Search Results (133)

Despite the significant advancements in treatment and prevention, the fight against cancer is ongoing worldwide. This study evaluated the pharmacological properties and anticancer activity of Afzelia quanzensis bark, traditionally used by the indigenous communities of KwaZulu Natal and Eastern Cape Provinces of South Africa to treat cancer and related illnesses. Phytochemical screening, high-performance liquid chromatography–diode array detection (HPLC-DAD), and Fourier-transform infrared spectroscopy (FTIR) analyses were carried out using established protocols. The antioxidant activity was assessed via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and nitric oxide radicals. The anticancer activity was evaluated using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Phytochemical analysis revealed the presence of saponins, flavonoids, terpenoids, alkaloids, steroids, cardiac glycosides, and phlobatannins. The HPLC-DAD analysis detected seven distinctive peaks in the aqueous extract and three distinctive peaks in the methanolic extract. The FTIR spectra of the aqueous extract displayed characteristic peaks corresponding to O-H, C=O, C=C, and =C–H functional groups. Among the tested extracts, the methanol extract exhibited the strongest antioxidant activity, followed by the ethanolic extract, in both DPPH and nitric oxide. The methanol extract showed a higher cell proliferation inhibition against the DU-145 cancer cell line with the percentage of inhibition of 37.8%, followed by the aqueous extract with 36.3%. In contrast, limited activity was observed against PC-3, SK-UT-1, and AGS cell lines. The results demonstrated notable dose-dependent antioxidant and antiproliferative activities supporting the ethnomedicinal use of Afzelia quanzensis bark in cancer management. These findings warrant further investigation into its bioactive constituents and mechanisms of action. Full article

Background: Estrogens play a protective role during the early stages of life. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression. Aim: The purpose of this study was to test for the significance of the sex-specific associations of gonadal hormones with the extent of the inflammatory response, myocardial damage, and ventricular arrhythmia risk in acute myocardial infarction (MI). Materials and Methods: Study design: single-center cohort study. Blood samples for the assessment of sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitivity C-reactive protein (CRP), white blood cell (WBC) counts, and cardiac enzymes were collected 48 h after the onset of symptoms (and within 6 h after PCI) from 111 patients (37% women) with acute MI. Coronary disease severity, left ventricular systolic function (LV), and indices of ventricular repolarization were assessed using coronary angiography, echocardiography, and a conventional electrocardiogram, respectively. Results: In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels, peak WBC count, and peak CRP plasma levels. T levels and the E2/T ratio were associated with post-PCI CRP in these men. For women, peak WBC count was a marker of highest testosterone, and only WBC count was a significant indicator of myocardial injury extent. The incidence of acute ventricular tachycardia detected in AMI was significantly associated with left ventricular ejection fraction and with peak WBC count (as a tendency) regardless of sex. A longer duration of cardiac repolarization prior to PCI was predicted by lower ejection fractions in men and by age, CRP, and testosterone levels in female patients. Conclusions: During acute MI, elevated endogenous estradiol levels in men and increased leukocytes in women indicate acute myocardial damage. Post-PCI plasma inflammatory markers are sex-specific confounding factors for acute endogenous E2 levels, T levels, and the E2/T ratio. LV systolic function in men and, characteristically, the acute inflammatory response and testosterone levels in women are predictors of longer ventricular repolarization and arrhythmia risk. Full article

The highly conserved Wnt signaling pathway, a complex network critical for embryonic development and adult tissue homeostasis, regulates diverse cellular processes, ultimately influencing tissue organization and organogenesis; its dysregulation is implicated in numerous diseases, and it is known to be affected by oxidative pathways. This report reviews the recent literature on major classes of natural products with pronounced anti-oxidant properties, such as cardiac glycosides, steroid saponins, ecdysteroids, withanolides, cucurbitacins, triterpenes, flavonoids, and iridoids, that modulate its activity in various pathological conditions, summarizing and critically analyzing their effects on the Wnt pathway in various therapeutically relevant experimental models and highlighting the role of ROS-mediated crosstalk with Wnt signaling in these studies. Models reviewed include not only cancer but also stroke, ischemia, bone or kidney diseases, and regenerative medicine, such as re-epithelialization, cardiac maintenance, and hair loss. It highlights the paramount importance of modulating this signaling by natural products to define future research directions. We also discuss controversies identified in the mode of action of several compounds in different models and directions on how to further improve the quality and depth of such studies. Full article

Introduction: Hereditary transthyretin amyloidosis (ATTRv) is a severe, multisystemic, autosomal dominant disease with variable penetrance caused by mutations in the TTR gene generating protein misfolding and accumulation of amyloid fibrils. The diagnosis is usually challenging because ATTRv may initially manifest with nonspecific multisystemic symptoms. Conversely, an early diagnosis is needed to start timely appropriate therapy. Hence, screening models have been proposed to improve ATTRv diagnosis. In this study, we propose a genetic screening model based on predefined “red flags” followed by “cascading screening” on first-degree relatives of patients who tested positive. Materials and methods: After obtaining written informed consent, genetic testing on salivary swabs was performed in individuals who met at least two major red flags for ATTRv (age > 65 years old, progressive sensory or sensorimotor neuropathy not responsive to steroids or immunomodulant therapies, recent and unexplained weight loss associated with gastrointestinal signs and symptoms, diagnosis of cardiac amyloidosis, bilateral or relapsing carpal tunnel syndrome, unexplained autonomic dysfunction) or one major flag and two minor flags (family history of neuropathy, ambulation disorders or cardiopathy, sudden cardiac death, a bedridden, wheelchaired patient without specific diagnosis excluding upper motor neuron diseases, infections, juvenile cardiac disease, ocular disorders, lumbar spine stenosis, biceps tendon rupture). Results: In the first screening phase, 29 suspected cases (individuals meeting at least two major red flags or one major red flag and two minor red flags) underwent genetic testing. One patient (3.5%) was diagnosed with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), carrying the Phe64Leu mutation. Then, cascade screening allowed for early recognition of two additional individuals (two pre-symptomatic carriers) among two first-degree relatives (100%). The identified patient was a 72-year-old man who had a family history of both cardiopathy, neuropathy, and a diagnosis of juvenile cardiac disease and progressive sensorimotor neuropathy unresponsive to steroids or immunomodulant therapies. Conclusions: ATTRv is a progressive and often fatal disease that should be promptly diagnosed and treated to stop progression and reduce mortality. Systematic screening for ATTRv yielded increased recognition of the disease in our neurological clinic. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, enabling timely intervention through close clinical monitoring and early treatment initiation at symptom onset. Full article

Out-of-hospital cardiac arrest (OHCA) is a major public health burden due to its high mortality rate, sudden nature, and long-term impact on survivors. Consequently, there is a crucial need to create prediction models to better understand patient trajectories and assist clinicians and families in making informed decisions. We studied 107 adult OHCA patients admitted at an academic Emergency Department (ED) from 2018–2023. Blood samples and ocular ultrasounds were acquired at 1, 6, and 24 h after return of spontaneous circulation (ROSC). Six classes of clinical and novel variables were used: (1) Vital signs after ROSC, (2) pre-hospital and ED data, (3) hospital admission data, (4) ocular ultrasound parameters, (5) plasma protein biomarkers and (6) sex steroid hormones. A base model was built using 1 h variables in classes 1–3, reasoning these are available in most EDs. Extending from the base model, we evaluated 26 distinct neural network models for prediction of neurological outcome by the cerebral performance category (CPC) score. The top-performing model consisted of all variables at 1 h resulting in an AUROC score of 0.946. We determined a parsimonious set of variables that optimally predicts CPC score. Our research emphasizes the added value of incorporating ocular ultrasound, plasma biomarkers, sex hormones in the development of more robust predictive models for neurological outcome after OHCA. Full article

Platycarpha glomerata (Thunb.) Less. has recently become a plant species of interest to researchers due to its biological activities and less toxic effects. Therefore, the aim of the study is to evaluate the in vitro anticancer potential and phytochemical constituents of P. glomerata plant extracts. Phytochemical screening and FTIR were carried out using standard methods. The antioxidant activity was accessed by determining its ability to scavenge the DPPH radical and nitric oxide radical, whereas the anticancer activity against prostate (DU-145 and PC-3), human T-lymphocyte (SKU-T), gastric adenocarcinoma (AGS), and human prostatic epithelial (PNTA1) cell line was evaluated using the MTT assay. The phytochemical analysis revealed the presence of tannins, flavonoids, saponins, steroids, terpenoids, and cardiac glycosides. The FTIR spectrum for the aqueous extract displayed characteristic peaks for O–H, C=O, C=C, and =C–H stretch. The aqueous ethanol and methanol extracts showed significant dose-dependent DPPH radical scavenging capacity. The aqueous, ethanol, and methanol extracts showed minimum NO scavenging activity of 4.3%, 9.6%, and 11.7% at 2500 µg/mL. The water extract demonstrated good activity against S. aureus, E. coli, and B. pumilus with an MIC of 0.195 mg/mL. The ethanol and methanol extracts significantly reduced the percentage proliferation of DU-145, PC-3, and SKU-T cells at 100 μg/mL. These extracts demonstrated strong dose-dependent DPPH and NO scavenging and antibacterial and cell proliferation inhibition activities. The strong bioactivity of P. glomerata makes it a good candidate for the isolation and identification of active compounds for anticancer and related illnesses. Full article

Background: Hydrophilic polymer embolization (HPE) is a scarcely reported complication associated with endovascular procedures where the hydrophilic coating dislodges and disseminates to more distal vascular beds, leading to ischemic complications. The aim of this study is to assess the clinical outcomes associated with HPE in the literature and try to quantify it in a scoping manner. Methods: All reports with regard to HPE in the PubMed database where clinical data were available were included. Reports were excluded if no clinical data were available and only histopathological descriptions are available, if the language of the report was not in English, and if access could not be obtained to that specific report. Results: A total of 60 publications containing 111 patients were identified. The majority (N = 45, 75%) of the publications were “single-patient” case reports. An overwhelming minority of the reports reported underlying hypertension (N = 27, 45.0%) and ischemic heart disease (N = 28, 46.7%). The most common implicated procedures for HPE occurence were cardiac procedures (N = 28, 46.7%), intracranial procedures (N = 13, 21.7%) and aortic procedures (N = 10, 16.7%). Steroids were trialled in nine (15%) of the reports, mainly for HPE to the CNS (7/9), with no mortality in that specific group. However, HPE-related mortality, identified in 48/111 patients, was largely due to HPE with pulmonary and cardiac involvement (combined 36/48 of all deaths). Conclusions: HPE seems to be a rare occurrence, although low-quality evidence (mainly case reports) comprises most of the research on the subject. Fatal outcomes seem relatively common, and steroid therapy may be trialled in select cases. Further research, potentially through prospective registry studies may aid in providing more knowledge on HPE. Full article

Chronic kidney disease (CKD) is a major public health concern around the world. It is a significant risk factor for cardiovascular disease (CVD), and, as it progresses, the risk of cardiovascular events increases. Furthermore, end-stage kidney disease severely affects life expectancy and quality of life. Type 2 diabetes and hypertension are not only primary causes of CKD but also independent risk factors for CVD, which underscores the importance of effective treatment strategies for these conditions. The current therapies, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and sodium–glucose co-transporter 2 inhibitors, are administered to control hypertension, slow the progression of CKD, and reduce cardiovascular risk. However, their efficacy remains suboptimal in certain instances. Mineralocorticoid receptor (MR), a nuclear receptor found in various tissues, such as the kidney and heart, plays a pivotal role in the progression of CKD. Overactivation of MR triggers inflammation and fibrosis, which exacerbates kidney damage and accelerates disease progression. MR antagonists (MRAs) have substantial beneficial effects in patients with cardiac and renal conditions; however, their use has been constrained because of adverse effects, such as hyperkalemia and kidney dysfunction. Recently, novel non-steroidal MRAs are more efficacious and have superior safety profiles to steroidal MRAs, making them promising potential components of future treatment strategies. Here, we discuss recent findings and the roles of MRAs in the management of hypertension and CKD, with a focus on the evidence obtained from fundamental research and major clinical trials. Full article

Momordica balsamina Linn is a well-known African traditional herb due to its tremendous medicinal and nutritional properties. It is used worldwide for the treatment of different ailments and diseases. In the present study, the phytochemical and antioxidant activity of South African M. balsamina fruit pulp extracts was evaluated. The fruit pulp extracts were obtained by using the serial exhaustive extraction procedure using the solvents hexane, DCM, acetone, and methanol. The resulting extracts were subjected to different standard colorimetric tests for phytochemical analysis. The presence of compounds with antioxidant activity was determined using dot plot and TLC. The DPPH radical scavenging assay, hydrogen peroxide activity, and reducing power assay, coupled with linear regression, were employed to determine the quantity of antioxidants and their IC50. The results for qualitative phytochemical screening have shown that the fruit pulp contains alkaloids, cardiac glycosides, saponins, phenolic compounds, tannins, flavonoids, terpenoids, and steroids. All the extracts revealed the presence of antioxidant activity in both dot plot and TLC. Acetone extracts (0.279 mg/mL) showed the lowest IC50 compared to the standards gallic acid (0.4 mg/mL) and diosgenin (0.42 mg/mL). These findings confirmed that M. balsamina is very rich in phytochemical compounds and has strong antioxidant potential; therefore, it could be a potential source of drugs which in the future may serve the production of synthetically improved therapeutic agents. Full article

Background. Pericarditis has a heterogeneous clinical spectrum and rate of relapse. Data on aetiology, real-life treatment strategies, and long-term course from contemporary pericarditis cohorts are lacking. Methods. Pericarditis patients referred to the Cardioimmunology Outpatient Clinic at Padua University Hospital in 2001–2020 were retrospectively included. Kaplan–Meier method was used for recurrence-free survival probability estimation. The appropriateness of treatment was assessed based on the European Society of Cardiology guidelines. Results. One-hundred forty-four patients (57% males, mean age 50 years) followed up for 18 months (IQR 7–45) were included; of those, 52% had acute, 35% recurrent, 8% incessant, and 5% chronic pericarditis; 9% had cardiac tamponade at diagnosis. Time to pericardial effusion resolution was 53 days (IQR 16–124); median medical treatment duration was 87 days (IQR 48–148). Treatment was readjusted following the ESC guidelines for nonsteroidal anti-inflammatory drugs in 29% of the cases, steroids in 12%, and colchicine in 25%. Eleven (8%) patients were treated with anti-IL1 agents. Recurrence-free survival probability was 86% at 1st-year follow-up, and 23 patients (16%) had at least one recurrence, with a mean of two relapses per patient. Compared to patients without recurrences, they had a higher frequency of cardiac tamponade (27% vs. 6%, p = 0.006) and left bundle branch block (14% vs. 1%, p = 0.034). Out of the 144 patients, 5 (3%) were diagnosed as having constrictive pericarditis at first evaluation at our clinic, underwent successful pericardiectomy, and are currently alive and asymptomatic. Conclusions. When treated following a guideline-based approach, pericarditis has a favourable evolution. A relevant quote of cases benefits from the treatment readjustment of previously prescribed medical therapy when not in line with ESC recommendations. Cases relapsing despite treatment readjustment should receive anti-IL1 therapies. Full article

Pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (PH-HFpEF) represents a frequent form of PH related to left ventricular dysfunction. The pathophysiology of PH-HFpEF is intricate, and varied and includes vascular, cardiac, and pulmonary factors that contribute synergistically to developing this clinical syndrome. Improved knowledge of the pathophysiology of PH-HFpEF has paved the way for the use of new drugs such as angiotensin receptor neprilysin inhibitors (ARNIs), non-steroidal mineral corticoid receptor antagonist (nsMRA), sodium-glucose cotransporter inhibitors (SGLT2is), levosimendan, and glucagon-like peptide 1 (GLP-1) agonists. ARNIs are a widely used drug for the treatment of PH associated with heart failure with reduced ejection fraction. They have also recently been used in PH-HFpEF patients with hemodynamic benefits that need to be confirmed in future research. Finerenone is an innovative non-steroidal mineralocorticoid receptor antagonist that exhibits notable cardioprotective and renoprotective properties in individuals suffering from chronic diabetic kidney disease. It also enhances outcomes for patients with heart failure, whether they have mildly reduced or preserved ejection fraction. Moreover, in experimental studies, finerenone has been found to lower pulmonary artery pressure, reduce muscularization, and decrease the wall thickness of pulmonary arteries. SGLT2i have revolutionized the treatment of patients with heart failure irrespective of left ventricular ejection fraction, and their treatment is also associated with an improvement in the hemodynamics profile in patients with PH-HFpEF. Levosimendan is a widely used inodilator in the treatment of acute and advanced heart failure. In addition, its use in patients with PH-HFpEF (supported by the positive effects on pulmonary hemodynamics that levosimendan exerts) has recently demonstrated hemodynamic benefit in a small phase 2 study that paved the way for phase 3 studies and the creation of an oral formulation of levosimendan. Finally, GLP1 agonists are a class of drugs that, in preliminary evidence, have shown a positive effect on cardiac hemodynamics, mainly by facilitating left ventricular unloading. These effects, along with the reduction in insulin resistance and weight loss, likely lead to beneficial outcomes for PH-HFpEF patients, especially those with obesity as a comorbidity. Full article

Background: SARS-CoV-2 infection can lead to a potentially life-threatening condition known as SARS-CoV-2-associated multisystem inflammatory syndrome in children (MIS-C), which differs from the severe lung disease and thrombotic complications commonly seen in adults. Recently, similar cases have been identified in adults, characterized by a clinical multisystem inflammatory syndrome referred to as MIS-A, which can emerge as a late and severe complication of SARS-CoV-2 infection. Case Presentation: We report two cases of MIS-A that were recently admitted to our hospital. Both patients developed a severe multisystem inflammatory syndrome despite experiencing only mild SARS-CoV-2 infection. Key clinical features in both cases included significant systemic inflammation, prominent cardiac involvement, and thrombocytopenia. Prior SARS-CoV-2 infection was confirmed through serological testing. Treatment protocols for MIS-C, including steroids and immunoglobulins, proved effective for both patients. Conclusions: Clinicians should remain vigilant for MIS-A in the context of ongoing SARS-CoV-2 infection worldwide. This infection, even when presenting with mild or no symptoms, can progress to a life-threatening hyperinflammatory syndrome with cardiac implications if not promptly recognized and treated. Full article

Annona senegalensis pers, Sutherlandia frutescens (L.), and Withania somnifera (L.) are abundant plants and widely distributed in the Limpopo, Gauteng, Kwazulu-Natal, North West and Mpumalanga provinces in South Africa. The three plants are among those used by traditional healers and herbalists in South Africa for the treatment of a variety of diseases, including cancer. The current study aimed at the phytochemical screening and characterization of volatile compounds from the three medicinal plants using GC-MS. The methanol leaf extracts were subjected to phytochemical screening using standard chemical tests to detect the presence of different classes of compounds. Volatile compounds were detected by GC-MS analysis, and detected compounds were identified by comparing the MS spectral data with those of compounds deposited in the NIST Library (NIST08). Phytochemical screening indicated the presence of different secondary metabolites such as alkaloids, quinones, steroids, cardiac glycosides, coumarins, and terpenoids in all plants. GC-MS chromatograms allowed the detection and identification of 19 volatile compounds among the three plants with known bioactivities that are important in the management of life-threatening diseases such as cancer and diabetes. The results confirm the leaves of Annona senegalensis, Sutherlandia frutescens, and Withania somnifera as sources of important phytochemicals and therefore justify their use for the treatment of various diseases by traditional healers. Full article

Na⁺-K⁺ ATPase is an integral component of cardiac sarcolemma and consists of three major subunits, namely the α-subunit with three isoforms (α₁, α₂, and α₃), β-subunit with two isoforms (β₁ and β₂) and γ-subunit (phospholemman). This enzyme has been demonstrated to transport three Na and two K ions to generate a trans-membrane gradient, maintain cation homeostasis in cardiomyocytes and participate in regulating contractile force development. Na⁺-K⁺ ATPase serves as a receptor for both exogenous and endogenous cardiotonic glycosides and steroids, and a signal transducer for modifying myocardial metabolism as well as cellular survival and death. In addition, Na⁺-K⁺ ATPase is regulated by different hormones through the phosphorylation/dephosphorylation of phospholemman, which is tightly bound to this enzyme. The activity of Na⁺-K⁺ ATPase has been reported to be increased, unaltered and depressed in failing hearts depending upon the type and stage of heart failure as well as the association/disassociation of phospholemman and binding with endogenous cardiotonic steroids, namely endogenous ouabain and marinobufagenin. Increased Na⁺-K⁺ ATPase activity in association with a depressed level of intracellular Na⁺ in failing hearts is considered to decrease intracellular Ca²⁺ and serve as an adaptive mechanism for maintaining cardiac function. The slight to moderate depression of Na⁺-K⁺ ATPase by cardiac glycosides in association with an increased level of Na⁺ in cardiomyocytes is known to produce beneficial effects in failing hearts. On the other hand, markedly reduced Na⁺-K⁺ ATPase activity associated with an increased level of intracellular Na⁺ in failing hearts has been demonstrated to result in an intracellular Ca²⁺ overload, the occurrence of cardiac arrhythmias and depression in cardiac function during the development of heart failure. Furthermore, the status of Na⁺-K⁺ ATPase activity in heart failure is determined by changes in isoform subunits of the enzyme, the development of oxidative stress, intracellular Ca²⁺-overload, protease activation, the activity of inflammatory cytokines and sarcolemmal lipid composition. Evidence has been presented to show that marked alterations in myocardial cations cannot be explained exclusively on the basis of sarcolemma alterations, as other Ca²⁺ channels, cation transporters and exchangers may be involved in this event. A marked reduction in Na⁺-K⁺ ATPase activity due to a shift in its isoform subunits in association with intracellular Ca²⁺-overload, cardiac energy depletion, increased membrane permeability, Ca²⁺-handling abnormalities and damage to myocardial ultrastructure appear to be involved in the progression of heart failure. Full article

Thevetia thevetioides is a species within the Apocynaceae family known for containing cardenolide-glycosides, commonly referred to as cardiac glycosides, which are characteristic of this genus. The seeds of the Thevetia species are frequently used as a model source for studying cardiac steroids, as these glycosides can be more readily extracted from the oil-rich seeds than from the plant’s green tissues. In this work, the cardenolide profile of ripe and immature seeds was determined and compared to establish the main differences. Ripe seeds contain six related cardenolides and triosides, with thevetin B being the predominant component. In contrast, immature seeds exhibit a total of thirteen cardiac glycosides, including monoglycosides such as neriifolin and peruvosides A, B, and C, as well as diglycosides like thevebiosides A, B, and C. Some of these compounds have previously been identified as degradation products of more complex cardiac glycosides; however, their presence in immature seeds, as described in this study, suggests that they may serve as biosynthetic precursors to the triosides observed in mature seeds. The glycoside patterns observed via HPTLC are associated with specific chemical structures characteristic of this genus, typically featuring thevetose or acetyl-thevetose at the first position, followed by glucose or gentibiose in di- or trisaccharides, independent of the trioside aglycones identified: digitoxigenin, cannogenin, or yccotligenin. Ripe seeds predominantly contain triosides, including thevetin B, C, and A, the latter of which has not been previously reported. Full article