promoted bone loss, decreased bone marrow adipogenesis, and increased osteoclast activity. These observations in mouse models suggest that the most prevalent use of EPO to treat anemia associated with chronic kidney disease may compromise bone health and increase fracture risk, especially at a high dose.
NAD+ Metabolism Regulates Preadipocyte Differentiation by Enhancing α-Ketoglutarate-Mediated Histone H3K9 Demethylation at the PPARγ Promoter
Authors: Okabe Keisuke , Nawaz Allah , Nishida Yasuhiro , Yaku Keisuke , Usui Isao , Tobe Kazuyuki , Nakagawa Takashi
Published: November 2020

Obesity has become a serious problem in public health worldwide, causing numerous metabolic diseases. Once the differentiation to mature adipocytes is disrupted, adipocyte hypertrophy and ectopic lipid accumulation leads to the inflammation in adipose tissue and systemic metabolic disorders. Intracellular metabolic state is known to change during cell differentiation and it affects the cell fate or the differentiation through epigenetic mechanism. Although the mechanism of preadipocyte differentiation has been well established, it is unknown how metabolic state changes and how it affects the differentiation in predipocyte differentiation. Nicotinamide adenine dinucleotide (NAD+) plays crucial roles in energy metabolism as a coenzyme in multiple redox reactions in major catabolic pathways and as a substrate of sirtuins or poly(ADP-ribose)polymerases. NAD+ is mainly synthesized from salvage pathway mediated by two enzymes, Nampt and Nmnat. The manipulation to NAD+ metabolism causes metabolic change in each tissue and changes in systemic metabolism. However, the role of NAD+ and Nampt in adipocyte differentiation remains unknown. In this study, we employed liquid chromatography-mass spectrometry (LC-MS)- and gas chromatography-mass spectrometry (GC-MS)-based targeted metabolomics to elucidate the metabolic reprogramming events that occur during 3T3-L1 preadipocyte differentiation. We found that the tricarboxylic acid (TCA) cycle was enhanced, which correlated with upregulated NAD+ synthesis. Additionally, increased alpha-ketoglutarate (αKG) contributed to histone H3K9 demethylation in the promoter region of PPARγ, leading to its transcriptional activation. Thus, we concluded that NAD+-centered metabolic reprogramming is necessary for the differentiation of 3T3-L1 preadipocytes.
Honokiol Inhibits Melanoma Growth by Targeting Keratin 18 in vitro and in vivo
Authors: Liu Tingting , Liu Hui , Wang Penglei , Hu Yamei , Yang Ran , Liu Fangfang , Kim Hong Gyum , Dong Zigang , Liu Kangdong
Published: November 2020

Honokiol, a natural compound, derived from Magnolia officinalis, has been shown to have anti-cancer effect in several cancer types. However, the underlying molecular mechanism associated with its anti-cancer properties has not been fully elucidated. In the current study, we showed that honokiol inhibited the growth of melanoma cells in a dose and time-dependent manner. Mechanistically, it directly interacts with keratin 18 (KRT18) protein and induces its degradation through ubiquitination. Furthermore, the expression of KRT18 was found to be higher in melanoma tissues compared to the normal skin tissues. In addition, KRT18 overexpression significantly promoted melanoma cell proliferation and growth. Our results showed that honokiol treatment significantly decreased KRT18 protein level and suppressed the tumor growth in melanoma cell-derived xenograft mice models. Hence, KRT18 plays an oncogenic role in melanoma and honokiol can be an inhibitor for KRT18.
Multifunctional Roles of the Actin-Binding Protein Flightless I in Inflammation, Cancer and Wound Healing
Authors: Strudwick Xanthe L. , Cowin Allison J.
Published: November 2020

Flightless I is an actin-binding member of the gelsolin family of actin-remodeling proteins that inhibits actin polymerization but does not possess actin severing ability. Flightless I functions as a regulator of many cellular processes including proliferation, differentiation, apoptosis, and migration all of which are important for many physiological processes including wound repair, cancer progression and inflammation. More than simply facilitating cytoskeletal rearrangements, Flightless I has other important roles in the regulation of gene transcription within the nucleus where it interacts with nuclear hormone receptors to modulate cellular activities. In conjunction with key binding partners Leucine rich repeat in the Flightless I interaction proteins (LRRFIP)1/2, Flightless I acts both synergistically and competitively to regulate a wide range of cellular signaling including interacting with two of the most important inflammatory pathways, the NLRP3 inflammasome and the MyD88-TLR4 pathways. In this review we outline the current knowledge about this important cytoskeletal protein and describe its many functions across a range of health conditions and pathologies. We provide perspectives for future development of Flightless I as a potential target for clinical translation and insights into potential therapeutic approaches to manipulate Flightless I functions.
Human Umbilical Cord Blood Derived-Mesenchymal Stem Cells Alleviate Dextran Sulfate Sodium-Induced Colitis by Increasing Regulatory T Cells in Mice
Authors: Li Ying , Ma Ke , Zhang Luping , Xu Hong , Zhang Nan
Published: November 2020

Inflammatory bowel disease (IBD), which main clinical manifestations include abdominal pain and diarrhea occurring repeatedly, is a kind of autoimmune disease. It has been reported in preceding studies that mesenchymal stem cells (MSCs) can reduce inflammation by regulating the function of immune cells. But studies about the interaction between MSCs and adaptive immune cells, especially in IBD models, are insufficient. Therefore, the objective of this research was to estimate the therapeutic effects of MSCs from human umbilical cord blood (hUCB-MSCs) in an IBD model of rodent and to clarify the therapeutic mechanisms of hUCB-MSCs. Dextran sulfate sodium (DSS) was used to induce colitis in rodent. Mice with colitis were treated with intraperitoneal infusions of hUCB-MSCs and evaluated for mortality and diverse disease symptoms containing weight reduction, diarrhea, and bloody stools. The levels of histopathologic severity and generation of regulatory T cells (Treg) were also determined. Treatment with hUCB-MSCs ameliorated the clinical and histopathologic severity of acute and chronic colitis in mice. Furthermore, T cell infiltration into the inflamed colon was significantly decreased (p = 0.0175), and Foxp3+ cells were substantially higher in the hUCB-MSC group than that of the DSS group. Our results suggest that hUCB-MSCs are able to alleviate inflammation via adding Foxp3+ Tregs in an IBD model of mouse. As a result, these findings suggest the opportunity of hUCB-MSC being applied to patients with IBD.
Rheostatic Balance of Circadian Rhythm and Autophagy in Metabolism and Disease
Authors: Wang Xiang , Xu Zhijie , Cai Yuan , Zeng Shuangshuang , Peng Bi , Ren Xinxin , Yan Yuanliang , Gong Zhicheng
Published: November 2020

Circadian rhythms are physical, behavioral and environmental cycles that respond primarily to light and dark, with a period of time of approximately 24 h. The most essential physiological functions of mammals are manifested in circadian rhythm patterns, including the sleep-wake cycle and nutrient and energy metabolism. Autophagy is a conserved biological process contributing to nutrient and cellular homeostasis. The factors affecting autophagy are numerous, such as diet, drugs, and aging. Recent studies have indicated that autophagy is activated rhythmically in a clock-dependent manner whether the organism is healthy or has certain diseases. In addition, autophagy can affect circadian rhythm by degrading circadian proteins. This review discusses the interaction and mechanisms between autophagy and circadian rhythm. Moreover, we introduce the molecules influencing both autophagy and circadian rhythm. We then discuss the drugs affecting the circadian rhythm of autophagy. Finally, we present the role of rhythmic autophagy in nutrient and energy metabolism and its significance in physiology and metabolic disease.
Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking
Authors: Ezugwu James A. , Okoro Uchechukwu C. , Ezeokonkwo Mercy A. , Bhimapaka China R. , Okafor Sunday N. , Ugwu David I. , Ekoh Ogechi C. , Attah Solomon I.
Published: November 2020

The increase of antimicrobial resistance (AMR) and antimalarial resistance are complex and severe health issues today, as many microbial strains have become resistant to market drugs. The choice for the synthesis of new dipeptide-carboxamide derivatives is as a result of their wide biological properties such as antimicrobial, anti-inflammatory, and antioxidant activities. The condensation reaction of substituted benzenesulphonamoyl pentanamides with the carboxamide derivatives using peptide coupling reagents gave targeted products (8a-j). The in silico antimalarial and antibacterial studies showed good interactions of the compounds with target protein residues and a higher dock score in comparison with standard drugs. In the in vivo study, compound 8j was the most potent antimalarial agent with 61.90% inhibition comparable with 67% inhibition for Artemisinin. In the in vitro antimicrobial activity, compounds 8a and 8b (MIC 1.2 × 10−3 M and 1.1 × 10−3 M) were most potent against S. aureus; compound 8a, 8b, and 8j with MIC 6.0 × 10−3 M, 5.7 × 10−4 M, and 6.5 × 10−4 M, respectively, were the most active against B. subtilis; compound 8b (MIC 9.5 × 10−4 M) was most active against E.coli while 8a, 8b and 8d were the most active against S. typhi. Compounds 8c and 8h (MIC 1.3 × 10−3 M) each were the most active against C. albicans, while compound 8b (MIC 1.3 × 10−4 M) was most active against A. niger.
The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders
Authors: Geesala Ramasatyaveni , Issuree Priya D. , Maretzky Thorsten
Published: November 2020

Chronic obesity is associated with metabolic imbalance leading to diabetes, dyslipidemia, and cardiovascular diseases (CVDs), in which inflammation is caused by exposure to inflammatory stimuli, such as accumulating sphingolipid ceramides or intracellular stress. This inflammatory response is likely to be prolonged by the effects of dietary and blood cholesterol, thereby leading to chronic low-grade inflammation and endothelial dysfunction. Elevated levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF) are predictive of CVDs and have been widely studied for potential therapeutic strategies. The release of TNF is controlled by a disintegrin and metalloprotease (ADAM) 17 and both are positively associated with CVDs. ADAM17 also cleaves most of the ligands of the epidermal growth factor receptor (EGFR) which have been associated with hypertension, atherogenesis, vascular dysfunction, and cardiac remodeling. The inactive rhomboid protein 2 (iRhom2) regulates the ADAM17-dependent shedding of TNF in immune cells. In addition, iRhom2 also regulates the ADAM17-mediated cleavage of EGFR ligands such as amphiregulin and heparin-binding EGF-like growth factor. Targeting iRhom2 has recently become a possible alternative therapeutic strategy in chronic inflammatory diseases such as lupus nephritis and rheumatoid arthritis. However, what role this intriguing interacting partner of ADAM17 plays in the vasculature and how it functions in the pathologies of obesity and associated CVDs, are exciting questions that are only beginning to be elucidated. In this review, we discuss the role of iRhom2 in cardiovascular-related pathologies such as atherogenesis and obesity by providing an evaluation of known iRhom2-dependent cellular and inflammatory pathways.
Seismo-Acoustic Characterization of Mount Cleveland Volcano Explosions
Authors: Iezzi Alexandra M. , Fee David , Haney Matthew M. , Lyons John J.
Published: November 2020

Volcanic explosions can produce large, ash-rich plumes that pose great hazard to aviation, yet may often have few precursory geophysical signals. Mount Cleveland is one of the most active volcanoes in the Aleutian Arc, Alaska (United States) with at least 65 explosions between December 2011 and June 2020. We characterize the seismo-acoustic signals from explosions at Mount Cleveland over a period of 4 years starting in 2014 when the permanent local instrumentation was installed. While the seismic explosion signals are similar, the acoustic signals vary between explosions. Some explosion acoustic waveforms exhibit a single main compressional phase while other waveforms have multiple compressions. The time lag between seismic and acoustic arrivals varies considerably (up to 2.20 s) at a single station ∼3 km from the vent, suggesting a change in propagation path for the signals between explosions. We apply a variety of methods to explore the potential contributions to this variable time lag from atmospheric conditions, nonlinear propagation, and source depth within the conduit. This variable time lag has been observed elsewhere, but explanations are often unresolved. Our results indicate that while changes in atmospheric conditions can explain some of the variation in acoustic arrival time relative to the seismic signal arrivals, substantial residual time lag variations often still exist. Additionally, nonlinear propagation modeling results do not yield a change in the onset time of the acoustic arrival with source amplitudes comparable to (and larger) than Cleveland explosions. We find that a spectrum of seismic cross-correlation values between events and particle motion dip angles suggests that a varying explosion source depth within the conduit likely plays a dominant role in the observed variations in time lag. Explosion source depths appear to range from very shallow depths down to ∼1.5–2 km. Understanding the seismo-acoustic time lag and the subsequent indication of a variable explosion source depth may help inform explosion source modeling for Mount Cleveland, which remains poorly understood. We show that even with a single co-located seismic and acoustic sensor that does not always remain on scale, it is possible to provide meaningful interpretations of the explosion source depth which may help monitoring agencies understand the volcanic system.
Tetrapropylammonium Hydroxide as a Zinc Dendrite Growth Suppressor for Rechargeable Aqueous Battery
Authors: Kurmanbayeva Indira , Rakhymbay Lunara , Korzhynbayeva Kuralay , Adi Akylbek , Batyrbekuly Dauren , Mentbayeva Almagul , Bakenov Zhumabay
Published: November 2020

Zinc metal is widely used as an anode in various aqueous systems. However, zinc anode suffers from the dendrite formation on the surface upon cycling leading to a poor cyclability of a cell and its termination due to short circuit. In this work, the effect of tetrapropylammonium hydroxide (TPAH) was studied as an electrolyte additive for aqueous Zn//ZnCl2 + LiCl//LiFePO4 battery. TPAH additive prolongs the battery cycle life depending on its concentration (0.01–0.1 M). The better capacity retention over 350 cycles was observed for a symmetrical Zn//ZnCl2 + LiCl//Zn cell with 0.05 M TPAH whereas without additives the cell worked for only 110 cycles. The mechanism of TPAH influence on capacity retention is proposed based on the results of SEM and XRD analysis of the Zn anode and FTIR and NMR studies of the electrolyte. The XRD patterns of the negative electrode of the cell with TPAH indicates that zinc was preferentially deposited in a highly oriented (002) direction, which is more resistant against dendrite formation. These differences in deposited structure of Zn dendrites were confirmed by SEM images as well. FTIR and NMR spectra showed that TPAH decomposes to propylamine (RnN+H) and propene during cycling. TPAH also has an effect on the size and uniform distribution of Zn growth sides.