Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model.</p> <p>Methods</p> <p>Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 μL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h.</p> <p>Results</p> <p>In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05).</p> <p>Conclusion</p> <p>MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model.</p

Intra-coronary administration of tacrolimus markedly attenuates infarct size and preserves heart function in porcine myocardial infarction

BACKGROUND: We test the hypothesis that intra-coronary tacrolimus administration can limit infarct size and preserve left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) through ligating left anterior descending coronary artery (LAD) in mini-pigs. METHODS: Twelve male mini-pigs were randomized into AMI-saline (MI-only) group and AMI-tacrolimus (MI-Tac) group that received intra-coronary saline (3.0 mL) and tacrolimus (0.5 mg in 2.5 mL saline) injection, respectively, beyond site of ligation 30 minutes after LAD occlusion. RESULTS: Larger infarct area was noted in MI-only group (p < 0.001). Inflammatory biomarkers at protein [oxidative stress, tumor necrotic factor-α, nuclear factor-κB], gene (matrix metalloproteinase-9, plasminogen activator inhibitor-1), and cellular (CD40+, CD68+ inflammatory cells) levels were remarkably higher in MI-only animals (p < 0.01). Conversely, anti-inflammatory biomarkers at gene level (Interleukin-10), gene and protein level (endothelial nitric oxide synthase), and anti-oxidant biomarkers at both gene and protein levels [heme oxygenase 1, NAD(P)H:quinone oxidoreductase] were lower in MI-only group (p < 0.01). Number of apoptotic nuclei and apoptotic biomarkers expressions at gene and protein levels (Bax, caspase 3) were notably higher, whereas anti-apoptotic biomarkers at gene and protein levels (Bcl-2), LVEF, and fractional shortening were markedly lower in MI-only group (p < 0.001). CONCLUSION: Intra-coronary administration of tacrolimus significantly attenuated infarct size and preserved LV function

Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy

<p>Abstract</p> <p>Background</p> <p>We investigated whether early combined autologous adipose-derived mesenchymal stem cell (ADMSC) and sildenafil therapy offers an additive benefit in preserving heart function in rat dilated cardiomyopathy (DCM).</p> <p>Methods</p> <p>Adult Lewis rats (n = 8 per group) were divided into group 1 (normal control), group 2 (saline-treated DCM rats), group 3 [2.0 × 10⁶ADMSC implanted into left ventricular (LV) myocardium of DCM rats], group 4 (DCM rats with sildenafil 30 mg/kg/day, orally), and group 5 (DCM rats with combined ADMSC-sildenafil). Treatment was started 1 week after DCM induction and the rats were sacrificed on day 90.</p> <p>Results</p> <p>The results showed that mitochondrial protein expressions of connexin43 and cytochrome-C were lowest in group 2, and lower in groups 3 and 4 than in group 5 (p < 0.002). Conversely, oxidative index was highest in group 2, and also higher in groups 3 and 4 than in group 5 (p < 0.0003). The mRNA expressions of interleukin (IL)-10, Gro/IL-8, endothelial nitric oxide synthase, and Bcl-2 were lowest in group 2, and lower in groups 3 and 4 compared with group 5 (p < 0.0001). The mRNA expressions of matrix metalloproteinase-9, Bax, caspase 3, and stromal-cell derived factor-1α were highest in group 2, and higher in groups 3 and 4 than in group 5 (p < 0.0004). Apoptosis and fibrosis in LV myocardium were most prominent in group 2 and higher in groups 3 and 4 than in group 5, whereas angiogenesis and LV ejection fraction were lowest in group 2 and lower in groups 3 and 4 than in group 5 (p < 0.003).</p> <p>Conclusion</p> <p>Early combined ADMSC/sildenafil is superior to either treatment alone in preserving LV function.</p

Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction

<p>Abstract</p> <p>Background</p> <p>Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR) injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury.</p> <p>Methods</p> <p>Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus immediate intra-renal administration of 1.0 × 10⁶autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR). The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed.</p> <p>Results</p> <p>Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p < 0.03). The mRNA expressions of inflammatory, oxidative stress, and apoptotic biomarkers were lower, whereas the anti-inflammatory, anti-oxidative, and anti-apoptotic biomarkers were higher in group 3 than in group 2 (all p < 0.03). Immunofluorescent staining showed a higher number of CD31+, von Willebrand Factor+, and heme oxygenase (HO)-1+ cells in group 3 than in group 2 (all p < 0.05). Western blot showed notably higher NAD(P)H quinone oxidoreductase 1 and HO-1 activities, two indicators of anti-oxidative capacity, in group 3 than those in group 2 (all p < 0.04). Immunohistochemical staining showed higher glutathione peroxidase and glutathione reductase activities in group 3 than in group 2 (all p < 0.02)</p> <p>Conclusion</p> <p>ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.</p

Acute kidney injury in patients with COVID-19 compared to those with influenza: a systematic review and meta-analysis

BackgroundCOVID-19 and influenza can both lead to acute kidney injury (AKI) as a common complication. However, no meta-analysis has been conducted to directly compare the incidence of AKI between hospitalized patients with COVID-19 and influenza. The objective of our study aims to investigate the incidence and outcomes of AKI among hospitalized patients between these two groups.Materials and methodsA systematic search of PubMed, Embase, and Cochrane databases was conducted from December 2019 to August 2023 to identify studies examining AKI and clinical outcomes among hospitalized patients with COVID-19 and influenza. The primary outcome of interest was the incidence of AKI, while secondary outcomes included in-hospital mortality, recovery from AKI, hospital and ICU stay duration. The quality of evidence was evaluated using Cochrane and GRADE methods.ResultsTwelve retrospective cohort studies, involving 17,618 hospitalized patients with COVID-19 and influenza, were analyzed. COVID-19 patients showed higher AKI incidence (29.37% vs. 20.98%, OR: 1.67, 95% CI 1.56–1.80, p &lt; 0.01, I2 = 92.42%), and in-hospital mortality (30.95% vs. 5.51%, OR: 8.16, 95% CI 6.17–10.80, p &lt; 0.01, I2 = 84.92%) compared to influenza patients with AKI. Recovery from AKI was lower in COVID-19 patients (57.02% vs., 80.23%, OR: 0.33, 95% CI 0.27–0.40, p &lt; 0.01, I2 = 85.17%). COVID-19 patients also had a longer hospital stay (SMD: 0.69, 95% CI 0.65–0.72, p &lt; 0.01, I2 = 98.94%) and longer ICU stay (SMD: 0.61, 95% CI 0.50–0.73, p &lt; 0.01, I2 = 94.80%) than influenza patients. In our study, evidence quality was high (NOS score 7–9), with low certainty for AKI incidence and moderate certainty for recovery form AKI by GRADE assessment.ConclusionCOVID-19 patients had higher risk of developing AKI, experiencing in-hospital mortality, and enduring prolonged hospital/ICU stays in comparison to influenza patients. Additionally, the likelihood of AKI recovery was lower among COVID-19 patients

Talent Sustainability and Development: How Talent Management Affects Employees’ Intention to Stay through Work Engagement and Perceived Organizational Support with the Moderating Role of Work–Life Balance

The pandemic and the war have caused challenges, creating a shortage of labor and talent crisis. Organizations have reviewed their work patterns to retain talent and increase employee retention. Data are collected from 344 employees working in Taiwan. This study divides the sample into “key talents” and “non-key talents” and aims to examine how talent management, work engagement, and perceived organizational support affect employees’ intention to stay. The results of this study indicate a significant positive relationship between talent management, work engagement, perceived organizational support, and the intention to stay. This study also confirmed the mediating role of work engagement and perceived organizational support in the relationship between talent management and the intention to stay. Furthermore, work–life balance exerts a notable moderating influence on the relationships among work engagement, perceived organizational support, and the intention to stay. The findings of this research reveal that when employees consider themselves “key talents”, talent management is positively and significantly correlated with the intention to stay. Companies must continuously innovate their talent management strategies to meet employees’ high expectations for a favorable work environment and development opportunities, achieving mutual benefit for both the organization and its employees

Improving Tirapazamine (TPZ) to Target and Eradicate Hypoxia Tumors by Gold Nanoparticle Carriers

Tumor hypoxia is a hallmark of solid tumors and emerged as the therapeutic target for cancer treatments, such as a prodrug Tirapazamine (TPZ) activated in hypoxia. To increase tumor accumulation, gold nanoparticles (GNPs) were selected to conjugate with TPZ. In this study, we successfully formulated and assessed the biochemical and therapeutic roles of the conjugated gold nanoparticles–Tirapazamine (GNPs–TPZ) on therapeutic assessments of MKN45-induced xenograft animal model. The results indicated that GNPs–TPZ was a potential nanomedicine for selectively targeting hypoxia tumors coupled with decreased side effects on healthy tissue or organs. TPZ significantly reduced cell viability of hypoxic gastric cancer MKN45 cells, but not in cells incubated in normoxia condition. For improving tumor targeting efficiency, furthermore, the GNPs drug carrier was conjugated to TPZ via biding mediator bovine serum albumin (BSA), and we demonstrated that this conjugated GNPs–TPZ retained the unique characteristics of hypoxic toxin and possessed the adequate feature of systemic bio-distributions in animals. GNPs–TPZ nanoparticles revealed their superior affinity to hypoxia tumors in the MKN45 xenograft. Moreover, GNPs–TPZ treatments did not significantly alter the biochemical parameters of blood samples acquired from animals. Taken together, TPZ, a prodrug activated by hypoxia, was conjugated with GNPs, whereas BSA severed as an excellent binding agent for preparing the conjugated GNPs–TPZ nanomedicines. We demonstrated that GNPs–TPZ enhanced tumor targeting, resulting in higher therapeutic efficacy compared to TPZ. We suggest that it may sever as an adjuvant treatment or combined therapy with other chemotherapeutics for the treatment of cancer patients in the future

Improving Tirapazamine (TPZ) to Target and Eradicate Hypoxia Tumors by Gold Nanoparticle Carriers

Tumor hypoxia is a hallmark of solid tumors and emerged as the therapeutic target for cancer treatments, such as a prodrug Tirapazamine (TPZ) activated in hypoxia. To increase tumor accumulation, gold nanoparticles (GNPs) were selected to conjugate with TPZ. In this study, we successfully formulated and assessed the biochemical and therapeutic roles of the conjugated gold nanoparticles&ndash;Tirapazamine (GNPs&ndash;TPZ) on therapeutic assessments of MKN45-induced xenograft animal model. The results indicated that GNPs&ndash;TPZ was a potential nanomedicine for selectively targeting hypoxia tumors coupled with decreased side effects on healthy tissue or organs. TPZ significantly reduced cell viability of hypoxic gastric cancer MKN45 cells, but not in cells incubated in normoxia condition. For improving tumor targeting efficiency, furthermore, the GNPs drug carrier was conjugated to TPZ via biding mediator bovine serum albumin (BSA), and we demonstrated that this conjugated GNPs&ndash;TPZ retained the unique characteristics of hypoxic toxin and possessed the adequate feature of systemic bio-distributions in animals. GNPs&ndash;TPZ nanoparticles revealed their superior affinity to hypoxia tumors in the MKN45 xenograft. Moreover, GNPs&ndash;TPZ treatments did not significantly alter the biochemical parameters of blood samples acquired from animals. Taken together, TPZ, a prodrug activated by hypoxia, was conjugated with GNPs, whereas BSA severed as an excellent binding agent for preparing the conjugated GNPs&ndash;TPZ nanomedicines. We demonstrated that GNPs&ndash;TPZ enhanced tumor targeting, resulting in higher therapeutic efficacy compared to TPZ. We suggest that it may sever as an adjuvant treatment or combined therapy with other chemotherapeutics for the treatment of cancer patients in the future