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Autoimmune thyroid disease (AITD) is the leading cause of thyroid dysfunction globally, characterized primarily by two distinct clinical manifestations: Hashimoto's thyroiditis (HT) and Graves' disease (GD). The prevalence of AITD is approximately twice as high in women compared to men, with a particularly pronounced risk during the reproductive years. Pregnancy exerts profound effects on thyroid physiology and immune regulation due to hormonal fluctuations and immune adaptations aimed at fostering maternal-fetal tolerance, potentially triggering or exacerbating AITD. The impact of AITD on pregnancy outcomes is multifaceted. Both HT and GD have been associated with adverse obstetric and neonatal outcomes, including miscarriage, preterm delivery, preeclampsia and fetal growth restriction. Inadequately managed AITD can also affect fetal neurodevelopment due to disrupted maternal thyroid hormone availability during critical periods of brain maturation. This review explores the complex interplay between the genetic, epigenetic and environmental factors that drive AITD during pregnancy, highlighting their roles in disease development and impacts on pregnancy outcomes. Gaining a deeper understanding of these mechanisms is crucial for improving diagnostic tools, treatment options and preventive measures to enhance the health and well-being of both the mother and the newborn.

Maintaining the physiological function of the vascular endothelium and endothelial glycocalyx is crucial for the prevention of cardiovascular disease, which is one of the leading causes of morbidity and mortality worldwide. Damage to these structures can lead to atherosclerosis, hypertension, and other cardiovascular problems, especially in individuals with risk factors such as diabetes and obesity. Endothelial dysfunction is associated with ischemic disease and has a negative impact on overall cardiovascular health. The aim of this review was to comprehensively summarize the crucial role of the vascular endothelium and glycocalyx in cardiovascular health and associated thrombo-inflammatory conditions. It highlights how endothelial dysfunction, influenced by factors such as diabetes, chronic kidney disease, and obesity, leads to adverse cardiovascular outcomes, including heart failure. Recent evidence suggests that hyperbaric oxygen therapy (HBOT) may offer therapeutic benefits in the treatment of cardiovascular risk factors and disease. This review presents the current evidence on the mechanisms by which HBOT promotes angiogenesis, shows antimicrobial and immunomodulatory effects, enhances antioxidant defenses, and stimulates stem cell activity. The latest findings on important topics will be presented, including the effects of HBOT on endothelial dysfunction, cardiac function, atherosclerosis, plaque stability, and endothelial integrity. In addition, the role of HBOT in alleviating cardiovascular risk factors such as hypertension, aging, obesity, and glucose metabolism regulation is discussed, along with its impact on inflammation in cardiovascular disease and its potential benefit in ischemia-reperfusion injury. While HBOT demonstrates significant therapeutic potential, the review also addresses potential risks associated with excessive oxidative stress and oxygen toxicity. By combining information on the molecular mechanisms of HBOT and its effects on the maintenance of vascular homeostasis, this review provides valuable insights into the development of innovative therapeutic strategies aimed at protecting and restoring endothelial function to prevent and treat cardiovascular diseases.

Since its introduction, the number of heart surgeries has risen continuously. It is a high-risk procedure, usually involving cardiopulmonary bypass, which is associated with an inflammatory reaction that can lead to perioperative and postoperative organ dysfunction. The extent of complications following cardiac surgery has been the focus of interest for several years because of their impact on patient outcomes. Recently, numerous scientific efforts have been made to uncover the complex mechanisms of interaction between inflammation, oxidative stress, and endothelial dysfunction that occur after cardiac surgery. Numerous factors, such as surgical and anesthetic techniques, hypervolemia and hypovolemia, hypothermia, and various drugs used during cardiac surgery trigger the development of systemic inflammatory response and the release of oxidative species. They affect the endothelium, especially endothelial glycocalyx (EG), a thin surface endothelial layer responsible for vascular hemostasis, its permeability and the interaction between leukocytes and endothelium. This review highlights the current knowledge of the molecular mechanisms involved in endothelial dysfunction, particularly in the degradation of EG. In addition, the major inflammatory events and oxidative stress responses that occur in cardiac surgery, their interaction with EG, and the clinical implications of these events have been summarized and discussed in detail. A better understanding of the complex molecular mechanisms underlying cardiac surgery, leading to endothelial dysfunction, is needed to improve patient management during and after surgery and to develop effective strategies to prevent adverse outcomes that complicate recovery.

The aim of this study was to evaluate the efficacy of autologous dentin (AD), bovine xenograft (BX) and magnesium-enriched bovine xenograft (BX + Mg) in the healing of critical cranial bone defects (CCBDs) in rats. Eighty male Wistar rats were divided into four groups: BX, BX + Mg, AD and the control group (no intervention). Eight mm CCBDs were created and treated with the respective biomaterials. Healing was assessed 7, 15, 21 and 30 days after surgery by micro-computed tomography (micro-CT), real-time polymerase chain reaction (RT-PCR) and immunohistochemical analysis. Micro-CT analysis showed that AD had the highest bone volume and the least amount of residual biomaterial at day 30, indicating robust bone formation and efficient resorption. BX + Mg showed significant bone volume but had more residual biomaterial compared to AD. RT-PCR showed that the expression of osteocalcin (OC), the receptor activator of nuclear factor κB (RANK) and sclerostin (SOST), was highest in the AD group at day 21 and vascular endothelial growth factor (VEGF) at day 15, indicating increased osteogenesis and angiogenesis in the AD group. Immunohistochemical staining confirmed intense BMP-2/4 and SMAD-1/5/8 expression in the AD group, indicating osteoinductive properties. The favorable gene expression profile and biocompatibility of AD and BX + Mg make them promising candidates for clinical applications in bone tissue engineering. Further research is required to fully exploit their potential in regenerative surgery.

It is not entirely clear how the interaction between joint inflammation and the central nervous system (CNS) response in rheumatoid arthritis (RA) works, and what pathophysiology underlies the sex differences in coexisting neuropsychiatric comorbidities. It is known that estrogen hormones reduce inflammation in RA and that this occurs mainly via the stimulation of G protein-coupled receptor-30 (GPR30), also known as G protein-coupled estrogen receptor (GPER) 1. However, changes in GPR30 expression and sex differences induced by local and systemic inflammation in RA are not yet known. Our aim was to reveal sex differences in the expression and association of joint GPR30 with local and systemic inflammation, clinical course and furthermore with hippocampal GPR30 expression during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Furthermore, we demonstrated sex-specific differences in the association between joint and systemic inflammation and hippocampal microglia during PIA. Our results suggest sex-specific differences not only in the clinical course and serum levels of pro-inflammatory cytokines but also in the expression of GPR30. Female rats show greater synovial inflammation and greater damage to the articular cartilage compared to males during PIA attack. Male rats express higher levels of synovial and cartilaginous GPR30 than females during PIA, which correlates with a less severe clinical course. The correlation between synovial and cartilaginous GPR30 and joint inflammation scores (Krenn and Mankin) in male rats suggests that the more severe the joint inflammation, the higher the GPR30 expression. At the same time, there is no particular upregulation of hippocampal GPR30 in males. On the other hand, female rats express higher levels of neuroprotective GPR30 in the hippocampus than male rats at the basic level and during PIA attack. In addition, females have a higher number of Iba-1+ cells in the hippocampus during PIA attack that strongly correlates with the clinical score, serum levels of IL-17A, and Krenn and Mankin scores. These results suggest that male rats are better protected from inflammation in the joints and female rats are better protected from the inflammation in the hippocampus during a PIA attack, independently of microglia proliferation. However, in the remission phase, synovial GPR30 expression suddenly increases in female rats, as does hippocampal GPR30 expression in males. Further experiments with a longer remission period are needed to investigate the molecular background of these sex differences, as well as microglia phenotype profiling.

The endothelial glycocalyx (EGC) is a layer of proteoglycans (associated with glycosaminoglycans) and glycoproteins, which adsorbs plasma proteins on the luminal surface of endothelial cells. Its main function is to participate in separating the circulating blood from the inner layers of the vessels and the surrounding tissues. Physiologically, the EGC stimulates mechanotransduction, the endothelial charge, thrombocyte adhesion, leukocyte tissue recruitment, and molecule extravasation. Hence, severe impairment of the EGC has been implicated in various pathological conditions, including sepsis, diabetes, chronic kidney disease, inflammatory disorders, hypernatremia, hypervolemia, atherosclerosis, and ischemia/reperfusion injury. Moreover, alterations in EGC have been associated with altered responses to therapeutic interventions in conditions such as cardiovascular diseases. Investigation into the function of the glycocalyx has expanded knowledge about vascular disorders and indicated the need to consider new approaches in the treatment of severe endothelial dysfunction. This review aims to present the current understanding of the molecular mechanisms underlying cardiovascular diseases and to elucidate the impact of heart surgery on EGC dysfunction.

Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves' disease (GD). The pathogenesis of AITD is caused by an inappropriate immune response related to genetic, non-genetic, and environmental factors. Pregnancy is one of the factors that have a great influence on the function of the thyroid gland because of the increased metabolic demand and the effects of hormones related to pregnancy. During pregnancy, an adaptation of the maternal immune system occurs, especially of the innate immune system engaged in maintaining adaptive immunity in the tolerant state, preventing the rejection of the fetus. Pregnancy-related hormonal changes (estrogen, progesterone, hCG) may modulate the activity of innate immune cells, potentially worsening the course of AITD during pregnancy. This especially applies to NK cells, which are associated with exacerbation of HD and GD. On the other hand, previous thyroid disorders can affect fertility and cause adverse outcomes of pregnancy, such as placental abruption, spontaneous abortion, and premature delivery. Additionally, it can cause fetal growth retardation and may contribute to impaired neuropsychological development of the fetus. Therefore, maintaining the thyroid equilibrium in women of reproductive age and in pregnant women is of the highest importance.

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid proliferation, early dissemination, acquired therapy resistance, and poor prognosis. Early diagnosis of SCLC is crucial since most patients present with advanced/metastatic disease, limiting the potential for curative treatment. While SCLC exhibits initial responsiveness to chemotherapy and radiotherapy, treatment resistance commonly emerges, leading to a five-year overall survival rate of up to 10%. New effective biomarkers, early detection, and advancements in therapeutic strategies are crucial for improving survival rates and reducing the impact of this devastating disease. This review aims to comprehensively summarize current knowledge on diagnostic options, well-known and emerging biomarkers, and SCLC treatment strategies and discuss future perspectives on this aggressive malignancy.

Cardiac surgery is one of the highest-risk procedures, usually involving cardiopulmonary bypass and commonly inducing endothelial injury that contributes to the development of perioperative and postoperative organ dysfunction. Substantial scientific efforts are being made to unravel the complex interaction of biomolecules involved in endothelial dysfunction to find new therapeutic targets and biomarkers and to develop therapeutic strategies to protect and restore the endothelium. This review highlights the current state-of-the-art knowledge on the structure and function of the endothelial glycocalyx and mechanisms of endothelial glycocalyx shedding in cardiac surgery. Particular emphasis is placed on potential strategies to protect and restore the endothelial glycocalyx in cardiac surgery. In addition, we have summarized and elaborated the latest evidence on conventional and potential biomarkers of endothelial dysfunction to provide a comprehensive synthesis of crucial mechanisms of endothelial dysfunction in patients undergoing cardiac surgery, and to highlight their clinical implications.

Sinomenine is a pharmacologically active alkaloid with antioxidant and anti-inflammatory properties. We aimed to investigate the mechanism of renoprotective activity of sinomenine in kidney injury induced by cisplatin (CP). Sinomenine (5 mg/kg) was administered to mice orally in two doses, the second day after intraperitoneal application of CP (13 mg/kg). Sinomenine ameliorated kidney injury and decreased serum levels of urea and creatinine and renal expression of NGAL and KIM-1. The increase in HO-1, 4-HNE, 3-NT and TNF-α renal expression was mitigated by sinomenine. Additionally, sinomenine reduced the expression of p21, Bax, Noxa, caspase-3 and -8 and PARP1 cleavage in mice kidneys as well as the number of TUNEL-positive cells. Sinomenine attenuated CP-induced activation of ERK1/2, Akt, FOXO3a, STAT3 and NF-κB and restored Sirtuin 6 expression. In the human proximal tubular cell line HK2, sinomenine 100 μM reduced the toxic effect of CP 30 μM. Our current findings suggest that sinomenine suppresses CP-induced oxidative stress, inflammation and apoptosis in mice kidneys by targeting multiple signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Oleanolic acid (OA) is a natural compound that possesses numerous beneficial health effects, including anticancer activity. The current study aimed to investigate the role of forkhead box O3a (FOXO3a) in autophagy/mitophagy by OA in HCT116 cell line. OA dose-dependently reduced viability of HCT116 cells, with IC 50  = 29.8 μΜ. The expression of cleaved caspase-3 and poly (ADP-ribose) polymerase 1 increased after OA treatment, suggesting induction of apoptosis. Concurrently, OA induced autophagy, evidenced by increased expression of Beclin-1, autophagy-related protein 5 and microtubule-associated protein1A/1B-light chain 3 beta (LC3B), which played a prosurvival role. The induction of mitophagy was suggested by increased expression of p62 and PTEN-induced kinase 1 and reduced expression of translocase of outer mitochondrial membrane 20, which colocalized with LC3B. OA also induced nuclear accumulation of forkhead box O3a (FOXO3a). The cytotoxic activity of OA coincided with upregulation of p38. Inhibition of p38 led to increase in FOXO3a and NAD + -dependent deacetylase sirtuin 6 expression. In vivo, OA inhibited tumor growth in colon cancer xenograft mice. Our results suggest concomitant induction of apoptosis and prosurvival mitophagy by OA in colon cancer via p38/FOXO3a/Sirt6 signaling. Additionally, our data demonstrate that OA can chemosensitize colon cancer cells to 5-fluorouracil (5-FU)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

BMPs regulate synovial quiescence and adult neurogenesis in the hippocampus in non-stress conditions. However, changes in BMP expression that are induced by inflammation during rheumatoid arthritis (RA) have not yet been reported. Here, we show that signalling with synovial BMPs (BMP-4 and -7) mediates the effect of systemic inflammation on adult neurogenesis in the hippocampus during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Moreover, we show gender differences in BMP expressions and their antagonists (Noggin and Gremlin) during PIA and their correlations with the clinical course and IL-17A and TNF-α levels in serum. Our results indicate gender differences in the clinical course, where male rats showed earlier onset and earlier recovery but a worse clinical course in the first two phases of the disease (onset and peak), which correlates with the initial increase of serum IL-17A level. The clinical course of the female rats worsened in remission. Their prolonged symptoms could be a reflection of an increased TNF-α level in serum during remission. Synovial inflammation was greater in females in PIA-remission with greater synovial BMP and antagonist expressions. More significant correlations between serum cytokines (IL-17A and TNF-α), and synovial BMPs and their antagonists were found in females than in males. On the other hand, males showed an increase in hippocampal BMP-4 expression during the acute phase, but both genders showed a decrease in antagonist expressions during PIA in general. Both genders showed a decrease in the number of Ki-67 + and SOX-2 + and DCX + cells and in the ratio of DCX + to Ki67 + cells in the dentate gyrus during PIA. However, in PIA remission, females showed a faster increase in the number of Ki67 + , SOX-2 + , and DCX + cells and a faster increase in the DCX/Ki67 ratio than males. Both genders showed an increase of hippocampal BMP-7 expression during remission, although males constantly showed greater BMP-7 expression at all time points. Our data show that gender differences exist in the BMP expressions in the periphery-hippocampus axis and in the IL-17A and TNF-α levels in serum, which could imply differences in the mechanisms for the onset and progression of the disease, the clinical course severity, and adult neurogenesis with subsequent neurological complications between genders.

Evidence is currently insufficient to know whether SARS-CoV-2 antibodies (Abs) protect from future infection and how long immunity will last. The kinetics of the immune response to SARS-CoV-2 infection and role of serology in estimating individual protective immunity is yet to be established. We evaluated diagnostic performances of three serological assays - Abbott Architect CMIA IgG, bioMerieux VIDAS ELFA IgG/IgM, and Diesse Chorus ELISA IgG/IgM, and analyzed longevity and potential neutralizing effect of SARS-CoV-2 Abs in COVID-19 patients. Clinical sensitivities of assessed IgG tests two to three weeks post symptom onset (PSO) were very high: 96.77 % for Architect, 96.77 % for Chorus, and 100.00 % for VIDAS. Sensitivities of two assessed IgM assays were moderate: 74.07 % for Chorus, and 76.92 % for VIDAS. Specificities were excellent for all assessed IgG assays: 99.01 % for Architect and 100 % for Chorus and VIDAS. Chorus and VIDAS IgM assays also achieved excellent specificity of 99.01 % and 100 %, respectively. In most cases IgG Abs were still present eight months PSO. Neutralizing antibodies were detected in majority of serum samples from convalescent patients. Serum samples from severe COVID-19 patients had higher antibody titers and higher neutralizing activity. We observed a strong positive correlation among SARS-CoV-2 IgG antibody titer and neutralizing activity. The strongest positive correlation to neutralizing activity was found for VIDAS IgG assay., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Drug-specific therapeutic approaches for colorectal cancer (CRC) have contributed to significant improvements in patient health. Nevertheless, there is still a great need to improve the personalization of treatments based on genetic and epigenetic tumor profiles to maximize the quality and efficacy while limiting cytotoxicity. Currently, CEA and CA 19-9 are the only validated blood biomarkers in clinical practice. For this reason, laboratories are trying to identify new specific prognostics and, more importantly, predictive biomarkers for CRC patient profiling. Thus, the unique landscape of personalized biomarker data should have a clinical impact on CRC treatment strategies and molecular genetic screening tests should become the standard method for diagnosing CRC. This review concentrates on recent molecular testing in CRC and discusses the potential modifications in CRC assay methodology with the upcoming clinical application of novel genomic approaches. While mechanisms for analyzing circulating tumor DNA have been proven too inaccurate, detecting and analyzing circulating tumor cells and protein analysis of exosomes represent more promising options. Blood liquid biopsy offers good prospects for the future if the results align with pathologists' tissue analyses. Overall, early detection, accurate diagnosis and treatment monitoring for CRC with specific markers and targeted molecular testing may benefit many patients.

Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence worldwide. Currently used treatments of UC are unsatisfactory, while natural bioactive compounds are considered to be emerging therapeutic agents. Luteolin (Lut) is a natural compound with beneficial effects in a variety of diseases, however, its effect in UC has been poorly studied. In this study we investigated the effect of Lut in posttreatment and cotreatment of dextran sulfate sodium (DSS)-induced experimental colitis in mice. In addition, the role of extracellular signal-regulated kinases 1/2 (ERK1/2) in the mechanism of action of Lut in experimental colitis was investigated using the ERK inhibitor PD0325901. Lut attenuated symptoms of DSS-induced colitis in mice, ameliorated colon tissue damage and reduced inflammation, apoptosis and autophagy. The effect was more pronounced if Lut was administered simultaneously with DSS. The administration of ERK inhibitor exacerbated DSS-induced colitis symptoms and prevented the protective effects of Lut. The results provide new mechanistic details underlying the anti-inflammatory, anti-apoptotic and anti-autophagic effects of Lut through the activation of the ERK signaling pathway. This suggested that Lut can be used as a novel therapeutic candidate in the treatment of UC or could be used as a supplement to existing therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aucubin is pharmacologically active natural compound which possesses numerous beneficial properties. This study aimed to evaluate the protective effect of aucubin against cisplatin (CP)-induced acute kidney injury in mice and the mechanism of its action. Aucubin was administrated to mice orally or intraperitoneally (ip) (1.5 and 5 mg/kg) for two consecutive days, two days after ip injection of cisplatin (CP), 11 mg/kg. Treatment with aucubin by both routes of administration ameliorated histopathological changes and reduced elevated serum markers of kidney injury. CP administration increased renal expression of heme oxygenase-1 (HO-1) and 4-hydroxynonenal (4-HNE), as well as tumor necrosis factor-alpha (TNF-α), which was dose-dependently ameliorated by aucubin. Moreover, aucubin reduced increased renal expression of cleaved caspase-3 and -9 and decreased poly (ADP-ribose) polymerase (PARP) cleavage. Mechanistically, aucubin suppressed the activation of several signaling pathways involved in inflammation and apoptosis, including nuclear factor-kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), Akt, extracellular signal-regulated kinase 1/2 (ERK1/2) and forkhead box O3a (FOXO3a). Parenteral application was marginally but statistically more effective in reducing CP-induced kidney injury than oral administration. The findings of this study suggest that aucubin acts as a protective agent against CP-induced nephrotoxicity, which should be further investigated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)