bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth Hormone Improves Adipose Tissue Browning and Muscle Wasting in Mice with Chronic Kidney Disease-Associated Cachexia
Authors: Mak Robert H. , Gunta Sujana , Oliveira Eduardo A. , Cheung Wai W.
Published: December 2022

Cachexia associated with chronic kidney disease (CKD) has been linked to GH resistance. In CKD, GH treatment enhances muscular performance. We investigated the impact of GH on cachexia brought on by CKD. CKD was induced by 5/6 nephrectomy in c57BL/6J mice. After receiving GH (10 mg/kg/day) or saline treatment for six weeks, CKD mice were compared to sham-operated controls. GH normalized metabolic rate, increased food intake and weight growth, and improved in vivo muscular function (rotarod and grip strength) in CKD mice. GH decreased uncoupling proteins (UCP)s and increased muscle and adipose tissue ATP content in CKD mice. GH decreased lipolysis of adipose tissue by attenuating expression and protein content of adipose triglyceride lipase and protein content of phosphorylated hormone-sensitive lipase in CKD mice. GH reversed the increased expression of beige adipocyte markers (UCP-1, CD137, Tmem26, Tbx1, Prdm16, Pgc1α, and Cidea) and molecules implicated in adipose tissue browning (Cox2/Pgf2α, Tlr2, Myd88, and Traf6) in CKD mice. Additionally, GH normalized the molecular markers of processes connected to muscle wasting in CKD, such as myogenesis and muscle regeneration. By using RNAseq, we previously determined the top 12 skeletal muscle genes differentially expressed between mice with CKD and control animals. These 12 genes’ aberrant expression has been linked to increased muscle thermogenesis, fibrosis, and poor muscle and neuron regeneration. In this study, we demonstrated that GH restored 7 of the top 12 differentially elevated muscle genes in CKD mice. In conclusion, GH might be an effective treatment for muscular atrophy and browning of adipose tissue in CKD-related cachexia.
Easy and Effective Method for Extracting and Purifying Wolbachia Genomic DNA
Authors: Andreenkova Olga V. , Shishkina Olga D. , Klimenko Alexandra I. , Korenskaia Aleksandra E. , Bobrovskikh Margarita A. , Shatskaya Natalja V. , Vasiliev Gennady V. , Gruntenko Nataly E.
Published: December 2022

A number of methods for extracting the DNA of maternally inherited obligate intracellular bacteria Wolbachia from an insect host and its subsequent purification have been described in previous scholarship. As Wolbachia is present in the hosts’ organisms in rather low quantities, these techniques used to be quite labor-intensive. For this paper, we analyzed them in detail, searched for a possibility to simplify and accelerate the protocol, and proposed an easy and effective method for isolating Wolbachia DNA from Drosophila melanogaster with a purity sufficient for genomic sequencing. Our method involves the centrifugation of homogenized flies or just their ovaries, as the most Wolbachia-enriched tissue, followed by the filtration of homogenate and extraction of DNA using a modified version of the Livak buffer protocol. The proportion of Wolbachia DNA in the total DNA was quantified based on the results of sequencing with the use of the Illumina MiSeq platform and a pipeline of bioinformatic analysis. For the two analyzed D. melanogaster lines infected with two different Wolbachia strains, the proportion was at least 68 and 94%, respectively.
Is Periodontitis Associated with Age-Related Cognitive Impairment? The Systematic Review, Confounders Assessment and Meta-Analysis of Clinical Studies
Authors: Dziedzic Arkadiusz
Published: December 2022

It has been suggested that molecular pathological mechanisms responsible for periodontitis can be linked with biochemical alterations in neurodegenerative disorders. Hypothetically, chronic systemic inflammation as a response to periodontitis plays a role in the etiology of cognitive impairment. This study aimed to determine whether periodontitis (PDS) is a risk factor for age-related cognitive impairment (ACI) based on evidence of clinical studies. A comprehensive, structured systematic review of existing data adhering to the Preferred Reporting Items for Systematic Review and Meta Analyses (PRISMA) guidelines was carried out. Five electronic databases, PubMed, Embase, Scopus, Web of Science, and Cochrane, were searched for key terms published in peer-reviewed journals until January 2021. The Newcastle–Ottawa scale was used to assess the quality of studies and risk of bias. The primary and residual confounders were explored and evaluated. A meta-analysis synthesizing quantitative data was carried out using a random-effects model. Seventeen clinical studies were identified, including 14 cohort, one cross-sectional, and two case-control studies. Study samples ranged from 85 to 262,349 subjects, with follow-up between 2 and 32 years, and age above 45 years, except for two studies. The findings of studies suggesting the PDS-ACI relationship revealed substantial differences in design and methods. A noticeable variation related to the treatment of confounders was observed. Quality assessment unveiled a moderate quality of evidence and risk of bias. The subgroups meta-analysis and pooled sensitivity analysis of results from seven eligible studies demonstrated overall that the presence of PDS is associated with an increased risk of incidence of cognitive impairment (OR = 1.36, 95% CI 1.03–1.79), particularly dementia (OR = 1.39, 95% CI 1.02–1.88) and Alzheimer’s disease (OR = 1.03 95% CI 0.98–1.07)). However, a considerable heterogeneity of synthesized data (I2 = 96%) and potential publication bias might affect obtained results. While there is a moderate statistical association between periodontitis and dementia, as well as Alzheimer’s disease, the risk of bias in the evidence prevents conclusions being drawn about the role of periodontitis as a risk factor for age-related cognitive impairment.
Genome-Wide Association Analysis for Hybrid Breeding in Wheat
Authors: Mokrzycka Monika , Stojałowski Stefan , Tyrka Mirosław , Matysik Przemysław , Żmijewska Barbara , Marcinkowski Rafał , Woźna-Pawlak Urszula , Martofel Róża , Rokicki Michał , Rakoczy-Trojanowska Monika , Krajewski Paweł
Published: December 2022

Disclosure of markers that are significantly associated with plant traits can help develop new varieties with desirable properties. This study determined the genome-wide associations based on DArTseq markers for six agronomic traits assessed in eight environments for wheat. Moreover, the association study for heterosis and analysis of the effects of markers grouped by linkage disequilibrium were performed based on mean values over all experiments. All results were validated using data from post-registration trials. GWAS revealed 1273 single nucleotide polymorphisms with biologically significant effects. Most polymorphisms were predicted to be modifiers of protein translation, with only two having a more pronounced effect. Markers significantly associated with the considered set of features were clustered within chromosomes based on linkage disequilibrium in 327 LD blocks. A GWAS for heterosis revealed 1261 markers with significant effects.
The Anaphase-Promoting Complex/Cyclosome Is a Cellular Ageing Regulator
Authors: Hu Xiangdong , Jin Xuejiao , Cao Xiuling , Liu Beidong
Published: December 2022

The anaphase-promoting complex/cyclosome (APC/C) is a complicated cellular component that plays significant roles in regulating the cell cycle process of eukaryotic organisms. The spatiotemporal regulation mechanisms of APC/C in distinct cell cycle transitions are no longer mysterious, and the components of this protein complex are gradually identified and characterized. Given the close relationship between the cell cycle and lifespan, it is urgent to understand the roles of APC/C in lifespan regulation, but this field still seems to have not been systematically summarized. Furthermore, although several reviews have reported the roles of APC/C in cancer, there are still gaps in the summary of its roles in other age-related diseases. In this review, we propose that the APC/C is a novel cellular ageing regulator based on its indispensable role in the regulation of lifespan and its involvement in age-associated diseases. This work provides an extensive review of aspects related to the underlying mechanisms of APC/C in lifespan regulation and how it participates in age-associated diseases. More comprehensive recognition and understanding of the relationship between APC/C and ageing and age-related diseases will increase the development of targeted strategies for human health.
Osteopontin Splicing Isoforms Contribute to Endometriotic Proliferation, Migration, and Epithelial-Mesenchymal Transition in Endometrial Epithelial Cells
Authors: Ho Nguyen-Tuong , Lin Shu-Wei , Lee Yi-Rong , Tzeng Chii-Ruey , Kao Shu-Huei
Published: December 2022

Osteopontin (OPN) isoforms, including OPNb and OPNc, promote malignancy and may contribute to the pathogenesis of endometriosis, a benign disorder with multiple characteristics resembling malignant tumors. In our experiments, OPNb and OPNc were significantly overexpressed in both endometriosis and adenomyosis compared to the normal endometrium. Upregulation of CD44v and the epithelial–mesenchymal transition (EMT) process was also present in endometriotic lesions. Overexpression of OPNb and OPNc splicing variants in endometriotic cells evoked morphological changes, actin remodeling, cell proliferation, cell migration, and EMT through binding OPN ligand receptors CD44 and αvβ3, subsequently activating the PI3K and NF-ĸB pathways. We elucidated the causal role of OPN splice variants in regulating endometriotic cell growth, which may promote the development of OPN-targeted therapies for patients suffering from endometriotic disorders.
SARS-CoV-2 Altered Hemorheological and Hematological Parameters during One-Month Observation Period in Critically Ill COVID-19 Patients
Authors: Bizjak Daniel Alexander , John Lucas , Matits Lynn , Uhl Alisa , Schulz Sebastian Victor Waldemar , Schellenberg Jana , Peifer Johannes , Bloch Wilhelm , Weiß Manfred , Grüner Beate , Bracht Hendrik , Steinacker Jürgen Michael , Grau Marijke
Published: December 2022

Hematological and hemorheological parameters are known to be altered in COVID-19; however, the value of combined monitoring in order to deduce disease severity is only scarcely examined. A total of 44 acute SARS-CoV-2-infected patients (aCOV) and 44 age-matched healthy controls (Con) were included. Blood of aCOV was sampled at admission (T0), and at day 2 (T2), day 5 (T5), day 10 (T10), and day 30 (T30) while blood of Con was only sampled once. Inter- and intra-group differences were calculated for hematological and hemorheological parameters. Except for mean cellular volume and mean cellular hemoglobin, all blood cell parameters were significantly different between aCOV and Con. During the acute disease state (T0–T5), hematological and hemorheological parameters were highly altered in aCOV; in particular, anemic conditions and increased immune cell response/inflammation, oxidative/nitrosative stress, decreased deformability, as well as increased aggregation, were observed. During treatment and convalescence until T30, almost all abnormal values of aCOV improved towards Con values. During the acute state of the COVID-19 disease, the hematological, as well as the hemorheological system, show fast and potentially pathological changes that might contribute to the progression of the disease, but changes appear to be largely reversible after four weeks. Measuring RBC deformability and aggregation, as well as oxidative stress induction, may be helpful in monitoring critically ill COVID-19 patients.
Mechanism of Extracellular Vesicle Secretion Associated with TGF-β-Dependent Inflammatory Response in the Tumor Microenvironment
Authors: Bonowicz Klaudia , Mikołajczyk Klaudia , Faisal Inaz , Qamar Murtaz , Steinbrink Kerstin , Kleszczyński Konrad , Grzanka Alina , Gagat Maciej
Published: December 2022

Extracellular vesicles (EVs) serve as central mediators in communication between tumor and non-tumor cells. These interactions are largely dependent on the function of the endothelial barrier and the set of receptors present on its surface, as endothelial cells (ECs) are a plenteous source of EVs. The molecular basis for EV secretion and action in the tumor microenvironment (TME) has not been fully elucidated to date. Emerging evidence suggests a prominent role of inflammatory pathways in promoting tumor progression and metastasis. Although transforming growth factor β (TGF-β) is a cytokine with strong immunomodulatory and protective activity in benign and early-stage cancer cells, it plays a pro-tumorigenic role in advanced cancer cells, which is known as the “TGF-β paradox”. Thus, the aim of this review is to describe the correlation between EV release, TGF-β-dependent inflammation, and dysregulation of downstream TGF-β signaling in the context of cancer development.
Dual CXCR4/IL-10 Gene-Edited Human Amniotic Mesenchymal Stem Cells Exhibit Robust Therapeutic Properties in Chronic Wound Healing
Authors: Han Seong-Ho , Chae Dong-Sik , Kim Sung-Whan
Published: December 2022

Although stem cells have attracted attention as a novel therapeutic solution for tissue regeneration, their minimal efficacy remains controversial. In the present study, we aimed to investigate the enhanced therapeutic property of CXCR4/IL-10 dual angiogenic/anti-inflammatory gene knock-in amniotic mesenchymal stem cells (AMM) in a wound-healing model. Dual CXCR4 and IL-10 genes were inserted into the AMM genome using transcription-activator-like effector nuclease (TALEN). Matrigel tube formation and anti-inflammatory effects were assessed in vitro, and efficacy was tested in vivo in a diabetic wound-healing model. CXCR4/IL-10-expressing amniotic MSCs (AMM/CI) strongly expressed CXCR4 and IL-10 genes and robustly promoted tube formation and anti-inflammatory potential. AMM/CI transplantation resulted in accelerated wound healing, as well as high engraftment and re-epithelialization potential. Transplanted AMM/CI also exhibited high angiogenic and decreased pro-inflammatory gene expression in the wound tissue, indicating direct therapeutic effects on wound healing. Taken together, these data indicate that dual angiogenic/anti-inflammatory gene knock-in may be a novel approach to enhance the therapeutic effects of stem cells, and transplantation of AMM/CI can be an alternative therapeutic option in chronic wound healing.
Regulation of Epstein-Barr Virus Minor Capsid Protein BORF1 by TRIM5α
Authors: Lin Lih-Tsern , Lu Yi-Shan , Huang Hsiang-Hung , Chen Hao , Hsu Shih-Wei , Chang Li-Kwan
Published: December 2022

TRIM5α is a host anti-retroviral restriction factor that destroys human immunodeficiency virus (HIV) virions and triggers innate immune signaling. TRIM5α also mediates the autophagic degradation of target proteins via TRIMosome formation. We previously showed that TRIM5α promotes Epstein-Barr virus (EBV) Rta ubiquitination and attenuates EBV lytic progression. In this study, we sought to elucidate whether TRIM5α can interact with and induce the degradation of EBV capsid proteins. Glutathione S-transferase (GST) pulldown and immunoprecipitation assays were conducted to identify interacting proteins, and mutants were generated to investigate key binding domains and ubiquitination sites. Results showed that TRIM5α binds directly with BORF1, an EBV capsid protein with a nuclear localization signal (NLS) that enables the transport of EBV capsid proteins into the host nucleus to facilitate capsid assembly. TRIM5α promotes BORF1 ubiquitination, which requires the surface patch region in the TRIM5α PRY/SPRY domain. TRIM5α expression also decreases the stability of BORF1(6KR), a mutant with all lysine residues mutated to arginine. However, chloroquine treatment restores the stability of BORF1(6KR), suggesting that TRIM5α destabilizes BORF1 via direct recognition of its substrate for autophagic degradation. These results reveal novel insights into the antiviral impact of TRIM5α beyond retroviruses.
Modulating the Activity of Androgen Receptor for Treating Breast Cancer
Authors: You Chan-Ping , Tsoi Ho , Man Ellen P. S. , Leung Man-Hong , Khoo Ui-Soon
Published: December 2022

The androgen receptor (AR) is a steroid hormone receptor widely detected in breast cancer. Evidence suggests that the AR might be a tumor suppressor in estrogen receptor alpha-positive (ERα+ve) breast cancer but a tumor promoter in estrogen receptor alpha-negative (ERα-ve) breast cancer. Modulating AR activity could be a potential strategy for treating breast cancer. For ERα+ve breast cancer, activation of the AR had been demonstrated to suppress the disease. In contrast, for ERα-ve breast cancer, blocking the AR could confer better prognosis to patients. These studies support the feasibility of utilizing AR modulators as anti-cancer drugs for different subtypes of breast cancer patients. Nevertheless, several issues still need to be addressed, such as the lack of standardization in the determination of AR positivity and the presence of AR splice variants. In future, the inclusion of the AR status in the breast cancer report at the time of diagnosis might help improve disease classification and treatment decision, thereby providing additional treatment strategies for breast cancer.
Crystallization Pathways of FABr-PbBr2-DMF and FABr-PbBr2-DMSO Systems: The Comprehensive Picture of Formamidinium-Based Low-Dimensional Perovskite-Related Phases and Intermediate Solvates
Authors: Fateev Sergey A. , Marchenko Ekaterina I. , Shatilova Alexandra S. , Khrustalev Victor N. , Goodilin Eugene A. , Tarasov Alexey B.
Published: December 2022

In this study, we systematically investigated the phase diversity and crystallization pathways of the FABr excessive regions of two ternary systems of FABr-PbBr2-DMF and FABr-PbBr2-DMSO (where FA+—formamidinium cations, DMF—dimethylformamide and DMSO—dimethyl sulfoxide solvents). In these systems, a new FA3PbBr5 phase with a structure containing chains of vertex-connected PbBr6 octahedra is discovered, and its crystal structure is refined. We experimentally assess fundamental information on differences in the mechanisms of crystallization process in FABr-PbBr2-DMF and FABr-PbBr2-DMSO systems and determine possible pathways of crystallization of hybrid perovskites. We show that intermediate solvate phases are not observed in the system with DMF solvent, while a number of crystalline solvates tend to form in the system with DMSO at various amounts of FABr excess.
Photoprocesses in Derivatives of 1,4- and 1,3-Diazadistyryldibenzenes
Authors: Atabekyan Levon S. , Freidzon Alexandra Y. , Ionov Dmitry S. , Nuriev Vyacheslav N. , Medved’ko Alexey V. , Vatsadze Sergey Z. , Gromov Sergey P. , Chibisov Alexander K.
Published: December 2022

Photoprocesses in 1,4-diazadistyrylbenzene (1) and 1,3-diazadistyrylbenzene derivative (2) diperchlorates in MeCN were studied by absorption, luminescence, and kinetic laser spectroscopies. For compound 1, trans-cis-photoisomerization and intersystem crossing to a triplet state are observed. For compound 2, photoelectrocyclization is suggested. Quantum chemical calculations of diazadistyrylbenzene structures in the ground and excited states were carried out. The schemes for photoreactions were proposed.
Super-Resolution Microscopy to Study Interorganelle Contact Sites
Authors: Nieto-Garai Jon Ander , Olazar-Intxausti June , Anso Itxaso , Lorizate Maier , Terrones Oihana , Contreras Francesc-Xabier
Published: December 2022

Interorganelle membrane contact sites (MCS) are areas of close vicinity between the membranes of two organelles that are maintained by protein tethers. Recently, a significant research effort has been made to study MCS, as they are implicated in a wide range of biological functions, such as organelle biogenesis and division, apoptosis, autophagy, and ion and phospholipid homeostasis. Their composition, characteristics, and dynamics can be studied by different techniques, but in recent years super-resolution fluorescence microscopy (SRFM) has emerged as a powerful tool for studying MCS. In this review, we first explore the main characteristics and biological functions of MCS and summarize the different approaches for studying them. Then, we center on SRFM techniques that have been used to study MCS. For each of the approaches, we summarize their working principle, discuss their advantages and limitations, and explore the main discoveries they have uncovered in the field of MCS.
Water-Soluble Carbon Nanotube Enhances Gossypol Production in Cotton Cell Suspension Culture
Authors: Dixit Sameer , Shukla Akanchha , Upadhyay Santosh Kumar , Verma Praveen Chandra
Published: December 2022

Plant secondary metabolites are well-recognized medicinally important compounds. Gossypol is an important plant secondary metabolite with several medicinal properties. Carbon nanotubes (CNTs) are allotropes of carbon with diverse applicability in chemical, physical, and biological sciences due to their high surface area. The current study demonstrates the enhancement of gossypol production in cotton cell suspension culture in culture media supplemented with water-soluble carbon nanotubes. The fresh and dry weights of cotton cell suspension culture grown in MS media with 20 µg/mL CNTs were, respectively, 1.9 and 2.13 fold higher than in control MS media after one month. The net enhancement of gossypol production in MS media supplemented with 20 µg/mL CNTs was 2.47 fold higher than the control. Confocal and SEM imaging showed the presence CNTs on the cell surface, which mediated the formation of extra channels that resulted in high biomass production in cotton cell suspension culture. The gossypol produced by this cell suspension culture showed antiproliferative activity against the prostate cancer cell line. Thus, this study demonstrated a new method for enhanced gossypol production, which can prove beneficial for the production of other plant-based biological active compounds.
Effect of Probiotics on Tenebrio molitor Larval Development and Resistance against the Fungal Pathogen Metarhizium brunneum
Authors: Dahal Sabina , Jensen Annette Bruun , Lecocq Antoine
Published: December 2022

In recent years, the yellow mealworm (Tenebrio molitor L.) has demonstrated its potential as a mass-produced edible insect for food and feed. However, challenges brought on by pathogens in intensive production systems are unavoidable and require the development of new solutions. One potential solution is the supplementation of probiotics in the insect’s diet to obtain the double benefits of improved growth and enhanced immune response. The aim of this study was to evaluate the effects of diet-based probiotic supplementation on T. molitor larval survival, growth, and resistance against a fungal pathogen. Three probiotic strains, namely Pediococcus pentosacceus KVL-B19-01 isolated from T. molitor and two commercialized strains for traditional livestock, Enterococcus faecium 669 and Bacillus subtilis 597, were tested. Additionally, when larvae were 9 weeks old, a pathogen challenge experiment was conducted with the fungus Metarhizium brunneum. Results showed that both P. pentosaceus and E. faecium improved larval growth and larval survival following fungal exposure compared to the non-supplemented control diet. Since B. subtilis did not improve larval performance in terms of either development or protection against M. brunneum, this study suggests the need for further research and evaluation of probiotic strains and their modes of action when considered as a supplement in T. molitor‘s diet.
Diversity but Not Overall Abundance of Moths and Butterflies (Insecta: Lepidoptera) Decreases around Two Arctic Polluters
Authors: Kozlov Mikhail V. , Zverev Vitali , Zvereva Elena L.
Published: December 2022

Alarming reports on the rapid decline of insects during the past decades call for the exploration of potential drivers of this process. Here, we test the hypothesis that the overall abundance and diversity of moths and butterflies (Lepidoptera) decrease under the impact of industrial pollution in the fragile arctic environment. For this purpose, experienced collectors netted adult Lepidoptera at five tundra sites located 0.5 to 45.3 km from the ore-roasting plant in Zapolyarnyy and at five forest sites located 1.4 to 37.8 km from the copper–nickel smelter at Nikel, in the Murmansk region of Russia. The analysis of the 100 samples collected from 2003 to 2008 and containing 2312 individuals of 122 species revealed that the diversity of Lepidoptera declined significantly near both of these polluters due to both decreases in species richness and changes in the abundance of individual species, whereas the overall abundance of moths and butterflies was independent of the pollution load. These patterns did not differ between Nikel and Zapolyarnyy, and they were consistent with patterns previously found near the copper–nickel smelter at Monchegorsk. The abundances of Lepidoptera species showed variable changes along pollution gradients, from significantly negative to significantly positive, but individual species showed similar density changes around these three polluters. Disproportional increases in the abundance of a few pollution-tolerant species change the community structure and explain why the overall abundance of moths and butterflies does not decline even in localities experiencing extreme loads of sulphur dioxide and heavy metals.
Socio-Cultural Factors Influencing the Perception and Management of Meningitis among Older Patients and Their Caregivers
Authors: Mahmoud Kafayat , Issah Moshood , Esiaka Darlingtina
Published: December 2022

Limited studies have investigated the socio-cultural factors influencing the management and control of Meningococcal Meningitis among older adults in Northern Nigeria. This study explored the lived experiences of older individuals with Meningococcal Meningitis and relationships with their caregivers in the Kaiama Local Government Area of Kwara State, Nigeria. Twenty (20) Meningococcal Meningitis patients aged 65+, their caregivers, and three (3) traditional healers were purposely selected for in-depth interviews. Results show that some older adults believed that their health conditions were caused by supernatural forces, thereby influencing the scope and type of care they receive. For such participants, traditional treatment options are fundamental for addressing the root causes of their ailment. Few participants mentioned that their health conditions were caused by excessive heat in their community and were more likely to consider biomedical treatments as the most effective for diagnosing, treating, and managing the ailment. Additionally, Meningococcal Meningitis might have caused physical, cognitive, and psychological frailties and impairments among the older patients, compelling family caregivers to support the older adult patients in their homes. We discuss the need for a policy that would benefit both those who care for older adults and the older adults themselves.
The Role of Combination Therapy with α-Blockers and Hexanic Extract of Serenoa repens in the Treatment of LUTS/BPH
Authors: De Nunzio Cosimo , Salonia Andrea , Gacci Mauro , Ficarra Vincenzo
Published: December 2022

The hexanic extract of Serenoa repens (HESr) has been in use for decades as an effective, safe and well-tolerated therapy for relieving bothersome lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH). This manuscript gives an overview of HESr as monotherapy for LUTS/BPH treatment and focuses on the currently available literature investigating the possible clinical benefits of HESr combination therapy with α-blockers. Combination therapy of HESr with α-blockers has been gaining significant interest in recent years, as an increasing body of evidence shows the beneficial pharmacological effects that HESr treatment can add to standard first-line treatment with α-blockers. By reducing persistent Prostatic Inflammatory Status (PIS), commonly present in LUTS/BPH patients, HESr complements the relaxation of prostate smooth muscle induced by α-blockers, thus providing additional symptom relief. Data suggest that patients harbouring PIS and having a specific clinical profile might especially benefit from the combination therapy. Future therapeutic efforts may take advantage of more personalised strategies for LUTS/BPH management.
Adiponectin Is a Contributing Factor of Low Appendicular Lean Mass in Older Community-Dwelling Women: A Cross-Sectional Study
Authors: Teixeira Leonardo , dos Santos Jousielle , Parentoni Adriana , Lima Liliana , Duarte Tamiris , Brant Franciane , Neves Camila , Pereira Fabiana , Avelar Núbia , Danielewicz Ana , Leopoldino Amanda , Costa Sabrina , Arrieiro Arthur , Soares Luana , Prates Ana , Nobre Juliana , de Carvalho Bastone Alessandra , de Oliveira Vinicius , Oliveira Murilo , Scheidt Figueiredo Pedro , Costa Henrique , Amaral Mendonça Vanessa , Taiar Redha , Rodrigues Lacerda Ana
Published: December 2022

inflammaging is a chronic, sterile, low-grade inflammation that develops with advanced age in the absence of overt infection and may contribute to the pathophysiology of sarcopenia, a progressive and generalized skeletal muscle disorder. Furthermore, a series of biomarkers linked to sarcopenia occurrence have emerged. To aid diagnostic and treatment strategies for low muscle mass in sarcopenia and other related conditions, the objective of this work was to investigate potential biomarkers associated with appendicular lean mass in community-dwelling older women. This is a cross-sectional study with 71 older women (75 ± 7 years). Dual-energy X-ray absorptiometry was used to assess body composition. Plasmatic blood levels of adipokines (i.e., adiponectin, leptin, and resistin), tumor necrosis factor (TNF) and soluble receptors (sTNFr1 and sTNFr2), interferon (INF), brain-derived neurotrophic factor (BDNF), and interleukins (IL-2, IL-4, IL-5, IL-6, IL-8, and IL-10) were determined by enzyme-linked immunosorbent assay. Older women with low muscle mass showed higher plasma levels of adiponectin, sTNFr1, and IL-8 compared to the regular muscle mass group. In addition, higher adiponectin plasma levels explained 14% of the lower appendicular lean mass. High adiponectin plasmatic blood levels can contribute to lower appendicular lean mass in older, community-dwelling women.
Lifestyle Factors and Their Influence on Rheumatoid Arthritis: A Narrative Review
Authors: Schäfer Christoph , Keyßer Gernot
Published: December 2022

In recent years, a possible association of lifestyle factors with rheumatoid arthritis (RA) has attracted increasing public interest. The aim of this review is to provide an overview of the extent and the limitations of current evidence regarding lifestyle factors and RA. The PubMed medical database was screened for epidemiological and prospective studies investigating the contribution of lifestyle factors to the development and the course of the disease. Large epidemiological studies have identified smoking, unhealthy diet and adiposity, as well as a low educational level and low socioeconomic status, as factors that increase the incidence of RA. In addition, several lifestyle habits influence the response of RA to antirheumatic drugs. Among others, smoking, obesity and poor physical activity are associated with a worse treatment outcome. Methodological problems often impair firm conclusions with respect to the causal role of these factors in the risk and the course of RA. However, current evidence is sufficient to recommend a healthy diet, the prevention of obesity, the cessation of smoking and the maintenance of a high level of physical activity to support the effectivity of modern antirheumatic medication.
Efficacy of Fu’s Subcutaneous Needling in Treating Soft Tissue Pain of Knee Osteoarthritis: A Randomized Clinical Trial
Authors: Chiu Po-En , Fu Zhonghua , Sun Jian , Jian Guan-Wei , Li Te-Mao , Chou Li-Wei
Published: December 2022

Purpose: Fu’s subcutaneous needling (FSN) is a new acupuncture technique that produces a long-lasting effect in soft-tissue injuries. In patients with degenerative knee osteoarthritis (OA), myofascial trigger points (MTrPs) are common in the lower-limb muscles. In this randomized clinical trial, we evaluated the immediate, 1-week and 2-week effectiveness of FSN therapy in the treatment of degenerative knee OA. Patients and methods: We randomly divided 32 patients with knee OA into the FSN group (mean age: 65.73 ± 6.79 years) or the transcutaneous electrical nerve stimulation (TENS) group (mean age: 62.81 ± 5.72 years). The pressure pain threshold (PPT) and tissue hardness (TH) of the muscle and tendon attachment sites, knee range of motion, and physical ability (average walking speed) were measured. The subjective pain intensity index, Western Ontario and McMaster Universities OA Index (WOMAC), and Lequesne index were used to determine the efficacy of FSN on MTrP-induced soft-tissue pain compared with that of TENS. Results: A significantly greater improvement in pain qualities in the VAS (p < 0.05) was found in the FSN group. Moreover, in muscle and tendon qualities (including PPT and TH), a significant difference in the PPT of the quadriceps muscle (p < 0.05) was also observed among the immediate treatments in the FSN group. As for the functional index questionnaire assessment, the FSN group exhibited significant improvements among the immediate, 1-week and 2-week efficacies in terms of WOMAC (p < 0.05) and Lequesne index scores (p < 0.05). Conclusion: FSN was effective in treating soft-tissue pain in degenerative knee OA in terms of alleviating pain, strengthening walking ability, and improving overall functional performance. Pain relief was the primary benefit of FSN and a significant correlation between pain relief and knee joint mobility improvement was found. Trial registration: ClinicalTrials.gov Protocol Registration and Results System (registration number: NCT04356651).
Secretoneurin as a Novel Biomarker of Cardiovascular Episodes: Are We There Yet? A Narrative Review
Authors: Plášek Jiří , Lazárová Marie , Dodulík Jozef , Šulc Patrik , Stejskal David , Švagera Zdeněk , Všianský František , Václavík Jan
Published: December 2022

Secretoneurin (SN) is a 33 amino-acid evolutionary conserved neuropeptide from the chromogranin peptide family. SN’s main effects may be cardioprotective and are believed to be mediated through its inhibition of calmodulin-dependent kinase II (CaMKII), which influences intracellular calcium handling. SN inhibition of CaMKII suppresses calcium leakage from the sarcoplasmic reticulum through the ryanodine receptor. This action may reduce the risk of ventricular arrhythmias and calcium-dependent remodelling in heart failure. SN is also involved in reducing the intracellular reactive oxygen species concentration, modulating the immune response, and regulating the cell cycle, including apoptosis. SN can predict mortality in different disease states, beyond the classical risk factors and markers of myocardial injury. Plasma SN levels are elevated soon after an arrhythmogenic episode. In summary, SN is a novel biomarker with potential in cardiovascular medicine, and probably beyond.
Sandwich (Amnion/Conjunctival-Limbal Autograft/Amnion) Transplantation for Recurrent Pterygium with Restrictive Strabismus
Authors: Wong Hang , Wang Jia-Song , Du Ya-Li , Xie Hua-Tao , Zhang Ming-Chang
Published: December 2022

(1) Background: This study aimed to evaluate the clinical outcome of Sandwich (Amnion/Conjunctival-Limbal Autograft/Amnion) transplantation for recurrent pterygium with restrictive strabismus. (2) Methods: This retrospective study included 11 eyes in 11 patients diagnosed with recurrent pterygium with restrictive strabismus who received sandwich transplantation. The outcomes were measured by pterygium recurrence, best-corrected visual acuity, esotropia (prism diopters), and treatment complications. (3) Results: Eleven patients (six males, five females) had a mean age of 60.5 (range 36–80) years. The previously received pterygium excision surgery number was 1.8 ± 1.02 (range 1–4). The mean follow-up period was 19.9 ± 8.41 (range 12–36) months. All patients had a restriction of abduction in the previously operated eye, causing esotropia in the primary position. Pre-operative esotropia was 17.2 (range 10–30) prims diopter (PD). Five eyes (45.5%) had symblepharon before surgery. All patients were orthotropic until the last follow-up. Symblepharon was released in all eyes. Free ocular motility was present in all eyes. No donor site scar formation, scleral melt, or corneal ulcer was noted. (4) Conclusions: Sandwich transplantation for recurrent pterygium with restrictive strabismus is safe and effective.
Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury
Authors: Jo Jungmin , Kim Jung-Yeon , Leem Jaechan
Published: December 2022

Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers, but its application is often limited due to complications such as acute kidney injury (AKI). Orexins are hypothalamic neuropeptides that modulate the sleep-wake cycle, neuroendocrine function, and the autonomic nervous system. Emerging evidence suggests that orexin A (OXA) has anti-inflammatory and neuroprotective effects in animal models of neuroinflammatory diseases of the central nervous system. However, the effect of OXA on kidney diseases has not been examined. Here, we investigated whether OXA has a protective effect in a murine model of cisplatin-induced AKI. Intraperitoneal administration of OXA ameliorated renal dysfunction, and histological abnormalities in mice injected with cisplatin. OXA inhibited cisplatin-induced oxidative stress through the modulation of prooxidant and antioxidant enzymes. This peptide reduced apoptotic cell death by inhibiting the p53-mediated pathway in mice injected with cisplatin. OXA also alleviated cisplatin-induced cytokine production and macrophage infiltration into injured kidneys. Taken together, these results showed that OXA ameliorates cisplatin-induced AKI via antioxidant, anti-apoptotic, and anti-inflammatory actions. This peptide could be a potential therapeutic agent for cisplatin-induced AKI.
New Developments, Challenges and Open Questions in Diagnosis and Treatment of Gestational Diabetes Mellitus
Authors: Linder Tina , Dressler-Steinbach Iris , Tura Andrea , Göbl Christian
Published: December 2022

The prevalence of gestational diabetes mellitus (GDM) is increasing alongside a rising maternal age at conception, an increasing number of people making unhealthy lifestyle choices and, especially, an increasing pregestational body weight [...]
Predictors of Total Hip Arthroplasty Following Pediatric Surgical Treatment of Developmental Hip Dysplasia at 20-Year Follow-Up
Authors: Young Ernest , Regan Christina , Milbrandt Todd A. , Grigoriou Emmanouil , Shaughnessy William J. , Stans Anthony A. , Larson A. Noelle
Published: December 2022

Long-term outcomes of surgical treatment for pediatric developmental dysplasia of the hip (DDH) are not well defined. The purpose of this study was to report long-term radiographic and clinical outcomes, survivorship free of total hip arthroplasty (THA), and predictors of subsequent THA following childhood treatment of DDH. This study was a single-institution retrospective review of hips treated for DDH with closed or open reduction at a minimum 10-year follow-up. 107 patients (119 hips) were included with a mean patient age of 3.3 years at childhood treatment. At mean 30.5 years follow-up, 24 hips had undergone THA (20%). Mean patient age at time of THA was 33.5 years. None of the hips treated with closed reduction alone required THA, whereas 8 hips treated with open reduction (25%) underwent THA. Hips with patient age > 4 years at the time of treatment had lower survivorship at 35 years follow-up (50% vs. 85%; p < 0.001). Additionally, femoral osteotomy (OR 2.0, p < 0.001), and previous treatment elsewhere (27% vs. 16%; p < 0.01) were associated with subsequent THA. Early referral and appropriate intervention may prove important, as age and prior treatment were predictive of subsequent THA.
Extraoral Root-End Resection May Promote Pulpal Revascularization in Autotransplanted Mature Teeth—A Retrospective Study
Authors: Rugani Petra , Kirnbauer Barbara , Mischak Irene , Ebeleseder Kurt , Jakse Norbert
Published: December 2022

Tooth germ autotransplantation of open apices of the teeth exhibits high pulpal healing rates, whereas that of mature permanent teeth normally causes irreversible pulpal necrosis. Extraoral root-end resection (EORER) during transplantation may promote pulpal revascularization (PRV) in transplanted mature teeth and reduce endodontic treatment requirement. This study compared the primary outcomes of survival rates, PRV, and root resorption and determined relevant confounders in autotransplanted mature and immature teeth. The medical charts of consecutive patients who underwent tooth autotransplantation between January 2017 and March 2021 were evaluated. Teeth with a documented follow-up of at least 1 year were included. During the study period, 59 teeth were transplanted in 44 patients. Overall, 2 teeth were excluded owing to missing data; 57 teeth were analyzed, including 25 mature teeth additionally treated with EORER. After a mean follow-up of 21.2 ± 16.1 months, no significant differences in primary outcomes were detected. Fifty-five teeth remained in situ (96.5%), and radiological signs of root resorption were detected in 9/57 teeth (15.8%). PRV was positive in 54/57 teeth (94.7%). Surgical duration and PRV failure were significantly associated with high incidences of root resorption. Mature teeth autotransplantation with EORER yielded similar results to immature teeth autotransplantation and is a feasible treatment option. Long surgery and failed revascularization increased root resorption rates. More factors should be evaluated in larger trials with longer observation periods.
Prognostic Value of Histological and Immunohistochemical Data in Diabetic Foot Ulcers
Authors: Koreyba Konstantin , Silina Ekaterina , Tsyplakov Dmitry , Litvitskiy Petr , Manturova Natalia , Balkizov Zalim , Achar Raghu Ram , Raju Nithya Rani , Stupin Victor
Published: December 2022

Diabetic foot ulcers are an extremely urgent medical and social problem throughout the world. The purpose of this study was to analyse the histological and immunohistochemical features of tissues and cells of different sections of wounds taken during the primary surgical treatment of chronic wounds in patients with diabetic foot syndrome with favourable and unfavourable outcomes. Material and methods. A clinical prospective observational study of the treatment outcomes of fifty-three patients with diabetic foot ulcers hospitalized twice in one specialized centre over the course of the year was conducted. The analysis of histological and immunohistochemical data of the tissues of the edges and the centre of the ulcer taken during the primary surgical treatment was performed. While performing histological analyses of wound tissues, special attention was given to the determination of cellular characteristics of leukocyte-necrotic masses, granulation tissue, and loose and dense connective tissue. Immunohistochemistry was performed using a set of monoclonal antibodies, allowing verification of neutrophilic leukocytes, fibroblasts, and endothelial cells. Results. Unfavourable outcomes (amputation, reamputation, death from cardiovascular diseases, nonhealing ulcer within a year) were registered in 52.8% of cases. Uniform distribution of neutrophils and endothelial cell fibroblasts in all parts of the wound was recorded in patients with a favourable outcome. An unfavourable outcome was predetermined by the uneven content of these cells with a significant increase in neutrophilic leukocytosis in the bottom of the wounds, as well as a significant decrease in the number of fibroblasts and endotheliocytes in the centre of the wounds. Conclusions: The datasets obtained during primary surgical treatment are extremely informative to predict the outcome of the treatment of diabetic foot ulcers and indicate more active surgical strategies with the potential to reduce the treatment time, increase its effectiveness, and eventually make the treatment cost-effective.
Pain Course after Total Knee Arthroplasty within a Standardized Pain Management Concept: A Prospective Observational Study
Authors: Schindler Melanie , Schmitz Stephanie , Reinhard Jan , Jansen Petra , Grifka Joachim , Benditz Achim
Published: December 2022

Background: Joint replacement surgeries have been known to be some of the most painful surgical procedures. Therefore, the options for postoperative pain management are of great importance for patients undergoing total knee arthroplasty (TKA). Despite successful surgery, up to 30% of the patients are not satisfied after the operation. The aim of this study is to assess pain development within the first 4 weeks after TKA in order to gain a better understanding and detect possible influencing factors. Methods: A total of 103 patients were included in this prospective cohort study. Postoperative pain was indicated using a numeric rating scale (NRS). Furthermore, demographic data and perioperative parameters were correlated with the reported postoperative pain. Results: The evaluation of postoperative pain scores showed a constant decrease in the first postoperative week (mean NRS score of 5.8 on day 1 to a mean NRS score of 4.6 on day 8). On day 9, the pain increased again. Thereafter, a continuous decrease in pain intensity from day 10 on was noted (continuous to a mean NRS score of 3.0 on day 29). A significant association was found between postoperative pain intensity and gender, body mass index (BMI), and preoperative leg axis. Conclusions: The increasing pain score after the first postoperative week is most likely due to more intensive mobilization and physiotherapy in the rehabilitation department. Patients that were female, had a low BMI, and a preoperative valgus leg axis showed a significantly higher postoperative pain scores. Pain management should consider these results in the future to improve patient satisfaction in the postoperative course after TKA.
State of the Art in the Role of Endovascular Embolization in the Management of Brain Arteriovenous Malformations—A Systematic Review
Authors: Pinkiewicz Miłosz , Pinkiewicz Mateusz , Walecki Jerzy , Zawadzki Michał
Published: December 2022

As a significant cause of intracerebral hemorrhages, seizures, and neurological decline, brain arteriovenous malformations (bAVMs) are a rare group of complex vascular lesions with devastating implications for patients’ quality of life. Although the concerted effort of the scientific community has improved our understanding of bAVM biology, the exact mechanism continues to be elucidated. Furthermore, to this day, due to the high heterogeneity of bAVMs as well as the lack of objective data brought by the lack of evaluative and comparative studies, there is no clear consensus on the treatment of this life-threatening and dynamic disease. As a consequence, patients often fall short of obtaining the optimal treatment. Endovascular embolization is an inherent part of multidisciplinary bAVM management that can be used in various clinical scenarios, each with different objectives. Well-trained neuro-interventional centers are proficient at curing bAVMs that are smaller than 3 cm; are located superficially in noneloquent areas; and have fewer, larger, and less tortuous feeding arteries. The transvenous approach is an emerging effective and safe technique that potentially offers a chance to cure previously untreatable bAVMs. This review provides the state of the art in all aspects of endovascular embolization in the management of bAVMs.