Medicinal signaling cells (MSC) hold promise for regenerative medicine due to their ability to repair damaged tissues. However, their effectiveness can be affected by how long they are cultured in the lab. This study investigated how passage number influences key properties for regenerative medicine of pig bone marrow MSC. The medicinal signiling cells derived from pig bone marrow (BM-MSC) were cultured in D-MEM High Glucose supplemented with 15% foetal bovine serum until the 25th passage and assessed their growth, viability, ability to differentiate into different cell types (plasticity), and cell cycle activity. Our findings showed that while the cells remained viable until the 25th passage, their ability to grow and differentiate declined after the 5th passage. Additionally, cells in later passages spent more time in a resting phase, suggesting reduced activity. In conclusion, the number of passages is a critical factor for maintaining ideal MSC characteristics. From the 9th passage BM-MSC exhibit decline in proliferation, differentiation potential, and cell cycle activity. Given this, it is possible to suggest that the use of 5th passage cells is the most suitable for therapeutic applications.

This study aimed to assess the utility of echocardiography-measured epicardial adipose tissue (EAT) thickness (EATT) as an independent predictor for coronary artery disease (CAD), examining its correlation with oxidative stress levels in epicardial tissue and the complexity of the disease in patients undergoing open-heart surgery. This study included a total of 25 patients referred for cardiac surgery with 14 in the CAD group and 11 in the non-CAD group. Epicardial fat was sampled from patients subjected to open-heart surgery EATT was higher in the CAD group compared to the non-CAD group (8.15 ± 2.09 mm vs. 5.12 ± 1.8 mm,  = 0.001). The epicardial reactive oxygen species level was higher in the CAD group compared to the non-CAD group (21.4 ± 2.47 nmol HO/g tisssue/h vs. 15.7 ± 1.55 nmol HO/g tisssue/h,  < 0.001). EATT greater than 6.05 mm was associated with CAD, with a sensitivity of 86% and specificity of 73%. Echocardiographically measured EATT is a significant, independent predictor of CAD. Its relationship with increased EAT oxidative stress levels suggests a potential mechanistic link between EATT and CAD pathogenesis. These findings highlight the importance of EATT as a diagnostic tool in assessing the complexity of CAD in patients undergoing cardiac surgery.

Integrating artificial intelligence (AI) into healthcare prompts the need to measure its proficiency relative to human experts. This study evaluates the proficiency of ChatGPT, an OpenAI language model, in offering guidance concerning bariatric surgery compared to bariatric surgeons. Five clinical scenarios representative of diverse bariatric surgery situations were given to ASMBS-accredited bariatric surgeons and ChatGPT. Both groups proposed medical or surgical management for the patients depicted in each scenario. The outcomes from both the surgeons and ChatGPT were examined and matched with the clinical benchmarks set by the American Society for Metabolic and Bariatric Surgery (ASMBS). There was a high degree of agreement between ChatGPT and physicians on the three simpler clinical scenarios. There was a positive correlation between physicians' and ChatGPT answers for not recommending surgery. ChatGPT's advice aligned with ASMBS guidelines 60% of the time, in contrast to bariatric surgeons, who consistently aligned with the guidelines 100% of the time. ChatGPT showcases potential in offering guidance on bariatric surgery, but it does not have the comprehensive and personalized perspective that doctors exhibit consistently. Enhancing AI's training on intricate patient situations will bolster its role in the medical field.

Jadomycin B, a natural product isolated from , exerts an anti-cancer effect on human triple negative breast cancer cells and has anti-tumoral effects in animal models of breast cancer. One proposed mechanism for this anti-cancer effect is through interaction with topoisomerase 2 (TOP2). Based on the previously described interactions between jadomycin B and TOP2 we hypothesized that jadomycin B will act additively with TOP2 poisons and produce a similar functional outcome in eliciting cell cycle arrest. Combined treatments of jadomycin B and the TOP2 poisons doxorubicin or mitoxantrone produced moderately synergistic to additive cytotoxicity (combination index values ranging from 0.72-0.94) in MDA-MB-231 cells. In comparison, combined mitoxantrone and doxorubicin produced additive cytotoxicity (combination index values 0.96-1.11). Jadomycin B combined with the proteosome inhibitor MG132 had additive cytotoxicity (combination index values 0.76-1.18). In contrast, mitoxantrone or doxorubicin cytotoxicity was antagonized by MG132 (combination index values 1.21-2.31). Jadomycin B treatment arrested cells in S-phase (P = 0.0024) as opposed to mitoxantrone which caused G/M-phase arrest (P < 0.0001). In conclusion, jadomycin B interacts differently than known TOP2 poisons in combination, supporting a novel pharmacological mechanism(s) of action for jadomycin B cytotoxicity.

Research on airway smooth muscle has traditionally focused on its putative detrimental role in asthma, emphasizing on how its shortening narrows the airway lumen, without much consideration about its potential role in subserving the function of the entire respiratory system. New experimental evidence on mice suggests that not only the smooth muscle is required to sustain life postnatally, but its stiffening effect on the lung tissue also protects against excessive airway narrowing and, most importantly, against small airway narrowing heterogeneity and closure. These results suggest that the smooth muscle plays an vital role in the lung periphery, essentially safeguarding alveolar ventilation by preventing small airway closure. These results also shed light on perplexing clinical observations, such as the long-standing doubts about the safety of bronchodilators. Since there seems to be an optimal level of smooth muscle contraction, at least in small airways, the therapeutic goal of maximizing the relaxation of the smooth muscle in asthma needs to be revisited. A bronchodilator with an excessive potency for inhibiting smooth muscle contraction, and that is still potent at concentrations reaching the lung periphery, may foster airway closure and air trapping, resulting in no net gain or even a decline in lung function.

Perivascular adipose tissue (PVAT) plays an important role in many physiological and pathological processes, such as regulation of vascular tone. The aim of this study is to evaluate the effects of pioglitazone on functional, structural, and biochemical properties of PVAT in an experimental model of type-2 diabetes (T2DM). T2DM was induced by high-fat-diet/low-dose-streptozotocin in rats, and pioglitazone (20 mg/kg/p.o.) was administered for 6 weeks. Changes in biochemical parameters, PVAT-mass, vascular-reactivity in thoracic-aorta, as well as PVAT adipocytokine and -expression levels, and histopathology were evaluated. Pioglitazone administration improved blood glucose and lipid profiles in T2DM. Pioglitazone did not change the anticontractile effect of PVAT on aortic contractile reactivity and besides, had no influence on endothelium-dependent and -independent relaxation responses. Pioglitazone administration increased PVAT-mass and tumor necrotizing factor-α levels, while adiponectin, leptin, and interleukin-6 levels were unchanged. Also, a prominent increase was observed in -expression in T2DM-Pio group. Moreover, pioglitazone decreased liver steatosis, aortic wall thickening, and myocardial damage, whereas increased adipocyte size and adiposity in PVAT. Overall, pioglitazone treatment changed the mass and in part the inflammatory profile of PVAT but did not modify vasoreactivity in T2DM. This study provides novel findings in relationship with the adipogenic effect of pioglitazone and PVAT function.

The heterocyclic 2-Aminothiazoles scaffolds are used in a wide range of therapeutic applications against various diseases for its antioxidant, anti-inflammatory, antimicrobial and anticancer actions. In the present study, we synthesized novel aniline aromatic ring-substituted 2-Aminothiazole derivatives. Molecular docking was performed using Glide module of the Schrödinger Suite to fit compounds JG-49, JG-62, and KBA-18 against the Nicotinamide phosphoribosyl transferase (Nampt) enzyme, an intracellular regulator of Nicotinamide adenine dinucleotide (NAD) redox cofactor involved in energy metabolism and epigenetics and are implicated in aging and metabolic diseases. The three compounds viz. JG-49, JG-62, and KBA-18 showed an increase in Nampt enzymatic activity in vitro. All three substituted derivatives of 2-Aminothiazole showed no cytotoxicity with the mouse C2C12 myoblasts cultures assessed with the MTT cell viability assay. Moreover, the wound closure of the mouse C2C12 myoblasts in vitro displayed no significant difference between the treatment groups of the 2-Aminothiazole derivatives compared with the control naïve and DMSO treated myoblasts cultures, except for the 2-Aminothiazole substituted derivatives JG-62 and KBA-18, which showed a significant increase in the wound closure compared with the control cells at different concentrations. Taken together, we demonstrated that 2-Aminothiazole substituted derivatives provide enhanced Nampt activity, wound closure, and no cytotoxic effects in vitro. Further studies will allow to improve the substitution of 2-Aminothiazole derivatives and test their potential therapeutic applications.

During cardiopulmonary resuscitation, pulmonary vasoconstriction due to hypoxia and hypercarbia restricts blood flow from the right to the left heart, resulting in reduced cardiac output that further inhibits adequate oxygenation and the ability to distribute oxygenated blood and medications. An inhaled pulmonary vasodilator could attenuate vasoconstriction and, therefore, increase cardiac output. We used rat isolated lungs to test if inhaled Argon leads to pulmonary vasodilation in phenylephrine-treated lungs. Lungs of 13 adult male Sprague Dawley rats were isolated, ventilated, and perfused. Pulmonary artery and left atrium were cannulated and lungs perfused at constant flow with 4% albumin physiological saline solution. Controls (n=6) were ventilated with 65% N, 5% CO, 30% O and Argon lungs (n=7) with 65% Argon, 5% CO, 30% O. Pulmonary mean arterial pressure (pMAP) and airway pressure (AWP) were recorded continuously, and pulmonary vascular resistance (PVR) was calculated. Following baseline readings, phenylephrine, a pulmonary vasoconstrictor, was perfused at increasing concentrations from 10 M to 10 M every 5 min. Statistics: Student's t-Test, α=0.05. Argon led to significantly lower pMAPs and PVRs, independent of AWP. Thus, it significantly dilated pre-constricted pulmonary vessels in an ex-vivo lung model. When given during resuscitation, this might aid to increase cardiac output.

Norepinephrine-dopamine reputake inhibitors (NDRIs), including bupropion, methylphenidate, atomoxetine, and reboxetine, are commonly prescribed for psychiatric disorders such as narcolepsy, attention-deficit/hyperactivity disorder, and depression. Cardiovascular adverse events have been reported to the FDA despite their effectiveness. This pharmacovigilance study analyzed cardiovascular adverse events associated with NDRIs using the FDA Adverse Event Reporting System data from January 2004 to December 2021. A retrospective analysis of adverse event reports was conducted, employing time-trend analysis and disproportionality evaluation to assess cardiovascular risks. Bupropion had the greatest reported odds ratios (RORs) for tachycardia (ROR = 4.2, 95% CI: 4.0-4.4) and hypertension (ROR = 3.5, 95% CI: 3.3-3.7), while methylphenidate showed greater ROR for arrhythmias (ROR = 2.8, 95% CI: 2.6-3.0) and palpitations (ROR = 3.1, 95% CI: 2.9-3.3). Reboxetine had signals for palpitations (ROR = 3.0, 95% CI: 2.8-3.2) and myocardial infarction (ROR = 2.7, 95% CI: 2.5-2.9), whereas atomoxetine revealed signals for hypertension (ROR = 2.9, 95% CI: 2.7-3.1) and syncope (ROR = 2.5, 95% CI: 2.3-2.7). Time-trend analysis revealed temporal variability in the cardiovascular risks connected with NDRIs. Our research elucidates cardiovascular safety profiles for NDRIs, highlighting the necessity for continuous pharmacovigilance. The observed variations in adverse events emphasize the need for ongoing surveillance to mitigate potential cardiovascular risks and enhance patient safety and treatment outcomes.

The purpose of this study was to determine the relationship between triptans (sumatriptan, rizatriptan, and zolmitriptan) and cardiovascular (CV) adverse events with data from the FDA Adverse Event Reporting System (FAERS). FAERS database was used to collect data on triptans from 1997 to 2023. Disproportionality methods were utilized to quantify triptan-associated CV events and to identify the potential risk. The reporting odds ratio was used to identify the risk signals. CV outcomes related to age, sex, clinical results, and other factors were also examined for triptans; 820 reports involving the triptans were recognized as CV adverse events out of total of 12 699 reports that were gathered from on FAERS database. Women reported more CV adverse events with rizatriptan and zolmitriptan as compared to men. The CV adverse event risk was highest among individuals aged 18-64. Clinical outcome analysis showed that sumatriptan carries a higher CV risk than rizatriptan and zolmitriptan, and most deaths and serious cases have been documented for sumatriptan. The patients prescribed sumatriptan or zolmitriptan were at a higher risk of reporting CV events for chest pain and chest discomfort, compared to rizatriptan. This finding may provide support for the clinical observation and risk evaluation of triptan treatment.

The cardiac rehabilitation quality indicators (CRQIs) developed by the Canadian Cardiovascular Society provide a means to standardize program assessment and identify sex-related inequities. No formal evaluation of the CRQIs has been conducted in Manitoba. An environmental scan for the CRQIs was performed using data in the electronic medical record at two cardiac rehabilitation (CR) sites in Winnipeg for 2016-2019 referrals. Of the 8116 referrals, 7758 (5491 males and 2267 females) had geographical access and were eligible for CR. The Manitoba Centre for Health Policy Data Quality Framework informed the data quality assessment. Thirteen CRQIs were available; four were considered high quality; nine demonstrated moderate to significant missing data. In addition to missing values, potential misclassification of risk (CR-4) and physiologically implausible and invalid dates were assessed and identified (CR-13 and CR-17). Each site had a physician medical director (CR-31) and a documented emergency response strategy (CR-32). Only high-quality data were evaluated for sex-related differences using chi-square and median tests. Women had lower enrollment (CR-3), and more women enrolled after the median of 41 days (CR-2b). Engagement with CR partners, including frontline staff, and utilizing strategies to assess and limit physiologically implausible values and dates will enhance data capture and quality.

Cyclophosphamide (CYP) is combined with cytoprotective agents to minimize its toxicity in the bladder, which is mediated by reactive oxygen species (ROS). Using multiple antioxidant mechanisms, nebivolol protects from oxidative stress in distinctive conditions. We hypothesized that nebivolol would attenuate both molecular and functional alterations induced by CYP in the bladder. Male C57BL/6 were pretreated or not with nebivolol (10 mg/kg/day, gavage), which was given 5 days before a single injection of CYP (300 mg/kg; i.p.). Molecular and functional parameters were assessed at 24 h in the bladder. Nebivolol prevented increases in ROS generation and lipoperoxidation as well as reduction of superoxide dismutase activity induced by CYP. Increased voiding frequency, decreased voiding interval, and reduced bladder capacity were found in CYP-treated mice. These responses were prevented by nebivolol. An augmented number of urinary spots and smaller urinary volumes were detected in CYP-injected mice, and nebivolol partially prevented these responses. The reduction of ROS levels is the primary mechanism by which nebivolol attenuates the deleterious effects of CYP in the bladder. The association of nebivolol with other cytoprotective agents could be an option to prevent CYP-associated oxidative damage to the bladder during chemotherapy.

Sarcopenia, a disorder marked by muscle loss and dysfunction, is a global health concern, particularly in aging populations. Sarcopenia is intricately related to various health conditions, including obesity, dysphagia, and frailty, which underscores the complexity. Despite recent advances in metabolomics and other omics data for early detection and treatment, the precise characterization and diagnosis of sarcopenia remains challenging. In the present review we provide an overview of the complex metabolic mechanisms that underlie sarcopenia, with particular emphasis on protein, lipid, carbohydrate, and bone metabolism. The review highlights the importance of leucine and other amino acids in promoting muscle protein synthesis and clarifies the critical role played by amino acid metabolism in preserving muscular health. In addition, the review provides insights regarding lipid metabolism on sarcopenia, with an emphasis on the effects of inflammation and insulin resistance. The development of sarcopenia is largely influenced by insulin resistance, especially with regard to glucose metabolism. Overall, the review emphasizes the complex relationship between bone and muscle health by highlighting the interaction between sarcopenia and bone metabolism. Furthermore, the review outlines various therapeutic approaches and potential biomarkers for diagnosing sarcopenia. These include pharmacological strategies such as hormone replacement therapy and anabolic steroids as well as lifestyle modifications such as exercise, nutrition, and dietary changes.

Lysophosphatidic acid (LPA) is a bioactive lipid that is mainly produced by the secreted lysophospholipase D, autotaxin (ATX), and signals through at least six G protein-coupled receptors (LPA1-6). Extracellular LPA is degraded through lipid phosphate phosphatases (LPP1, LPP2, and LPP3) at the plasmamembrane, terminating LPA receptor signaling. The ATX-LPA-LPP3 pathway is critically involved in a wide range of physiological processes, including cell survival, migration, proliferation, angiogenesis, and organismal development. Similarly, dysregulation of this pathway has been linked to many pathological processes, including cardiovascular disease. This review summarizes and interprets current literature examining the regulation and role of the ATX-LPA-LPP3 axis in heart disease. Specifically, the contribution of altered LPA metabolism via ATX and LPP3 and resulting changes to LPA receptor signaling in obesity cardiomyopathy, cardiac mitochondrial dysfunction, myocardial infarction/ischemia-reperfusion injury, hypertrophic cardiomyopathy, and aortic valve stenosis is discussed.