bluuebunny/crossref_metadata_2025 huggingface dataset:
The Anfinsen Dogma: Intriguing Details Sixty-Five Years Later
Authors: Gambardella Giorgia , Notari Sara , Cavaterra Dario , Iavarone Federica , Castagnola Massimo , Bocedi Alessio , Ricci Giorgio
Published: July 2022

The pioneering experiments of Anfinsen on the oxidative folding of RNase have been revisited discovering some details, which update the statement of his dogma and shed new light on the leading role of the correct disulfide in the attainment of the native structure. CD analysis, mass spectrometry, fluorescence spectroscopy and enzyme activity indicate that native disulfides drive the formation of the secondary and tertiary structures that cannot be entirely formed in their absence. This opposes a common opinion that these structures are first formed and then stabilized by the native disulfides. Our results also indicate that a spontaneous re-oxidation of a reduced RNase cannot produce a complete recovery of activity, as described by many textbooks; this can be obtained only in the presence of a reshuffling solution such as GSH/GSSG.
The Role of Dysregulated miRNAs in the Pathogenesis, Diagnosis and Treatment of Age-Related Macular Degeneration
Authors: Urbańska Karolina , Stępień Piotr Witold , Nowakowska Katarzyna Natalia , Stefaniak Martyna , Osial Natalia , Chorągiewicz Tomasz , Toro Mario Damiano , Nowomiejska Katarzyna , Rejdak Robert
Published: July 2022

Age-related macular degeneration (AMD) is an eye disease causing damage to the macular region of the retina where most of the photoreceptors responsible for central visual acuity are located. MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that negatively regulate genes by silent post-transcriptional gene expressions. Previous studies have shown that changes in specific miRNAs are involved in the pathogenesis of eye diseases, including AMD. Altered expressions of miRNAs are related to disturbances of regulating oxidative stress, inflammation, angiogenesis, apoptosis and phagocytosis, which are known factors in the pathogenesis of AMD. Moreover, dysregulation of miRNA is involved in drusen formation. Thus, miRNAs may be used as potential molecular biomarkers for the disease and, furthermore, tailoring therapeutics to particular disturbances in miRNAs may, in the future, offer hope to prevent irreversible vision loss. In this review, we clarify the current state of knowledge about the influence of miRNA on the pathogenesis, diagnosis and treatment of AMD. Our study material consisted of publications, which were found in PubMed, Google Scholar and Embase databases using “Age-related macular degeneration”, “miRNA”, “AMD biomarkers”, “miRNA therapeutics” and “AMD pathogenesis” as keywords. Paper search was limited to articles published from 2011 to date. In the section “Retinal, circulating and vitreous body miRNAs found in human studies”, we limited the search to studies with patients published in 2016–2021.
New Insights into TRP Ion Channels in Stem Cells
Authors: Guo Jing , Shan Chang , Xu Jiao , Li Mei , Zhao Jiayu , Cheng Wei
Published: July 2022

Transient receptor potential (TRP) ion channels are cationic permeable proteins located on the plasma membrane. TRPs are cellular sensors for perceiving diverse physical and/or chemical stimuli; thus, serving various critical physiological functions, including chemo-sensation, hearing, homeostasis, mechano-sensation, pain, taste, thermoregulation, vision, and even carcinogenesis. Dysregulated TRPs are found to be linked to many human hereditary diseases. Recent studies indicate that TRP ion channels are not only involved in sensory functions but are also implicated in regulating the biological characteristics of stem cells. In the present review, we summarize the expressions and functions of TRP ion channels in stem cells, including cancer stem cells. It offers an overview of the current understanding of TRP ion channels in stem cells.
Perforated Hydrogels Consisting of Cholesterol-Bearing Pullulan (CHP) Nanogels: A Newly Designed Scaffold for Bone Regeneration Induced by RANKL-Binding Peptides and BMP-2
Authors: Xie Cangyou , Satake-Ozawa Michiko , Rashed Fatma , Khan Masud , Ikeda Masaomi , Hayashi Shunya , Sawada Shinichi , Sasaki Yoshihiro , Ikeda Tohru , Mori Yoshiyuki , Akiyoshi Kazunari , Aoki Kazuhiro
Published: July 2022

The receptor activator of NF-κB ligand (RANKL)-binding peptide, OP3-4, is known to stimulate bone morphogenetic protein (BMP)-2-induced bone formation, but peptides tend to aggregate and lose their bioactivity. Cholesterol-bearing pullulan (CHP) nanogel scaffold has been shown to prevent aggregation of peptides and to allow their sustained release and activity; however, the appropriate design of CHP nanogels to conduct local bone formation needs to be developed. In the present study, we investigated the osteoconductive capacity of a newly synthesized CHP nanogel, CHPA using OP3-4 and BMP-2. We also clarified the difference between perforated and nonperforated CHPA impregnated with the two signaling molecules. Thirty-six, five-week-old male BALB/c mice were used for the calvarial defect model. The mice were euthanized at 6 weeks postoperatively. A higher cortical bone mineral content and bone formation rate were observed in the perforated scaffold in comparison to the nonperforated scaffold, especially in the OP3-4/BMP-2 combination group. The degradation rate of scaffold material in the perforated OP3-4/BMP-2 combination group was lower than that in the nonperforated group. These data suggest that perforated CHPA nanogel could lead to local bone formation induced by OP3-4 and BMP–2 and clarified the appropriate degradation rate for inducing local bone formation when CHPA nanogels are designed to be perforated.
Procyanidin B2 Alleviates Heat-Induced Oxidative Stress through the Nrf2 Pathway in Bovine Mammary Epithelial Cells
Authors: Wang Hongzhuang , Hao Weiguang , Yang Liang , Li Tingting , Zhao Chongchong , Yan Peishi , Wei Shengjuan
Published: July 2022

The objective of this study was to investigate the protective effects and potential molecular mechanisms of procyanidin B2 (PB2) in MAC-T (mammary alveolar cells-large T antigen) cells during heat stress (HS). The MAC-T cells were divided into three treatment groups: control (37 °C), HS (42 °C), and PB2 + HS (42 °C). Compared with MAC-T cells that were consistently cultured at 37 °C, acute HS treatment remarkably decreased cell viability, reduced activities of catalase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), and elevated intracellular levels of malondialdehyde (MDA) and reactive oxygen species (ROS). Additionally, nuclear factor erythroid 2-related factor 2 (Nrf2) was activated and translocated to the nucleus, in accompaniment with upregulation of Nrf2, heme oxygenase 1 (HO-1), thioredoxin reductase 1 (Txnrd1), and heat shock protein 70 (HSP70). In parallel, both mRNA transcript and actual protein secretion of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were increased by heat stress. Pretreatment of MAC-T cells with 0~25 μM PB2 alleviated the decline of cell viability by HS in a dose-dependent fashion and protected cells against HS-induced oxidative stress, as evidenced by significantly improved CAT, SOD, and T-AOC activity, as well as with decreased MDA and ROS generation. Furthermore, PB2 further activated the Nrf2 signaling pathway and reversed the inflammatory response induced by HS. Silencing of Nrf2 by si-Nrf2 transfection not only exacerbated HS-induced cell death and provoked oxidative stress and the inflammatory response, but also greatly abolished the cytoprotective effects under HS of PB2. In summary, PB2 protected MAC-T cells against HS-induced cell death, oxidative stress, and inflammatory response, partially by operating at the Nrf2 signal pathway.
Identification of Candidate Biomarker and Drug Targets for Improving Endometrial Cancer Racial Disparities
Authors: Javadian Pouya , Xu Chao , Sjoelund Virginie , Borden Lindsay E. , Garland Justin , Benbrook Doris Mangiaracina
Published: July 2022

Racial disparities in incidence and survival exist for many human cancers. Racial disparities are undoubtedly multifactorial and due in part to differences in socioeconomic factors, access to care, and comorbidities. Within the U.S., fundamental causes of health inequalities, including socio-economic factors, insurance status, access to healthcare and screening and treatment biases, are issues that contribute to cancer disparities. Yet even these epidemiologic differences do not fully account for survival disparities, as for nearly every stage, grade and histologic subtype, survival among Black women is significantly lower than their White counterparts. To address this, we sought to investigate the proteomic profiling molecular features of endometrial cancer in order to detect modifiable and targetable elements of endometrial cancer in different racial groups, which could be essential for treatment planning. The majority of proteins identified to be significantly altered among the racial groups and that can be regulated by existing drugs or investigational agents are enzymes that regulate metabolism and protein synthesis. These drugs have the potential to improve the worse outcomes of endometrial cancer patients based on race.
Oxidation Stress as a Mechanism of Aging in Human Erythrocytes: Protective Effect of Quercetin
Authors: Remigante Alessia , Spinelli Sara , Basile Nancy , Caruso Daniele , Falliti Giuseppe , Dossena Silvia , Marino Angela , Morabito Rossana
Published: July 2022

Aging is a multi-factorial process developing through a complex net of interactions between biological and cellular mechanisms and it involves oxidative stress (OS) as well as protein glycation. The aim of the present work was to verify the protective role of Quercetin (Q), a polyphenolic flavonoid compound, in a d-Galactose (d-Gal)-induced model of aging in human erythrocytes. The anion-exchange capability through the Band 3 protein (B3p) measured by the rate constant of the SO42− uptake, thiobarbituric acid reactive substances (TBARS) levels—a marker of lipid peroxidation—total sulfhydryl (-SH) groups, glycated hemoglobin (A1c), and a reduced glutathione/oxidized glutathione (GSH-GSSG) ratio were determined following the exposure of erythrocytes to 100 mM d-Gal for 24 h, with or without pre-incubation with 10 µM Q. The results confirmed that d-Gal activated OS pathways in human erythrocytes, affecting both membrane lipids and proteins, as denoted by increased TBARS levels and decreased total sulfhydryl groups, respectively. In addition, d-Gal led to an acceleration of the rate constant of the SO42− uptake through the B3p. Both the alteration of the B3p function and oxidative damage have been improved by pre-treatment with Q, which preferentially ameliorated lipid peroxidation rather than protein oxidation. Moreover, Q prevented glycated A1c formation, while no protective effect on the endogenous antioxidant system (GSH-GSSG) was observed. These findings suggest that the B3p could be a novel potential target of antioxidant treatments to counteract aging-related disturbances. Further studies are needed to confirm the possible role of Q in pharmacological strategies against aging.
Application of Lactic Acid Bacteria (LAB) in Sustainable Agriculture: Advantages and Limitations
Authors: Raman Jegadeesh , Kim Jeong-Seon , Choi Kyeong Rok , Eun Hyunmin , Yang Dongsoo , Ko Young-Joon , Kim Soo-Jin
Published: July 2022

Lactic acid bacteria (LAB) are significant groups of probiotic organisms in fermented food and are generally considered safe. LAB regulate soil organic matter and the biochemical cycle, detoxify hazardous chemicals, and enhance plant health. They are found in decomposing plants, traditional fermented milk products, and normal human gastrointestinal and vaginal flora. Exploring LAB identified in unknown niches may lead to isolating unique species. However, their classification is quite complex, and they are adapted to high sugar concentrations and acidic environments. LAB strains are considered promising candidates for sustainable agriculture, and they promote soil health and fertility. Therefore, they have received much attention regarding sustainable agriculture. LAB metabolites promote plant growth and stimulate shoot and root growth. As fertilizers, LAB can promote biodegradation, accelerate the soil organic content, and produce organic acid and bacteriocin metabolites. However, LAB show an antagonistic effect against phytopathogens, inhibiting fungal and bacterial populations in the rhizosphere and phyllosphere. Several studies have proposed the LAB bioremediation efficiency and detoxification of heavy metals and mycotoxins. However, LAB genetic manipulation and metabolic engineered tools provide efficient cell factories tailor-made to produce beneficial industrial and agro-products. This review discusses lactic acid bacteria advantages and limitations in sustainable agricultural development.
Antifungal Potential of Bacillus velezensis CE 100 for the Control of Different Colletotrichum Species through Isolation of Active Dipeptide, Cyclo-(D-phenylalanyl-D-prolyl)
Authors: Kim Tae Yoon , Hwang Seo Hyun , Noh Jun Su , Cho Jeong-Yong , Maung Chaw Ei Htwe
Published: July 2022

Colletotrichum species are important fungal pathogens causing anthracnose of tropical and subtropical fruit and vegetable crops. Dual culture assay indicated that Bacillus velezensis CE 100 was a strong antagonist against C. acutatum, C. coccodes, C. dematium, and C. gloeosporioides. The volatile organic compounds produced by B. velezensis CE 100 affected mycelial growth of Colletotrichum species tested in our study and caused twisted hyphal structures of all these fungal species. Chloroform crude compounds of B. velezensis CE 100 inhibited four Colletotrichum species in a concentration-dependent manner and induced severe damage in hyphal morphology of these fungal pathogens, including swelling, bulging, and multiple branching. Moreover, the active cyclic dipeptide, cyclo-(D-phenylalanyl-D-prolyl), was isolated from chloroform crude extract and identified by nuclear magnetic resonance (NMR) and mass spectrometry. The inhibitory effect of cyclo-(D-phenylalanyl-D-prolyl) on conidial germination of C. gloeosporioides occurred in a concentration-dependent manner. The conidial germination rate was completely inhibited by a concentration of 3 mg/mL of cyclo-(D-phenylalanyl-D-prolyl). Scanning electron micrographs revealed that the exposure to cyclic dipeptide resulted in seriously deformed hyphae and conidia with shriveled surfaces in dipeptide-treated C. gloeosporioides. Therefore, active dipeptide-producing B. velezensis CE 100 is a promising biocontrol agent for Colletotrichum species causing anthracnose.
Purinergic Signaling in Oral Tissues
Authors: Zuccarini Mariachiara , Giuliani Patricia , Ronci Maurizio , Caciagli Francesco , Caruso Vanni , Ciccarelli Renata , Di Iorio Patrizia
Published: July 2022

The role of the purinergic signal has been extensively investigated in many tissues and related organs, including the central and peripheral nervous systems as well as the gastrointestinal, cardiovascular, respiratory, renal, and immune systems. Less attention has been paid to the influence of purines in the oral cavity, which is the first part of the digestive apparatus and also acts as the body’s first antimicrobial barrier. In this review, evidence is provided of the presence and possible physiological role of the purinergic system in the different structures forming the oral cavity including teeth, tongue, hard palate, and soft palate with their annexes such as taste buds, salivary glands, and nervous fibers innervating the oral structures. We also report findings on the involvement of the purinergic signal in pathological conditions affecting the oral apparatus such as Sjögren’s syndrome or following irradiation for the treatment of head and neck cancer, and the use of experimental drugs interfering with the purine system to improve bone healing after damage. Further investigations are required to translate the results obtained so far into the clinical setting in order to pave the way for a wider application of purine-based treatments in oral diseases.
Deep Phenotyping of Superficial Epidermolytic Ichthyosis due to a Recurrent Mutation in KRT2
Authors: Suzuki Yuika , Takeichi Takuya , Tanahashi Kana , Muro Yoshinao , Suga Yasushi , Ogi Tomoo , Akiyama Masashi
Published: July 2022

Superficial epidermolytic ichthyosis (SEI) is an autosomal dominant inherited ichthyosis. SEI is caused by mutations in KRT2 and frequently shows erythroderma and widespread blistering at birth. We report the clinical manifestations of two patients from a Japanese family with SEI caused by a hotspot mutation, p.Glu487Lys, in KRT2. In addition, we summarize previous reports on SEI patients with the identical mutation. One of the two patients had disease onset at the age of 7 months. The other patient’s age of onset is unknown, but it was in childhood. Neither of the two patients showed erythroderma. To perform deep phenotyping, we studied the age of onset and the frequency of erythroderma in 34 reported SEI cases with the p.Glu487Lys mutation, including the present cases. Among the cases with sufficient clinical information, 44.4% of the cases that were due to p.Glu487Lys in KRT2 occurred at birth. Erythroderma was observed in 11.1% of the cases with p.Glu487Lys in KRT2.
Nutritional Calcium Supply Dependent Calcium Balance, Bone Calcification and Calcium Isotope Ratios in Rats
Authors: Rott Jeremy , Toepfer Eva Teresa , Bartosova Maria , Kolevica Ana , Heuser Alexander , Rabe Michael , Behets Geert , D’Haese Patrick C. , Eichwald Viktoria , Jugold Manfred , Damgov Ivan , Zarogiannis Sotirios G. , Shroff Rukshana , Eisenhauer Anton , Schmitt Claus Peter
Published: July 2022

Serum calcium isotopes (δ44/42Ca) have been suggested as a non-invasive and sensitive Ca balance marker. Quantitative δ44/42Ca changes associated with Ca flux across body compartment barriers relative to the dietary Ca and the correlation of δ44/42CaSerum with bone histology are unknown. We analyzed Ca and δ44/42Ca by mass-spectrometry in rats after two weeks of standard-Ca-diet (0.5%) and after four subsequent weeks of standard- and of low-Ca-diet (0.25%). In animals on a low-Ca-diet net Ca gain was 61 ± 3% and femur Ca content 68 ± 41% of standard-Ca-diet, bone mineralized area per section area was 68 ± 15% compared to standard-Ca-diet. δ44/42Ca was similar in the diets, and decreased in feces and urine and increased in serum in animals on low-Ca-diet. δ44/42CaBone was higher in animals on low-Ca-diet, lower in the diaphysis than the metaphysis and epiphysis, and unaffected by gender. Independent of diet, δ44/42CaBone was similar in the femora and ribs. At the time of sacrifice, δ44/42CaSerum inversely correlated with intestinal Ca uptake and histological bone mineralization markers, but not with Ca content and bone mineral density by µCT. In conclusion, δ44/42CaBone was bone site specific, but mechanical stress and gender independent. Low-Ca-diet induced marked changes in feces, serum and urine δ44/42Ca in growing rats. δ44/42CaSerum inversely correlated with markers of bone mineralization.
Superhydrophobic Paper-Based Microfluidic Field-Effect Transistor Biosensor Functionalized with Semiconducting Single-Walled Carbon Nanotube and DNAzyme for Hypocalcemia Diagnosis
Authors: Wang Hui , Chen Ruipeng , Zhang Fan , Yu Zhixue , Wang Yue , Tang Zhonglin , Yang Liang , Tang Xiangfang , Xiong Benhai
Published: July 2022

Hypocalcemia is caused by a sharp decline in blood calcium concentration after dairy cow calving, which can lead to various diseases or even death. It is necessary to develop an inexpensive, easy-to-operate, reliable sensor to diagnose hypocalcemia. The cellulose-paper-based microfluidic field-effect biosensor is promising for point-of-care, but it has poor mechanical strength and a short service life after exposure to an aqueous solution. Octadecyltrichlorosilane (OTS), as a popular organosilane derivative, can improve the hydrophobicity of cellulose paper to overcome the shortage of cellulose paper. In this work, OTS was used to produce the superhydrophobic cellulose paper that enhances the mechanical strength and short service life of MFB, and a microfluidic field-effect biosensor (MFB) with semiconducting single-walled carbon nanotubes (SWNTs) and DNAzyme was then developed for the Ca2+ determination. Pyrene carboxylic acid (PCA) attached to SWNTs through a non-covalent π-π stacking interaction provided a carboxyl group that can bond with an amino group of DNAzyme. Two DNAzymes with different sensitivities were designed by changing the sequence length and cleavage site, which were functionalized with SPFET/SWNTs-PCA to form Dual-MFB, decreasing the interference of impurities in cow blood. After optimizing the detecting parameters, Dual-MFB could determine the Ca2+ concentration in the range of 25 μM to 5 mM, with a detection limit of 10.7 μM. The proposed Dual-MFB was applied to measure Ca2+ concentration in cow blood, which provided a new method to diagnose hypocalcemia after dairy cow calving.
Ketamine plus Alcohol: What We Know and What We Can Expect about This
Authors: Kobayashi Natalia Harumi Correa , Farias Sarah Viana , Luz Diandra Araújo , Machado-Ferraro Kissila Márvia , Conceição Brenda Costa da , Silveira Cinthia Cristina Menezes da , Fernandes Luanna Melo Pereira , Cartágenes Sabrina de Carvalho , Ferreira Vânia Maria Moraes , Fontes-Júnior Enéas Andrade , Maia Cristiane do Socorro Ferraz
Published: July 2022

Drug abuse has become a public health concern. The misuse of ketamine, a psychedelic substance, has increased worldwide. In addition, the co-abuse with alcohol is frequently identified among misusers. Considering that ketamine and alcohol share several pharmacological targets, we hypothesize that the consumption of both psychoactive substances may synergically intensify the toxicological consequences, both under the effect of drugs available in body systems and during withdrawal. The aim of this review is to examine the toxicological mechanisms related to ketamine plus ethanol co-abuse, as well the consequences on cardiorespiratory, digestive, urinary, and central nervous systems. Furthermore, we provide a comprehensive discussion about the probable sites of shared molecular mechanisms that may elicit additional hazardous effects. Finally, we highlight the gaps of knowledge in this area, which deserves further research.
FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure
Authors: Camuzi Diego , Buexm Luisa Aguirre , Lourenço Simone de Queiroz Chaves , Grazziotin Rachele , Guaraldi Simone , Valverde Priscila , Rapozo Davy , Brooks Jill M. , Mehanna Hisham , Ribeiro Pinto Luis Felipe , Soares-Lima Sheila Coelho
Published: July 2022

Squamous cell carcinoma is the main histological tumor type in the upper aerodigestive tract (UADT), including the esophagus (ESCC) and the head and neck sites, as well as the oral cavity (OCSCC), larynx (LSCC) and oropharynx (OPSCC). These tumors are induced by alcohol and tobacco exposure, with the exception of a subgroup of OPSCC linked to human papillomavirus (HPV) infection. Few genes are frequently mutated in UADT tumors, pointing to other molecular mechanisms being involved during carcinogenesis. The F-box and leucine-rich repeat protein 7 (FBXL7) is a potential tumor-suppressing gene, one that is frequently hypermethylated in pancreatic cancer and where the encoded protein promotes the degradation of AURKA, BIRC5 and c-SRC. Thus, the aim of this study was to evaluate the methylation and expression profile of FBXL7 in the UADT and the gene’s association with the clinical, etiological and pathological characteristics of patients, as well as the expression of its degradation targets. Here we show that the FBXL7 gene’s body is hypomethylated in the UADT, independently of histology, but not in virus-associated tumors. FBXL7 body methylation and gene expression levels were correlated in the ESCC, LSCC, OCSCC and OPSCC. Immunohistochemistry analysis showed that FBXL7 protein levels are not correlated with the levels of its degradation targets, AURKA and BIRC5, in the UADT. The high discriminatory potential of FBXL7 body hypomethylation between non-tumor and tumor tissues makes it a promising biomarker.
Field Tests of Three Alternative Insecticides with Protein Bait for the Development of an Insecticide Rotation Program to Control Melon Flies, Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae)
Authors: Shikano Ikkei , Gutierrez-Coarite Rosemary , Streit Christian , Perez Edwin , Fujitani Earl , Mau Ronald F. L.
Published: July 2022

High levels of resistance to the spinosad-based insecticidal protein bait GF-120 have been detected in some populations of melon fly, Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae), in Hawaii in 2017. To provide cucurbit farmers in Hawaii with alternative insecticides, we field-tested the effectiveness of Agri-Mek SC (a.i., abamectin), Mustang Maxx (a.i., zeta-cypermethrin), and Malathion 5EC (a.i., malathion), added to a protein bait spray (Nu-Lure Insect Bait). The insecticide and protein bait combinations were applied to the roosting plants of Z. cucurbitae around the perimeter of the cucurbit fields at one-week intervals. When individually tested, all three insecticides in combination with protein bait significantly reduced or suppressed the numbers of female flies caught in torula yeast traps. A two-week rotation of weekly applications of the three insecticides and GF-120 significantly reduced Z. cucurbitae numbers on a commercial zucchini farm on Maui. The percentage of marketable fruits harvested increased from 51% to 98% after implementing the insecticide rotation. Our findings will be used to provide cucurbit farmers with additional products to control Z. cucurbitae. The future focus will be on educating cucurbit farmers to use the insecticide rotation strategy to prevent or delay resistance development.
Characterization of a Novel Heterochromatin Protein 1 Homolog “HP1c” in the Silkworm, Bombyx mori
Authors: Hino Masato , Tatsuke Tsuneyuki , Morio Akihiro , Mon Hiroaki , Lee Jae Man , Masuda Akitsu , Kakino Kohei , Tonooka Yoshino , Kusakabe Takahiro
Published: July 2022

Heterochromatin protein 1 plays an important role in chromatin structure and gene expression regulation. Three HP1 genes have been found in Homo sapiens, and five HP1 genes have been reported in Drosophila melanogaster. On the other hand, in Bombyx mori, only two HP1 genes, BmHP1a and BmHP1b, were reported. In this research, we have reported the molecular and functional characterization of a novel Bombyx mori HP1 gene (BmHP1c), which had stronger transcriptional repression activity than BmHP1a. BmHP1a and BmHP1b is reported to form homo- and heterodimers, but in co-immunoprecipitation experiments, no homo- or hetero-dimer formation of BmHP1c with the other silkworm HP1s is detected. The intracellular localization of BmHP1c is not only in the nucleus but also in the cytoplasm like mammalian HP1γ. In contrast to human HP1a and b, all three BmHP1s were localized preferentially in the regions poorly stained with DAPI. Interestingly, the double knockdown of BmHP1a and b, but not BmHP1c with a or b, arrested the cell cycle at the G2/M phase. These results suggest that BmHP1c is not essential for cell progression and plays a different role than BmHP1a and BmHP1b.
The Effect of Species Soybean Vein Necrosis Orthotospovirus (SVNV) on Life Table Parameters of Its Vector, Soybean Thrips (Neohydatothrips variabilis Thysanoptera: Thripidae)
Authors: Hameed Asifa , Rosa Cristina , Rajotte Edwin G.
Published: July 2022

Soybean vein necrosis orthotospovirus (SVNV: Tospoviridae: Orthotospovirus), the causal agent of soybean vein necrosis disease, is vectored by soybean thrips Neohydatothrips variabilis (Beach, 1896), and to a lesser extent by five other thrips species. There is increasing incidence of soybean vein necrosis (SVN) disease in all soybean growing states in the United States, Canada, Egypt and Pakistan, necessitating a study of the system’s ecology and management. We addressed the effect of SVNV on the life table parameters of the vector. We used an ‘age-stage two-sex’ life table approach, which provided detailed life stage durations of each larval instar and adults (both sexes). Our results showed that the intrinsic rate of increase (r), finite rate of increase (λ) and mortality index (qx) were higher in the infected population, while the net reproduction rate (Ro), cumulative probability of survival (lx) and gross reproduction rate (GRR) were lower in the uninfected population. Overall, in both infected and uninfected populations, the number of eggs producing haploid males via arrhenotoky ranged from 9–12 per female. Male to female ratio was female biased in the infected population. Overall, our study provided evidence that virus infection, by decreasing the population doubling time, could enhance the virus and vector populations in soybeans.
Comment on Marasca et al. Teledermatology and Inflammatory Skin Conditions during COVID-19 Era: New Perspectives and Applications. J. Clin. Med. 2022, 11, 1511
Authors: Borgia Francesco , Li Pomi Federica , Alessandrello Clara , Gangemi Sebastiano
Published: July 2022

We welcome an enthusiastic article titled “Teledermatology and Inflammatory Skin Conditions during COVID-19 Era: New Perspectives and Applications” by Marasca et al. [...]
Is the Adrenal Incidentaloma Functionally Active? An Approach-To-The-Patient-Based Review
Authors: Bernardi Stella , Calabrò Veronica , Cavallaro Marco , Lovriha Sara , Eramo Rita , Fabris Bruno , de Manzini Nicolò , Dobrinja Chiara
Published: July 2022

Adrenal incidentalomas are a common occurrence. Most of them are adrenocortical adenomas that do not cause harm and do not require surgery, but a non-negligible proportion of incidentalomas is represented by functionally active masses, including cortisol-secreting adenomas (12%), pheochromocytomas (3–6%), aldosterone-secreting adenomas (2–3%), as well as malignant nodules, such as adrenocortical carcinomas (2–5%), which can be either functioning or non-functioning. All patients with an adrenal incidentaloma should undergo a few biochemical screening and confirmatory tests to exclude the presence of a functionally active mass. In this approach-to-the-patient-based review, we will summarize current recommendations on biochemical evaluation and management of functionally active adrenal incidentalomas. For this purpose, we will present four case vignettes, whereby we will describe how patients were managed, then we will review and discuss additional considerations tied to the diagnostic approach, and conclude with practical aspects of patient perioperative management. To improve the perioperative management of patients with functional adrenal incidentalomas, multidisciplinary meetings are advocated.
Association between Functional Parameters of Coagulation and Conventional Coagulation Tests in the Setting of Fluid Resuscitation with Balanced Crystalloid or Gelatine: A Secondary Analysis of an In Vivo Prospective Randomized Crossover Study
Authors: Wiórek Agnieszka , Mazur Piotr K. , Niemiec Bożena , Krzych Łukasz J.
Published: July 2022

Functional point-of-care tests (POCTs) have evolved into useful tools for diagnosing disorders of blood coagulation and fibrinolysis. We aimed to describe the in vivo association between standard and functional parameters of coagulation and fibrinolysis in the setting of acute hemodilution induced by an infusion of balanced crystalloid or synthetic gelatine solutions. This prospective randomized crossover in vivo study included healthy male volunteers aged 18–30 years. Enrolled participants were randomly assigned to receive either the Optilyte® or Geloplasma® infusion. Laboratory analysis included conventional coagulation parameters and rotational thromboelastometry (ROTEM) assays. A total of 25 healthy Caucasian males were included. ROTEM viscoelastic assays presented moderate to strong correlations with conventional coagulation tests, regardless of the fluid type utilized. Irrespectively of the extent of hemodilution, significant correlations remained unaffected. The strongest associations were found between the ROTEM clot formation and clot strength and the fibrinogen concentration and platelet count, and between the ROTEM clotting time and the APTT and PT. This in vivo experimental study in healthy male volunteers demonstrated that ROTEM may be used as a credible alternative to standard laboratory tests to assess blood coagulation and fibrinolysis in the setting of fluid resuscitation with both crystalloid and colloid solutions. The study was registered online in the ClinicalTrials.gov database (NCT05148650).
Impact of COVID-19 on Subclinical Placental Thrombosis and Maternal Thrombotic Factors
Authors: Carbonnel Marie , Daclin Camille , Tourne Morgan , Roux Emmanuel , Le-Marchand Mathilde , Racowsky Catherine , Kennel Titouan , Farfour Eric , Vasse Marc , Ayoubi Jean-Marc
Published: July 2022

Background: In the context of the SARS-CoV-2 pandemic, our interest was to evaluate the effect of COVID-19 during pregnancy on placenta and coagulation factors. Methods: a prospective cohort study between January and July 2021 of 55 pregnant women stratified into: Group O, 16 patients with ongoing SARS-CoV-2 infection at delivery; Group R, 21 patients with a history of SARS-CoV-2 infection during pregnancy but who recovered prior to delivery; Group C, 18 control patients with no infection at any time. All women had nasopharyngeal SARS-CoV-2 RT-PCR tests performed within 72 h of delivery. Obstetrical complications were recorded and two physiological inhibitors of coagulation, protein Z (PZ) and dependent protease inhibitor (ZPI), were analyzed in maternal and cord blood. All placentae were analyzed by a pathologist for vascular malperfusion. Results: No patient in any group had a severe COVID-19 infection. More obstetrical complications were observed in Group O (O: n = 6/16 (37%), R: n = 2/21 (10%), C: n = 1/18 (6%), p = 0.03). The incidence of placental vascular malperfusion was similar among the groups (O: n = 9/16 (56%), R: n = 8/21 (42%), C: n = 8/18 (44%), p = 0.68). No PZ or ZPI deficiency was associated with COVID-19. However, an increased ZPI/PZ ratio was observed in neonates of Group R (O: 82.6 (min 41.3–max 743.6), R: 120.7 (29.8–203.5), C: 66.8 (28.2–2043.5), p = 0.04). Conclusion: COVID-19 was associated with more obstetrical complications, but not an increased incidence of placental lesions or PZ and ZPI abnormalities.
Identification of Target Proteins Involved in Cochlear Hair Cell Progenitor Cytotoxicity following Gentamicin Exposure
Authors: Davies Camron , Mittal Rahul , Li Crystal Y. , Marwede Hannah , Bergman Jenna , Hilton Nia , Mittal Jeenu , Bhattacharya Sanjoy K. , Eshraghi Adrien A.
Published: July 2022

Given the non-labile, terminal differentiation of inner-ear sensory cells, preserving their function is critical since sensory cell damage results in irreversible hearing loss. Gentamicin-induced cytotoxicity is one of the major causes of sensory cell damage and consequent sensorineural hearing loss. However, the precise molecular mechanisms and target proteins involved in ototoxicity are still unknown. The objective of the present study was to identify target proteins involved in gentamicin-induced cytotoxicity to better characterize the molecular pathways involved in sensory cell damage following ototoxic drug administration using House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). We identified several unique proteins involved in gentamicin-induced cytotoxicity, expression of which were further confirmed using confocal microscopy. Further investigation of these pathways can inform the design and discovery of novel treatment modalities to prevent sensory cell damage and preserve their function.
Women’s Access to Sexual and Reproductive Health Services during Confinement Due to the COVID-19 Pandemic in Spain
Authors: Leon-Larios Fatima , Silva Reus Isabel , Lahoz Pascual Isabel , Quílez Conde José Cruz , Puente Martínez María José , Gutiérrez Ales José , Correa Rancel Marta
Published: July 2022

(1) Background: The COVID-19 pandemic has created a challenge for women’s sexual and reproductive health care. The objective of this research was to analyse access to sexual and reproductive health services during confinement in Spain. (2) Methods: A descriptive and cross-sectional study was conducted with a random sample that was stratified by age in July and August 2020. (3) Results: A total of 1800 women were invited to participate, obtaining a response rate of 98.72%. The frequency of sexual relationships reduced during confinement. Counselling was offered both in person (30.7%) and telematically (39%), although there were also women who experienced access problems (30%). Of those women who required some LARC, only half had access to it, mainly due to the contact difficulties as a result of the limited number of consultations with their prescribing physicians. The use of emergency oral contraception and the use of services for the voluntary interruption of pregnancy were considerably reduced. The women who stated having been victims of gender-based violence were those that lived with their aggressors during confinement and had children. (4) Conclusions: It is necessary to ensure sexual and reproductive rights in confinement times and, for such a purpose, telemedicine can be a good tool that helps to avoid unmet contraceptive needs and unplanned pregnancies.
Retinal Artery Occlusion and Its Impact on the Incidence of Stroke, Myocardial Infarction, and All-Cause Mortality during 12-Year Follow-Up
Authors: Roskal-Wałek Joanna , Wałek Paweł , Biskup Michał , Sidło Jacek , Cieśla Elżbieta , Odrobina Dominik , Mackiewicz Jerzy , Wożakowska-Kapłon Beata
Published: July 2022

The aim of the study was to evaluate the incidence of ischemic stroke, myocardial infarction, and all-cause mortality in patients with retinal artery occlusion (RAO). This single-center retrospective study included 139 patients diagnosed with RAO between 2009 and 2020. The control group included 139 age- and sex-matched patients without RAO who underwent cataract surgery. The year of the surgery corresponded to the year of RAO onset. During the 12-year follow-up, patients with RAO had a shorter time to death (49.95 vs. 15.74 months; p = 0.043), a higher all-cause mortality rate (log-rank p = 0.026, and a higher rate of the composite endpoint, including ischemic stroke, myocardial infarction, and all-cause mortality (log-rank p = 0.024), as compared with controls. Patients with RAO younger than 75 years showed a higher risk of cerebral ischemic stroke (log-rank p = 0.008), all-cause mortality (log-rank p = 0.023), and the composite endpoint (log-rank p = 0.001) than controls. However, these associations were not demonstrated for patients aged 75 years or older. Our study confirms that patients with RAO have a higher risk of all-cause mortality than those without RAO. Moreover, patients with RAO who are younger than 75 years are significantly more likely to experience ischemic stroke, death, or the composite endpoint after an occlusion event, as compared with individuals without RAO.
Serum Concentration of Selected Angiogenesis-Related Molecules Differs among Molecular Subtypes, Body Mass Index and Menopausal Status in Breast Cancer Patients
Authors: Balalis Dimitrios , Tsakogiannis Dimitrios , Kalogera Eleni , Kokkali Stefania , Tripodaki Elli , Ardavanis Alexandros , Manatakis Dimitrios , Dimas Dionysios , Koufopoulos Nektarios , Fostira Florentia , Korkolis Dimitrios , Misitzis Ioannis , Vassos Nikolaos , Spiliopoulou Chara , Vlachodimitropoulos Dimitrios , Bletsa Garyfalia , Arkadopoulos Nikolaos
Published: July 2022

Background: Angiogenesis is a hallmark of breast cancer (BC) and is mediated by the vascular endothelial growth factor (VEGF) signaling axis. It is regulated by different proangiogenic factors, including platelet-derived growth factor-CC (PDGF-CC) and heparin-binding EGF-like growth factor (HB-EGF), as well as co-receptors, such as neuropilin-1, which could have prognostic implications in BC patients. Patients and methods: We assessed the serum levels of VEGF, HB-EGF, PDGF-CC and neuropilin-1 in 205 patients with early BC (invasive, n = 187; in situ, n = 18) and in 31 healthy donors (HD) and investigated the potential associations with clinical and histopathological parameters. Results: VEGF serum levels were significantly higher in patients with invasive versus ductal carcinomas in situ. PDGF-CC serum concentrations varied among BC molecular subtypes. Furthermore, we observed a differential expression of most biomarkers between overweight/obese (body mass index (BMI) ≥ 25 kg/m2) and non-obese patients among the BC molecular subtypes. Finally, the classification of subjects according to menopausal status revealed a significant difference in specific biomarker levels between patients and HD. Conclusion: The serum concentrations of angiogenic molecules differ among breast cancer molecular subtypes and are affected by the BMI and menopausal status, which could have possible clinical or prognostic implications.
Symptom-Level Disability Status Assessed with an Electronic Unsupervised Patient-Reported Expanded Disability Status Scale (ePR-EDSS) in Multiple Sclerosis Patients—The Example of Croatia
Authors: Jerković Ana , Pavelin Sanda , Šoda Joško , Vujović Igor , Rogić Vidaković Maja
Published: July 2022

The present study aimed to apply an electronic, unsupervised patient-reported Expanded Disability Status Scale (ePR-EDSS) to investigate disability severity in people with multiple sclerosis (pwMS) as a case study in Croatia in 2021, including demographic and comorbidity characteristics and multiple sclerosis (MS) disease-related factors. The cross-sectional study was conducted as an online survey from 4 October 2021 to 31 December 2021. Symptom-level disability status was assessed with ePR-EDSS for MS capturing MS-related disability across the spectrum of severity.The study enrolled 147 pwMS patients, of which 84% were women. The mean age ± standard deviation in the sample was 41.1 ± 11.3, and the mean disease duration was 8.5 ± 7.4 years, with a median EDSS score of 3.0 (range, 0–8). The distribution of the participants according to clinical forms of MS was as follows: 71% had relapsing-remitting MS, 13% had primary progressive MS, 4% had secondary progressive PMS, and 12% did not provide information on their MS type. Twenty-nine point two percent (29.2%) of the participants had comorbidities in addition to MS. EDSS scores indicate significant differences with regard to age (t = −3.51, p < 0.001), gender (χ2 = 8.04, p < 0.01), and immunomodulatory drug use (χ2 = 5.89, p < 0.05). An ePR-EDSS analysis of disability symptoms showed a significant difference in symptoms with regard to strength, sensation, coordination, vision, fatigue, mobility, and overall wellness among MS types. Participants with PPMS and SPMS were older on average, had higher EDSS, and had more pronounced symptoms of disability measured with ePR-EDSS compared to those with RRMS. Application of ePR-EDSS shows it to be a reliable eHealth tool for clinical assessment of pwMS disability status, and future studies should correlate it with standard self-report scales capturing MS symptoms such as fatigue, depression, anxiety, and stress.
Infective Endocarditis in People Who Inject Drugs: Report from the Italian Registry of Infective Endocarditis
Authors: Cecchi Enrico , Corcione Silvia , Lupia Tommaso , De Benedetto Ilaria , Shbaklo Nour , Chirillo Fabio , Moreo Antonella , Rinaldi Mauro , Faggiano Pompilio , Cecconi Moreno , Bargiacchi Olivia , Cialfi Alessandro , Del Ponte Stefano , Squeri Angelo , Gaddi Oscar , Carmina Maria Gabriella , Lazzaro Alessandro , Ciccone Giovannino , Castiglione Anna , De Rosa Francesco Giuseppe
Published: July 2022

Intravenous drug use is a predisposing condition for infective endocarditis (IE). We report the clinical features of IE, taken from the Italian Registry of IE, in people who inject drugs (PWIDs). The registry prospectively collected epidemiological, clinical, in-hospital, and follow-up data on patients with IE from 17 Italian centers. A total of 677 patients were enrolled, and 61 (9%) were intravenous drug users (IDUs). Most PWIDs were male (78.6%), and aged between 41 and 50 years old (50%). The most frequent comorbidities were HIV (34.4%) and chronic liver disease (32%). Predisposing factors for IE were present in 6.5% of the patients, and 10% had minor valvular abnormalities. IE had occurred previously in 16.4% of the patients, and 50% of them had undergone heart surgery. Overall mortality was 9.8% in IDUs and 20% in patients with recurrent IE. IE in PWIDs mostly affected the native valves (90%). The echocardiographic diagnosis of IE was based on the detection of vegetation in 91.82% of cases. Staphylococcus aureus was the main microorganism isolated (70%) from blood cultures. Thirty patients (49%) underwent heart surgery: thirteen had aortic valves, eleven had mitral valves, and six had tricuspid valve interventions. IE in PWIDs was relatively common, and patients with native valve right-sided IE had a better prognosis, with a low rate of surgical interventions.
The Effect of Intermittent versus Continuous Non-Invasive Blood Pressure Monitoring on the Detection of Intraoperative Hypotension, a Sub-Study
Authors: Wijnberge Marije , van der Ster Björn , Vlaar Alexander P. J. , Hollmann Markus W. , Geerts Bart F. , Veelo Denise P.
Published: July 2022

Intraoperative hypotension is associated with postoperative complications. However, in the majority of surgical patients, blood pressure (BP) is measured intermittently with a non-invasive cuff around the upper arm (NIBP-arm). We hypothesized that NIBP-arm, compared with a non-invasive continuous alternative, would result in missed events and in delayed recognition of hypotensive events. This was a sub-study of a previously published cohort study in adult patients undergoing surgery. The detection of hypotension (mean arterial pressure below 65 mmHg) was compared using two non-invasive methods; intermittent oscillometric NIBP-arm versus continuous NIBP measured with a finger cuff (cNIBP-finger) (Nexfin, Edwards Lifesciences). cNIBP-finger was used as the reference standard. Out of 350 patients, 268 patients (77%) had one or more hypotensive events during surgery. Out of the 286 patients, 72 (27%) had one or more missed hypotensive events. The majority of hypotensive events (92%) were detected with NIBP-arm, but were recognized at a median of 1.2 (0.6–2.2) minutes later. Intermittent BP monitoring resulted in missed hypotensive events and the hypotensive events that were detected were recognized with a delay. This study highlights the advantage of continuous monitoring. Future studies are needed to understand the effect on patient outcomes.