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Prognostic Evaluation Value of Thyroid Function Tests plus B-type Natriuretic Peptide Tests for Patients with Heart Failure
No full textObjective: This research was performed to analyze the diagnostic and prognostic value of thyroid function tests plus B-type natriuretic peptide (BNP) tests in patients with heart failure (HF). Methods: This study matched 120 patients with HF (HF group) at a single institution from January 2019 and January 2021 with 120 healthy subjects (control group) (1:1 ratio) during the same period. All eligible participants received BNP and thyroid function tests. Results: Patients with HF exhibited markedly higher BNP levels than healthy controls (p < 0.05). Patients with HF showed remarkably lower concentrations of free triiodothyronine (FT3) versus healthy controls (p < 0.05), while the concentrations of free thyroxine (FT4) and thyroid-stimulating hormone (TSH) showed no marked alterations (p > 0.05). The aggravation of HF causes a remarkable decrease in FT3 levels and an elevation in BNP levels (p < 0.05), while the alterations in the serum concentrations of FT4 and TSH levels were mild (p > 0.05). After treatment, markedly elevations of FT3 levels and a decline of BNP levels were found in the HF group (p < 0.05). Hybrid detection allows for a larger coverage of the detection area than the stand-alone test. The combined detection provided a larger area under the curve (AUC) and a higher 95% confidence interval and sensitivity versus single tests (p < 0.05), suggesting a superior diagnostic efficiency of the combined BNP and thyroid function tests. Conclusion: The combination of BNP and thyroid function tests offers a viable diagnostic alternative for HF patients, with high diagnostic efficiency and prognostic assessment value. Clinical Trial Registration: ChiCTR2200069567
Artificial Blood and Nanotechnology: Where do We Stand?
No full textBlood is vital fluid where cellular components are suspended within a non-cellular liquid matrix. The dysfunction or deficiency of these cellular components can cause serious morbidity and even mortality. Meanwhile, transfusion of blood components serves as a cornerstone during surgery, myelosuppression, and congenital disorders of the blood. However, donor-derived blood products are hindered by several challenges such as scarcity of supply, the requirement for matching, significant risks of pathogenic contamination, restricted shelf-life, and several other negative consequences. Currently, ongoing research focuses on addressing these issues, clinical interests have emerged in the bioengineering of artificial blood substitutes, aiming to mimic natural blood while avoiding the aforementioned concerns. Nanotechnology has offered innovative methods, including the development of synthetic red blood cells (RBCs) substitutes for oxygen transport, synthetic platelet substitutes for hemostasis, and synthetic white blood cells (WBCs) substitutes for immune responses. The study presents an overview of the role of nanotechnology in the production of synthetic blood substitutes, as well as an evaluation of the achievements and limitations of the existing state-of-the-art in this area. One area of research currently focuses on using cell culture technologies to make blood cells from stem cells, while another is investigating the use of nanotechnology to create blood cell replacements. In the near future, the product of ongoing research as well as comprehensive preclinical and clinical evaluations might lead to fully synthetic blood replacements for transfusion. Nanotechnology has offered a new perspective on the concept of artificial blood substitutes
AZA Protects against Cardiomyocyte Injury by Ameliorating Mitochondrial Dysfunction Attenuating Oxidative Stress, Inflammation and Apoptosis via VDAC1
No full textBackground: Azathioprine (AZA) is a purine-derived drug used for immunosuppression. The molecular mechanisms by which AZA protects cardiomyocytes remain unclear. This experiment will further elaborate, on the basis of the previous study, the mechanism of AZAs protection against hypoxia-induced cardiomyocyte injury in high glucose conditions. Methods: We utilized a high glucose (HG) and hypoxia/reoxygenation (H/R) cell model and a diabetic Sprague-Dawley (SD) rat ischaemia/reperfusion (I/R) model to detect cellular calcium ions, mitochondrial membrane potential, and reactive oxygen species (ROS) levels using Fluo-4 AM, MitoTracker Red, and ROS Assay Kit. Malondialdehyde (MDA), superoxide dismutase (SOD) and pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α) levels were measured using the appropriate kits. Cellular energy metabolism was analyzed by oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). The expression of Voltage-dependent anion channel 1 (VDAC1), Nucleotide-binding oligomerization domain-like receptor protein 3 (NALP3), Nuclear factor-kappa B p65 (NF-κB p65), ATP synthase subunit alpha (ATP5A1), ATP synthase subunit beta (ATP5B), B-cell lymphoma 2 (Bcl-2), Caspase-3 and Bcl-2 associated X protein (Bax) was detected. Results: It was shown in the HG+H/R cell model that AZA up-regulated the levels of calcium ions (p < 0.05) and mitochondrial membrane potential (p < 0.05). AZA reduced ROS accumulation (p < 0.01) and oxidative stress marker MDA levels (p < 0.01), improved cellular energy metabolism, and increased expression of the antioxidant defense enzyme SOD (p < 0.05). AZA treatment inhibited VDAC1, NALP3, and NF-κB activation, upregulated ATP synthase (ATP5A1, ATP5B), and Bcl-2 expression, as well as inhibited apoptosis by downregulating Bax and Caspase3 expression in HG+H/R cells and I/R rat cardiomyocytes (p < 0.001). We constructed a VDAC1 siRNA cell model, and knockdown of VDAC1 significantly promoted the expression of ATP synthases (ATP5A1, ATP5B) under HG+H/R conditions (p < 0.001). Conclusion: Our data reveal the molecular mechanisms by which AZA protects cardiomyocytes from injury induced by HG+H/R and I/R in diabetic rats. We demonstrate that AZA ameliorates mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis by modulating VDAC1 and ATP synthase expression. Our findings suggest that AZA may be a potential therapeutic agent for mitigating myocardial ischemic injury in diabetes
Antioxidant Activity of the Chrysanthemum Family and Quantitative Analysis of Phenolic Compounds by HPLC/UV
No full textBackground: This research focused on evaluating the antioxidant properties and phenolic compound content of three different Chrysanthemum species from various regions in South Korea. Phenolic compounds play crucial roles in plant defense; they also attract pollinators and have applications in diverse industries, such as cosmetics, food supplements, and food packaging. Moreover, their radical-scavenging abilities make them promising in combating diseases like diabetes, Alzheimers, and cancer. Methods: The study encompassed a total of eight samples from three Chrysanthemum species, including Dendranthema indicum, Dendranthema boreale (D. boreale), and Aster spathulifolius (A. spathulifolius). These samples were collected from distinct regions in South Korea, namely Jeju Island, Pohang, Busan, and Gubong Island, and were extracted using methanol (MeOH). High-performance liquid chromatography (HPLC) analysis was conducted using a Waters Alliance system and a YMC Pack Pro C18 column. To prepare the samples, extracts were dissolved in MeOH, and stock solutions were created for standard compounds. Antioxidant activity was assessed using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-casino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, and HPLC was used to identify phenolic compounds in the plants. Results: The study found strong antioxidant activity in all samples, with D. boreale samples from Jejudo Sanguk Flower (JSF) showing the highest potential for medicinal use. In the DPPH assay, JSF exhibited the most potent scavenging activity with a half-maximal inhibitory concentration (IC50) of 5.8 mg/mL. In the ABTS assay, JSF also scored highest at 2.8 mg/mL. Further research is needed to explore their medicinal applications due to their exceptional antioxidant properties. HPLC analysis successfully detected ten out of twelve standard phenolic compounds. Conclusions: These findings underline the significant antioxidant potential of these Chrysanthemum samples, with JSF showing the most promise. The study underscores the need for further investigation into their potential medicinal and therapeutic applications, given their remarkable antioxidant properties. Overall, this study can help improve the market value of the Chrysanthemum family in various industries
Licoricidin Hinders Proliferation and Induces Cell Cycle Arrest and Apoptosis in Hepatocellular Carcinoma Cells by Regulating the PDK1/AKT/P21 Pathway
No full textBackground: Licoricidin (LCD) is a bioactive compound isolated from licorice with anticancer properties. This study aimed to investigate the effect of LCD on the biological behaviors of hepatocellular carcinoma (HCC) and to explore its underlying molecular mechanisms. Methods: The effect of LCD, at gradient concentrations (0, 5, 10, 15 and 20 μM), on the viability of human normal liver epithelial cells (THLE-3) and HCC cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, the impacts of LCD, at different concentrations (0, 5 and 10 μM), on the HCC cell cycle, apoptosis, proliferation, and migration were evaluated using flow cytometry, colony formation experiment, and Transwell assay. Furthermore, the levels of cell cycle-related proteins, protein kinase B (AKT)/p21 pathway-related proteins, and pyruvate dehydrogenase kinase isoform 1 (PDK1)-related proteins were assessed using western blot assay and quantitative real-time polymerase chain reaction (qRT-PCR). Rescue experiments were performed to conform whether the LCD works through PDK1. Results: It was found that cell viability remained unaffected in THLE-3 cells but reduced in HCC cells (p < 0.001) following LCD treatment. Furthermore, LCD hampered the proliferation and migration, boosted apoptosis, and induced cell cycle arrest in the G0/G1 phase of HCC cells (p < 0.05). Moreover, LCD reduced the expression levels of B-cell lymphoma-2 (Bcl-2), cyclin A, cyclin-dependent kinase 2 (CDK2), and phosphorylated-AKT (p-AKT) while elevating Bcl-2 associated X protein (Bax) and p21 levels (p < 0.05). Additionally, LCD decreased PDK1 expression level, but overexpression of PDK1 reversed its regulatory impacts on the AKT/p21 pathway (p < 0.001). Moreover, overexpressed PDK1 counteracted the impacts of LCD on repressing the proliferation and migration and boosting cell cycle arrest in the G0/G1 phase and apoptosis of HCC cells (p < 0.05). Conclusion: LCD hinders the proliferation and migration of HCC cells and enhances the apoptosis and cycle arrest at the G0/G1 phase by modulating the PDK1/AKT/p21 pathway
Exploring the Mechanism of JAK-STAT Signaling Pathway Promoting Cervical Cancer Lymph Node Metastasis Based on CD8+ T Cell Senescence
No full textBackground: The incidence and mortality of cervical cancer are increasing, which seriously threatens the life and health of women. Lymph node metastasis is a critical factor involved in the survival rate of patients. Research has shown that the immune system plays a key role in suppressing tumor development and metastasis. Thus, to study the relationship between immunity and tumor metastasis, we explored the mechanism by which Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway promotes lymph node metastasis in cervical cancer based on CD8+T cell senescence. Methods: The level of JAK-STAT protein was detected by collecting cervical cancer tissues and adjacent normal tissues. JAK-STAT protein levels were compared in patients with different Federation International of Gynecology and Obstetrics (FIGO) stages and lymph node metastasis. To analyze the diagnostic value of JAK-STAT level in cervical cancer lymph node metastasis, cervical cancer cell lines were infected with JAK-STAT pathway inhibitors to detect cell viability, migration, and invasion. Concurrently, CD8+ T cells were co-cultured with cervical cancer cell lines to assess CD8+ T cell count, surface molecule expression (CD28, CD27, and CD57), and inflammatory factor levels. The lymphoid metastasis model of cervical cancer in nude mice was constructed to observe changes in the general state and lymph node metastasis of nude mice. Cervical cancer infiltration in lymph nodes was certified by pathological method, and the expression of JAK-STAT in lymph tissues was detected. The expressions of CD8+ T cells and surface molecules (CD28, CD27, and CD57), as well as inflammatory factors in lymph nodes were examined. Result: JAK-STAT signaling pathway was activated in cervical cancer tissues, correlated with different FIGO stages and lymph node metastasis, and exhibited a certain degree of clinical diagnostic value (p < 0.05). After JAK-STAT inhibition, cervical cancer cell viability decreased, and migration and invasion ability weakened (p < 0.05). The co-cultivation of CD8+ T cells with cervical cancer cell lines revealed a time-dependent fluctuation in the cell vitality, initially increasing and subsequently decreasing (p < 0.05). Moreover, the expressions of CD28 and CD27 decreased (p < 0.05), and the expression of CD57 increased (p < 0.05). While the cell vitality in the JAK-STAT inhibition + co-culture group initially increased and then slowly decreased (p < 0.05), with an increase in the expressions of CD28 and CD27 and a decrease in the expression of CD57 (p < 0.05). The lymphatic metastasis model of cervical cancer in nude mice revealed that after JAK-STAT inhibition, the lymph nodes were fewer and smaller, and the cervical invasion in the lymph nodes was reduced (p < 0.05). Podoplanin and p-cytokeratin (p-CK) confirmed cervical cancer metastasis in lymph nodes. The number and function of CD8+ T cells in vitro showed that the expressions of CD28, CD27, and CD57 tended to be normal in the blank and the solvent groups. Nevertheless, inflammatory factors Interleukin (IL)-6, IL-1β, and Tumor Necrosis Factor (TNF)-α exhibited an increase, and inhibiting JAK-STAT led to elevated expressions of CD28 and CD27 (p < 0.05). Conversely, CD57 expressions and levels of inflammatory cytokines IL-6, IL-1β, and TNF-α demonstrated a significant reduction (p < 0.05). Conclusions: The JAK-STAT signaling pathway is activated in cervical cancer, contributing to the growth and metastasis of the disease, and influencing the senescence of CD8+ T cells. Inhibition of the JAK-STAT pathway can delay the senescence of CD8+ T cells, weaken the biological behavior of cervical cancer cells, and inhibit tumor metastasis
Ras GTPase-Activating Protein-Binding Protein 1 Affected the Proliferation, Apoptosis, and Oxidative Stress Damage of Gastric Cancer Cells by Regulating the Methylation Level of the Vezatin DNA
No full textBackground: Gastric cancer (GC) is a prevalent malignancy of the digestive tract, posing substantial challenges and serious threats to human life. The crucial roles of Ras GTPase-activating protein-binding protein 1 (G3BP1) as an enhancer and Vezatin (VEZT) as a suppressor of cancer progression have been recognized. Therefore, this study aimed to elucidate the molecular mechanisms underlying the role of G3BP1/VEZT in GC cell activity and the consequent oxidative stress damage. Methods: The expression levels of G3BP1 and VEZT in GC cells were assessed utilizing Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) and western blot assays. Subsequently, both G3BP1 and VEZT were knocked down in GC cells and their efficiency was evaluated using qRT-PCR. Additionally, methylation levels of the VEZT gene were evaluated using pyrosequencing technology. Moreover, DNA Methyltransferase 1 (DNMT1) enzyme activity, as well as levels of Reactive Oxygen Species (ROS), Malondialdehyde (MDA), 4-Hydroxynonenal (4-HNE), and Iron were assessed in GC cells utilizing Enzyme-Linked Immunosorbent Assay (ELISA). Furthermore, the proliferation activity and apoptosis levels of GC cells were determined by the Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Results: G3BP1 was upregulated and VEZT was downregulated in GC (p < 0.01, and p < 0.001). The knockdown of G3BP1 (si-G3BP1) led to a decrease in VEZ-silencing-induced DNA methylation level and DNMT1 activity (p < 0.05, and p < 0.01). The si-G3BP1 reversed the enhanced cell viability, decreased apoptosis rate, and decreased levels of ROS, MDA, and 4-HNE in GC cells induced by VEZT silencing (p < 0.01, and p < 0.001). Moreover, si-G3BP1 also reversed the elevation of Thioredoxin-dependent peroxide reductase (T-SOD), Glutathione (GSH), and Glutathione Peroxidase 4 (GPx4) levels induced by si-VEZT (p < 0.05, p < 0.01, and p < 0.001). Conclusion: Our study confirms the aberrant activation of G3BP1 and the suppression of VEZT in GC. Furthermore, we observed that G3BP1 affects the proliferation, apoptosis, oxidative stress-induced damage, and iron damage of GC cells by regulating the methylation level of VEZT
Mutational Frequencies in the Immune System Interacting Proteins NS2A and NS2B in Dengue Virus Isolates
No full textBackground: The genome of the dengue virus (DENV) encodes a total of ten proteins, three of which are structural and seven of which are non-structural (NS). Among the NS proteins, nonstructural protein 2A (NS2A) and NS2B play pivotal roles in the replication and assembly of DENV. This study aimed to determine the frequency of mutations occurring in the NS2A and NS2B regions of DENV within the Punjab Province of Pakistan. Methods: About 4 mL of blood was collected from DENV patients. RNA was isolated from serum samples and confirmed using an RNA Kit. The RNA was converted to complementary DNA (cDNA) followed by amplification using polymerase chain reaction. The cDNA was subjected to library preparation for whole genome sequencing. We selected 23 samples to undergo whole genome sequencing. Among these, 19 isolates exhibited a significant number of mutations. Results: In the NS2A, a total of 25 mutations were detected, with 23 being novel in the N-terminal and domains. The most common mutation, I15V, was found in seven genomic isolates, followed by I171A (n = 4), M150R (n = 2), and T34A (n = 2). Within NS2B, there were 20 different mutations, 18 of which were novel. Notably, the N and C-terminal regions exhibited a higher mutation frequency compared to the central two helices of NS2B. Specifically, seven mutations were located in the α1 helix of NS2B. Additionally, four mutations (A10E, V11F, I73F, and K127E) were detected in two isolates, respectively. Conclusions: The most conserved region was the C-terminal domains extending beyond the 181 amino acids. This study represents the first comprehensive analysis of mutations in the NS2A and NS2B regions, which may help design effective vaccines and antiviral therapies for DENV
Treatment with Risperidone Attenuates Oxidative Stress in the Kidney after Whole-Body Ischemia and Reperfusion Injury Induced by Cardiac Arrest in Rats
No full textBackground: Whole-body ischemia and reperfusion (IR) injury following the return of spontaneous circulation (ROSC) after cardiac arrest (CA) can cause multiple organ dysfunction syndrome accompanied by adverse outcomes, including serious mortality. Renal IR injury following ROSC after CA is associated with complicated pathological processes. Renal IR injury is commonly observed in inpatients with heart failure and is associated with high mortality. Risperidone (Risp), an atypical antipsychotic drug, has been reported to exert beneficial effects against IR. This study investigated whether treatment with risperidone enhanced survival rates and reduced kidney failure following CA-induced whole-body IR injury. Methods: Rats were subjected to asphyxial CA for five minutes followed by ROSC induction, and risperidone (10 mg/kg) or saline was intravenously injected. Survival rate was evaluated using Kaplan-Meier survival analysis was used to evaluate the survival rate. Changes in serum levels of creatinine, lactate dehydrogenase (LDH), and blood urea nitrogen (BUN) were assessed. We carried out hematoxylin and eosin staining and immunohistochemistry for 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2′-deoxyguanosine (8-OHdG), superoxide dismutase 1 (SOD-1), and superoxide dismutase 2 (SOD-2). Results: Treatment with risperidone significantly improved the survival rate after CA and attenuated LDH, creatinine, and BUN levels. Histopathological injury was remarkably improved in the renal cortex following risperidone treatment including a significant attenuation of the immunoreactivities of 4-HNE and 8-OHdG. Conversely, immunoreactivities of SODs were significantly improved by risperidone treatment. Conclusions: The current results demonstrated that treatment with risperidone reduced the CA-induced renal injury by reducing oxidative stress and retaining antioxidant enzymes, which significantly influenced the improvement of survival rate after CA
Notch1 Inhibits the Development of Skin Squamous Cell Carcinoma by Regulating HIF1A-Mediated Glycolysis
No full textBackground: Skin squamous cell carcinoma (SSCC) is a common malignancy of skin, and its occurrence is a multifactorial process. Glycolysis plays a vital role in its occurrence and development. This study investigated the effect of neurogenic locus notch homolog protein 1 (Notch1) on malignant behavior of SSCC cells through glycolysis mediated by hypoxia-inducible factor 1 alpha (HIF1A). Methods: Notch1 expressions in normal human skin cells human keratinocytes (HaCaT) and three SSCC cell lines (SCL-1, Colo-16, and A431) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Colo-16 cells with Notch1 or HIF1A overexpression were constructed by liposome-mediated transfection technology. Colo-16 cells were divided into negative control of Notch1 overexpression (pc-NC1), Notch1 overexpression (pc-Notch1), Notch1 overexpression+negative control of HIF1A overexpression (pc-Notch1+pc-NC2), and Notch1 overexpression+HIF1A overexpression (pc-Notch1+pc-HIF1A) groups. Clone formation, scratch healing and Transwell tests were used to detect the effect of Notch1 overexpression on Colo-16 cell proliferation, migration and invasion ability, respectively. Glucose and lactic acid test kits were used to detect glucose and lactic acid levels. The protein expression levels of Notch1, HIF1A and key glycolytic proteases were detected by western blot. Results: Notch1 expression in SSCC cells was lower than in the control group (p < 0.01, p < 0.001). Notch1 overexpression reduced cell proliferation, invasion and migration, and inhibited glucose consumption and lactic acid formation (p < 0.01, p < 0.001). Notch1 overexpression also inhibited expression of glucose transporter type 1 (GLUT1) and related key glycolytic proteases (p < 0.01, p < 0.001, p < 0.0001). Upregulation of Notch1 decreased HIF1A protein expression (p < 0.01, p <0.001). HIF1A overexpression partially reversed the inhibitory effect of Notch1 on cell malignant behavior and glycolysis. Conclusions: Notch1 inhibits proliferation, migration and invasion of SSCC cells through HIF1A-mediated glycolysis and may be a target for SSCC diagnosis and treatment