Mitochondrial transfer from Adipose stem cells to breast cancer cells drives multi-drug resistance.

BACKGROUND: Breast cancer (BC) is a complex disease, showing heterogeneity in the genetic background, molecular subtype, and treatment algorithm. Historically, treatment strategies have been directed towards cancer cells, but these are not the unique components of the tumor bulk, where a key role is played by the tumor microenvironment (TME), whose better understanding could be crucial to obtain better outcomes. METHODS: We evaluated mitochondrial transfer (MT) by co-culturing Adipose stem cells with different Breast cancer cells (BCCs), through MitoTracker assay, Mitoception, confocal and immunofluorescence analyses. MT inhibitors were used to confirm the MT by Tunneling Nano Tubes (TNTs). MT effect on multi-drug resistance (MDR) was assessed using Doxorubicin assay and ABC transporter evaluation. In addition, ATP production was measured by Oxygen Consumption rates (OCR) and Immunoblot analysis. RESULTS: We found that MT occurs via Tunneling Nano Tubes (TNTs) and can be blocked by actin polymerization inhibitors. Furthermore, in hybrid co-cultures between ASCs and patient-derived organoids we found a massive MT. Breast Cancer cells (BCCs) with ASCs derived mitochondria (ADM) showed a reduced HIF-1α expression in hypoxic conditions, with an increased ATP production driving ABC transporters-mediated multi-drug resistance (MDR), linked to oxidative phosphorylation metabolism rewiring. CONCLUSIONS: We provide a proof-of-concept of the occurrence of Mitochondrial Transfer (MT) from Adipose Stem Cells (ASCs) to BC models. Blocking MT from ASCs to BCCs could be a new effective therapeutic strategy for BC treatment.

Efficacy and safety of semaglutide in patients with heart failure with preserved ejection fraction and obesity.

BACKGROUND: Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has shown promise in weight management and cardiovascular outcomes in other populations. This study aimed to evaluate the efficacy of semaglutide in heart failure with preserved ejection fraction (HFpEF) patients with obesity. METHODS: A retrospective study analyzed 318 patients with HFpEF, of which 104 received semaglutide and 214 received placebo. Primary endpoints included evaluating changes in exercise capacity and weight management. RESULTS: Semaglutide treatment led to significant improvements in the primary endpoints. Patients in the semaglutide group demonstrated substantial enhancements in exercise capacity, as measured by the 6-min walk distance, compared to the placebo group (mean difference 15.1 meters, 95% CI 5.8 to 24.4, p = 0.002). Additionally, semaglutide resulted in substantial weight loss compared to placebo (mean difference -2.9%, 95% CI -4.1--1.7, p = 0.001). Several secondary endpoints, including reductions in C-reactive protein levels and improvements in other clinical parameters, further supported the efficacy of semaglutide. Adverse events were generally well-tolerated, with no unexpected safety concerns. CONCLUSION: Semaglutide demonstrated significant clinical benefits in HFpEF patients with obesity, as evidenced by improved symptoms, physical function, and weight reduction.

Coronary Stent Infection: A Systematic Review of Literature.

Coronary stent infection is a rare yet serious complication of coronary artery stenting, with potentially significant morbidity and mortality. This systematic review aimed to comprehensively assess the available evidence on the diagnosis, management, and outcomes of coronary stent infection. A comprehensive search of electronic databases, including PubMed, Embase, Cochrane Library, and Scopus, was conducted from inception until March 2023, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 1 case series and 41 case reports, covering a cumulative sample size of 44 patients, were included in the analysis. The predominant stent types were drug-eluting stents in 22 studies, bare-metal stents in 3 studies, and a combination of drug-eluting stents and bare-metal stents in 4 studies. Staphylococcus aureus was the predominant identified organism in microbiological profiles. Primary outcomes, including mortality, morbidity, and recurrence rates, were evaluated. The aggregate mortality rate across studies was 18%, underscoring the severity of coronary stent infections. Morbidity ranged from 3% to 60%, with a spectrum of complications such as sepsis, heart failure, and embolic events. Recurrence rates varied from 3% to 33%, emphasizing the importance of effective management. Treatment strategies encompassed antibiotics alone, antibiotics with stent removal, and antibiotics with stent retention, with the duration of antibiotic therapy ranging from 2 weeks to 12 months. The optimal management strategy remains uncertain due to limited high-quality evidence. Early diagnosis and treatment were emphasized as critical factors in improving outcomes. Prophylactic antibiotics during stenting procedures and increased awareness among healthcare providers were suggested as preventive measures.

Outcomes of European Society of Cardiology 0/1-h algorithm with high-sensitivity cardiac troponin T among patients with coronary artery disease.

OBJECTIVE: The European Society of Cardiology (ESC) 0/1-h Algorithm with high-sensitivity cardiac troponin T (hs-cTnT) has shown promising results in risk stratification and management of patients with coronary artery disease (CAD). However, its outcomes and clinical implications in the context of developing countries remain understudied. METHODS: This cohort study aimed to evaluate the outcomes and clinical significance of the ESC 0/1-h Algorithm in a developing country setting. A total of 3534 patients with CAD were enrolled, with 1125 in the Rule-Out group and 2409 in the Rule-In group. Baseline characteristics, performance metrics, primary and secondary outcomes, and predictors of Rule-In and Rule-Out groups were assessed. RESULTS: The study enrolled 3534 patients with CAD, with 1125 in the Rule-Out group and 2409 in the Rule-In group. The 0/1-h Algorithm with hs-cTnT demonstrated improved performance compared to Troponin T at Presentation. It exhibited higher sensitivity, specificity, negative predictive value, positive predictive value, and area under the curve (AUC) for risk stratification in patients with CAD. Significant differences were observed in baseline characteristics between the Rule-Out and Rule-In groups, including age, gender, and comorbidities. The Rule-In group had a higher incidence of adverse cardiac events and underwent more invasive procedures compared to the Rule-Out group. Age, gender, hypertension, diabetes, and smoking were identified as significant predictors of Rule-In and Rule-Out. These findings highlight the clinical significance of implementing the 0/1-h Algorithm in the management of patients with CAD in a developing country setting. CONCLUSION: The algorithm's performance, along with its ability to identify high-risk patients and predict outcomes, highlights its potential to enhance patient care and outcomes in resource-limited settings.

Mesenchymal Stem Cells in Soft Tissue Regenerative Medicine: A Comprehensive Review.

Soft tissue regeneration holds significant promise for addressing various clinical challenges, ranging from craniofacial and oral tissue defects to blood vessels, muscle, and fibrous tissue regeneration. Mesenchymal stem cells (MSCs) have emerged as a promising tool in regenerative medicine due to their unique characteristics and potential to differentiate into multiple cell lineages. This comprehensive review explores the role of MSCs in different aspects of soft tissue regeneration, including their application in craniofacial and oral soft tissue regeneration, nerve regeneration, blood vessel regeneration, muscle regeneration, and fibrous tissue regeneration. By examining the latest research findings and clinical advancements, this article aims to provide insights into the current state of MSC-based therapies in soft tissue regenerative medicine.

Graphene-grafted bimetallic MOF membranes for hazardous & toxic contaminants treatment.

Development of membrane with improved carbon dioxide (CO2) gas separation capability is a significant challenge. However, the fabrication of membrane that efficiently separate and purification CO2-containing gases has been the focus of global attention. Cellulose Acetate (CA) has robust reinforcing characteristics when incorporated within a suitable polymer matrix. This work focus on the synthesis of novel mixed matrix membranes (MMMs) by introducing Graphene-grafted bimetallic MOFs in Cellulose Acetate polymer. The graphene-grafted bimetallic MOF (GG-BM MOFs) was prepared by a hydrothermal technique. Whereas, the solution casting approach used to fabricate membranes. The 1-5 wt% of GG-BM MOFs incorporated into the CA matrix. The mechanical, hydrophilicity and adsorption characteristics of fabricated MMMs were investigated. The crystallinity of MMM enhanced after the addition of GG-BM MOFs. In addition, the mechanical characteristics of MMMs were improved with the incorporation of GG-BM MOFs inside the polymer matrix. Maximum stress and strain was obtained for 2 wt% MMM (36.4 N/mm2 and 11% respectively). The CO2 adsorption performance was evaluated at 10 bar and 45 °C. The FTIR results represent insignificant bond shifting with the addition GG-BM MOFs at these conditions. The overall results showed that MMMs containing 2 wt% GG-BM MOFs have good adsorption properties for CO2 i.e 3.15 wt% of CO2. The MMMs have shown a decrease in the mechanical properties and CO2 adsorption at the higher GG-BM MOFs loading due to the presence of agglomeration which was confirmed through SEM. Thus, the addition of GG-BM MOFs in the CA matrix positively altered the physicochemical characteristics of the resulting MMMs, which could assist them in achieving remarkable CO2 adsorption at 2 wt%.

Cellulose acetate based sustainable nanostructured membranes for environmental remediation.

Membrane-based gas separation has a great potential for reducing environmentally hazardous carbon dioxide (CO2) gas. The polymeric membranes developed for CO2 capturing have some limitations in their selectivity and permeability. There is a need to overcome these issues and developed such membranes having high-performance CO2 capture with cost-effectiveness. The present study aimed to synthesize mixed matrix membranes (MMMs) having improved properties CO2 adsorption performance and stability than that of pure polymer. Further, the effect on CO2 adsorption by increasing the filler concentration in MMMs was investigated. The MMMs were synthesized by incorporating (1-5 wt%) Cu-MOF-GO composites as filler into cellulose-acetate (CA) polymer matrix by adopting the solution casting method. The performance of MMMs was studied by changing the Cu-MOF-GO composite concentration (1-5 wt%) in the polymer matrix at 45 °C up to 15 bar. Morphological analysis by using SEM confirms that by increasing the concentration of Cu-MOF-GO more than 3% will result in their agglomeration in MMM. The successful incorporation of MOF within the polymer matrix of MMMs was confirmed through the presence of functional groups using FTIR and Raman spectroscopy. XRD analysis revealed that pure CA changes its semi-crystalline behaviour into crystalline by the addition of Cu-MOF-GO. The maximum tensile stress and strain rate of MMMs was 45.1 N/mm2 and 12.8%. In addition, with an increase in (4-5 wt%) Cu-MOF-GO concentration the hydrophilicity of MMMs decreases. The maximum uptake rate of CO2 was 1.79 mmol/g and 7.98 wt% at 15 bar. The adsorption results conclude that Cu-MOF-GO composite and CA-based MMM can be effective for CO2 capture.

Biogenic Selenium Nanoparticles: Potential Solution to Oxidative Stress Mediated Inflammation in Rheumatoid Arthritis and Associated Complications.

Rheumatoid arthritis (RA) is a common chronic inflammation-mediated disorder having systematic complications. RA triggers a self-directed inflammatory and immunological cascade that culminates in joint destruction. Though a range of treatment options are available, none of them are without adverse effects and this has led researchers to search for alternative solutions. Nanomedicine has emerged as a powerful therapeutic alternative, and selenium (Se) is an essential micronutrient trace element that has a crucial role in human health and disease. Selenium nanoparticles (SeNPs) derived from biological sources, such as plants, bacteria, fungi, and proteins, have exhibited remarkable candidate properties and toxicological profiles, and hence have shown potential to be used as antirheumatic agents. The potential of SeNPs can be attributed to the effect of functional groups bound to them, concentration, and most importantly to their nano range size. The antirheumatic effect of SeNPs is considerable due to its potential in amelioration of oxidative stress-mediated inflammation via downregulation of radical and nonradical species, markers of inflammation, and upregulation of inherent antioxidant defenses. The size and concentration impact of SeNPs has been shown in the subsequent antioxidant and anti-inflammatory properties. Moreover, the article emphasizes the role of these biogenic SeNPs as a notable option in the nanomedicine arena that needs to be further studied as a prospective remedial alternative to cure RA and medication-related adverse events.

Adsorption of CO2 on amine-functionalized green metal-organic framework: an interaction between amine and CO2 molecules.

The efficient capture of CO2 is a critical problem for porous adsorbents. The inadequacy of conventional adsorbents has low adsorption capacity towards CO2 removal. Metal organic frame work has been considered as very effective for CO2 adsorption as it shows higher rate of CO2 adsorption at room temperature. In conventional amine processes, a comparatively high energy penalty is required, whereas a novel class of metal-organic framework by the combination of amine solvent have improve the potential of adsorption process and also the efficiency of separation. Amine-functionalized MOFs become more fascinated due to strong interaction between carbon dioxide and amine-functionalized MOF. A renewable green γCD-MOF was synthesized by using vapor diffusion method. Post-synthetic modification of γCD-MOF was done with piperazine and analyzed to expose its crystalline structure, morphology, and porous structure. The main aim of this paper is to enhance the CO2 adsorption by functionalization of inexpensive, green, nanoporous γCD-MOF and also to highlight the effects of amine-based functionalization towards potential application. Gravimetric CO2 adsorption isotherms for γCD-MOF, pip-γCD-MOF are reported up to 60 °C and found to follow a pseudo-second-order reaction. The pip-γCD-MOF confirms comparatively increased rapid adsorption rate of CO2 than that of γCD-MOF and desorption of CO2, and need less energy for regeneration. These results are the complete evidence of piperazine as an efficient amine group for increasing the CO2 adsorption uptake capacity.

Evaluation of prescription errors and prescribing indicators in the private practices in Bahawalpur, Pakistan.

BACKGROUND: Appropriate use of medicines is important to provide quality health. The aim of this study was to assess the prescribing practices and prescription errors in the private clinic practices of Bahawalpur, Pakistan. METHODS: A cross-sectional observational study was performed in March 2015 to assess the prescribing practices and prescription errors in the private clinical practices of Bahawalpur, Pakistan. We used the standard World Health Organization (WHO) methodology to achieve the study objectives. A convenience sampling technique was used to collect the prescriptions from five community pharmacies. RESULTS: A total of 300 prescriptions were collected. Among the prescribing indicators, the average number of drugs per encounter was 4.5, 23.3% of drugs were prescribed by generic name, 39.6% of encounters resulted in the prescription of antibiotics, in 19% of encounters injections were prescribed and 54.5% of the drugs prescribed were from the Essential Drugs List. A total of 1218 omissions, 510 commissions and 199 drug interaction-related errors were recorded. CONCLUSION: Irrational prescribing of medicines and low compliance with the standards of prescription writing were observed in the private clinical practices of Bahawalpur.