Tumoroids, a valid preclinical screening platform for monitoring cancer angiogenesis.

In recent years, biologists and clinicians have witnessed prominent advances in in vitro 3D culture techniques related to biomimetic human/animal tissue analogs. Numerous data have confirmed that unicellular and multicellular (tumoroids) tumor spheroids with dense native cells in certain matrices are sensitive and valid analytical tools for drug screening, cancer cell dynamic growth, behavior, etc. in laboratory settings. Angiogenesis/vascularization is a very critical biological phenomenon to support oxygen and nutrients to tumor cells within the deep layer of solid masses. It has been shown that endothelial cell (EC)-incorporated or -free spheroid/tumoroid systems provide a relatively reliable biological platform for monitoring the formation of nascent blood vessels in micron/micrometer scales. Besides, the paracrine angiogenic activity of cells within the spheroid/tumoroid systems can be monitored after being treated with different therapeutic approaches. Here, we aimed to collect recent advances and findings related to the monitoring of cancer angiogenesis using unicellular and multicellular tumor spheroids. Vascularized spheroids/tumoroids can help us in the elucidation of mechanisms related to cancer formation, development, and metastasis by monitoring the main influencing factors.

Plastic particle impacts on the cardiovascular system and angiogenesis potential.

The extensive application of plastics in different sectors such as packaging, building, textiles, consumer products, and several industries has increased in recent years. Emerging data have confirmed that plastic wastes and segregates are problematic issues in aquatic and terrestrial ecosystems. The decomposition of plastic particles (PPs) leads to the release of microplastics (MPs) and nanoplastics (NPs) into the surrounding environment and entry of these particles will be problematic in unicellular and multicellular creatures. It was suggested that PPs can easily cross all biological barriers and reach different organs, especially the cardiovascular system, with the potential to modulate several molecular pathways. It is postulated that the direct interaction of PPs with cellular and subcellular components induces genotoxicity and cytotoxicity within the cardiovascular system. Meanwhile, being inert carriers, PPs can intensify the toxicity of other contaminants inside the cardiovascular system. Here, in this review article, several underlying mechanisms related to PP toxicity in the cardiovascular system were discussed in detail.

Cardiorenal syndrome: Plasmonic biosensors.

Cardiorenal syndrome (CRS) is defined as a broad spectrum of conditions encompassing both the heart and kidneys in which acute or chronic heart disorder may induce acute or chronic tubular injury in the kidneys and vice versa. Early diagnosis allows timely intervention and attenuates disease progression. Two well-established biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and brain (B-type) natriuretic peptide (BNP), are reflective of impaired cardiac and kidney function associated with poor prognosis in various cardiac disorders, including heart failure and coronary artery disease. Given the ongoing contribution of CRS to the high morbidity and mortality post-MI, early risk stratification and preventive measures are highly significant. In this review, we examine Surface Plasmon Resonance (SPR) optical biosensors for detection of these biomarkers and discuss potential implications of this highly sensitive and specific technology in CRS detection, treatment and outcomes.

Therapeutic Impact of Tocilizumab in the Setting of Severe COVID-19; an Updated and Comprehensive Review on Current Evidence.

Introduction: The COVID-19 pandemic caused by SARS-CoV-2 has been the major health concern in 2019 globally. Considering the severity and phase of the disease, various pharmacotherapy schedules were proposed. Here, we set out to provide close-up insights on the clinical utility of Tocilizumab (TCZ), a biologic monoclonal antibody in this regard. Methods: In this comprehensive review, various databases, including Scopus, PubMed Central, Medline, Embase, Google Scholar, and preprint publishers (med/bioRxiv) were searched until January 30, 2024, according to the keywords and search criteria. Results: Besides the pros and cons, compelling evidence purported the safety and efficacy of TCZ and indicated that it exhibits great potential to reduce short-term and all-cause (28-30-day) mortality. TCZ significantly drops the adverse events if administered in the right time course (in the inflammatory phase) during critical/severe COVID-19 pneumonia. Despite contradictory results, the benefits of TCZ appear significant, especially in combination with add-on therapies, such as corticosteroids. Although the safety of TCZ is acceptable, solid data is lacking as to its benefits during pregnancy. There are limited data on TCZ combination therapies, such as hemoperfusion, intravenous immunoglobulin (IVIG), simple O2 therapy, vasopressor support, convalescent plasma therapy, and even in vaccinated patients and COVID-19 reinfection, especially in elderly persons. In addition, the impact of TCZ therapy on the long-lasting COVID-19 is unclear. Conclusion: Personalized medicine based on individual characteristics and pertinent clinical conditions must be considered in the clinicians' decision-making policy. Finally, to mitigate the risk-to-benefit ratio of TCZ, a treatment algorithm, based on available literature and updated national institute of health (NIH) and Infectious Diseases Society of America (IDSA) guidelines, is also proposed.

Strict association between development of psychological conditions and hypertension incidence: A cross-sectional study.

Background/Aims: Previous studies indicated a significant association between mental disorders and cardiovascular diseases, including heart failure (HF) and coronary artery disease (CAD) with comorbidity hypertension (HTN), and vice versa, leading to a challenge in the final decision. To resolve this issue, we aimed to exclude comorbidities and further assessed to better find any association between mental disorders and cardiovascular diseases (CVD). Methods: The cross-sectional study involved 300 participants: 100 with HTN (without HF or CAD), 100 with HF (without HTN or CAD), 100 with CAD (without HTN or HF), and 100 healthy individuals as a control group. To evaluate depression, anxiety, and stress levels, the Depression, Anxiety, and Stress Scale - 21 (DASS-21) was applied. For further analysis, the SPSS ver.20 was used. Results: The analysis showed that the score of depression, anxiety, and stress was higher in the HTN patients compared to the control (p < 0.001), CAD (p < 0.001), and HF (p < 0.001) groups, respectively. However, no significant differences were observed between the other study groups. Notably, patients with HF and CAD without concurrent HTN had similar psychological distress levels to healthy participants. Conclusion: The present study emphasized the higher prevalence of psychological distress in HTN patients and suggests a requirement for further research regarding the etiology involved in this association.

Relationship between angiogenesis biomarker endocan and apolipoproteins in patients with acute myocardial infarction.

Aim: In the current study, serum levels of endocan in patients attended with ST-elevation myocardial infarction, as well as the possible correlation with apolipoprotein-A1 (APO-A1) and APO-B were investigated. Materials & methods: In 80 men, endocan, cTnI, APO-A1, and APO-B levels were measured. Finally, the correlation of endocan with APO-A1, APO-B, and APO-B/ APO-A1 ratio was assessed. Results: Significant changes in APO-A1, APO-B, endocan levels, and APO-B/APO-A1 ratio were found in acute myocardial infarction cases compared with the control arm (p < 0.05). In addition, our finding showed a significant correlation between APO-B and endocan levels, but not APO-A. Conclusion: High endocan level is an independent indicator of endothelial dysfunction and ischemic cardiovascular conditions, which could be related to APO-B.

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STING agonists as promising vaccine adjuvants to boost immunogenicity against SARS-related coronavirus derived infection: possible role of autophagy.

As a major component of innate immunity and a positive regulator of interferons, the Stimulator of interferon gene (STING) has an immunotherapy potential to govern a variety of infectious diseases. Despite the recent advances regarding vaccines against COVID-19, nontoxic novel adjuvants with the potential to enhance vaccine efficacy are urgently desired. In this connection, it has been well-documented that STING agonists are applied to combat COVID-19. This approach is of major significance for boosting immune responses most likely through an autophagy-dependent manner in susceptible individuals against infection induced by severe acute respiratory syndrome Coronavirus (SARS­CoV­2). Given that STING agonists exert substantial immunomodulatory impacts under a wide array of pathologic conditions, these agents could be considered novel adjuvants for enhancing immunogenicity against the SARS-related coronavirus. Here, we intend to discuss the recent advances in STING agonists' recruitment to boost innate immune responses upon vaccination against SARS-related coronavirus infections. In light of the primordial role of autophagy modulation, the potential of being an antiviral vaccine adjuvant was also explored.

Biosensors; a novel concept in real-time detection of autophagy.

Autophagy is an early-stage response with self-degradation properties against several insulting conditions. To date, the critical role of autophagy has been well-documented in physiological and pathological conditions. This process involves various signaling and functional biomolecules, which are involved in different steps of the autophagic response. During recent decades, a range of biochemical analyses, chemical assays, and varied imaging techniques have been used for monitoring this pathway. Due to the complexity and dynamic aspects of autophagy, the application of the conventional methodology for following autophagic progression is frequently associated with a mistake in discrimination between a complete and incomplete autophagic response. Biosensors provide a de novo platform for precise and accurate analysis of target molecules in different biological settings. It has been suggested that these devices are applicable for real-time monitoring and highly sensitive detection of autophagy effectors. In this review article, we focus on cutting-edge biosensing technologies associated with autophagy detection.

Role of autophagy in angiogenic potential of vascular pericytes.

The vasculature system is composed of a multiplicity of juxtaposed cells to generate a functional biological barrier between the blood and tissues. On the luminal surface of blood vessels, endothelial cells (ECs) are in close contact with circulating cells while supporting basal lamina and pericytes wrap the abluminal surface. Thus, the reciprocal interaction of pericytes with ECs is a vital element in the physiological activity of the vascular system. Several reports have indicated that the occurrence of pericyte dysfunction under ischemic and degenerative conditions results in varied micro and macro-vascular complications. Emerging evidence points to the fact that autophagy, a conserved self-digestive cell machinery, can regulate the activity of several cells like pericytes in response to various stresses and pathological conditions. Here, we aim to highlight the role of autophagic response in pericyte activity and angiogenesis potential following different pathological conditions.

Exosomes as Theranostic Agents in Reproduction System.

Exosomes (Exos), belonging to extracellular vesicles, are cell-derived nano-sized vesicles with the potential to carry different kinds of biological molecules. Many studies have proved the impacts of exosomal cargo on several biological processes in female and male reproductive systems. It is also hypothesized that changes in exosomal cargo are integral to the promotion of certain pathological conditions, thus Exos can be used as valid biomarkers for the diagnosis of infertility and other abnormal conditions. Here, efforts are made to collect some recent data related to the physiological significance of Exos in the reproductive system, and their potential therapeutic effects. It is anticipated that the current review article will lay the groundwork for elucidating the source and mechanisms by which Exos control the reproductive system additionally supplying fresh methods and concepts for the detection and treatment of disorders associated with fertility for future studies.

Type 2 diabetes mellitus induced autophagic response within pulmonary tissue in the rat model.

Introduction: The current experiment aimed to address the impact of type 2 diabetes mellitus on autophagy status in the rat pulmonary tissue. Methods: In this study, 20 male Wistar rats were randomly allocated into two groups as follows: control and diabetic groups. To induce type 2 diabetes mellitus, rats received a combination of streptozotocin (STZ) and a high-fat diet. After confirmation of diabetic condition, rats were maintained for 8 weeks and euthanized for further analyses. The pathological changes were assessed using H&E staining. We also measured transforming growth factor-ß (TGF-ß), bronchoalveolar lavage fluid (BALF), and tumor necrosis factor-α (TNF-α) in the lungs using ELISA and real-time PCR analyses, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were monitored in diabetic lungs to assess oxidative status. We also measured the expression of becline-1, LC3, and P62 to show autophagic response under diabetic conditions. Using immunofluorescence staining, protein levels of LC3 was also monitored. Results: H&E staining showed pathological changes in diabetic rats coincided with the increase of TNF-α (~1.4-fold) and TGF-ß (~1.3-fold) compared to those in the normal rats (P<0.05). The levels of MDA (5.6 ± 0.4 versus 6.4 ± 0.27 nM/mg protein) were increased while SOD (4.2 ± 0.28 versus 3.8 ± 0.13 U/mL) activity decreased in the diabetic rats (P<0.05). Real-time polymerase chain reaction (PCR) analysis showed the up-regulation of Becline-1 (~1.35-fold) and LC3 (~2-fold) and down-regulation of P62 (~0.8-fold) (P<0.05), showing incomplete autophagic flux. We noted the increase of LC3+ cells in diabetic condition compared to that in the control samples. Conclusion: The prolonged diabetic condition could inhibit the normal activity of autophagy flux, thereby increasing pathological outcomes.

The Progress and Research Trends of Statin Medications: Advanced Epidemiological and Bibliometrical Assessment.

Statin medications are considered as important lipid lowering agents to prevent subsequent cardiovascular events. However, there was limited evidence regarding the bibliometric analysis on preclinical and clinical studies. In January, 2021, the data was retrieved from Scopus and Dimensions database. For detail analysis, we focused on Scopus. Thirty-three thousand two hundred forty-seven research documents were found in the database which contained the word "Statin" either in titles, abstracts and/or keywords of the research documents. They mostly comprised of research articles (n = 22586/67.93%), reviews (n = 6366/19.15%). Scopus classified these documents in various subject categorized like medicine, biochemistry, genetics and molecular biology, pharmacology, toxicology and pharmaceutics, nursing, neuroscience, biological sciences, immunology, and microbiology to name a few. The highest documents are published in 2016 (n = 540/7.16%), followed by 2015 (n = 534/7.08%), 2017 (n = 527/6.99%), 2014 (n = 514/6.81%), and 2020 (n = 504/6.68%). The top sources as well as total number of authors, institutes, and countries involved in publications are described. For detail analysis, we designed the publication and citation clubs. Based on Vosviewer analysis we also provided details about co-authorship network for authors, institutes, and countries. In order to understanding the research focus of the publications, we performed the co-words analysis. The present study may provide details and research trends about statin publications.

Putative Therapeutic Impact of Inflammasome Inhibitors against COVID-19-Induced ARDS.

Given the importance of COVID-19-induced ARDS, recently, researchers have strived to determine underlying mechanisms involved in the inflammatory responses. In this regard, inflammasomes possess a distinct priority for cytokine storm occurrence and, subsequently, ARDS progression in ill patients with SARS-CoV-2 infection. In this minireview, the characteristics of known inflammasome inhibitors and designed research in this field were concretely deciphered.

Novel diagnostic potential of miR-1 in patients with acute heart failure.

BACKGROUND: A number of circulating micro-ribonucleic acids (miRNAs) have been introduced as convincing predictive determinants in a variety of cardiovascular diseases. This study aimed to evaluate some miRNAs' diagnostic and prognostic value in patients with acute heart failure (AHF). METHOD: Forty-four AHF patients were randomly selected from a tertiary heart center, and 44 healthy participants were included in the control group. Plasma levels of assessed miRNAs, including miR -1, -21, -23, and -423-5-p were measured in both groups. The patients were followed for one year, and several clinical outcomes, including in-hospital mortality, one-year mortality, and the number of readmissions, were recorded. RESULTS: An overall 88 plasma samples were evaluated. There was no significant difference in terms of demographic characteristics between the AHF and healthy groups. Our findings revealed that mean levels of miR-1, -21, -23, and -423-5-p in AHF patients were significantly higher than in the control group. Although all assessed miRNAs demonstrated high diagnostic potential, the highest sensitivity (77.2%) and specificity (97.7%) is related to miR-1 for the values above 1.22 (p = 0.001, AUC = 0.841; 95%CI, 0.751 to 946). Besides, the levels of miR-21 and -23 were significantly lower in patients with ischemia-induced HF. However, the follow-up data demonstrated no significant association between miRNAs and prognostic outcomes including in-hospital mortality, one-year mortality, and the number of readmissions. CONCLUSION: The result of our study demonstrated that miR-1, -21, -23, and -423-5-p can be taken into account as diagnostic aids for AHF. Nevertheless, there was no evidence supporting the efficacy of these miRNAs as prognostic factors in our study.

Pharmacotherapy consideration of thrombolytic medications in COVID-19-associated ARDS.

BACKGROUND: In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for coronavirus disease (COVID-19), was identified as the new pathogen to lead pneumonia in Wuhan, China, which has spread all over the world and developed into a pandemic. Despite the over 1 year of pandemic, due to the lack of an effective treatment plan, the morbidity and mortality of COVID-19 remains high. Efforts are underway to find the optimal management for this viral disease. MAIN BODY: SARS-CoV-2 could simultaneously affect multiple organs with variable degrees of severity, from mild to critical disease. Overproduction of pro-inflammatory mediators, exacerbated cellular and humoral immune responses, and coagulopathy such as Pulmonary Intravascular Coagulopathy (PIC) contributes to cell injuries. Considering the pathophysiology of the disease and multiple microthrombi developments in COVID-19, thrombolytic medications seem to play a role in the management of the disease. Beyond the anticoagulation, the exact role of thrombolytic medications in the management of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) is not explicit. This review focuses on current progress in underlying mechanisms of COVID-19-associated pulmonary intravascular coagulopathy, the historical use of thrombolytic drugs in the management of ARDS, and pharmacotherapy considerations of thrombolytic therapy, their possible benefits, and pitfalls in COVID-19-associated ARDS. CONCLUSIONS: Inhaled or intravenous administration of thrombolytics appears to be a salvage therapy for severe ARDS associated with COVID-19 by prompt attenuation of lung injury. Considering the pathogenesis of COVID-19-related ARDS and mechanism of action of thrombolytic agents, thrombolytics appear attractive options in stable patients without contraindications.

Application of exosomes for the alleviation of COVID-19-related pathologies.

The pandemic of COVID-19 caused worldwide concern. Due to the lack of appropriate medications and the inefficiency of commercially available vaccines, lots of efforts are being made to develop de novo therapeutic modalities. Besides this, the possibility of several genetic mutations in the viral genome has led to the generation of resistant strains such as Omicron against neutralizing antibodies and vaccines, leading to worsening public health status. Exosomes (Exo), nanosized vesicles, possess several therapeutic properties that participate in intercellular communication. The discovery and application of Exo in regenerative medicine have paved the way for the alleviation of several pathologies. These nanosized particles act as natural bioshuttles and transfer several biomolecules and anti-inflammatory cytokines. To date, several approaches are available for the administration of Exo into the targeted site inside the body, although the establishment of standard administration routes remains unclear. As severe acute respiratory syndrome coronavirus 2 primarily affects the respiratory system, we here tried to highlight the transplantation of Exo in the alleviation of COVID-19 pathologies.

Putative therapeutic impacts of cardiac CTRP9 in ischaemia/reperfusion injury.

Recently, cytokines belonging to C1q/tumour necrosis factor-related proteins (CTRPs) superfamily have attracted increasing attention due to multiple metabolic functions and desirable anti-inflammatory effects. These various molecular effectors exhibit key roles upon the onset of cardiovascular diseases, making them novel adipo/cardiokines. This review article aimed to highlight recent findings correlated with therapeutic effects and additional mechanisms specific to the CTRP9, particularly in cardiac ischaemia/reperfusion injury (IRI). Besides, the network of the CTPR9 signalling pathway and its possible relationship with IRI were discussed. Together, the discovery of all involved underlying mechanisms could shed light to alleviate the pathological sequelae after the occurrence of IRI.

Cervical and preauricular lymphadenopathies as atypical manifestations in the setting of COVID-19: a case report.

Besides the common symptoms in COVID-19, it has been thought to be a more imperative measure to identify the extraordinary manifestations of the illness, which would be more helpful to improve clinical management. In the current report, a 39-year-old woman and a 44-year-old man showed reactive cervical and preauricular lymphadenopathies, respectively, upon a range of the common symptoms of the disease. Interestingly, none of them showed the symptoms of lower respiratory tract infection as well. Notably, a herpes-like skin lesion was also observed on the right lower eyelid in one of the positive patients.

Dichotomous effects of autophagy on infarct volume in experimental permanent/transient ischemic stroke model: a systematic review and meta-analysis.

According to the recent findings, autophagy modulation is being a potential therapeutic target in the management of ischemic stroke in a pre-clinical setting. However, the pros and cons of autophagic response strongly depend on the activation time of autophagy after injury. In this systematic review, we aimed to explore the impacts of pharmacological modulation of autophagy on infarct size in experimental ischemic stroke models. Based on our preliminary search, 3551 publications were identified. Of twenty-nine publications that met the inclusion criteria, twenty studies reported infarct volume reduction by percentage (%) with no evidence of any publication bias while nine studies reported by mm3, which had publication bias (39.25 units, standardized mean differences (SMD) = 41.92, 95% confidence interval (CI): 30.33 to 53.51). Based on a meta-analysis, the point estimate (pooled mean difference) for improvement of infarct volume during autophagy modulation according to the mm3 and percentage were 35.64 (mean differences (MD) = 35.64, 95% CI: 26.43 to 44.85, z-value = 7.58, p-value < 0.001) and 14.38 (MD = 14.38, 95% CI = 10.50 to 18.26, z-value = 7.26, p < 0.001) units, respectively. Despite the undeniable role of autophagy in ischemic stroke, the dichotomous effects of autophagy regarding infarct volume reduction should be taken into account. Based on our findings, the studies included in this meta-analysis mostly reported a negative relation between autophagy induction and stroke volume development due to over-activity of autophagy upon the severe ischemic stroke; therefore, further pre-clinical studies are also recommended to establish adjusted autophagy with considering a time-dependent effect as a promising therapeutic target.