Discovery medicine最新文献

Background: Myocardial ischemia/reperfusion (I/R) injury stands as a primary contributor to ischemic heart disease. Sevoflurane (SEVO), a commonly used inhalation anesthetic, has been shown to exert a direct protective effect on ischemic heart injury. However, the specific mechanism by which it exerts the protective effect remains unclear. This study was designed to investigate the role of SEVO in myocardial I/R injury and its potential molecular mechanisms.

Methods: Blood samples were collected from patients with acute myocardial infarction (AMI) (n = 20) and healthy volunteers (n = 20). The human cardiomyocytes AC16 models of I/R injury were induced by hypoxia/reoxygenation. The mRNA expression levels of growth differentiation factor 11 (GDF11) in the cells and blood were determined by reverse transcription quantitative real-time PCR (RT-qPCR). The cell proliferation was detected by Cell Counting Kit-8 (CCK-8). Enzyme-Linked Immunosorbent Assay (ELISA) was utilized to detect the levels of inflammatory factors interleukin (IL)-8, IL-1β and IL-6 in the cells. And biochemical assay kits were applied for the measurement of the activity of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as well as the malondialdehyde (MDA) level in the cells. Moreover, western blot was employed to evaluate the levels of the p-serine-threonine protein kinase (AKT), AKT, and phosphatidylinositol 3-kinase (PI3K), protein expression in the cells.

Results: The GDF11 expression was decreased in the blood of AMI patients and cardiomyocytes induced by I/R (p < 0.01). Besides, 1% SEVO was presented to promote cardiomyocyte proliferation, inhibit apoptosis, oxidative stress and inflammation, and activate the PI3K/AKT signaling pathway through up-regulation of GDF11 expression (p < 0.01).

Conclusion: SEVO promotes proliferation and inhibits inflammatory response, apoptosis, and oxidative stress of I/R-treated cardiomyocytes by elevating GDF11 expression, thereby reducing myocardial I/R injury. Notably, the mechanism underlying the alleviation of the I/R injury may involve the activation of PI3K/AKT signaling pathway.

Diabetes mellitus (DM) and its associated complications, including diabetic kidney disease, neuropathy, and retinopathy, impose significant challenges on healthcare systems due to their high morbidity, mortality, and associated costs. Existing treatments often yield unsatisfactory clinical outcomes, underscoring the need for innovative approaches to mitigate debilitating effects on patients' health-related quality of life. Photobiomodulation (PBM) is a non-invasive treatment that utilizes specific wavelengths of light in the treatment of various medical complications associated with DM. The specific wavelength used during PBM is critical in determining the therapeutic outcomes for managing diabetic complications. This paper aimed to explore the therapeutic potential of PBM in the management of diabetic complications, focusing on blue, red, and near-infrared (NIR) wavelengths. Relevant literature from Google Scholar, PubMed and ClinicalTrials databases from inception to date was searched using the keywords 'photobiomodulation', 'diabetes', 'diabetic complications', 'wound healing', 'neuropathy', 'retinopathy', and 'chronic wounds'. Red and NIR wavelengths are commonly used for a range of complications, while blue light has primarily been explored for treating diabetic wounds due to its antimicrobial nature. PBM treatment parameters for the same diabetic complication vary across clinical trials and preclinical research, with minimal clinical trials conducted on most diabetic complications. This inconsistency hinders the establishment of standardized PBM parameters, particularly concerning the optimal application setting.

This article explores the correlation between vitamin D levels and cardiovascular health, focusing on hypertension, atherosclerosis, and cardiac dysfunction. Cardiovascular diseases (CVDs) rank as the leading global cause of death, underscoring the significance of exploring vitamin D's potential role in maintaining a healthy cardiovascular system. It discusses vitamin D's mechanisms of action, including genomic and non-genomic pathways, and explores risk factors like smoking, obesity, and hypertension, linked to vitamin D deficiency. Additionally, it delves into its role in regulating the renin-angiotensin system, cardiac hypertrophy, and inflammation. The link between vitamin D supplementation and a lower risk of cardiovascular events, including hypertension, atherosclerosis, and heart failure, is considered. However, inconsistent results from supplementation trials call for further research to establish efficacy for cardiovascular health. In conclusion, the article emphasizes the importance of vitamin D for cardiovascular well-being and calls for comprehensive studies to explore its therapeutic potential in treating cardiovascular disease (CVD).

Background: The best treatment option for patients with resectable gastric cancer is radical gastric cancer surgery. However, the postoperative overall survival rate is low. Lymphovascular invasion (LVI) is a risk factor for cancer recurrence and a stand-alone predictor of a poor post-operative prognosis for gastric cancer (GC) patients. Current evaluation of tumor LVI performed on histological specimens, which can only be assessed after surgery, is also limited by intra-tumoural heterogeneity via biopsy. This study explored the value of CT volume perfusion in assessing tumors' lymphovascular invasion of gastric cancer.

Methods: 59 gastric cancer patients confirmed by pathology who underwent both computed tomography (CT) volume perfusion examinations and gastrectomy surgery were prospectively included. Tumour lymphovascular invasion (LVI, positive or negative) was evaluated. The relationship between clinicopathological variables associated with LVI and CT perfusion parameters was analyzed by univariate analysis, followed by multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis.

Results: The LVI-positive and LVI-negative groups differed significantly in terms of time to start (TTS), mean transit time (MTT), Tmax, and flow extraction product (FEP). Both FEP (odds ratio (OR), 1.048; 95% confidence interval (CI): 1.005-1.092) and MTT (OR, 0.549; 95% CI: 0.351-0.858) have the potential to be employed as independent predictors of LVI (both p < 0.05). There were different correlations between LVI, lower MTT and greater FEP. The specificity of MTT (87.88%) was higher than that of FEP (72.73%), while the sensitivity of MTT (53.85%) was lower than that of FEP (57.69%). Compared to MTT and FEP alone, the combination demonstrated a comparatively higher area under the curve (AUC) (0.797) and sensitivity (84.62%).

Conclusions: CT volume perfusion helps evaluate LVI in gastric cancer before surgery. MTT and FEP are independent predictors for LVI, and the combination variation has better diagnostic performance. Clinical Trial Register: Jiangmen Central Hospital, https://www.chictr.org.cn/showproj.html?proj=24375, ChiCTR1800014455.

Background: Sepsis often leads to cardiomyopathy, contributing to increased mortality rates. 2,6-Diisopropylphenol (propofol), an anesthetic, has demonstrated efficacy in protecting cardiomyocytes from cell death caused by hypoxia and reoxygenation. This study examined the effects of propofol on sepsis-associated myocardial dysfunction and explored the underlying mechanism of action.

Methods: Mice and rat cardiomyocytes (H9C2 cell line) were used to establish a sepsis-induced myocardial dysfunction model. Lipopolysaccharides (LPS)-treated mice and H9C2 cells were treated with propofol, with rapamycin used for mechanistic studies in H9C2 cells. Cardiac function was evaluated by echocardiographic measurements. Heart tissues were stained with hematoxylin and eosin, and heart weight/body weight ratio along with the levels of cardiac biomarkers were measured using Enzyme Linked Immunosorbent Assay (ELISA). Activation of the mammalian target of rapamycin (mTOR) pathway was assessed by western blotting. Apoptosis in heart tissues and H9C2 cells was evaluated using Terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay, and cell viability was quantified using Cell Counting Kit (CCK)-8 assay. Oxidative stress in H9C2 cells was assessed by measuring reactive oxygen species (ROS) levels through immunofluorescence staining and malondialdehyde (MDA) and superoxide dismutase (SOD) levels using ELISA.

Results: Propofol reversed LPS-induced myocardial changes and cardiac dysfunction (p < 0.05). In mouse tissues and H9C2 cells, propofol reversed LPS-induced mTOR pathway inhibition and apoptosis (p < 0.001). Moreover, propofol alleviated oxidative stress in LPS-treated cells. The activation of the mTOR pathway by propofol, along with its inhibitory effects on oxidative stress and apoptosis in cardiomyocytes, was negated by rapamycin (p < 0.001).

Conclusion: Propofol ameliorates sepsis-induced myocardial dysfunction triggered by LPS through the mTOR pathway, thereby promoting antioxidative stress and reducing cell apoptosis.

Alzheimer's disease (AD) is an incurable and progressive neurodegenerative disease with increasing prevalence worldwide. Previous trials of anti-amyloid and anti-tau immunotherapy indicate that additional research needs to be conducted on other mechanisms to find curative or disease-modifying therapy. This review focuses on apolipoprotein E (ApoE), a critical protein in brain lipid metabolism that acts specifically in the clearance and transport of lipids and cholesterol. The ApoE4 allele confers substantial gene dose-dependent risk of developing AD and lowers the age of onset of AD, although the mechanisms of influence remain incompletely understood. The other isoforms bring different levels of AD risk. ApoE2 is protective while ApoE3 is the most common isoform and is considered neutral. An overview is presented of the latest information on the role of ApoE in AD pathogenesis with an emphasis on pathways that are involved in AD development and interactions with crucial processes in different cell types in the brain. Elucidating the key interactions of ApoE with multiple aspects of brain function can be useful for designing novel ApoE-targeted therapeutic approaches.

Background: Gastric cancer (GC) is one of the most common types of cancer. Earlier research has suggested an association of microfibril-associated protein 5 (MFAP5) and collagen type I alpha 1 (COL1A1) with the progression of various tumors. However, the specific roles and mechanisms of action of MFAP5 and COL1A1 in the context of GC are yet to be fully elucidated. Thus, the objective of this study is to investigate the functions of MFAP5 and COL1A1 in the epithelial-mesenchymal transition (EMT) of GC and to unravel the associated molecular mechanisms.

Methods: We examined the MFAP5 expression level in GC through real-time polymerase chain reaction (RT-PCR), western blotting, and immunohistochemistry. Subsequently, shRNA interference was employed to knockdown the expression of MFAP5 or COL1A1 in GC cells. Cell viability assay, Transwell assay, RT-PCR, and western blotting were then used to explore the impact of MFAP5 and COL1A1 on GC progression and metastasis, along with GC cell proliferation, migration, and EMT.

Results: Increased MFAP5 levels were observed in both GC tissues and cells (p < 0.05), with decreased MFAP5 levels significantly impeding GC cell activity and GC progression and metastasis (p < 0.05). Additionally, the pronounced reduction in the COL1A1 expression level effectively alleviated the migration and EMT processes induced by MFAP5 overexpression in GC cells (p < 0.05).

Conclusions: These results indicate that MFAP5 plays a role in initiating the process of EMT in GC cells through the upregulation of COL1A1 expression.

Background: Papillary thyroid cancer (PTC) is one of the most frequent endocrine malignancies. Kelch domain containing 8A (KLHDC8A) is reported as an epigenetically driven oncogene, but the role of KLHDC8A in PTC is still unclear. This study aimed to explore the function of KLHDC8A in PTC progression.

Methods: KLHDC8A expression was analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA) website, quantitative real-time PCR (qRT-PCR), and western blot. The viability of PTC cells (TPC-1 and BCPAP) was assessed by cell counting kit-8 (CCK-8) kit. A transwell assay was carried out to evaluate the invasion and migration of PTC cells. Macrophage polarization-associated markers were determined by qRT-PCR and western blot. Mice tumor xenograft models were established to analyze the role of KLHDC8A in vivo. Pathway-related proteins (programmed cell death protein 1 (PD-1) and signal transducer and activator of transcription 3 (STAT3)) were determined by western blot.

Results: GEPIA demonstrated that KLHDC8A was highly expressed in PTC (p < 0.05). Knockdown of KLHDC8A hindered cell viability, invasion, and migration of PTC cells (p < 0.0001). Additionally, KLHDC8A knockdown inhibited M2 polarization while promoting M1 polarization (p < 0.0001). Meanwhile, KLHDC8A silencing inhibited tumor growth in mice xenografted models (p < 0.0001). Moreover, the PD-1/STAT3 pathway was suppressed by KLHDC8A silencing (p < 0.01), and the STAT3 activator (colivelin) attenuated the inhibitory effects of KLHDC8A silencing on PTC progression (p < 0.01).

Conclusions: Through in vivo and in vitro experiments, KLHDC8A silencing could restrain PTC cell viability, migration, and invasion, inhibit tumor growth, and promote M1 polarization via the PD-1/STAT3 axis, providing a new therapeutic idea for PTC clinical treatment.

No abstract present.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of interest BA.2.87.1 has not driven any Coronavirus disease 2019 (COVID-19) pandemic wave. Nevertheless, it has served to test the reaction times of modern virology laboratories. In this commentary, we highlight how fast the reaction has been at characterizing this sublineage, leading at an unprecedented pace to almost as many papers as the number of viral sequences.