bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetrahydrobiopterin (BH4) Supplementation Prevents the Cardiorenal Effects of Diabetes in Mice by Reducing Oxidative Stress, Inflammation and Fibrosis
Authors: Novoa Ulises , Soto Karen , Valdés Cristian , Villaseñor Jorge , Treuer Adriana V. , González Daniel R.
Published: October 2022

Background: The effects of diabetes on the cardiovascular system as well as in the kidney are profound, which include hypertrophy and fibrosis. Diabetes also induces oxidative stress, at least in part due to the uncoupling of nitric oxide synthase (NOS); this is a shift in NO production toward superoxide production due to reduced levels of the NOS cofactor tetrahydrobiopterin (BH4). With this in mind, we tested the hypothesis that BH4 supplementation may prevent the development of diabetic cardiomyopathy and nephropathy. Methods: Diabetes was induced in Balb/c mice with streptozotocin. Then, diabetic mice were divided into two groups: one group provided with BH4 (sapropterin) in drinking water (daily doses of 15 mg/kg/day, during eight weeks) and the other that received only water. A third group of normoglycemic mice that received only water were used as the control. Results: Cardiac levels of BH4 were increased in mice treated with BH4 (p = 0.0019). Diabetes induced cardiac hypertrophy, which was prevented in the group that received BH4 (p < 0.05). In addition, hypertrophy was evaluated as cardiomyocyte cross-sectional area. This was reduced in diabetic mice that received BH4 (p = 0.0012). Diabetes induced cardiac interstitial fibrosis that was reduced in mice that received BH4 treatment (p < 0.05). We also evaluated in the kidney the impact of BH4 treatment on glomerular morphology. Diabetes induced glomerular hypertrophy compared with normoglycemic mice and was prevented by BH4 treatment. In addition, diabetic mice presented glomerular fibrosis, which was prevented in mice that received BH4. Conclusions: These results suggest that chronic treatment with BH4 in mice ameliorates the cardiorenal effects of diabetes,, probably by restoring the nitroso–redox balance. This offers a possible new alternative to explore a BH4-based treatment for the organ damage caused by diabetes.
Stereotactic Body Radiotherapy (SBRT) of Pancreatic Cancer—A Critical Review and Practical Consideration
Authors: Burkoň Petr , Trna Jan , Slávik Marek , Němeček Radim , Kazda Tomáš , Pospíšil Petr , Dastych Milan , Eid Michal , Novotný Ivo , Procházka Tomáš , Vrzal Miroslav
Published: October 2022

Pancreatic cancer is the third leading cause of cancer death in the developed world and is predicted to become the second by 2030. A cure may be achieved only with surgical resection of an early diagnosed disease. Surgery for more advanced disease is challenging and can be contraindicated for many reasons. Neoadjuvant therapy may improve the probability of achieving R0 resection. It consists of systemic treatment followed by radiation therapy applied concurrently or sequentially with cytostatics. A novel approach to irradiation, stereotactic body radiotherapy (SBRT), has the potential to improve treatment results. SBRT can deliver higher doses of radiation to the tumor in only a few treatment fractions. It has attracted significant interest for pancreatic cancer patients, as it is completed quickly, requires less time away from full-dose chemotherapy, and is well-tolerated than conventional radiotherapy. In this review, we aim to provide the reader with a basic overview of current evidence for SBRT indications in the treatment of pancreatic tumors. In the second part of the review, we focus on practical information with respect to SBRT treatment plan preparation the performance of such therapy. Finally, we discuss future directions related to the use of magnetic resonance linear accelerators.
Interplay between Partial EMT and Cisplatin Resistance as the Drivers for Recurrence in HNSCC
Authors: Ingruber Julia , Dudas Jozsef , Sprung Susanne , Lungu Bianca , Mungenast Felicitas
Published: October 2022

This study aims to investigate the role of partial epithelial to mesenchymal transition (pEMT)-related proteins in modulating Cisplatin resistance in head and neck squamous cell carcinoma (HNSCC). SCC-25 cells were pre-treated with TGF-beta1 followed by transient Krüppel-like Factor 4 (KLF4)-overexpression and Cisplatin treatment. Cell growth, cell morphological changes and cell migration were assessed using Juli BR live cell video-microscopy. In addition, Ki-67 and Slug immunostaining and follow-up image cytometric analysis of primary and recurrent HNSCC tumors were performed to evaluate the proliferation index (PI) and the EMT-like phenotype. We observed that proliferating and Slug-positive tumor cells expand after therapy in HNSCC. Subsequently, protein analysis revealed the stabilization of Slug, upregulation of Vimentin and phospho-p38 (p-p38) in Cisplatin-resistant SCC-25 cells. Moreover, KLF4-overexpression contributed to Cisplatin sensitivity by reduction of Slug at the protein level. This work strongly suggests that an pEMT-like pathway is activated in recurrent and Cisplatin-resistant HNSCC. Finally, stable KLF4-overexpression might sensitize HNSCC tumor cells for Cisplatin treatment.
Plasma Exchange May Enhance Antitumor Effects by Removal of Soluble Programmed Death-Ligand 1 and Extracellular Vesicles: Preliminary Study
Authors: Oya Kazumasa , Shen Larina Tzu-Wei , Maruo Kazushi , Matsusaka Satoshi
Published: October 2022

The antitumor effect of antibody-drug conjugates (ADC) is the main factor in achieving cures. Although the mechanism of tumor resistance to treatment is multifaceted, tumor-derived extracellular vesicles (T-EVs) have been implicated as contributing to the attenuation of ADC therapeutic efficacy. Thus, strategies to eliminate T-EVs are highly promising for overcoming drug resistance. Here we demonstrate plasma exchange therapy to remove T-EVs, decreasing their amount in vitro by 75%. Although trastuzumab emtansine (T-DM1) treatment alone was effective in our rat tumor model, the combination therapy of T-DM1 and T-EV filtration achieved early tumor shrinkage. Our results indicate that T-EV filtration plus ADC is a promising strategy for overcoming drug resistance.
Tumor HPV Status, Level of Regulatory T Cells and Macrophage Infiltration Predict up to 20-Year Non-Disease-Specific Survival in Oropharynx Squamous Cell Carcinoma Patients
Authors: Haave Hilde , Ljokjel Borghild , Lybak Helene , Moe Svein E. , Berge Jan E. , Vintermyr Olav K. , Helgeland Lars , Aarstad Hans J.
Published: October 2022

Oropharynx squamous cell carcinoma (OPSCC) is of special interest because human papilloma virus (HPV) and/or smoking cause this disease. Influxes of inflammatory cells into such tumors are known to vary with prognoses. Aims: To study whether the density of tumor-infiltrating T lymphocytes and tumor-infiltrating macrophages predicted general 20-year overall survival (OS), as well as OS with only disease-specific survival (DSS) patients included. Methods: Biopsies from patients treated for OPSCC (n = 180) were stained by immunohistochemistry and the tumor cell macrophage (CD68), pan T lymphocytes (CD3), and regulatory T lymphocytes (Foxp3) densities were determined. The HE-determined percentage of matured tumor cells and the rate of invasion were calculated, and stromal desmoplasia were performed. Tumor HPV presence was studied by PCR. Twenty-year OS and five-year DSS patients were determined. Results: Tumor HPV status strongly predicted survival. High tumor infiltration of CD3, Foxp3 and CD68-positive cells predicted better twenty-year OS, with and without HPV stratification. Foxp3 and CD68 levels predicted OS, and 20-year among DSS patients, primarily among HPV(+) patients. Tumor HE-derived variables did not predict such survival. Conclusions: Tumor HPV status, level of Foxp3 tumor-infiltrating lymphocytes and CD68 tumor-infiltrating macrophages predicted up to 20-year OS of both all patients and disease-specific survived patients.
Allergic Rhinitis: Pathophysiology and Treatment Focusing on Mast Cells
Authors: Zoabi Yara , Levi-Schaffer Francesca , Eliashar Ron
Published: October 2022

Allergic rhinitis (AR) is a common rhinopathy that affects up to 30% of the adult population. It is defined as an inflammation of the nasal mucosa, develops in allergic individuals, and is detected mostly by a positive skin-prick test. AR is characterized by a triad of nasal congestion, rhinorrhea, and sneezing. Mast cells (MCs) are innate immune system effector cells that play a pivotal role in innate immunity and modulating adaptive immunity, rendering them as key cells of allergic inflammation and thus of allergic diseases. MCs are typically located in body surfaces exposed to the external environment such as the nasal mucosa. Due to their location in the nasal mucosa, they are in the first line of defense against inhaled substances such as allergens. IgE-dependent activation of MCs in the nasal mucosa following exposure to allergens in a sensitized individual is a cardinal mechanism in the pathophysiology of AR. This review is a comprehensive summary of MCs’ involvement in the development of AR symptoms and how classical AR medications, as well as emerging AR therapies, modulate MCs and MC-derived mediators involved in the development of AR.
Conventional MRI-Derived Biomarkers of Adult-Type Diffuse Glioma Molecular Subtypes: A Comprehensive Review
Authors: Feraco Paola , Franciosi Rossana , Picori Lorena , Scalorbi Federica , Gagliardo Cesare
Published: October 2022

The introduction of molecular criteria into the classification of diffuse gliomas has added interesting practical implications to glioma management. This has created a new clinical need for correlating imaging characteristics with glioma genotypes, also known as radiogenomics or imaging genomics. Although many studies have primarily focused on the use of advanced magnetic resonance imaging (MRI) techniques for radiogenomics purposes, conventional MRI sequences remain the reference point in the study and characterization of brain tumors. A summary of the conventional imaging features of glioma molecular subtypes should be useful as a tool for daily diagnostic brain tumor management. Hence, this article aims to summarize the conventional MRI features of glioma molecular subtypes in light of the recent literature.
Vascular Calcification: In Vitro Models under the Magnifying Glass
Authors: Ceccherini Elisa , Cecchettini Antonella , Gisone Ilaria , Persiani Elisa , Morales Maria Aurora , Vozzi Federico
Published: October 2022

Vascular calcification is a systemic disease contributing to cardiovascular morbidity and mortality. The pathophysiology of vascular calcification involves calcium salt deposition by vascular smooth muscle cells that exhibit an osteoblast-like phenotype. Multiple conditions drive the phenotypic switch and calcium deposition in the vascular wall; however, the exact molecular mechanisms and the connection between vascular smooth muscle cells and other cell types are not fully elucidated. In this hazy landscape, effective treatment options are lacking. Due to the pathophysiological complexity, several research models are available to evaluate different aspects of the calcification process. This review gives an overview of the in vitro cell models used so far to study the molecular processes underlying vascular calcification. In addition, relevant natural and synthetic compounds that exerted anticalcifying properties in in vitro systems are discussed.
The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases
Authors: Tudorancea Ivona Maria , Ciorpac Mitică , Stanciu Gabriela Dumitrița , Caratașu Cătălin , Săcărescu Alina , Ignat Bogdan , Burlui Alexandra , Rezuș Elena , Creangă Ioana , Alexa-Stratulat Teodora , Tudorancea Ionuț , Tamba Bogdan Ionel
Published: October 2022

The endocannabinoid system (ECS) dynamically regulates many aspects of mammalian physiology. ECS has gained substantial interest since growing evidence suggests that it also plays a major role in several pathophysiological conditions due to its ability to modulate various underlying mechanisms. Furthermore, cannabinoids, as components of the cannabinoid system (CS), have proven beneficial effects such as anti-inflammatory, immunomodulatory, neuromodulatory, antioxidative, and cardioprotective effects. In this comprehensive review, we aimed to describe the complex interaction between CS and most common age-related diseases such as neuro-degenerative, oncological, skeletal, and cardiovascular disorders, together with the potential of various cannabinoids to ameliorate the progression of these disorders. Since chronic inflammation is postulated as the pillar of all the above-mentioned medical conditions, we also discuss in this paper the potential of CS to ameliorate aging-associated immune system dysregulation.
Iatrogenic Barotrauma in COVID-19-Positive Patients: Is It Related to the Pneumonia Severity? Prevalence and Trends of This Complication Over Time
Authors: Maggialetti Nicola , Piemonte Stefano , Sperti Emanuela , Inchingolo Francesco , Greco Sabrina , Lucarelli Nicola Maria , De Chirico Pierluigi , Lofino Stefano , Coppola Federica , Catacchio Claudia , Gravili Anna Maria , Sardaro Angela , Stabile Ianora Amato Antonio
Published: October 2022

COVID-19 has attracted worldwide attention ever since the first case was identified in Wuhan (China) in December 2019 and was classified, at a later time, as a public health emergency of international concern in January 2020 and as a pandemic in March 2020. The interstitial pneumonia caused by COVID-19 often requires mechanical ventilation, which can lead to pulmonary barotrauma. We assessed the relationship between pneumonia severity and the development of barotrauma in COVID-19-positive patients mechanically ventilated in an intensive care unit; we therefore analyzed the prevalence of iatrogenic barotrauma and its trends over time during the pandemic in COVID-19-positive patients undergoing mechanical ventilation compared to COVID-19-negative patients, making a distinction between different types of ventilation (invasive mechanical ventilation vs. noninvasive mechanical ventilation). We compared CT findings of pneumomediastinum and pneumothorax in 104 COVID-19-positive patients hospitalized in an intensive care unit and 101 COVID-19-negative patients undergoing mechanical ventilation in the period between October 2020 and December 2021. The severity of pneumonia was not directly correlated with the development of barotrauma. Furthermore, a higher prevalence of complications due to barotrauma was observed in the group of mechanically ventilated COVID-19-postive patients vs. COVID-19-negative patients. A higher rate of barotrauma was observed in subgroups of COVID-19-positive patients undergoing mechanical ventilation compared to those treated with invasive mechanical ventilation. The prevalence of barotrauma in COVID 19-positive patients showed a decreasing trend over the period under review. CT remains an essential tool in the early detection, diagnosis, and monitoring of the clinical course of SARS-CoV2 pneumonia; in evaluating the disease severity; and in the assessment of iatrogenic complications such as barotrauma pathology.
Model of Acute Liver Failure in an Isolated Perfused Porcine Liver—Challenges and Lessons Learned
Authors: Hefler Joshua , Hatami Sanaz , Thiesen Aducio , Olafson Carly , Durand Kiarra , Acker Jason , Karvellas Constantine J. , Bigam David L. , Freed Darren H. , Shapiro Andrew Mark James
Published: October 2022

Acute liver failure (ALF) is a rare but devastating disease associated with substantial morbidity and a mortality rate of almost 45%. Medical treatments, apart from supportive care, are limited and liver transplantation may be the only rescue option. Large animal models, which most closely represent human disease, can be logistically and technically cumbersome, expensive and pose ethical challenges. The development of isolated organ perfusion technologies, originally intended for preservation before transplantation, offers a new platform for experimental models of liver disease, such as ALF. In this study, female domestic swine underwent hepatectomy, followed by perfusion of the isolated liver on a normothermic machine perfusion device. Five control livers were perfused for 24 h at 37 °C, while receiving supplemental oxygen and nutrition. Six livers received toxic doses of acetaminophen given over 12 h, titrated to methemoglobin levels. Perfusate was sampled every 4 h for measurement of biochemical markers of injury (e.g., aspartate aminotransferase [AST], alanine aminotransferase [ALT]). Liver biopsies were taken at the beginning, middle, and end of perfusion for histological assessment. Acetaminophen-treated livers received a median dose of 8.93 g (8.21–9.75 g) of acetaminophen, achieving a peak acetaminophen level of 3780 µmol/L (3189–3913 µmol/L). Peak values of ALT (76 vs. 105 U/L; p = 0.429) and AST (3576 vs. 4712 U/L; p = 0.429) were not significantly different between groups. However, by the end of perfusion, histology scores were significantly worse in the acetaminophen treated group (p = 0.016). All acetaminophen treated livers developed significant methemoglobinemia, with a peak methemoglobin level of 19.3%, compared to 2.0% for control livers (p = 0.004). The development of a model of ALF in the ex vivo setting was confounded by the development of toxic methemoglobinemia. Further attempts using alternative agents or dosing strategies may be warranted to explore this setting as a model of liver disease.
Cancer as a Dysfunctional Immune Disorder: Pro-Tumor TH1-like Immune Response and Anti-Tumor THαβ Immune Response Based on the Complete Updated Framework of Host Immunological Pathways
Authors: Lee Yi-Hsin , Tsai Kuo-Wang , Lu Kuo-Cheng , Shih Li-Jane , Hu Wan-Chung
Published: October 2022

Host immunological pathways are delicate to cope with different types of pathogens. In this article, we divide immunological pathways into two groups: Immunoglobulin G-related eradicable immunities and Immunoglobulin A-related tolerable immunities. Once immune cells encounter an antigen, they can become anergic or trigger immune reactions. Immunoglobulin D B cells and γδ T cells are recognizing self-antigens to become anergic. Immunoglobulin M B cells and αβ T cells can trigger host immune reactions. Eradicable immune responses can be divided into four groups: TH1/TH2/TH22/THαβ (TH—T Helper cell groups). Tolerable immune responses can be divided into four groups: TH1-like/TH9/TH17/TH3. Four groups mean hosts can cope with four types of pathogens. Cancer is related to immune dysfunction. TH1-like immunity is pro-tumor immunity and THαβ is anti-tumor immunity. TH1-like immunity is the host tolerable immunity against intracellular micro-organisms. THαβ immunity is the host eradicable immunity against viruses. Cancer is also related to clonal anergy by Immunoglobulin D B cells and γδ T cells. Oncolytic viruses are related to the activation of anti-viral THαβ immunity. M2 macrophages are related to the tolerable TH1-like immunity, and they are related to metastasis. This review is key to understanding the immune pathogenesis of cancer. We can then develop better therapeutic agents to treat cancer.
Actualities in the Morphology and Immunohistochemistry of Cutaneous and Ocular Melanoma: What Lies Ahead? A Single-Centre Study
Authors: Tinca Andreea Cătălina , Moraru Raluca , Cocuz Iuliu Gabriel , Șincu Mihaela Cornelia , Niculescu Raluca , Sabău Adrian Horațiu , Chiorean Diana Maria , Szoke Andreea Raluca , Morariu Silviu-Horia , Cotoi Ovidiu Simion
Published: October 2022

Melanoma is the most aggressive melanocytic tumor whose incidence is continuously increasing worldwide. Methods: We highlight the morphological, immunohistochemistry, and particularities of various melanoma types based on the cases diagnosed in our department from 2017 to 2021. Results: We present 100 melanoma cases and one capsular nevus case. The most common type was nodular melanoma. The immunohistochemistry markers used were SRY-box transcription factor 10 (SOX10), S100 protein, human melanoma black 45 (HMB45), and melanoma antigen recognized by T cells 1 (Melan-A). Uveal melanoma and conjunctival melanoma represent particular tumors with independent prognostic factors. Uveal melanoma requires assessment of macrophages, microvascularisation, and mitoses. Sentinel lymph node metastases are essential targets that provide staging tools. Conjunctival melanoma and capsular nevi are diagnostic pitfalls. Conclusion: Melanoma can appear in various forms, and sometimes the diagnosis might be unclear. Today, immunohistochemistry remains the most important tool in confirming the diagnosis and prognosis for this type of neoplasia.
Impact of the First COVID-19 Wave on French Hospitalizations for Myocardial Infarction and Stroke: A Retrospective Cohort Study
Authors: Mariet Anne-Sophie , Duloquin Gauthier , Benzenine Eric , Roussot Adrien , Pommier Thibaut , Eicher Jean-Christophe , Baptiste Laura , Giroud Maurice , Cottin Yves , Béjot Yannick , Quantin Catherine
Published: October 2022

The COVID-19 pandemic modified the management of myocardial infarction (MI) and stroke. We aimed to evaluate the effect of the COVID-19 pandemic on the volume and spatial distribution of hospitalizations for MI and stroke, before, during and after the first nationwide lockdown in France in 2020, compared with 2019. Hospitalization data were extracted from the French National Discharge database. Patient’s characteristics were compared according to COVID-19 status. Changes in hospitalization rates over time were measured using interrupted time series analysis. Possible spatial patterns of over or under-hospitalization rates were investigated using Moran’s indices. We observed a rapid and significant drop in hospitalizations just before the beginning of the lockdown with a nadir at 36.5% for MI and 31.2% for stroke. Hospitalization volumes returned to those seen in 2019 four weeks after the end of the lockdown, except for MI, which rebounded excessively. Older age, male sex, elevated rate of hypertension, diabetes, obesity and mortality characterized COVID-19 patients. There was no evidence of a change in the spatial pattern of over- or under-hospitalization clusters over the three periods. After a steep drop, only MI showed a significant rebound after the first lockdown with no change in the spatial distribution of hospitalizations.
Is Restless Legs Syndrome De Facto Thyroid Disease?
Authors: Suwała Szymon , Rzeszuto Jakub , Glonek Rafał , Krintus Magdalena , Junik Roman
Published: October 2022

While a primary role in the pathogenesis of restless legs syndrome (RLS) has been attributed to dysfunction of the dopaminergic system and impaired iron metabolism (particularly in the central nervous system), it has been hypothesized that an imbalance between thyroid hormones and dopaminergic activity may be the starting point for all aspects of RLS. Although this hypothesis was proposed more than a decade ago, it has not yet been verified beyond doubt. The main aim of this study is to compare the prevalence of RLS in a population of patients with the most common thyroid gland diseases with a population of individuals with a healthy thyroid gland. The study included 237 participants divided into smaller groups according to the thyroid disease concerning them. Each participant had a laboratory diagnosis, an ultrasound scan and an assessment of the fulfilment of RLS criteria according to the International Restless Legs Syndrome Study Group (IRLSSG) criteria. The results obtained were subjected to statistical analysis. RLS is significantly more common in patients with known thyroid disease; Hashimoto’s disease, among others, manifests a 2.56× higher risk of a positive diagnosis for RLS than the general population. The association of RLS with thyroid disease is notable, although it is difficult to conclude unequivocally that there is a cause-and-effect relationship between the two. Further investigation into a potentially autoimmune cause of restless legs syndrome should be considered.
The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis
Authors: Schüler-Toprak Susanne , Ortmann Olaf , Buechler Christa , Treeck Oliver
Published: October 2022

Polycystic ovary syndrome (PCOS) and endometriosis are frequent diseases of the female reproductive tract causing high morbidity as they can significantly affect fertility and quality of life. Adipokines are pleiotropic signaling molecules secreted by white or brown adipose tissues with a central role in energy metabolism. More recently, their involvement in PCOS and endometriosis has been demonstrated. In this review article, we provide an update on the role of adipokines in both diseases and summarize previous findings. We also address the results of multi-omics approaches in adipokine research to examine the role of single nucleotide polymorphisms (SNPs) in genes coding for adipokines and their receptors, the secretome of adipocytes and to identify epigenetic alterations of adipokine genes that might be conferred from mother to child. Finally, we address novel data on the role of brown adipose tissue (BAT), which seems to have notable effects on PCOS. For this review, original research articles on adipokine actions in PCOS and endometriosis are considered, which are listed in the PubMed database.
Slower Growth during Lactation Rescues Early Cardiovascular and Adipose Tissue Hypertrophy Induced by Fetal Undernutrition in Rats
Authors: Rodríguez-Rodríguez Pilar , Monedero-Cobeta Ignacio , Ramiro-Cortijo David , Puthong Sophida , Quintana-Villamandos Begoña , Gil-Ramírez Alicia , Cañas Silvia , Ruvira Santiago , Arribas Silvia M.
Published: October 2022

Low birth weight (LBW) and accelerated growth during lactation are associated with cardiometabolic disease development. LBW offspring from rats exposed to undernutrition during gestation (MUN) develops hypertension. In this rat model, we tested if slower postnatal growth improves early cardiometabolic alterations. MUN dams were fed ad libitum during gestation days 1–10, with 50% of the daily intake during days 11–21 and ad libitum during lactation. Control dams were always fed ad libitum. Pups were maintained with their own mother or cross-fostered. Body weight and length were recorded weekly, and breastmilk was obtained. At weaning, the heart was evaluated by echocardiography, and aorta structure and adipocytes in white perivascular fat were studied by confocal microscopy (size, % beige-adipocytes by Mitotracker staining). Breastmilk protein and fat content were not significantly different between groups. Compared to controls, MUN males significantly accelerated body weight gain during the exclusive lactation period (days 1–14) while females accelerated during the last week; length growth was slower in MUN rats from both sexes. By weaning, MUN males, but not females, showed reduced diastolic function and hypertrophy in the heart, aorta, and adipocytes; the percentage of beige-type adipocytes was smaller in MUN males and females. Fostering MUN offspring on control dams significantly reduced weight gain rate, cardiovascular, and fat hypertrophy, increasing beige-adipocyte proportion. Control offspring nursed by MUN mothers reduced body growth gain, without cardiovascular modifications. In conclusion, slower growth during lactation can rescue early cardiovascular alterations induced by fetal undernutrition. Exclusive lactation was a key period, despite no modifications in breastmilk macronutrients, suggesting the role of bioactive components. Our data support that lactation is a key period to counteract cardiometabolic disease programming in LBW and a potential intervention window for the mother.
Anti-Müllerian Hormone and Polycystic Ovary Syndrome in Women and Its Male Equivalent
Authors: di Clemente Nathalie , Racine Chrystèle , Rey Rodolfo A.
Published: October 2022

This article reviews the main findings on anti-Müllerian hormone (AMH) and its involvement in the pathogenesis of polycystic ovary syndrome (PCOS) and its male equivalent. In women, AMH is produced by granulosa cells from the mid-fetal life to menopause and is a reliable indirect marker of ovarian reserve. AMH protects follicles from atresia, inhibits their differentiation in the ovary, and stimulates gonadotrophin-releasing hormone neurons pulsatility. AMH overexpression in women with PCOS likely contributes to the increase of the follicle cohort and of androgen levels, leading to follicular arrest and anovulation. In the male, AMH is synthesized at high levels by Sertoli cells from fetal life to puberty when serum AMH falls to levels similar to those observed in women. AMH is involved in the differentiation of the genital tract during fetal life and plays a role in Sertoli and Leydig cells differentiation and function. Serum AMH is used to assess Sertoli cell function in children with disorders of sex development and various conditions affecting the hypothalamic–pituitary–testicular axis. Although the reproductive function of male relative of women with PCOS has been poorly investigated, adolescents have elevated levels of AMH which could play a detrimental role on their fertility.
Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease
Authors: Hojná Silvie , Kotsaridou Zoe , Vaňourková Zdeňka , Rauchová Hana , Behuliak Michal , Kujal Petr , Kadlecová Michaela , Zicha Josef , Vaněčková Ivana
Published: October 2022

Gliflozins (sodium-glucose transporter-2 inhibitors) exhibited renoprotective effects not only in diabetic but also in non-diabetic patients with chronic kidney disease (CKD). Controversial results were reported in experimental non-diabetic models of CKD. Therefore, we examined empagliflozin effects in three CKD models, namely, in fawn-hooded hypertensive (FHH) rats, uninephrectomized salt-loaded (UNX + HS) rats, and in rats with Goldblatt hypertension (two-kidney, one-clip 2K1C) that were either untreated or treated with empagliflozin (10 mg/kg/day) for eight weeks. Plethysmography blood pressure (BP) was recorded weekly, and renal parameters (proteinuria, plasma urea, creatinine clearance, and sodium excretion) were analyzed three times during the experiment. At the end of the study, blood pressure was also measured directly. Markers of oxidative stress (TBARS) and inflammation (MCP-1) were analyzed in kidney and plasma, respectively. Body weight and visceral adiposity were reduced by empagliflozin in FHH rats, without a significant effect on BP. Experimentally induced CKD (UNX + HS and 2K1C) was associated with a substantial increase in BP and relative heart and kidney weights. Empagliflozin influenced neither visceral adiposity nor BP in these two models. Although empagliflozin increased sodium excretion, suggesting effective SGLT-2 inhibition, it did not affect diuresis in any experimental model. Unexpectedly, empagliflozin did not provide renoprotection because proteinuria, plasma urea, and plasma creatinine were not lowered by empagliflozin treatment in all three CKD models. In line with these results, empagliflozin treatment did not decrease TBARS or MCP-1 levels in either model. In conclusion, empagliflozin did not provide the expected beneficial effects on kidney function in experimental models of CKD.
Evolution of Electrospinning in Liver Tissue Engineering
Authors: Vasudevan Ashwini , Tripathi Dinesh M. , Sundarrajan Subramanian , Venugopal Jayarama Reddy , Ramakrishna Seeram , Kaur Savneet
Published: October 2022

The major goal of liver tissue engineering is to reproduce the phenotype and functions of liver cells, especially primary hepatocytes ex vivo. Several strategies have been explored in the recent past for culturing the liver cells in the most apt environment using biological scaffolds supporting hepatocyte growth and differentiation. Nanofibrous scaffolds have been widely used in the field of tissue engineering for their increased surface-to-volume ratio and increased porosity, and their close resemblance with the native tissue extracellular matrix (ECM) environment. Electrospinning is one of the most preferred techniques to produce nanofiber scaffolds. In the current review, we have discussed the various technical aspects of electrospinning that have been employed for scaffold development for different types of liver cells. We have highlighted the use of synthetic and natural electrospun polymers along with liver ECM in the fabrication of these scaffolds. We have also described novel strategies that include modifications, such as galactosylation, matrix protein incorporation, etc., in the electrospun scaffolds that have evolved to support the long-term growth and viability of the primary hepatocytes.
Neodymium Selenide Nanoparticles: Greener Synthesis and Structural Characterization
Authors: Ansary Abu A. , Syed Asad , Elgorban Abdallah M. , Bahkali Ali H. , Varma Rajender S. , Khan Mohd Sajid
Published: October 2022

This investigation presents the greener biomimetic fabrication of neodymium selenide nanoparticles (Nd2Se3 NPs) deploying nitrate-dependent reductase as a reducing (or redox) agent, extracted from the fungus, Fusarium oxysporum. The Nd2Se3 NPs, with an average size of 18 ± 1 nm, were fabricated with the assistance of a synthetic peptide comprising an amino acid sequence (Glu-Cys)n-Gly, which functioned as a capping molecule. Further, the NPs were characterized using multiple techniques such as UV-Vis spectroscopy, fluorescence, dynamic light scattering (DLS), and XRD. The hydrodynamic radii of biogenic polydispersed Nd2Se3 NPs were found to be 57 nm with PDI value of 0.440 under DLS. The as-made Nd2Se3NPs were water-dispersible owing to the existence of hydrophilic moieties (-NH2, -COOH, -OH) in the capping peptide. Additionally, these functionalities render the emulsion highly stable (zeta potential −9.47 mV) with no visible sign of agglomeration which bodes well for their excellent future prospects in labeling and bioimaging endeavors.
Revealing the Wonder of Natural Photonics by Nonlinear Optics
Authors: Mara Dimitrije , Bokic Bojana , Verbiest Thierry , Mouchet Sébastien R. , Kolaric Branko
Published: October 2022

Nano-optics explores linear and nonlinear phenomena at the nanoscale to advance fundamental knowledge about materials and their interaction with light in the classical and quantum domains in order to develop new photonics-based technologies. In this perspective article, we review recent progress regarding the application of nonlinear optical methods to reveal the links between photonic structures and functions of natural photonic geometries. Furthermore, nonlinear optics offers a way to unveil and exploit the complexity of the natural world for developing new materials and technologies for the generation, detection, manipulation, and storage of light at the nanoscale, as well as sensing, metrology, and communication.
Critical Design Factors for Electrochemical Aptasensors Based on Target-Induced Conformational Changes: The Case of Small-Molecule Targets
Authors: Onaş Andra Mihaela , Dascălu Constanţa , Raicopol Matei D. , Pilan Luisa
Published: October 2022

Nucleic-acid aptamers consisting in single-stranded DNA oligonucleotides emerged as very promising biorecognition elements for electrochemical biosensors applied in various fields such as medicine, environmental, and food safety. Despite their outstanding features, such as high-binding affinity for a broad range of targets, high stability, low cost and ease of modification, numerous challenges had to be overcome from the aptamer selection process on the design of functioning biosensing devices. Moreover, in the case of small molecules such as metabolites, toxins, drugs, etc., obtaining efficient binding aptamer sequences proved a challenging task given their small molecular surface and limited interactions between their functional groups and aptamer sequences. Thus, establishing consistent evaluation standards for aptamer affinity is crucial for the success of these aptamers in biosensing applications. In this context, this article will give an overview on the thermodynamic and structural aspects of the aptamer-target interaction, its specificity and selectivity, and will also highlight the current methods employed for determining the aptamer-binding affinity and the structural characterization of the aptamer-target complex. The critical aspects regarding the generation of aptamer-modified electrodes suitable for electrochemical sensing, such as appropriate bioreceptor immobilization strategy and experimental conditions which facilitate a convenient anchoring and stability of the aptamer, are also discussed. The review also summarizes some effective small molecule aptasensing platforms from the recent literature.
A SiPM-Enabled Portable Delayed Fluorescence Photon Counting Device: Climatic Plant Stress Biosensing
Authors: Pietro William J. , Mermut Ozzy
Published: October 2022

A portable and sensitive time-resolved biosensor for capturing very low intensity light emission is a promising avenue to study plant delayed fluorescence. These weak emissions provide insight on plant health and can be useful in plant science as well as in the development of accurate feedback indicators for plant growth and yield in applications of agricultural crop cultivation. A field-based delayed fluorescence device is also desirable to enable monitoring of plant stress response to climate change. Among basic techniques for the detection of rapidly fluctuating low intensity light is photon counting. Despite its vast utility, photon counting techniques often relying on photomultiplier tube (PMT) technology, having restricted use in agricultural and environment measurements of plant stress outside of the laboratory setting, mainly due to the prohibitive cost of the equipment, high voltage nature, and the complexity of its operation. However, recent development of the new generation solid-state silicon photomultiplier (SiPM) single photon avalanche diode array has enabled the availability of high quantum efficiency, easy-to-operate, compact, photon counting systems which are not constrained to sophisticated laboratories, and are accessible owing to their low-cost. In this contribution, we have conceived, fabricated and validated a novel SiPM-based photon counting device with integrated plug-and-play excitation LED, all housed inside a miniaturized sample chamber to record weak delayed fluorescence lifetime response from plant leaves subjected to varying temperature condition and drought stress. Findings from our device show that delayed fluorescence reports on the inactivation to the plant’s photosystem II function in response to unfavorable acute environmental heat and cold shock stress as well as chronic water deprivation. Results from our proof-of-concept miniaturized prototype demonstrate a new, simple and effective photon counting instrument is achieved, one which can be deployed in-field to rapidly and minimally invasively assess plant physiological growth and health based on rapid, ultra-weak delayed fluorescence measurements directly from a plant leaf.
Direct Capture and Early Detection of Lyme Disease Spirochete in Skin with a Microneedle Patch
Authors: Kight Emily , Alfaro Rosana , Gadila Shiva Kumar Goud , Chang Shuang , Evans David , Embers Monica , Haselton Frederick
Published: October 2022

Borrelia burgdorferi sensu lato family of spirochetes causes Lyme disease (LD) in animals and humans. As geographic territory of ticks expands across the globe, surveillance measures are needed to measure transmission rates and provide early risk testing of suspected bites. The current standard testing of LD uses an indirect two-step serological assay that detects host immune reactivity. Early detection remains a challenge because the host antibody response develops several weeks after infection. A microneedle (MN) device was developed to sample interstitial fluid (ISF) and capture spirochetes directly from skin. After sampling, the MN patch is easily dissolved in water or TE buffer, and the presence of spirochete DNA is detected by PCR. Performance was tested by spiking porcine ear skin with inactivated Borrelia burgdorferi, which had an approximate recovery of 80% of spirochetes. With further development, this simple direct PCR method could be a transformative approach for early detection of the causative agent of Lyme disease and enable rapid treatment to patients when infection is early, and numbers of systemic spirochetes are low.
New Horizons for MXenes in Biosensing Applications
Authors: Lu Decheng , Zhao Huijuan , Zhang Xinying , Chen Yingying , Feng Lingyan
Published: October 2022

Over the last few decades, biosensors have made significant advances in detecting non-invasive biomarkers of disease-related body fluid substances with high sensitivity, high accuracy, low cost and ease in operation. Among various two-dimensional (2D) materials, MXenes have attracted widespread interest due to their unique surface properties, as well as mechanical, optical, electrical and biocompatible properties, and have been applied in various fields, particularly in the preparation of biosensors, which play a critical role. Here, we systematically introduce the application of MXenes in electrochemical, optical and other bioanalytical methods in recent years. Finally, we summarise and discuss problems in the field of biosensing and possible future directions of MXenes. We hope to provide an outlook on MXenes applications in biosensing and to stimulate broader interests and research in MXenes across different disciplines.
An Origami Paper-Based Biosensor for Allergen Detection by Chemiluminescence Immunoassay on Magnetic Microbeads
Authors: Lazzarini Elisa , Pace Andrea , Trozzi Ilaria , Zangheri Martina , Guardigli Massimo , Calabria Donato , Mirasoli Mara
Published: October 2022

Food allergies are adverse health effects that arise from specific immune responses, occurring upon exposure to given foods, even if present in traces. Egg allergy is one of the most common food allergies, mainly caused by egg white proteins, with ovalbumin being the most abundant. As allergens can also be present in foodstuff due to unintended contamination, there is a need for analytical tools that are able to rapidly detect allergens in food products at the point-of-use. Herein, we report an origami paper-based device for detecting ovalbumin in food samples, based on a competitive immunoassay with chemiluminescence detection. In this biosensor, magnetic microbeads have been employed for easy and efficient immobilization of ovalbumin on paper. Immobilized ovalbumin competes with the ovalbumin present in the sample for a limited amount of enzyme-labelled anti-ovalbumin antibody. By exploiting the origami approach, a multistep analytical procedure could be performed using reagents preloaded on paper layers, thus providing a ready-to-use immunosensing platform. The assay provided a limit of detection (LOD) of about 1 ng mL−1 for ovalbumin and, when tested on ovalbumin-spiked food matrices (chocolate chip cookies), demonstrated good assay specificity and accuracy, as compared with a commercial immunoassay kit.
Artificial Intelligence-Assisted Terahertz Imaging for Rapid and Label-Free Identification of Efficient Light Formula in Laser Therapy
Authors: Shi Jia , Guo Zekang , Chen Hongli , Xiao Zhitao , Bai Hua , Li Xiuyan , Niu Pingjuan , Yao Jianquan
Published: October 2022

Photodynamic therapy (PDT) is considered a promising noninvasive therapeutic strategy in biomedicine, especially by utilizing low-level laser therapy (LLLT) in visible and near-infrared spectra to trigger biological responses. The major challenge of PDT in applications is the complicated and time-consuming biological methodological measurements in identification of light formulas for different diseases. Here, we demonstrate a rapid and label-free identification method based on artificial intelligence (AI)-assisted terahertz imaging for efficient light formulas in LLLT of acute lung injury (ALI). The gray histogram of terahertz images is developed as the biophysical characteristics to identify the therapeutic effect. Label-free terahertz imaging is sequentially performed using rapid super-resolution imaging reconstruction and automatic identification algorithm based on a voting classifier. The results indicate that the therapeutic effect of LLLT with different light wavelengths and irradiation times for ALI can be identified using this method with a high accuracy of 91.22% in 33 s, which is more than 400 times faster than the biological methodology and more than 200 times faster than the scanning terahertz imaging technology. It may serve as a new tool for the development and application of PDT.
Low-Cost Antenna-Array-Based Metamaterials for Non-Invasive Early-Stage Breast Tumor Detection in the Human Body
Authors: Hamza Musa N. , Abdulkarim Yadgar I. , Saeed Salah Raza , Altıntaş Olcay , Mahmud Rashad H. , Appasani Bhargav , Ravariu Cristian
Published: October 2022

Microstrip patch antennas have been used in many applications since their appearance. Despite their great promise, their narrow bandwidth and the loss at high-frequency bands have limited their usage in medical applications. This work proposes a developed low-cost microstrip patch antenna suitable for microwave imaging (MWI) applications within the wideband frequency range. The proposed antenna is loaded with an artificial magnetic conductor (AMC) to improve the antenna performance. The simulated results obtained using computer simulation technology (CST) indicate that the presence of the AMC has improved the frequency selectivity of the antenna at 8.6 GHz with a peak realized gain of 9.90443 dBi and 10.61 dBi for simulated and measured results, respectively. The proposed microstrip antenna has been fabricated to validate the simulated results, and its performance is tested experimentally. Additionally, the fidelity factor of face-to-face (FtF) and side-by-side (SbS) scenarios have been presented. The breast phantom models with a tumor and the antenna operating as a transceiver have been numerically simulated for the application of cancer tumor cell detection. The work will have a significant impact on the design of electromagnetic biosensors.
Label-Free Fluorescent Turn-On Glyphosate Sensing Based on DNA-Templated Silver Nanoclusters
Authors: Cheng Yuliang , Li Guowen , Huang Xiufang , Qian Zhijuan , Peng Chifang
Published: October 2022

In this work, a label-free fluorescent detection method for glyphosate, based on DNA-templated silver nanoclusters (DNA-Ag NCs) and a Cu2+-ion-modulated strategy, was developed. In the presence of Cu2+, the fluorescence of the DNA-Ag NCs was quenched. Glyphosate can restore the fluorescence of DNA-Ag NCs. By analyzing the storage stability of the obtained DNA-Ag NCs using different DNA templates, specific DNA-Ag NCs were selected for the construction of the glyphosate sensor. The ultrasensitive detection of glyphosate was achieved by optimizing the buffer pH and Cu2+ concentration. The sensing of glyphosate demonstrated a linear response in the range of 1.0–50 ng/mL. The limit of detection (LOD) was 0.2 ng/mL. The proposed method was successfully applied in the detection of glyphosate in a real sample, indicating its high application potential for glyphosate detection.