bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Acute Lower Back Pain Associated with Heart Rate Variability Changes? A Protocol for Systematic Reviews
Authors: Sanchis-Soler Gema , Tortosa-Martinez Juan , Sebastia-Amat Sergio , Chulvi-Medrano Ivan , Cortell-Tormo Juan Manuel
Published: February 2024

Acute lower back pain (ALBP) is an extremely common musculoskeletal problem. ALBP consists of a sudden onset of short-duration pain in the lower back. However, repeated attacks can make the pain chronic. It can be measured through a self-report scale as well as through physical and physiological evaluations. Heart Rate Variability (HRV) has been used to evaluate the body’s response to pain. However, to the best of our knowledge, no clear consensus has been reached regarding the relationship between both variables and on an optimal protocol for ALBP evaluation based on HRV. The objective of this review is to analyze the relationship and effectiveness of HRV as an instrument for measuring ALBP. Furthermore, we consider the influence of different types of interventions in this relationship. The protocol of this review was previously recorded in the International Prospective Register of Systematic Reviews (number CRD42023437160). The PRISMA guidelines for systematic reviews and PubMed, WOS and Scopus databases are employed. Studies with samples of adults with ALBP are included. This study sets out a systematic review protocol to help identify the relationship between HRV and ALBP. Understanding this relationship could help in designing early detection or action protocols that alleviate ALBP.
The Concept of Neuromuscular Repatterning in Dancers: A Systematic Review
Authors: Gómez-Lozano Sebastián , Zhang Ningyi , Armstrong Ross , León Kiko , Kelly-Lahon Clare , Sánchez-González Pedro , Martínez-González-Moro Ignacio , Hurtado-Guapo María Antonia , Vargas-Macías Alfonso
Published: February 2024

Repatterning is a term that can be used in different fields, including genetics, molecular biology, neurology, psychology, or rehabilitation. Our aim is to identify the key concept of neuromuscular repatterning in somatic training programmes for dancers. A systematic search of eight databases was conducted using the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. The Quality Assessment Tool for Quantitative Studies and the Oxford Levels of Evidence scales were used. The search yielded 1218 results, of which 5 met the inclusion criteria. Five studies (n = 5) were related to psychosomatic health (n = 5), two studies highlighted integration and inter-articular connectivity in movement (n = 2), four studies investigated the neurological component of alignment and efficiency in dance practice (n = 4), and two studies investigated self-confidence (n = 2). Five studies (n = 5) used imagery based on the anatomical and physiological experience of body systems as the main analytical method. Four studies (n = 4) used developmental movement through Bartenieff fundamentals as the main technique for this methodology. Developmental movement and imagery are two methodologies strongly connected to the concept of neuromuscular repatterning in somatic training programmes for dancers. The acquisition of further quantitative experimental or quasi-experimental studies is warranted to better define the level of improvement or impact of neuromuscular repatterning in dancers.
Integrative Medicine for Cancer-Related Pain: A Narrative Review
Authors: Samuels Noah , Ben-Arye Eran
Published: February 2024

Cancer-related pain (C-RP) is a prevalent and debilitating concern among patients with cancer, with conventional treatments limited in their ability to provide adequate relief, and by the adverse effects associated with their use. Complementary and integrative medicine (CIM) modalities have been shown to be potentially effective and safe for the treatment of pain and related symptoms, when used in conjunction with conventional medications and under medical supervision. An increasing number of oncology centers provide CIM within their conventional supportive and palliative care service, in an “Integrative Oncology” (IO) setting. A large body of clinical research, including systematic reviews and guidelines such as those published in 2022 by the Society for Integrative Oncology (SIO), in collaboration with the American Society for Clinical Oncology (ASCO), support the use of some CIM modalities for C-RP and related concerns. These include acupuncture for general and peri-operative/procedural pain, as well as aromatase inhibitor-associated arthralgia (AIA); reflexology or acupressure for pain during systemic therapy for cancer; hypnosis for procedural pain or pain due to diagnostic workup; and massage for pain experienced by patients during palliative and hospice care. Further research is needed, within both randomized control trials and pragmatic non-controlled studies which are more reflective of the real-life IO setting. This review summarizes the evidence supporting the use of CIM for C-RP; the analgesic mechanism of the modalities presented; and the challenges facing IO researchers, as well as the implementation of the 2022 SIO-ASCO guideline recommendations.
Assessing the Hands-on Usability of the Healthy Jeart App Specifically Tailored to Young Users
Authors: Roldán-Ruiz Ana Maria , Merino-Godoy María-de-los-Ángeles , Peregrín-Rubio Antonio , Yot-Dominguez Carmen , da Costa Emília Isabel Martins Teixeira
Published: February 2024

Background: The widespread adoption of mobile devices by adolescents underscores the potential to harness these tools to instill healthy habits into their daily lives. An exemplary manifestation of this initiative is the Healthy Jeart app, crafted with the explicit goal of fostering well-being. Methodology: This study, framed within an applied investigation, adopts an exploratory and descriptive approach, specifically delving into the realm of user experience analysis. The focus of this research is a preliminary examination aimed at understanding users’ perceived usability of the application. To glean insights, a comprehensive questionnaire was administered to 101 teenagers, seeking their evaluations on various usability attributes. The study took place during 2022. Results: The findings reveal a considerable consensus among users regarding the evaluated usability aspects. However, the areas for improvement predominantly revolve around managing the information density, particularly for a subset of end users grappling with overwhelming content. Additionally, recommendations are put forth to streamline the confirmation process for user suggestions and comments. Conclusion: This analysis illuminates both the strengths of the app and areas ripe for refinement, paving the way for a more user-centric and efficacious Healthy Jeart application.
Can I Leave the Past Behind? Associations between Childhood Abuse and Adult Psychopathology
Authors: Nagar Maayan , Nakash Ora
Published: February 2024

Background: Research consistently shows that abuse during childhood is related to adult psychopathology. Information regarding childhood abuse is frequently collected from either previous documentation or from participants’ self-reports. Objective: In the current study, we combined information on reports of childhood abuse from several informants (patients, treating clinicians, and independent interviewer), as well as diagnostic assessments of adult patients based on independent interviewer assessments based on structured diagnostic interviews (SCID) and clinician judgments, to better examine the association between exposure to abuse during childhood and adult psychopathology. Participants and Setting: A convenience sample of patients in community mental health and hospital-based clinics (N = 170) and their clinicians (N = 80) participated in the study. Methods: Patients and clinicians completed the Clinical Data Form. Patients also completed the Childhood Trauma Questionnaire. Independent interviewer-assessed patients and completed the Familial Experiences Interview. Clinicians completed a diagnostic assessment of their patients based on clinical judgment. Independent interviewers completed the Structured Clinical Interview (SCID). Results: Reports of exposure to physical, emotional, and sexual abuse during childhood from all informants correlated with the treating clinician’s diagnosis of borderline personality disorder (BPD; r range 0.23–0.37, p < 0.05), but not with SCID diagnosis of BPD. Clinician and SCID diagnosis of post-traumatic stress disorder (PTSD) correlated with patient and interviewer reports of childhood sexual abuse (r range 0.23–0.30, p < 0.05), but there were no correlations with treating clinician’s reports of sexual abuse. Conclusions: The association between BPD and childhood abuse is consistent across different ratings and measurements. The study raises questions of the ability of a structured interview to accurately capture BPD and highlights the connection between sexual abuse and PTSD, and the importance of treating clinicians’ examination of childhood sexual abuse among their patients.
In Vitro Propagation Journey of Ornamental Gladiolus (Gladiolus Species): A Systematic Review Analysis Based on More Than 50 Years Research
Authors: Kumar Mukesh , Chaudhary Veena , Sirohi Ujjwal , Singh Jitender , Yadav Manoj Kumar , Prakash Satya , Kumar Arvind , Kumar Vipin , Pal Virendra , Chauhan Chetan , Kaushik Krishna , Shukla Devanshu , Motla Rishubh , Kumar Satendra , Malik Sunil
Published: February 2024

Traditional gladiolus propagation methods are now supplemented with in vitro propagation to meet the demands of modern floriculture in terms of quick production of disease-free, quality planting material. Due to virus infections, vegetative propagation in gladiolus in the field is slow, and is a serious concern in the propagation of gladiolus. In vitro propagation provides an enormous increase in propagation rate and the ability to produce disease-free plant material. Numerous elements, including cultivars, explant type, size of explants, position of explants on medium, plant growth regulators and certain additives, incubation conditions, and sub-culturing time, all have a significant impact on in vitro clonal propagation of gladiolus plants as well as the development of in vitro cormel efficiency. There are certain obstacles and challenges that arise in the in vitro development of plants and the cormels of gladiolus. However, numerous studies and review reports on gladiolus for in vitro propagation have been reported, but very little is known about the factors influencing gladiolus’ in vitro effectiveness. In the present review, we focused on and analyzed research data accumulated over 50 years on diverse strategies for in vitro propagation such as direct, indirect organogenesis, and somatic embryogenesis, as well as various factors such as physical, nutritional, and hormonal influences on in vitro propagation, in vitro cormel formation efficiency, difficulties that arise, and new insights into in vitro development in gladiolus from the available literature worldwide. Future possibilities for further improvement in the in vitro propagation of ornamental gladiolus are also discussed. The current review provides insight into a comprehensive protocol for gladiolus in vitro propagation and emphasizes the importance of continuously advancing tissue culture techniques and factors influencing the in vitro efficiency towards improving in vitro plantlets and cormels in gladiolus (Gladiolus spp.).
The Use of Cubic Smoothing Spline Models for Predicting Early Fruit Size in ‘Keenan’ Valencia (Citrus sinensis L. Osbeck) Oranges
Authors: Khurshid Tahir , Braysher Ben , Khurshid Jane Elizabeth
Published: February 2024

Fruit size is an important factor for the sale of fruit in fresh markets. Fruit size prediction early in the growing season would help with planning harvest operations, administering marketing strategies and an advance determination of the proportion of fruit that will be suitable for certain size classes. Fruit diameter growth of ‘Keenan’ Valencia oranges was measured over five consecutive growing seasons (2014–2018) during Stage II (cell enlargement) and Stage III (maturation) periods between January and October. Fruits were randomly selected and tagged from around the tree canopy to record the fruit diameter at fortnightly intervals until harvest. The data were used to develop a fruit size prediction model using the cubic smoothing splines technique. Results indicated that from the fruit growth patterns, an accurate prediction of the final fruit size and distribution were possible during the early Stage II fruit development phase, 6–7 months ahead of the final harvest. It was concluded that fruit size must be 66 mm in diameter by 30 March to attain a fruit size > 77 mm at harvest. This model was tested in 2019 with an accuracy of 97% in predicting fruit size distribution harvest across three size classes.
Expanding Karst Groundwater Tracing Techniques: Incorporating Population Genetic and Isotopic Data to Enhance Flow-Path Characterization
Authors: Tobin Benjamin W. , Miller Benjamin V. , Niemiller Matthew L. , Erhardt Andrea M.
Published: February 2024

Karst aquifers are unique among groundwater systems because of variable permeability and flow-path organization changes resulting from dissolution processes. Over time, changes in flow-path connectivity complicate interpretations of conduit network evolution in karst hydrogeology. Natural and artificial tracer techniques have long provided critical information for protecting karst aquifers and understanding the potential impacts on ecosystems and human populations. Conventional tracer methods are useful in karst hydrogeologic studies for delineating flow paths and defining recharge, storage, and discharge properties. However, these methods only provide snapshots of the current conditions and do not provide sufficient information to understand the changes in interconnection or larger-scale evolution of flow paths in the aquifer over time. With advances in population genetics, it is possible to assess population connectivity, which may provide greater insights into complex groundwater flow paths. To assess this potential, we combined the more traditional approaches collected in this and associated studies, including artificial (dye) and natural (geochemistry, isotopes, and discharge) tracers, with the population genetic data of a groundwater crustacean to determine whether these data can provide insights into seasonal or longer changes in connections between conduits. The data collected included dye trace, hydrographs, geochemistry, and asellid isopod (Caecidotea bicrenenta) population genetics in Fern Cave, AL, USA, a 25 km-long cave system. Combined, these data show the connections between two separate flow paths during flood events as the downstream populations of isopods belonging to the same subpopulation were measured in both systems. Additionally, the sub-populations found in higher elevations of the cave suggest a highly interconnected unsaturated zone that allows for genetic movement in the vadose zone. Although upstream populations show some similarities in genetics, hydrologic barriers, in the form of large waterfalls, likely separate populations within the same stream.
The Relationship between Patients’ Demands and Workplace Violence among Healthcare Workers: A Multilevel Look Focusing on the Moderating Role of Psychosocial Working Conditions
Authors: Balducci Cristian , Rafanelli Chiara , Menghini Luca , Consiglio Chiara
Published: February 2024

Workplace violence against healthcare workers is a widespread phenomenon with very severe consequences for the individuals affected and their organizations. The role played by psychosocial working conditions in healthcare workers’ experiences of violence from patients and their family members has received relatively scant attention. In the present study, we investigated the idea that psychosocial working conditions (workload, job control, supervisor support, and team integration), by affecting the well-being and job performance of healthcare workers, play a critical role in the relationship between patients’ demands and the escalation of workplace violence. Specifically, we tested the hypothesis that psychosocial working conditions moderate the relationship between patients’ demands and workplace violence. Participants were 681 healthcare workers distributed in 55 work groups of three public healthcare facilities in Italy. Multilevel analysis showed significant interactions between patients’ demands and each of the investigated psychosocial factors on workplace violence, which in all the cases were in the expected direction. The results suggest that improving the quality of the psychosocial work environment in which healthcare workers operate may be a critical aspect in the prevention of workplace violence.
Prescription of Opioid Analgesics for Chronic Non-Cancer Pain in Germany despite Contraindications: Administrative Claims Data Analysis
Authors: Niemann Anja , Schrader Nils F. , Speckemeier Christian , Abels Carina , Blase Nikola , Weitzel Milena , Neumann Anja , Riederer Cordula , Nadstawek Joachim , Straßmeir Wolfgang , Wasem Jürgen , Neusser Silke
Published: February 2024

In Germany, long-term opioid treatment (L-TOT) for chronic non-tumor pain (CNTP) is discussed as not being performed according to the German guideline on L-TOT for CNTP. In the present analysis, the occurrence and predictors of inappropriate care/overuse in a cohort of German insureds with L-TOT for CNTP by the presence of a contraindication with concurrent opioid analgesic (OA) therapy were investigated. We also analyzed whether prescribing physicians themselves diagnosed a contraindication. The retrospective cohort study was based on administrative claims data from a German statutory health insurance. Eight contraindication groups were defined based on the German guideline. Logistic regressions were performed in order to identify predictors for OA prescriptions despite contraindications. The possible knowledge of the prescribing physician about the contraindication was approximated by analyzing concordant unique physician identification numbers of OA prescriptions and contraindication diagnoses. A total of 113,476 individuals (75% female) with a mean age of 72 years were included. The most common documented contraindications were primary headaches (8.7%), severe mood disorders (7.7%) and pain in somatoform disorders (4.5%). The logistic regressions identified a younger age, longer history of OA therapy, opioid related psychological problems, and outpatient psychosomatic primary care as positive predictors for all contraindication groups.
Investigation of Gastrointestinal Toxicities Associated with Concurrent Abdominal Radiation Therapy and the Tyrosine Kinase Inhibitor Sunitinib in a Mouse Model
Authors: Prebble Amber R. , Latka Bailey , Burdekin Braden , Leary Del , Harris Mac , Regan Daniel , Boss Mary-Keara
Published: February 2024

Tyrosine kinase inhibitors (TKIs) may be combined with radiation therapy (RT) to enhance tumor control; however, increased incidences of gastrointestinal (GI) toxicity have been reported with this combination. We hypothesize that toxicity is due to compromised intestinal healing caused by inhibition of vascular repair and proliferation pathways. This study explores underlying tissue toxicity associated with abdominal RT and concurrent sunitinib in a mouse model. Four groups of CD-1 mice were treated with 12 Gy abdominal RT, oral sunitinib, abdominal RT + sunitinib, or sham treatment. Mice received oral sunitinib or the vehicle via gavage for 14 days. On day 7, mice were irradiated with 12 Gy abdominal RT or sham treated. Mice were euthanized on day 14 and intestinal tract was harvested for semiquantitative histopathologic evaluation and immunohistochemical quantification of proliferation (Ki67) and vascular density (CD31). Non-irradiated groups had stable weights while abdominal irradiation resulted in weight loss, with mice receiving RT + SUN having greater weight loss than mice receiving RT alone. Semiquantitative analysis showed significant increases in inflammation in irradiated groups. The difference in the density of CD31+ cells was significantly increased in RT alone compared to SUN alone. Ki67+ density was not significant. In summary, we identify a lack of angiogenic response in irradiated GI tissues when abdominal RT is combined with a TKI, which may correlate with clinical toxicities seen in canine and human patients receiving combined treatment.
AAV-RPGR Gene Therapy Rescues Opsin Mislocalisation in a Human Retinal Organoid Model of RPGR-Associated X-Linked Retinitis Pigmentosa
Authors: Sladen Paul E. , Naeem Arifa , Adefila-Ideozu Toyin , Vermeule Tijmen , Busson Sophie L. , Michaelides Michel , Naylor Stuart , Forbes Alexandria , Lane Amelia , Georgiadis Anastasios
Published: February 2024

Variants within the Retinitis Pigmentosa GTPase regulator (RPGR) gene are the predominant cause of X-Linked Retinitis Pigmentosa (XLRP), a common and severe form of inherited retinal disease. XLRP is characterised by the progressive degeneration and loss of photoreceptors, leading to visual loss and, ultimately, bilateral blindness. Unfortunately, there are no effective approved treatments for RPGR-associated XLRP. We sought to investigate the efficacy of RPGRORF15 gene supplementation using a clinically relevant construct in human RPGR-deficient retinal organoids (ROs). Isogenic RPGR knockout (KO)-induced pluripotent stem cells (IPSCs) were generated using established CRISPR/Cas9 gene editing methods targeting RPGR. RPGR-KO and isogenic wild-type IPSCs were differentiated into ROs and utilised to test the adeno associated virus (AAV) RPGR (AAV-RPGR) clinical vector construct. The transduction of RPGR-KO ROs using AAV-RPGR successfully restored RPGR mRNA and protein expression and localisation to the photoreceptor connecting cilium in rod and cone photoreceptors. Vector-derived RPGR demonstrated equivalent levels of glutamylation to WT ROs. In addition, treatment with AAV-RPGR restored rhodopsin localisation within RPGR-KO ROs, reducing mislocalisation to the photoreceptor outer nuclear layer. These data provide mechanistic insights into RPGRORF15 gene supplementation functional potency in human photoreceptor cells and support the previously reported Phase I/II trial positive results using this vector construct in patients with RPGR-associated XLRP, which is currently being tested in a Phase III clinical trial.
Milk Antiviral Proteins and Derived Peptides against Zoonoses
Authors: Santos Isabel , Silva Mariana , Grácio Madalena , Pedroso Laurentina , Lima Ana
Published: February 2024

Milk is renowned for its nutritional richness but also serves as a remarkable reservoir of bioactive compounds, particularly milk proteins and their derived peptides. Recent studies have showcased several robust antiviral activities of these proteins, evidencing promising potential within zoonotic viral diseases. While several publications focus on milk’s bioactivities, antiviral peptides remain largely neglected in reviews. This knowledge is critical for identifying novel research directions and analyzing potential nutraceuticals within the One Health context. Our review aims to gather the existing scientific information on milk-derived antiviral proteins and peptides against several zoonotic viral diseases, and their possible mechanisms. Overall, in-depth research has increasingly revealed them as a promising and novel strategy against viruses, principally for those constituting a plausible pandemic threat. The underlying mechanisms of the bioactivity of milk’s proteins include inhibiting viral entry and attachment to the host cells, blocking replication, or even viral inactivation via peptide–membrane interactions. Their marked versatility and effectiveness stand out compared to other antiviral peptides and can support future research and development in the post-COVID-19 era. Overall, our review helps to emphasize the importance of potentially effective milk-derived peptides, and their significance for veterinary and human medicines, along with the pharmaceutical, nutraceutical, and dairy industry.
Hematopoietic Prostaglandin D Synthase Is Increased in Mast Cells and Pericytes in Autopsy Myocardial Specimens from Patients with Duchenne Muscular Dystrophy
Authors: Hamamura Kengo , Yoshida Yuya , Oyama Kosuke , Li Junhao , Kawano Shimpei , Inoue Kimiko , Toyooka Keiko , Yamadera Misaki , Matsunaga Naoya , Matsumura Tsuyoshi , Aritake Kosuke
Published: February 2024

The leading cause of death for patients with Duchenne muscular dystrophy (DMD), a progressive muscle disease, is heart failure. Prostaglandin (PG) D2, a physiologically active fatty acid, is synthesized from the precursor PGH2 by hematopoietic prostaglandin D synthase (HPGDS). Using a DMD animal model (mdx mice), we previously found that HPGDS expression is increased not only in injured muscle but also in the heart. Moreover, HPGDS inhibitors can slow the progression of muscle injury and cardiomyopathy. However, the location of HPGDS in the heart is still unknown. Thus, this study investigated HPGDS expression in autopsy myocardial samples from DMD patients. We confirmed the presence of fibrosis, a characteristic phenotype of DMD, in the autopsy myocardial sections. Additionally, HPGDS was expressed in mast cells, pericytes, and myeloid cells of the myocardial specimens but not in the myocardium. Compared with the non-DMD group, the DMD group showed increased HPGDS expression in mast cells and pericytes. Our findings confirm the possibility of using HPGDS inhibitor therapy to suppress PGD2 production to treat skeletal muscle disorders and cardiomyopathy. It thus provides significant insights for developing therapeutic drugs for DMD.
Modification of Preservative Fluids with Antioxidants in Terms of Their Efficacy in Liver Protection before Transplantation
Authors: Ostróżka-Cieślik Aneta
Published: February 2024

Transplantation is currently the only effective treatment for patients with end-stage liver failure. In recent years, many advanced studies have been conducted to improve the efficiency of organ preservation techniques. Modifying the composition of the preservation fluids currently used may improve graft function and increase the likelihood of transplantation success. The modified fluid is expected to extend the period of safe liver storage in the peri-transplantation period and to increase the pool of organs for transplantation with livers from marginal donors. This paper provides a literature review of the effects of antioxidants on the efficacy of liver preservation fluids. Medline (PubMed), Scopus, and Cochrane Library databases were searched using a combination of MeSH terms: “liver preservation”, “transplantation”, “preservation solution”, “antioxidant”, “cold storage”, “mechanical perfusion”, “oxidative stress”, “ischemia-reperfusion injury”. Studies published up to December 2023 were included in the analysis, with a focus on publications from the last 30 years. A total of 45 studies met the inclusion criteria. The chemical compounds analyzed showed mostly bioprotective effects on hepatocytes, including but not limited to multifactorial antioxidant and free radical protective effects. It should be noted that most of the information cited is from reports of studies conducted in animal models, most of them in rodents.
Toxicity Tolerance in the Carcinogenesis of Environmental Cadmium
Authors: Cirovic Aleksandar , Satarug Soisungwan
Published: February 2024

Cadmium (Cd) is an environmental toxicant of worldwide public health significance. Diet is the main non-workplace Cd exposure source other than passive and active smoking. The intestinal absorption of Cd involves transporters for essential metals, notably iron and zinc. These transporters determine the Cd body burden because only a minuscule amount of Cd can be excreted each day. The International Agency for Research on Cancer listed Cd as a human lung carcinogen, but the current evidence suggests that the effects of Cd on cancer risk extend beyond the lung. A two-year bioassay demonstrated that Cd caused neoplasms in multiple tissues of mice. Also, several non-tumorigenic human cells transformed to malignant cells when they were exposed to a sublethal dose of Cd for a prolonged time. Cd does not directly damage DNA, but it influences gene expression through interactions with essential metals and various proteins. The present review highlights the epidemiological studies that connect an enhanced risk of various neoplastic diseases to chronic exposure to environmental Cd. Special emphasis is given to the impact of body iron stores on the absorption of Cd, and its implications for breast cancer prevention in highly susceptible groups of women. Resistance to cell death and other cancer phenotypes acquired during Cd-induced cancer cell transformation, under in vitro conditions, are briefly discussed. The potential role for the ZnT1 efflux transporter in the cellular acquisition of tolerance to Cd cytotoxicity is highlighted.
Obstructive Sleep Apnea-Associated Intermittent Hypoxia-Induced Immune Responses in Males, Pregnancies, and Offspring
Authors: Song Ruolin , Baker Tracy L. , Watters Jyoti J. , Kumar Sathish
Published: February 2024

Obstructive sleep apnea (OSA), a respiratory sleep disorder associated with cardiovascular diseases, is more prevalent in men. However, OSA occurrence in pregnant women rises to a level comparable to men during late gestation, creating persistent effects on both maternal and offspring health. The exact mechanisms behind OSA-induced cardiovascular diseases remain unclear, but inflammation and oxidative stress play a key role. Animal models using intermittent hypoxia (IH), a hallmark of OSA, reveal several pro-inflammatory signaling pathways at play in males, such as TLR4/MyD88/NF-κB/MAPK, miRNA/NLRP3, and COX signaling, along with shifts in immune cell populations and function. Limited evidence suggests similarities in pregnancies and offspring. In addition, suppressing these inflammatory molecules ameliorates IH-induced inflammation and tissue injury, providing new potential targets to treat OSA-associated cardiovascular diseases. This review will focus on the inflammatory mechanisms linking IH to cardiovascular dysfunction in males, pregnancies, and their offspring. The goal is to inspire further investigations into the understudied populations of pregnant females and their offspring, which ultimately uncover underlying mechanisms and therapeutic interventions for OSA-associated diseases.
Impact of Glucagon-Like Peptide 1 Receptor Agonists on Biochemical Markers of the Initiation of Atherosclerotic Process
Authors: Hachuła Marcin , Kosowski Michał , Ryl Sabina , Basiak Marcin , Okopień Bogusław
Published: February 2024

Atherosclerosis stands out as one of the leading causes of global mortality. The inflammatory response against vascular wall components plays a pivotal role in the atherogenic process. The initiation of this process is notably driven by oxidized low-density lipoprotein (oxLDL) and a range of pro-inflammatory cytokines, with interleukin-1β (Il-1β) and tumor necrosis factor α (TNFα) emerging as particularly significant in the early stages of atherosclerotic plaque formation. In recent years, researchers worldwide have been diligently exploring innovative therapeutic approaches for metabolic diseases, recognizing their impact on the atherogenesis process. Our study aimed to investigate the influence of glucagon-like peptide 1 receptor agonists (GLP-1RA) on cytokine concentrations associated with the initiation of atherosclerotic plaque formation in a group of patients with type 2 diabetes and dyslipidemia. The study encompassed 50 subjects aged 41–81 (mean: 60.7), all diagnosed with type 2 diabetes, dyslipidemia and confirmed atherosclerosis based on B-mode ultrasound. Following a 180-day treatment with dulaglutide or semaglutide, we observed a statistically significant reduction in biochemical markers (oxLDL, TNFα and Il-1β) associated with the initiation of the atherosclerotic process (p < 0.001) within our study group. In addition to the already acknowledged positive effects of GLP-1RA on the metabolic parameters of treated patients, these drugs demonstrated a notable reduction in proinflammatory cytokine concentrations and may constitute an important element of therapy aimed at reducing cardiovascular risk.
Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages
Authors: Suleimanov Shakir K. , Efremov Yuri M. , Klyucherev Timofey O. , Salimov Emin L. , Ragimov Aligeydar A. , Timashev Peter S. , Vlasova Irina I.
Published: February 2024

Macrophages are the major players and orchestrators of inflammatory response. Expressed proteins and secreted cytokines have been well studied for two polar macrophage phenotypes—pro-inflammatory M1 and anti-inflammatory regenerative M2, but little is known about how the polarization modulates macrophage functions. In this study, we used biochemical and biophysical methods to compare the functional activity and mechanical properties of activated human macrophages differentiated from monocyte with GM-CSF (M0_GM) and M-CSF (M0_M) and polarized into M1 and M2 phenotypes, respectively. Unlike GM-CSF, which generates dormant cells with low activity, M-CSF confers functional activity on macrophages. M0_M and M2 macrophages had very similar functional characteristics—high reactive oxygen species (ROS) production level, and higher phagocytosis and survival compared to M1, while M1 macrophages showed the highest radical-generating activity but the lowest phagocytosis and survival among all phenotypes. All phenotypes decreased their height upon activation, but only M1 and M2 cells increased in stiffness, which can indicate a decrease in the migration ability of these cells and changes in their interactions with other cells. Our results demonstrated that while mechanical properties differ between M0 and polarized cells, all four phenotypes of monocyte-derived macrophages differ in their functional activities, namely in cytokine secretion, ROS production, and phagocytosis. Within the broad continuum of human macrophages obtained in experimental models and existing in vivo, there is a diversity of phenotypes with varying combinations of both markers and functional activities.
Protein and Polysaccharide-Based Optical Materials for Biomedical Applications
Authors: Riviello Gianna , Connor Brendan , McBrearty Jake , Rodriguez Gianna , Hu Xiao
Published: February 2024

Recent advances in biomedical research, particularly in optical applications, have sparked a transformative movement towards replacing synthetic polymers with more biocompatible and sustainable alternatives. Most often made from plastics or glass, these materials ignite immune responses from the body, and their production is based on environmentally harsh oil-based processes. Biopolymers, including both polysaccharides and proteins, have emerged as a potential candidate for optical biomaterials due to their inherent biocompatibility, biodegradability, and sustainability, derived from their existence in nature and being recognized by the immune system. Current extraction and fabrication methods for these biomaterials, including thermal drawing, extrusion and printing, mold casting, dry-jet wet spinning, hydrogel formations, and nanoparticles, aim to create optical materials in cost-effective and environmentally friendly manners for a wide range of applications. Present and future applications include optical waveguides and sensors, imaging and diagnostics, optical fibers, and waveguides, as well as ocular implants using biopolymers, which will revolutionize these fields, specifically their uses in the healthcare industry.
Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts
Authors: Hilliard Brendan A. , Amin Mamta , Popoff Steven N. , Barbe Mary F.
Published: February 2024

A role for substance P has been proposed in musculoskeletal fibrosis, with effects mediated through transforming growth factor beta (TGFβ). We examined the in vitro effects of substance P on proliferation, collagen secretion, and collagen deposition in rat primary dermal fibroblasts cultured in medium containing 10% fetal bovine serum, with or without TGFβ. In six-day cultures, substance P increased cell proliferation at concentrations from 0.0002 to 100 nM. TGFβ increased proliferation at concentrations from 0.0002 to 2 pg/mL, although higher concentrations inhibited proliferation. Substance P treatment alone at concentrations of 100, 0.2, and 0.00002 nM did not increase collagen deposition per cell, yet when combined with TGFβ (5 ng/mL), increased collagen deposition compared to TGFβ treatment alone. Substance P treatment (100 nM) also increased smooth muscle actin (SMA) expression at 72 h of culture at a level similar to 5 ng/mL of TGFβ; only TGFβ increased SMA at 48 h of culture. Thus, substance P may play a role in potentiating matrix deposition in vivo when combined with TGFβ, although this potentiation may be dependent on the concentration of each factor. Treatments targeting substance P may be a viable strategy for treating fibrosis where both substance P and TGFβ play roles.
Human-Induced Pluripotent Stem Cells in Plastic and Reconstructive Surgery
Authors: Hadzimustafic Nina , D’Elia Andrew , Shamoun Valentina , Haykal Siba
Published: February 2024

A hallmark of plastic and reconstructive surgery is restoring form and function. Historically, tissue procured from healthy portions of a patient’s body has been used to fill defects, but this is limited by tissue availability. Human-induced pluripotent stem cells (hiPSCs) are stem cells derived from the de-differentiation of mature somatic cells. hiPSCs are of particular interest in plastic surgery as they have the capacity to be re-differentiated into more mature cells, and cultured to grow tissues. This review aims to evaluate the applications of hiPSCs in the plastic surgery context, with a focus on recent advances and limitations. The use of hiPSCs and non-human iPSCs has been researched in the context of skin, nerve, vasculature, skeletal muscle, cartilage, and bone regeneration. hiPSCs offer a future for regenerated autologous skin grafts, flaps comprised of various tissue types, and whole functional units such as the face and limbs. Also, they can be used to model diseases affecting tissues of interest in plastic surgery, such as skin cancers, epidermolysis bullosa, and scleroderma. Tumorigenicity, immunogenicity and pragmatism still pose significant limitations. Further research is required to identify appropriate somatic origin and induction techniques to harness the epigenetic memory of hiPSCs or identify methods to manipulate epigenetic memory.
Oxime-Linked Peptide–Daunomycin Conjugates as Good Tools for Selection of Suitable Homing Devices in Targeted Tumor Therapy: An Overview
Authors: Mező Gábor , Gomena Jacopo , Ranđelović Ivan , Dókus Endre , Kiss Krisztina , Pethő Lilla , Schuster Sabine , Vári Balázs , Vári-Mező Diána , Lajkó Eszter , Polgár Lívia , Kőhidai László , Tóvári József , Szabó Ildikó
Published: February 2024

Chemotherapy is still one of the main therapeutic approaches in cancer therapy. Nevertheless, its poor selectivity causes severe toxic side effects that, together with the development of drug resistance in tumor cells, results in a limitation for its application. Tumor-targeted drug delivery is a possible choice to overcome these drawbacks. As well as monoclonal antibodies, peptides are promising targeting moieties for drug delivery. However, the development of peptide–drug conjugates (PDCs) is still a big challenge. The main reason is that the conjugates have to be stable in circulation, but the drug or its active metabolite should be released efficiently in the tumor cells. For this purpose, suitable linker systems are needed that connect the drug molecule with the homing peptide. The applied linker systems are commonly categorized as cleavable and non-cleavable linkers. Both the groups possess advantages and disadvantages that are summarized briefly in this manuscript. Moreover, in this review paper, we highlight the benefit of oxime-linked anthracycline–peptide conjugates in the development of PDCs. For instance, straightforward synthesis as well as a conjugation reaction proceed in excellent yields, and the autofluorescence of anthracyclines provides a good tool to select the appropriate homing peptides. Furthermore, we demonstrate that these conjugates can be used properly in in vivo studies. The results indicate that the oxime-linked PDCs are potential candidates for targeted tumor therapy.
Mitochondrial Unfolded Protein Response Gene Clpp Is Required for Oocyte Function and Female Fertility
Authors: Ergun Yagmur , Imamoglu Aysegul Gizem , Cozzolino Mauro , Demirkiran Cem , Basar Murat , Garg Akanksha , Yildirim Raziye Melike , Seli Emre
Published: February 2024

Mitochondrial unfolded protein stress response (mtUPR) plays a critical role in regulating cellular and metabolic stress response and helps maintain protein homeostasis. Caseinolytic peptidase P (CLPP) is one of the key regulators of mtUPR and promotes unfolded protein degradation. Previous studies demonstrated that global deletion of Clpp resulted in female infertility, whereas no impairment was found in the mouse model with targeted deletion of Clpp in cumulus/granulosa cells. These results suggest the need to delineate the function of Clpp in oocytes. In this study, we aimed to further explore the role of mtUPR in female reproductive competence and senescence using a mouse model. Oocyte-specific targeted deletion of Clpp in mice resulted in female subfertility associated with metabolic and functional abnormalities in oocytes, thus highlighting the importance of CLPP-mediated protein homeostasis in oocyte competence and reproductive function.
A Novel Tendon Injury Model, Induced by Collagenase Administration Combined with a Thermo-Responsive Hydrogel in Rats, Reproduces the Pathogenesis of Human Degenerative Tendinopathy
Authors: Vidal Laura , Lopez-Garzon Maria , Venegas Vanesa , Vila Ingrid , Domínguez David , Rodas Gil , Marotta Mario
Published: February 2024

Patellar tendinopathy is a common clinical problem, but its underlying pathophysiology remains poorly understood, primarily due to the absence of a representative experimental model. The most widely used method to generate such a model is collagenase injection, although this method possesses limitations. We developed an optimized rat model of patellar tendinopathy via the ultrasound-guided injection of collagenase mixed with a thermo-responsive Pluronic hydrogel into the patellar tendon of sixty male Wistar rats. All analyses were carried out at 3, 7, 14, 30, and 60 days post-injury. We confirmed that our rat model reproduced the pathophysiology observed in human patients through analyses of ultrasonography, histology, immunofluorescence, and biomechanical parameters. Tendons that were injured by the injection of the collagenase–Pluronic mixture exhibited a significant increase in the cross-sectional area (p < 0.01), a high degree of tissue disorganization and hypercellularity, significantly strong neovascularization (p < 0.01), important changes in the levels of types I and III collagen expression, and the organization and presence of intra-tendinous calcifications. Decreases in the maximum rupture force and stiffness were also observed. These results demonstrate that our model replicates the key features observed in human patellar tendinopathy. Collagenase is evenly distributed, as the Pluronic hydrogel prevents its leakage and thus, damage to surrounding tissues. Therefore, this model is valuable for testing new treatments for patellar tendinopathy.
Ctp1 and Yhm2: Two Mitochondrial Citrate Transporters to Support Metabolic Flexibility of Saccharomyces cerevisiae
Authors: Assalve Graziana , Lunetti Paola , Zara Vincenzo , Ferramosca Alessandra
Published: February 2024

Differently from higher eukaryotic cells, in the yeast Saccharomyces cerevisiae there are two mitochondrial carrier proteins involved in the transport of citrate: Ctp1 and Yhm2. Very little is known about the physiological role of these proteins. Wild-type and mutant yeast strains deleted in CTP1 and YHM2 were grown in media supplemented with a fermentable (glucose) or a nonfermentable (ethanol) carbon source. To assess changes in Ctp1 and Yhm2 mRNA expression levels, real-time PCR was performed after total RNA extraction. In the wild-type strain, the metabolic switch from the exponential to the stationary phase is associated with an increase in the expression level of the two citrate transporters. In addition, the results obtained in the mutant strains suggest that the presence of a single citrate transporter can partially compensate for the absence of the other. Ctp1 and Yhm2 differently contribute to fermentative and respiratory metabolism. Moreover, the two mitochondrial carriers represent a link between the Krebs cycle and the glyoxylate cycle, which play a key role in the metabolic adaptation strategies of S. cerevisiae.
OsACA9, an Autoinhibited Ca2+-ATPase, Synergically Regulates Disease Resistance and Leaf Senescence in Rice
Authors: Wang Xinyu , Wang Ziyao , Lu Yiduo , Huang Jiani , Hu Zhuoer , Lou Junlei , Fan Xinyue , Gu Zhimin , Liu Pengcheng , Ma Bojun , Chen Xifeng
Published: February 2024

Calcium (Ca2+) is a versatile intracellular second messenger that regulates several signaling pathways involved in growth, development, stress tolerance, and immune response in plants. Autoinhibited Ca2+-ATPases (ACAs) play an important role in the regulation of cellular Ca2+ homeostasis. Here, we systematically analyzed the putative OsACA family members in rice, and according to the phylogenetic tree of OsACAs, OsACA9 was clustered into a separated branch in which its homologous gene in Arabidopsis thaliana was reported to be involved in defense response. When the OsACA9 gene was knocked out by CRISPR/Cas9, significant accumulation of reactive oxygen species (ROS) was detected in the mutant lines. Meanwhile, the OsACA9 knock out lines showed enhanced disease resistance to both rice bacterial blight (BB) and bacterial leaf streak (BLS). In addition, compared to the wild-type (WT), the mutant lines displayed an early leaf senescence phenotype, and the agronomy traits of their plant height, panicle length, and grain yield were significantly decreased. Transcriptome analysis by RNA-Seq showed that the differentially expressed genes (DEGs) between WT and the Osaca9 mutant were mainly enriched in basal immune pathways and antibacterial metabolite synthesis pathways. Among them, multiple genes related to rice disease resistance, receptor-like cytoplasmic kinases (RLCKs) and cell wall-associated kinases (WAKs) genes were upregulated. Our results suggest that the Ca2+-ATPase OsACA9 may trigger oxidative burst in response to various pathogens and synergically regulate disease resistance and leaf senescence in rice.