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Robotic manipulations of single cells using a large-volume piezoelectric micropipette with nanoliter precision.
Colloids Surf B Biointerfaces
Boglarka Kovacs, Szabolcs Novak, Igor Sallai +5 more
Single-cell manipulations are a limiting factor in single-cell omics (genomics, transcriptomics, proteomics), in vitro fertilization, and cloning. Cellular adhesion force often plays a pivotal role in various biological contexts, spanning from lower organisms to the human body. Investigating the mechanism of adhesive interactions at the individual cell level holds significant importance. We used a computer-controlled piezoelectric micropipette (NanoPick) built onto an inverted microscope, offering subnanoliter precision liquid handling in the range of 0.1-600 nanoliters with a temporal resolution of 1 millisecond. In contrast to previous pipette-based cell manipulations, in our device, phase contrast and fluorescent imaging of the microscope was not limited by the micropipette. Moreover, this compact setup efficiently enabled single-cell detection, targeting, picking, and isolation without fluidic tubes and syringes. We investigated the integrin-mediated adhesion between an RGD (Arg-Gly-Asp) motif displaying surface and the HeLa Fucci tumor cell line. Using a 70 µm inner diameter micropipette, we found that increasing the pipetting speed (voltage ramp rate applied on the piezoelectric head) improved the cell picking success rate to almost 100 %. Although the more strongly attached unmodified HeLa cells could not be picked up even at the highest flow rates. However, vibrating the fluid in the micropipette successfully detached fully flattened cells without any biochemical treatment. This vibration micropipetting method enabled the detachment of 79.9 % of the strongly adherent HeLa cells, preserving mechanical integrity for downstream omics analyses despite a loss in viability. Compared to valve-controlled systems, NanoPick demonstrated higher efficiency and precision, particularly in handling THP-1 cells. Its rigid design minimized transient delays, allowing time-dependent flow profiles and enhanced detachment at lower flow rates. Our method allows adhesion measurements on hundreds of cells and offers precise control over fluid volume and timing, suitable for manipulating adherent cells or larger objects such as organoids, spheroids, oocytes, or larvae. The introduced vibration micropipetting method could be employed for the mechanical stimulation of single cells.
Unmasking the intestinal impact: Acute Toxoplasma gondii infection induces severe morphological and immunological changes in female C57BL/6 mice.
Exp Parasitol
Paulo Watanabe, Vivian Fuguhara de Lima, Amanda Gubert Alves Dos Santos +6 more
Toxoplasmosis, caused by the protozoan Toxoplasma gondii (T. gondii), is a common zoonotic disease with a seropositivity rate of up to 60 % in adults. While often asymptomatic, it can cause severe complications in immunocompromised individuals. Oral transmission is the primary route of infection, leading to intestinal inflammation. This study evaluated morphoquantitative changes in the colons of female C57BL/6 mice acutely infected with T. gondii. Mice were divided into control and infected groups and euthanized five days post-infection for colon collection. Histological analyses quantified intraepithelial lymphocytes, goblet cells, mast cells, and collagen fibres, while immunostaining assessed neurons and vasoactive intestinal peptide (VIP) expression. Infected mice exhibited increased intraepithelial lymphocytes and myeloperoxidase activity, alongside a significant reduction in AB-1.0-positive goblet cells, indicating impaired mucus secretion. Notably, the longitudinal muscle layer showed increased thickness, whereas the submucosal layer and crypt depth were reduced. Histopathological evaluation revealed epithelial hyperplasia, mucosal ulceration, and abscess formation. A decrease in myenteric neurons was also observed, although VIP expression remained unchanged. These findings demonstrate that acute T. gondii infection induces substantial alterations in intestinal structure, including immune cell infiltration, goblet cell depletion, and muscle layer remodelling. The reduction in myenteric neurons, despite stable VIP expression, suggests specific neuroimmune interactions in the infected gut. Collectively, this study highlights the profound impact of T. gondii on colonic morphology and function, underscoring the complexity of host-parasite interactions during acute infection.
Young first-episode psychosis patients exhibit impaired microvascular function in the skin and low systemic nitric oxide availability, independent of classical cardiovascular risk factors.
Schizophr Res
Joanna Suraj-Prażmowska, Brygida Marczyk, Natalia Śmierciak +7 more
Impaired endothelial function in patients with psychotic disorders may contribute to increased cardiovascular mortality, but the mechanisms involved remain unclear. Here, we comprehensively analyzed endothelial function in 33 young (median age 18: IQR 17-27) patients diagnosed with first-episode psychosis (FEP), examining large vessels (flow-mediated dilation; FMD) and the microcirculation in peripheral vessels (peripheral arterial tonometry following reactive hyperemia; RH-PAT) and in the skin (flow-mediated skin fluorescence; FMSF). We also measured the plasma concentration of nitric oxide (NO) metabolites (nitrite/nitrate) and 18 biomarkers related to endothelial function, including those representative of glycocalyx damage (SDC-1), endothelial inflammation (sVCAM-1), disrupted endothelial permeability (Angpt-1, Angpt-2), and hemostasis (TAFI, THBS-1). In FEP patients, FMD and RH-PAT remained largely unchanged, but skin microcirculation measured by FMSF was impaired, with pronounced alterations in baseline microvascular oscillations and reactive hyperemic response. Plasma nitrite concentration in FEP patients was significantly lowered, but the profile of biomarkers did not display typical pattern of pro-inflammatory and pro-thrombotic changes associated with endothelial dysfunction, but prominent lowering of adrenomedullin and annexin A5 levels. FEP patients had higher white blood cell counts, total cholesterol, and triglycerides levels, but these parameters did not correlate with any of the vascular readouts. In conclusion, young FEP patients displayed a distinct endotype of endothelial dysfunction with impaired systemic NO bioavailability and prominent functional alterations in the microcirculation of the skin. These results indicate that the assessment of functional changes in skin microcirculation by FMSF may provide novel insights into the early negative effects of psychosis on the microvasculature.
Self-assembly driven nano-salinomycin for high-efficiency cancer immunotherapy by reticulum stress mediated stemness suppression.
Biomaterials
Longqin Wang, Wenting Cheng, Siyuan Qin +6 more
Cancer cells with stemness characteristics effectively escape the recognition and killing of immune-active cells, such as T cells, which has been considered as the root cause of cancer recurrence and metastasis. To sensitize cancer immunotherapy, we have developed salinomycin-repurposed endoplasmic reticulum (ER) stress nanoinducers (DTSS NPs) to synergistically suppress cancer cell stemness. Salinomycin, as a polyether antibiotic demonstrating robust cytotoxicity against tumor stem cell, is co-assembled with thymopentin (TP5) and ER-targeted phototherapeutic agent s-780, and tailored with DSPE-PEG-biotin to obtain DTSS NPs. This nanoplatform not only improves the bioavailability of TP5 and salinomycin, but also ensures controlled drug release and reduces the side effects of therapeutic agents. Moreover, the hyperpyrexia and ROS produced by s-780 further induced ER stress, which downregulates PD-L1 expression and activates the cGAS-STING pathway, while TP5 significantly promotes the proliferation and differentiation of T lymphocytes, resulting in the augment of the anti-tumor immunity. Importantly, salomycin synergistically boosted s-780-mediated ER stress to effectively inhibit the stemness of cancer cells, thereby enhancing the responsiveness of cancer cells to T cells. As expected, DTSS NPs activate systemic immunity and suppress cancer metastasis and recurrence, providing promising solutions for sensitizing cancer immunotherapy by inhibiting cancer cell stemness.
Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids.
Diabetes Obes Metab
Yi Wen, Deven Lemen, Yanzhu Lin +10 more
The aim of this study was to determine if retatrutide, a triple agonist of glucose-dependent insulinotropic polypeptide (GIP) receptor, glucagon-like peptide 1 (GLP-1) receptor and glucagon (GCG) receptor, may lower serum triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels in part by decreasing circulating concentrations of the angiopoietin-like protein 3/8 complex (ANGPTL3/8).
B1344 ameliorates non-alcoholic steatohepatitis in HFCD-HF/G-induced mice: exploring the therapeutic efficacy and mechanism of a novel FGF21 analogue.
Eur J Pharmacol
Zhiwei Chen, Tao Liu, Ping Huang +6 more
The endocrine cytokine, fibroblast growth factor 21 (FGF21), shows therapeutic potential for non-alcoholic steatohepatitis (NASH) but has pharmacokinetic limitations. B1344 is a modified PEGylated FGF21 analogue with enhanced stability and bioactivity. Researches are required to further explore its effect and possible mechanisms against NASH. C57BL/6J mice were induced by 10-week high-fat/calorie diet with high fructose/glucose water (HFCD-HF/G). B1344 was then administered for 8 weeks. Systemic metabolic parameters, hepatic injury, insulin resistance, adipose tissue (AT) function, and FGF21 resistance were evaluated. RNA-sequencing of liver and adipose tissues was carried out. B1344 attenuated HFCD-HF/G-induced metabolic disorder and hepatic damages. Liver transcriptomics revealed its multi-target modulation of lipid metabolism, inflammation, fibrosis, etc. Systemic insulin resistance and downsream signaling in liver, muscle and AT was improved by B1344. Notably, it restored AT dysfunction and alleviated FGF21 resistance. AT RNA-sequencing further identified its regulation in inflammation, angiogenesis, hypoxia and senescence. Collectively, B1344 demonstrates robust efficacy against NASH in HFCD-HF/G-induced mice. The multi-target modulation in liver and AT including FGF21 resistance was involved in its underlying mechanisms. This study not only provides support for further clinical trials of B1344, but also benefits deeper understanding of FGF21 function.
Effect of Incretin-Based Therapies on Blood Pressure: A Systematic Review and Meta-Analysis.
Eur J Prev Cardiol
Christian Basile, Aurora Merolla, Costantino Mancusi +7 more
Hypertension and obesity frequently coexist and synergistically increase cardiovascular (CV) risk. Incretin-based therapies with glucagon-like peptide-1 receptor agonists (GLP-1-RAs), gastric inhibitory polypeptide (GIP)/GLP1-RAs, and glucagon/GIP/GLP-1RAs lead to substantial weight loss. However, their antihypertensive efficacy and safety profile have not been comprehensively quantified. Our study aimed to evaluate the effects of incretin-based therapies on office systolic blood pressure (BP) (SBP), diastolic BP (DBP), all-cause mortality, and key safety outcomes, i.e., hypoglycemia and pancreatitis episodes, in adults with overweight or obesity.
Concerning BPC-157, a natural pentadecapeptide, that acts as a cytoprotectant and is believed to protect the gastro-intestinal tract (GIT).
Inflammopharmacology
Michael Whitehouse
This article discusses the lengthy review by Pedrag Sikiric and twenty one (21) co-authors in Inflammopharmacology (2024) 32:3119-3161.
MOTS-c Promotes Glycolysis via AMPK-HIF-1α-PFKFB3 Pathway to Ameliorate Cardiopulmonary Bypass-induced Lung Injury.
Am J Respir Cell Mol Biol
Zihao Shen, Peng Lu, Wanjun Jin +11 more
Cardiopulmonary bypass (CPB) is essential during cardiac surgery but frequently leads to lung ischemia-reperfusion injury (LIRI), a significant contributor to postoperative complications. We investigated the protective effects of mitochondrial open reading frame of the 12S ribosomal RNA type C (MOTS-c), a mitochondrial-derived peptide, against LIRI-induced acute lung injury (ALI), emphasizing glycolytic reprogramming and ferroptosis in pulmonary microvascular endothelial cells. We hypothesized that MOTS-c exerts its protective effects by regulating glycolysis and suppressing ferroptosis via metabolic signaling pathways. We conducted a prospective, controlled trial involving 107 patients undergoing CPB, evaluating plasma concentrations of MOTS-c and inflammatory markers. MOTS-c concentrations were significantly reduced in patients with ALI. In vivo and in vitro experiments demonstrated that MOTS-c pretreatment alleviated LIRI by enhancing glycolytic flux, reducing oxidative stress, and suppressing ferroptosis in pulmonary microvascular endothelial cells. In particular, MOTS-c reinstated the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), an essential glycolytic enzyme, thus preserving cellular energy homeostasis and diminishing lipid peroxidation. The findings further emphasize the involvement of the AMPK (AMP-activated protein kinase)-hypoxia inducible factor-1α (HIF-1α) signaling pathway in the protective benefits facilitated by MOTS-c. MOTS-c elevated phosphorylated AMPKα and HIF-1α expression, indicating a vital function for these pathways in enhancing glycolysis and antioxidant defenses. Genetic and pharmacological inhibition of PFKFB3 abrogated the protective effects of MOTS-c, thereby confirming the essential role of PFKFB3-mediated glycolysis in alleviating LIRI. Our research indicates that MOTS-c could serve as a potential therapeutic agent for the prevention or treatment of LIRI-induced ALI by enhancing glycolysis, suppressing ferroptosis, and activating the AMPK-HIF-1α pathway. Future study should explore the clinical application of MOTS-c, potentially improving outcomes for patients undergoing high-risk cardiac operations.
Afamelanotide for Treatment of the Protoporphyrias: Impact on Quality of Life and Laboratory Parameters in a US Cohort.
Life (Basel)
Rebecca K Leaf, Hetanshi Naik, Paul Y Jiang +11 more
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity. Afamelanotide, an α-melanocyte-stimulating hormone analogue, is the only approved treatment for protoporphyria and leads to increased light tolerance and improved quality of life (QoL). However, published experience with afamelanotide in the US is limited.
Adherence, duration and healthcare costs in a real-world population of patients with acromegaly.
J Comp Eff Res
Tiffany P Quock, Eunice Chang, Ashis K Das +5 more
Aim: The aim of this study was to describe treatment patterns among patients with acromegaly who are newly treated with acromegaly medical therapy. Materials & methods: Data from IQVIA Pharmetrics Plus® Database from 1 January 2013 to 30 June 2023 were used to identify patients with acromegaly who started a new acromegaly medical therapy and observe their treatment patterns. Patients were required to have at least 12 months of data without any acromegaly therapy (medication or surgery) prior to the index date and at least 6 months of follow-up. Comorbidities were measured during the baseline period. Adherence, persistence, medication and switching were measured during follow-up. Results: A total of 453 patients with acromegaly who were newly treated with acromegaly medical therapy and had no evidence of acromegaly therapy for at least 12 months were identified. Among these patients, 46.1% (n = 206) were treated with cabergoline as their index treatment, 24.5% (n = 111) with injectable octreotide, 15.0% (n = 68) with lanreotide, 5.5% (n = 25) with bromocriptine, 4.9% (n = 22) with pegvisomant, 2.2% (n = 10) with pasireotide, 1.1% (n = 5) with oral octreotide, 0.4% (n = 2) with cabergoline + octreotide, and 0.2% (n = 1) with cabergoline + lanreotide. By the end of the follow-up period, 54.3% (n = 246) were not on any treatment, 19.6% (n = 89) remained on the index treatment, and the remaining 26.0% (n = 118) switched to another treatment. Conclusion: This study contributed to the growing evidence that patients with acromegaly are not well-served by current therapeutic options, as indicated by high rates of treatment discontinuation, switching and add-on therapy. However, treatment switching and add-on therapy represent ongoing efforts to optimize patient care toward more effective and tolerable treatments. Expanded treatment options may serve an unmet need in this patient population.
Withdrawn: Stable Gastric Pentadecapeptide BPC 157 as a Therapy of Severe Electrolyte Disturbances in Rats.
Curr Neuropharmacol
Marija Medvidovic Grubisic, Sanja Strbe, Ivan Barisic +19 more
The article has been withdrawn at the author's request from the website of the journal Current Neuropharmacology. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php
Neonatal Freeze Lesion-Induced Cortical Malformation Alters Hippocampal Gene Expression and Leads to Persistent Cognitive and Emotional Deficits in Adult Male Wistar Rats.
J Neurosci Res
Olga E Zubareva, Anna A Kovalenko, Denis S Sinyak +4 more
Cortical malformations, including microgyria, are often associated with neurodevelopmental comorbidities such as epilepsy and cognitive impairments in humans. To investigate how early cortical disruption leads to persistent behavioral impairments, we employed a neonatal neocortical focal freeze lesion (FFL) model of polymicrogyria in male Wistar rats. Unilateral cortical lesions were induced at postnatal day 0 (P0), and molecular changes in hippocampal gene expression (glutamatergic signaling: Grin1, Grin2a, Grin2b, Gria1, Gria2; neuroinflammation: Nlrp3, Il1b, Il1rn; glial markers: Gfap, Aif1; neurotrophic factors: Bdnf, Fgf2) were analyzed at P21. Behavioral outcomes, including locomotor activity, exploratory behavior, anxiety-like behavior, social interaction, and recognition memory, were assessed in adulthood (P70-P90). Neonatal cortical lesions induced subregion-specific alterations in hippocampal gene expression: Grin2b and Gria1 expression decreased in the ipsilateral dorsal hippocampus, while Grin2a, Bdnf, and Fgf2 increased in the contralateral ventral hippocampus. These molecular changes were associated with subsequent cognitive deficits (impaired recognition memory) and emotional dysregulation (heightened anxiety-like behavior) in adult rats, alongside reduced exploratory activity. Basic motor functions and sociability remained unaffected, and seizure susceptibility (assessed via maximal electroshock threshold) was unchanged, highlighting the specificity of the observed impairments. Our findings suggest a potential mechanistic link between early-life cortical malformations with microgyrus formation, dysregulation of hippocampal synaptic plasticity and neurotrophic signaling, and persistent neurobehavioral deficits. These results underscore the translational relevance of the freeze lesion model for studying the neurodevelopmental trajectory of cortical malformation-related comorbidities.
A Novel Pathogenic Variant of the AVPR2 Gene Leading to Arginine Vasopressin Resistance Since the Neonatal Period.
Genes (Basel)
Agnieszka Szmigielska, Piotr Skrzypczyk, Dorota Czapczak +4 more
Background: Diabetes insipidus (DI) in newborns is an extremely rare condition, with the age of presentation strongly suggesting a genetic background of the disease. The differential diagnosis should include arginine vasopressin deficiency (AVD) and arginine vasopressin resistance (AVR). Some novel diagnostic tools such as copeptin evaluation and genetic tests are vital for early diagnosis. Case report: We present the case of a 1-month-old boy with polyuria observed since birth. Laboratory tests showed persistent hypernatremia, elevated plasma and low urine osmolality. An attempt at oral administration of desmopressin had no effect; additionally the copeptin level was increased. A genetic study (NGS of the AVP, AVPR2 and AQP2 genes) was considered and a new pathogenic variant in the AVPR2 gene (hemizygous c.157del) was detected. After the genetic test result was obtained, treatment with hydrochlorothiazide was started. The patient is now 3 months old, developing normally, and the weight and height are normal. Conclusions: Newborns with DI should be subjected to extensive multidisciplinary diagnostics, including endocrine and renal causes. Copeptin evaluation and prompt genetic diagnosis allows for the early diagnosis and implementation of appropriate treatment.
Repurposing the Antibiotic D-Cycloserine for the Treatment of Hyperpigmentation: Therapeutic Potential and Mechanistic Insights.
Int J Mol Sci
Ye-Jin Lee, Chang-Gu Hyun
Melanin overproduction contributes to hyperpigmentation disorders such as melasma and solar lentigines, leading to increasing demand for safe and effective skin-lightening agents. D-cycloserine (DCS), a known antimicrobial agent, has not been previously evaluated for dermatological applications. This study aimed to explore the potential of DCS as a novel anti-melanogenic compound and to elucidate its underlying molecular mechanisms in melanogenesis inhibition. The cytotoxicity and anti-melanogenic effects of DCS were assessed in B16F10 melanoma cells stimulated with α-MSH. Cell viability was determined via MTT assays, while melanin content, tyrosinase activity, and the expression levels of MITF, TYR, TRP-1, TRP-2, and major signaling proteins (e.g., CREB, MAPKs, GSK-3β/β-catenin) were evaluated using colorimetric assays and Western blotting. A 3D human skin model was also used to confirm in vitro findings, and a primary skin irritation test was conducted to assess dermal safety. DCS significantly reduced α-MSH-induced melanin content and tyrosinase activity without cytotoxicity at concentrations ≤100 µM. It downregulated MITF and melanogenic enzyme expression and modulated signaling pathways by enhancing ERK activation while inhibiting CREB, JNK, and p38 phosphorylation. Additionally, DCS suppressed β-catenin stabilization via GSK-3β activation. These effects were confirmed in a 3D human skin model, and a clinical skin irritation study revealed no adverse reactions in human volunteers. DCS exerts its anti-melanogenic effect by targeting multiple pathways, including CREB/MITF, MAPK, and GSK-3β/β-catenin signaling. Its efficacy and safety profiles support its potential as a novel cosmeceutical agent for the treatment of hyperpigmentation. Further clinical studies are warranted to confirm its therapeutic utility in human skin pigmentation disorders.
De Novo Design of Integrin α5β1 Modulating Proteins to Enhance Biomaterial Properties.
Adv Mater
Xinru Wang, Jordi Guillem-Marti, Saurav Kumar +23 more
Integrin α5β1 is crucial for cell attachment and migration in development and tissue regeneration, and α5β1 binding proteins can have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5β1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5β1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin (FN) and RGD peptides in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed FN- and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.
Erythropoietic protoporphyria in childhood: clinical clues, missed diagnoses and emerging therapy.
Eur J Pediatr
Moritz Toenne, Tim Schaefer
Erythropoietic protoporphyria (EPP) is a rare photodermatosis presenting in early childhood with severe pain upon exposure to visible light, including sunlight and artificial sources, often without visible skin changes in the early phase. However, skin changes such as erythema, oedema or crusting may develop after prolonged exposure. This mini-review highlights key clinical features and proposes a structured diagnostic approach, illustrated by a representative paediatric case. Emerging therapies, including off-label afamelanotide and experimental visible light protection, are discussed alongside practical management in primary care. The review also addresses the psychosocial impact and systemic challenges in European care structures. The aim is to raise awareness among paediatricians and general practitioners, promote earlier diagnosis and support equitable care for affected children. What is Known: • EPP is the most common porphyria in childhood. It typically manifests with painful photosensitivity and no visible skin changes. Despite characteristic features, diagnosis is often delayed due to low awareness in paediatric care. What is New: • This mini-review proposes a practical diagnostic algorithm for paediatric primary care and highlights key clinical clues to sensitise general paediatricians to EPP. It also reviews emerging treatment options such as afamelanotide, already approved for adults, with promising adolescent data. These advances must now be widely communicated and translated into equitable access for children across Europe.
Diabetes insipidus as a presentation of lung adenocarcinoma: a case report.
J Med Case Rep
Maryam Alsadat Tabatabaei, Reza Manouchehri Ardakani
Paraneoplastic syndromes are rare complications associated with malignancies, and central diabetes insipidus represents one of their uncommon manifestations. Central diabetes insipidus is most frequently observed in association with specific malignancies, such as lung cancer, and often results from metastatic involvement of the pituitary gland and the sellar region.
Kinetic Analysis of SARS-CoV-2 S1-Integrin Binding Using Live-Cell, Label-Free Optical Biosensing.
Biosensors (Basel)
Nicolett Kanyo, Krisztina Borbely, Beatrix Peter +6 more
The SARS-CoV-2 spike (S1) protein facilitates viral entry through binding to angiotensin-converting enzyme 2 (ACE2), but it also contains an Arg-Gly-Asp (RGD) motif that may enable interactions with RGD-binding integrins on ACE2-negative cells. Here, we provide quantitative evidence for this alternative binding pathway using a live-cell, label-free resonant waveguide grating (RWG) biosensor. RWG technology allowed us to monitor real-time adhesion kinetics of live cells to RGD-displaying substrates, as well as cell adhesion to S1-coated surfaces. To characterize the strength of the integrin-S1 interaction, we determined the dissociation constant using two complementary approaches. First, we performed a live-cell competitive binding assay on RGD-displaying surfaces, where varying concentrations of soluble S1 were added to cell suspensions. Second, we recorded the adhesion kinetics of cells on S1-coated surfaces and fitted the data using a kinetic model based on coupled ordinary differential equations. By comparing the results from both methods, we estimate that approximately 33% of the S1 molecules immobilized on the Nb2O5 biosensor surface are capable of initiating integrin-mediated adhesion. These findings support the existence of an alternative integrin-dependent entry route for SARS-CoV-2 and highlight the effectiveness of label-free RWG biosensing for quantitatively probing virus-host interactions under physiologically relevant conditions without the need of the isolation of the interaction partners from the cells.
Hypogonadism in men with prolactinoma: Diagnosis, treatment, and management of persistent hypogonadism.
Vitam Horm
Yaron Rudman, Ilan Shimon
Prolactin-secreting adenomas comprise approximately 50 % of all clinically relevant pituitary adenomas. Most men with prolactinomas present with large and invasive tumors. Despite effective medical therapy with dopamine agonists and prolactin normalization, over 20 % of men with prolactinomas will remain with hypogonadism. There are two suggested mechanisms for hypogonadism: central suppression of the hypothalamic-pituitary-gonadal axis caused by elevated prolactin levels leading to inhibition of the kisspeptin neurons in the hypothalamus and loss of pulsatile luteinizing hormone secretion, and tumor mass effect with compression of the normal pituitary tissue and destruction of gonadotroph cells. Hypogonadism in men results in sexual dysfunction, low libido, anemia, fatigue, and infertility. Identification of patients who are likely to recover the damaged gonadal axis upon prolactin suppression is important. These are men that harbor smaller tumors, with higher testosterone levels at diagnosis, no visual field defects, and without impairment in the secretion of other pituitary hormones. Testosterone replacement should be offered to patients with lower chance of restoring normal function of the gonadal axis. However, most men will achieve spontaneous recovery of the hypothalamic-pituitary-gonadal axis within 12 months after prolactin normalization. For men with prolactinoma and hypogonadism persistence who wish to restore fertility, treatment with gonadotropins or with clomiphene citrate has been found to be safe and effective. In the present review, we propose an algorithm for the management of hypogonadism persistence in men with macroprolactinomas.