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Simple Summary: In recent years, cancer has gradually become a terrible killer of human health. Due to various factors such as tumor heterogeneity and the complexity of the microenvironment, completely conquering cancer has always been a major problem in the scientific research community. Therefore, more detailed research and individualized treatment are essential. Everyone knows that tumor cells in the process of rapid proliferation need replenishing nutrients to sustain their energy supply. Intervention of tumor cell metabolism is gradually becoming a way to treat cancer. As an important transporter of glutamine, ASCT2 can uptake glutamine from the tumor microenvironment to support the growth and metabolism of cancer cells. Deficiency of ASCT2 can significantly inhibit tumor progression. However, not all patients benefit from this treatment. Our study aims to explore the metabolic heterogeneity of breast cancer and its related mechanisms, as well as to find metabolic-sensitive populations for further precision treatment. As a crucial amino acid, glutamine can provide the nitrogen and carbon sources needed to support cancer cell proliferation, invasion, and metastasis. Interestingly, different types of breast cancer have different dependences on glutamine. This research shows that basal-like breast cancer depends on glutamine, while the other types of breast cancer may be more dependent on glucose. Glutamine transporter ASCT2 is highly expressed in various cancers and significantly promotes the growth of breast cancer. However, the key regulatory mechanism of ASCT2 in promoting basal-like breast cancer progression remains unclear. Our research demonstrates the significant change in fatty acid levels caused by ASCT2, which may be a key factor in glutamine sensitivity. This phenomenon results from the mutual activation between ASCT2-mediated glutamine transport and lipid metabolism via the nuclear receptor PPARα. ASCT2 cooperatively promoted PPARα expression, leading to the upregulation of lipid metabolism. Moreover, we also found that C118P could inhibit lipid metabolism by targeting ASCT2. More importantly, this research identifies a potential avenue of evidence for the prevention and early intervention of basal-like breast cancer by blocking the glutamine–lipid feedback loop. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, liquid biopsy has been introduced as a new method for the detection and management of cancer, but the studies on oral squamous cell carcinoma (OSCC) are lacking conclusive evidence. The aim of this study was to evaluate the expression of six circulating salivary and plasmatic miRNAs (-21, -31, -138, -145, -184, and -424) as diagnostic biomarkers in patients affected by OSCC and by oral potentially malignant disorders (OPMDs). Our results showed that liquid biopsy from saliva may be a useful tool for the identification of these biomarkers; in particular, miR-138 and miR-424 showed decreased expression levels in saliva samples in OSCC and OPMD patients compared to healthy controls. The introduction of liquid biopsy in daily clinical practice could revolutionize the approach to oral lesions by allowing the mass screening, stratification and monitoring of patients at risk, the monitoring of the response to treatment and the early identification of any recurrences. This study aims to evaluate the expression of salivary and plasmatic miRNAs as diagnostic biomarkers in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A total of 25 patients were divided into three groups, according to their diagnosis: OSCC patients (n = 14); OPMDs patients (n = 6); and healthy controls (n = 5). At the time at diagnosis/enrolment, patients underwent salivary and plasmatic collection. The expression of miRNA -21, -31, -138, -145, -184, and -424 were evaluated by real-time PCR. An F-test and ANOVA test were performed to evaluate the miRNA levels (significance at p < 0.05). By comparing miRNA expression levels from saliva, a statistically significant difference emerged in the expression of miR-138 and miR-424 between the three groups (p < 0.05). In particular, these two miRNAs showed decreased expression levels in saliva samples from OSCC and OPMD patients compared to those from healthy controls. On the other hand, miRNA expression levels in plasma were low in all the groups, and no statistically significant differences were found. Overall, our results showed that liquid biopsy from saliva may be a useful tool for the identification of diagnostic molecular biomarkers in OSCC and OPMDs. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is one of the most common causes of death worldwide. Today, this disease does not have an effective treatment, leading to the exploration of novel pharmacological molecules. In this paper, we design and synthesize with a new synthetic route the lipophilic cation derived from gallic acid (TPP+C10) and gentisic acid (GA-TPP+C10), both able to reach mitochondria and uncouple the electron transport chain. Our results show that combining 5-fluorouracil with GA-TPP+C10 has a synergistic cytotoxic effect on CRC cells. Both compounds show antimigratory effects, decreasing signaling pathways and biomarkers. Our results show that mitochondrial agents could be an alternative to standard CRC drugs against this disease. Colorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC—such as 5-fluorouracil (5FU)—remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal Squamous Cell Carcinoma (OPSCC) represents a significant fraction of head and neck cancers, with a challenging five-year survival rate of only 50%. Key risk factors include tobacco and alcohol consumption and infection with human papillomavirus (HPV), particularly HPV16. Distinct biological differences exist between HPV-positive and HPV-negative OPSCC, including differences in mutation patterns and gene expression profiles. This study focuses on aldo-keto reductases (AKRs), specifically AKR1C2, which are involved in cellular stress management and detoxification processes, particularly in cisplatin-resistant tumors. This study investigates the role of AKR1C2 in HPV-positive OPSCC and its effect on patient outcomes. The findings indicate that increased levels of AKR1C2 are linked to unfavorable prognosis, particularly in male patients, while higher levels in female patients indicate a favorable prognosis. Head and Neck Squamous Cell Carcinoma (HNSCC), particularly Oropharyngeal Squamous Cell Carcinoma (OPSCC), is a major global health challenge due to its increasing incidence and high mortality rate. This study investigates the role of aldo-keto reductase 1C2 (AKR1C2) in OPSCC, focusing on its expression, correlation with Human Papillomavirus (HPV) status, oxidative stress status, and clinical outcomes, with an emphasis on sex-specific differences. We analyzed AKR1C2 expression using immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples from 51 OPSCC patients. Additionally, we performed RT-qPCR in cultured HPV16-E6*I and HPV16-E6 overexpressing HEK293 cell lines (p53WT). Statistical analyses were performed to assess the correlation between AKR1C2 expression and patient data. Our results indicate a significant association between increased AKR1C2 expression and higher AJCC classification (p = 0.009) as well as positive HPV status (p = 0.008). Prognostic implications of AKR1C2 varied by sex, whereby female patients with high AKR1C2 expression had better overall survival, whereas male patients exhibited poorer outcomes. Additionally, AKR1C2 expression was linked to HPV status, suggesting a potential HPV-specific regulatory mechanism. These findings underscore the complex interplay among AKR1C2, HPV, and patient sex, highlighting the need for personalized treatment strategies for OPSCC. Targeted inhibition of AKR1C2, considering sex-specific differences, may enhance therapeutic outcomes. Future research should investigate these mechanisms to enhance treatment efficacy. [ABSTRACT FROM AUTHOR]

Purpose: Glaucoma, one of the leading causes of irreversible blindness, is a common progressive optic neuropathy characterised by visual field defects and structural changes to the optic nerve head (ONH). There is extracellular matrix (ECM) accumulation and fibrosis of the lamina cribrosa (LC) in the ONH, and consequently increased tissue stiffness of the LC connective tissue. Integrins are cell surface proteins that provide the key molecular link connecting cells to the ECM and serve as bidirectional sensors transmitting signals between cells and their environment to promote cell adhesion, proliferation, and remodelling of the ECM. Here, we investigated the expression of αVβ3 integrin in glaucoma LC cell, and its effect on stiffness-induced ECM gene transcription and cellular proliferation rate in normal (NLC) and glaucoma (GLC) LC cells, by down-regulating αVβ3 integrin expression using cilengitide (a known potent αVβ3 and αVβ5 inhibitor) and β3 integrin siRNA knockdown. Methods: GLC cells were compared to age-matched controls NLC to determine differential expression levels of αVβ3 integrin, ECM genes (Col1A1, α-SMA, fibronectin, vitronectin), and proliferation rates. The effects of αVβ3 integrin blockade (with cilengitide) and silencing (with a pool of four predesigned αVβ3 integrin siRNAs) on ECM gene expression and proliferation rates were evaluated using both reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting in the human NLC cells cultured on soft (4 kPa) and stiff (100 kPa) substrate and in GLC cells grown on standard plastic plates. Results: αVβ3 integrin gene and protein expression were enhanced (p < 0.05) in GLC cells as compared to NLC. Both cilengitide and siRNA significantly reduced αVβ3 expression in GLC. When NLC were grown in the stiff substrate, cilengitide and siRNA also significantly reduced the increased expression in αVβ3, ECM components, and proliferation rate. Conclusions: Here, we provide evidence of cilengitide- and siRNA-mediated silencing of αVβ3 integrin expression, and inhibition of ECM synthesis in LC cells. Therefore, αVβ3 integrin may be a promising target for the development of novel anti-fibrotic therapies for treating the LC cupping of the ONH in glaucoma. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is an emerging human-to-human infectious disease that broke out in early December 2019 and threatens global public health, causing widespread concern. This respiratory disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The development of reliable techniques for COVID-19 diagnosis is a significant step to prevent further infection. Thus in this study we see the prevalence of Covid 19 cases in eastern part of Uttar Pradesh by a molecular diagnostic method. Aim and Objective: To study the diagnosis of sars-cov-2 virus with real time PCR in patients attending the tertiary care centre. Material and Methods: This was a Retrospective study carried out in the Department of Microbiology between September 2020 to June 2022. The Samples were collected from COVID19 clinically suspected patients at GMC, Ambedkarnagar and evaluated with real time reverse transcriptase polymerase chain reaction (RT-PCR) tests. Also few samples were sent for genome sequencing and analysed. Results: In our study a total of 2999 patients were diagnosed with COVID-19. Five samples showed emerging delta strain in mid part of study. Conclusion: RT-PCR amplification of viral nucleic acid has been widely recognized as the gold standard for diagnosis of COVID-19 and can effectively confirm timely and accurate SARS-CoV2 infection. [ABSTRACT FROM AUTHOR]

Wildfires have become increasingly common across the United States in recent decades, with significant implications for ecosystem health and sustainability. The viability and metabolic activity of soil bacteria are key for maintaining global nitrogen-cycling processes and are likely to be impacted as burn severity continues to increase. To this end, wildfire-affected soils were studied to examine the impact on nitrogen-cycling bacteria in soils affected by low, moderate, and high wildfire severities. This objective was achieved by characterizing soil bacterial communities in control (i.e., unburned) and burned soils collected one year following the Woolsey wildfire (Los Angeles and Ventura Counties, CA, USA) using Illumina MiSeq 16S sequencing and profiling nitrogen-cycling gene expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Six families and 17 genera were significantly (Spearman rs > |0.4|; p < 0.05) negatively associated with wildfire severity, and three families and six genera were significantly positively associated with wildfire severity. Many of these taxa contain species that are known to be critical contributors to maintaining global nitrogen cycles. NosZ and NirS nitrifying genes had significantly lower transcription rates in high-severity samples compared with control and low/moderate-severity samples. Collectively, these results suggest that high-severity wildfires significantly negatively alter the community structures and functions of nitrogen-cycling bacteria, which may have significant ramifications for ecosystem recovery in postwildfire landscapes. [ABSTRACT FROM AUTHOR]

Introduction: The study explored the effects of SHOX2 and RASSF1A DNA methylation in lung cancer (LC). Method: Bronchoalveolar lavage fluid (BALF) samples as well as LC and normal adjacent tissues were collected from 72 LC patients and 35 patients with benign pulmonary nodules. Quantitative analysis of SHOX2 and RASSF1A DNA methylation was performed in benign pulmonary nodules and different stages of LC. The diagnostic value of SHOX2 and RASSF1A DNA methylation in LC and benign pulmonary nodules was determined by receiver operating characteristics analysis. Gain/loss-of-function experiments were constructed in LC cells and mouse models of xenograft and pulmonary nodule metastasis. The levels of SHOX2 and transfer-associated genes were tested through quantitative reverse transcription polymerase chain reaction and Western blot. Malignant phenotype of LC cells was assessed by functional experiment. The tumor volume and weight of mice in xenograft models were measured. Pulmonary nodule metastasis was determined through HE staining assay. 5-azacytidine appeared as a positive control drug. Result: SHOX2 DNA methylation or RASSF1A DNA methylation had diagnostic efficiency in pulmonary nodules and early LC, with the two combined having better diagnostic value. SHOX2 expression was upregulated in LC. Similar to 5-azacytidine, SHOX2 knockdown inhibited LC cell viability, migration, and invasion in vitro as well as restrained LC tumorigenesis and pulmonary nodule metastasis in vivo, whereas overexpressed SHOX2 had the opposite effects. Conclusion: The combination of SHOX2 and RASSF1A DNA methylation had a diagnostic value in pulmonary nodules and early LC. SHOX2 positively modulated the tumorigenesis and metastasis of LC by regulating DNA methylation processes. [ABSTRACT FROM AUTHOR]

Purpose: Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions. Methods: Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR. Results: All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered. Conclusion: Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes. [ABSTRACT FROM AUTHOR]

Introduction: Although microRNA (miR)-150-5p participates in the progression of renal fibrosis, its mechanism of action remains elusive. Methods: A mouse model of unilateral ureteral obstruction was used. The in vitro renal fibrosis model was established by stimulating human kidney 2 (HK-2) cells with transforming growth factor beta 1 (TGF-β1). The expression profiles of miR-150-5p, zinc finger E-box binding homeobox 1 (ZEB1), and other fibrosis- and epithelial-mesenchymal transition (EMT)-linked proteins were determined using Western blot and quantitative reverse transcription polymerase chain reaction. The relationship between miR-150-5p and ZEB1 in HK-2 cells was confirmed by a dual-luciferase reporter assay. Results: Both in vivo and in vitro renal fibrosis models revealed reduced miR-150-5p expression and elevated ZEB1 level. A significant decrease in E-cadherin levels, as well as increases in alpha smooth muscle actin (α-SMA) and collagen type I (Col-I) levels, was seen in TGF-β1-treated HK-2 cells. The overexpression of miR-150-5p ameliorated TGF-β1-mediated fibrosis and EMT. Notably, miR-150-5p acts by directly targeting ZEB1. A significant reversal of the inhibitory impact of miR-150-5p on TGF-β1-mediated fibrosis and EMT in HK-2 cells was observed upon ZEB1 overexpression. Conclusion: MiR-150-5p suppresses TGF-β1-induced fibrosis and EMT by targeting ZEB1 in HK-2 cells, providing helpful insights into the therapeutic intervention of renal fibrosis. [ABSTRACT FROM AUTHOR]

Watermelon is a highly cultivated fruit crop renowned for its quality properties of fruit flesh. Among various quality factors, fruit flesh firmness is a crucial quality parameter influencing the fruit texture, shelf life and its commercial value. The auxin/indole-3-acetic acid (Aux/IAA) plays a significant role in fruit development and ripening of non-climacteric fruits. However, the regulatory mechanism of Aux/IAA in controlling fruit flesh firmness and ripening in watermelon remains unknown. In this study, we employed an integrative approach combining genome-wide association study (GWAS) and bulked segregant RNA-Seq analysis (BSR-Seq) to identify an overlapping candidate region between 12 776 310 and 12 968 331 bp on chromosome 6, underlying an auxin-responsive gene (Aux/IAA) associated with flesh firmness in watermelon. Transcriptome analysis, followed by real-time quantitative reverse transcription PCR (qRT-PCR), confirmed that the expression of Aux/IAA was consistently higher in fruits with high flesh firmness. The sequence alignment revealed a single base mutation in the coding region of Aux/IAA. Furthermore, the concomitant Kompetitive/Competitive allele-specific PCR (KASP) genotyping data sets for F2 population and germplasm accessions identified Aux/IAA as a strong candidate gene associated with flesh firmness. Aux/IAA was enriched in the plant hormone signal transduction pathway, involving cell enlargement and leading to low flesh firmness. We determined the higher accumulation of abscisic acid (ABA) in fruits with low flesh firmness than hard flesh. Moreover, overexpression of Aux/IAA induced higher flesh firmness with an increased number of fruit flesh cells while reducing ABA content and flesh cell sizes. Additionally, the allelic variation in Aux/IAA for soft flesh firmness was found to exist in Citrullus mucosospermus and gradually fixed into Citrullus lanatus during domestication, indicating that soft flesh firmness was a domesticated trait. These findings significantly enhanced our understanding of watermelon fruit flesh firmness and consequently the watermelon fruit quality. [ABSTRACT FROM AUTHOR]

This research aims to examine the impact of programmed cell death 4 (PDCD4), microRNA‐21 (miR‐21) and microRNA‐208a (miR‐208a) transcripts, and protein levels on oral epithelial dysplasia (OED) development in oral squamous cell carcinoma (OSCC). Methods: The research investigation involved the collection of saliva, blood, and tissue samples from a total of 20 patients diagnosed with OSCC, 15 patients diagnosed with OED, and 15 healthy individuals. PDCD4, miR‐21, and miR‐208a expression was performed by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). PDCD4 protein levels were assessed using enzyme‐linked immunosorbent assay (ELISA) in both saliva and blood samples. For statistical analysis, the Kruskal–Wallis test and the Spearmen rank test were utilised. Results: PDCD4 expression levels were considerably lower in patients with OSCC and OED (p < 0.05) in three biological samples. In contrast, miR‐21 expression was higher in OED and OSCC patients. Patients with low PDCD4 mRNA levels and strong miR‐21 expression had a significant connection (p < 0.05) with tumor size and depth. Conclusions: Examining PDCD4 and miR‐21 transcript levels may help detect the transition from OED to OSCC. This work suggests that PDCD4 and miR‐21 expression levels in liquid biopsies may be biomarkers for OED monitoring in the future. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's Disease (PD) is a neurodegenerative disorder distinguished from other neurodegenerative disorders by the loss of dopaminergic neurons in the substantia nigra region of the brain, and is the most common neurodegenerative disorder, along with Alzheimer's Disease. PD is characterized by the presence of Lewy bodies when evaluated pathologically. Recent studies showed that the incidence of PH development as a result of genetic mutations alone is very low among all PD cases, and that environmental effects contribute significantly to the disease progression. The molecular mechanisms of diseases are associated with the maintenance of gene and protein expressions as a result of epigenetic regulations. The role of these regulations in the development and pathogenesis of neurodegenerative diseases is still not clearly understood. Methods: In our study, we examined the expression levels of H3C1, H3C12, HDAC4, HDAC5, ANKRD11, ANKRD12, ITM2B and GABBR1, which are genes involved in epigenetic processes in patients with idiopathic PD. Seventy five patients diagnosed with idiopathic PD and 50 healthy controls were included in the study. Peripheral Blood Mononuclear Cell (PBMC) was obtained from whole blood taken from the patient and control groups, and then total RNA was isolated from PBMC. Results: According to the comparison of the patient and control groups, the expression of H3C1, H3C12, ITM2B was high, and the expression of ANKRD11, HDAC4, HDAC5 and GABBR1 was low (p<0.05). Conclusion: As conclusion, we propose that histone regulation is one of the epigenetic mechanisms related to the presence of PD. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we aimed to investigate the clinical effects of COVID-19 infection and vaccines on Myasthenia gravis (MG) during the pandemic. Methods: A total of 141 MG patients between April 2020 and December 2021 were retrospectively analyzed. Data including demographic and clinical characteristics of patients, COVID-19 test results, and vaccine types (mRNA-BNT162b2 and/or inactivated-CoronaVac) were recorded. All patients were followed by face-to-face interviews and/or phone calls. Worsening MG symptoms after COVID-19 infection or vaccines were noted. Results: A total of 60 patients were diagnosed with COVID-19, and reverse transcriptase-polymerase chain reaction test results were COVID-19 positive in 54 (90%) patients. Twenty-eight (46.7%) patients had lung involvement, while 20(33.3%) patients were followed in the ward. Twelve (20%) patients were followed in the intensive care unit, and two of them (3.3%) died. Both deceased patients were unvaccinated. The most common symptoms were fatigue (78.3%), and 13(21.7%) patients were asymptomatic. Of the patients, 96(68%) received at least one dose BNT162b2 or CoronaVac, while 30.4% of the patients received ≥3 doses of vaccines. The local skin irritation and fatigue rate was significantly higher with BNT162b2 vaccine than CoronaVac (p<0.001 and p=0.004, respectively). No serious side effect was observed with either vaccine. Five patients had worsening MG symptoms after vaccination during a six-week follow-up. None of the patients experienced myasthenic crises. Conclusion: Our study results suggest that COVID-19 infection affects MG similar to the general population and does not lead to worsening MG symptoms. Both mRNA and inactivated vaccines with proven efficacy can be used safely in MG patients. [ABSTRACT FROM AUTHOR]

A nationwide cohort study investigated the association between prior respiratory syncytial viral (RSV) infection and the severity of COVID-19. The study found that individuals with a history of RSV infection had a higher susceptibility to COVID-19, increased risk of hospitalization, and greater severity of the disease. This association was particularly pronounced in older individuals and those with underlying conditions such as diabetes and congestive heart failure. The study suggests that recent RSV infection contributes to the burden of COVID-19 and highlights the potential benefits of RSV vaccination in mitigating the clinical course of COVID-19. [Extracted from the article]

Human enteric viruses, such as hepatitis A virus (HAV), hepatitis E virus (HEV), and norovirus genogroups I and II (NoVGI and NoVGII), cause infections, and it has been largely demonstrated that mussels play an important role if consumed as raw or undercooked food matrices. This study aimed to investigate, through qualitative and quantitative biomolecular assays, the detection of partial genomic regions belonging to the most relevant enteropathogenic viruses for humans (HAV, HEV, NoVGI and NoVGII) in mussels (Mytilus galloprovincialis) farmed along the coasts of two Italian regions on the central Adriatic Sea: Abruzzo (Casalbordino, Chieti) and Molise (Termoli, Campobasso). A total of 425 animals were sampled, and the respective georeferentiations were registered. A total of 85 pools, each composed of five subjects/aliquots, were formed (22 from Abruzzo and 63 from Molise regions). This step was followed by homogenization and RNA extraction, and then the biomolecular assays [nested reverse transcription polymerase chain reaction (PCR) and real-time reverse transcription-quantitative PCR] were performed. 1.17% of the pool was positive for HAV RNA detection (10² copies/mL), 9.41% for HEV (10²-10³ copies/µL), 2.35% for NoVGI (10¹ copies/µL), and no pool was positive for NoVGII. This study demonstrated the human enteric viruses' presence in mussels farmed in a low-investigated marine area. Based on a one-health point of view, this paper aims to enforce the importance of biomolecular and epidemiological screenings as surveillance systems to guarantee human, animal, and environmental health. [ABSTRACT FROM AUTHOR]

Background: The relationship between erectile dysfunction (ED) and type 1 diabetes mellitus (T1DM) is currently a hot topic of medical research. It has been reported that autophagy plays a crucial role in causing erectile dysfunction in T1DM. Recent research has shown that mitochondrial 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2 (HMGCS2) is strongly linked to the development of T1DM. However, the specific mechanism by which it regulates the erectile function is not yet fully understood. Objectives: To investigate whether HMGCS2 affects erectile function in type 1 diabetic rats by regulating autophagy in corpus cavernosum endothelial cells (CCECs). Materials and methods: First, the rat model of T1DM was established. Then, the ratio of maximum penile intracavernous pressure (ICPmax) and mean arterial pressure (MAP) was detected to assess the erectile function in various groups, and the protein expression of HMGCS2, mTOR and p‐mTOR was evaluated by western blot (WB) and immunohistochemistry (IHC). To explore the relationship between HMGCS2 and the mTOR signaling pathway in T1DM ED rats, we silenced the expression of HMGCS2 and activated the mTOR signaling pathway with MHY1485 in CCECs and then assessed the expression of beclin1, P62, LC3, autophagosome, endothelial nitric oxide synthase (eNOS), phosphorylation of eNOS (p‐eNOS), and nitric oxide (NO) to evaluate autophagy and the erectile function by reverse transcription quantitative polymerase chain reaction and western blot. Results: The study conducted on T1DM ED rats showed that the expression of HMGCS2 was significantly increased, while the autophagy was suppressed. Additionally, the mTOR signaling pathway was highly activated. In contrast, when HMGCS2 was silenced in vitro, p‐mTOR/mTOR was reduced, and autophagy was improved. These effects were accompanied by the enhanced activity of eNOS. Furthermore, when HMGCS2 was silenced and the mTOR signaling pathway was simultaneously activated, the results revealed a decrease in autophagy as well as a reduction in activity of eNOS in comparison to just silencing HMGCS2 alone. Discussion and conclusion: HMGCS2 upregulation in T1DM rats inhibited autophagy and eNOS activity by activating the mTOR pathway and led to a decrease in the erectile function. [ABSTRACT FROM AUTHOR]

Eimeria bovis is a pathogenic protozoan that causes cattle digestive tract infections, which can cause economic losses to farmers. It is necessary to develop specific and accurate detection methods to conserve livestock and prevent coccidiosis in Indonesia. This study aims to detect E. bovis by nested PCR and determine the relationship with reference sequences. A total of 167 samples of beef cattle feces were taken randomly from community farms spread across 18 provinces in Indonesia. The feces were examined natively, and then the oocysts were purified by the sugar flotation method, extracted by KIT extraction, and amplified by the nPCR technique. Positive samples were followed by sequencing and phylogenetic analysis using MEGA 11 software. This study used two pairs of primers (outer and inner) taken from ITS-1 molecular markers. As many as 96 out of 167 samples (57.5%) were positive for Eimeria spp., and 48 of the 96 samples were positive for Eimeria spp. (50%) were detected to be positive for E. bovis based on the presence of a 238 bp DNA fragment. The results of the phylogenetic analysis showed that the study sample formed a separate cluster from the E. bovis cluster from abroad. In conclusion, E. bovis was detected in 16 out of 18 provinces in this study, and the nPCR technique proved to have better sensitivity and specificity. [ABSTRACT FROM AUTHOR]

The association of air pollution and greenspace with respiratory pathogen acquisition and respiratory health was investigated in a community-based birth-cohort of 158 Australian children. Weekly nasal swabs and daily symptom-diaries were collected for 2-years, with annual reviews from ages 3-7-years. Annual exposure to fine-particulate-matter (PM2.5), nitrogen-dioxide (NO2), and normalised-difference-vegetation-index (NDVI) was estimated for pregnancy and the first 2-years-of-life. We examined rhinovirus, any respiratory virus, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae detections in the first 3-months-of-life, age at initial pathogen detection, wheezing in the first 2-years, and asthma at ages 5-7-years. Our findings suggest that higher NDVI was associated with fewer viral and M. catarrhalis detections in the first 3-months, while increased PM2.5 and NO2 were linked to earlier symptomatic rhinovirus and H. influenzae detections, respectively. However, no associations were observed with wheezing or asthma. Early-life exposure to air pollution and greenspace may influence early-life respiratory pathogen acquisition and illness. [ABSTRACT FROM AUTHOR]

Background: Type-2 diabetes mellitus is a metabolic disorder characterised by hyperglycemia and insulin resistance. This study aims to explore the role and mechanism of DIRAS family GTPase 3 (DIRAS3) in mediating pancreatic β-cell death and insulin secretion. Materials and Methods: A bioinformatic analysis of the GSE118230 and GSE150281 datasets was performed to screen differentially expressed genes. The pancreatic β-cell lines, INS-1 and MIN6, were treated with palmitic acid (PA) to mimic the cell models of type-2 diabetes mellitus. CCK-8 assay, 5-ethynyl-2'-deoxyuridine staining, flow cytometry, enzyme-linked immunoassay, immunofluorescence, qRT-PCR, and western immunoblotting were conducted to illustrate the role of DIRAS3 in the cell models. Results: Unlike in normal controls, DIRAS3 was highly expressed in PA-treated pancreatic β-cells in a dose- and time-dependent manner. Moreover, the silencing of DIRAS3 in the INS-1 cells attenuated PA-induced cell loss by improving cell proliferation and inhibiting apoptosis and prevented the PA-induced impairment of insulin secretion. Consistently, the overexpression of DIRAS3 in the MIN6 cells accelerated PA-induced cell loss and impaired insulin secretion. A Gene Set Enrichment Analysis predicted that phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) was a downstream signalling pathway of DIRAS3, as the inhibitory effects of DIRAS3 on the activation of the PI3K/AKT signalling pathway were confirmed in the INS-1 and MIN6 cells. Moreover, the PI3K inhibitor, LY294002, effectively reversed the protective effects of DIRAS3 silencing on the INS-1 cells. Conclusion: DIRAS3 was highly expressed in the cell models of type-2 diabetes mellitus, contributing to PA-induced cell death and impaired insulin secretion in pancreatic β-cells through the inhibition of the PI3K/AKT signalling pathway. [ABSTRACT FROM AUTHOR]

Netrin-4 (NTN4), a secreted protein from the Netrin family, has been recognized for its role in vascular development, endothelial homeostasis and angiogenesis. Vascular endothelial (VE)-cadherin is a specialized adhesion protein located at the intercellular junctions of endothelial cells (ECs), and regulates migration, proliferation and permeability. To date, the relationship between NTN4 and VE-cadherin in ECs remains unclear. In the present study, human umbilical vein ECs (HUVECs) were transfected with NTN4 overexpression plasmid, resulting in NTN4 overexpression. Reverse transcription-quantitative PCR and western blotting were used to determine gene and protein expression. CCK8, wound healing, and Transwell assays were performed to evaluate cell proliferation, migration and permeability. NTN4 overexpression decreased HUVEC viability and migration. In addition, NTN4 overexpression increased the expression of VE-cadherin and decreased the permeability of HUVECs. Subsequent studies showed that NTN4 overexpression increased the NF-κB protein level and decreased IκB-α protein expression in HUVECs. In HUVECs treated with NF-κB inhibitor pyrrolidine dithiocarbamate, the expression of VE-cadherin failed to increase with NTN4 overexpression. Taken together, the results indicated that NTN4 overexpression increased VE-cadherin expression through the activation of the NF-κB signaling pathway in HUVECs. The present findings revealed a novel regulatory mechanism for VE-cadherin expression and suggested a novel avenue for future research on the role of NTN4 in endothelial barrier-related diseases. [ABSTRACT FROM AUTHOR]

Ischemic heart disease (IHD) remains a leading cause of mortalities worldwide, necessitating timely reperfusion to reduce acute mortality. Paradoxically, reperfusion can induce myocardial ischemia/reperfusion (I/R) injury, which is primarily characterized by mitochondrial dysfunction. Translocator protein (TSPO) participates in multiple cellular events; however, its role in IHD, especially in the process of myocardial I/R injury, has not been well determined. The aim of the present study was to investigate the functional role of TSPO in myocardial I/R injury and dissect the concomitant cellular events involved. This study utilized small interfering RNA (siRNA) technology to knock down TSPO expression. The I/R process was simulated using an anoxia/reoxygenation (A/R) model. The role of TSPO in H9c2 cardiomyocytes was assessed using various techniques, such as Western blotting, Flow cytometry, Reverse transcription-quantitative PCR (RT-qPCR), Immunofluorescence, Co-immunoprecipitation (co-IP) and similar methods. It was found that A/R markedly upregulated the expression of TSPO in cardiomyocytes. Inhibition of TSPO improved myocardial cell apoptosis and damage following A/R stimulation. Additionally, targeting TSPO alleviated mitochondrial damage, reduced mitochondrial ROS release and enhanced ATP synthesis following A/R stimulation. It was further confirmed that A/R stimulation induced a significant increase in the expression of pivotal markers [phosporylated-PKR-like ER kinase (PERK)/PERK, activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1] involved in the adaptive unfolded protein response, which is accompanied by downstream signaling during endoplasmic reticulum (ER) stress. Notably, TSPO knockdown increased the expression of the aforementioned markers and, subsequently, TSPO was confirmed to interact with ATF6, suggesting that TSPO might play a role in ER stress during myocardial I/R injury. Finally, inhibition of TSPO upregulated mitophagy, as indicated by further decreases in P62 and increases in Parkin and PINK1 levels following A/R stimulation. Together, the results suggest that TSPO plays a multifaceted role in myocardial I/R injury. Understanding TSPO-induced cellular responses could inform targeted therapeutic strategies for patients with IHD. [ABSTRACT FROM AUTHOR]

Background Psoriasis is a T cell-mediated chronic inflammatory skin condition characterized by the interaction of T cells with various cell types, forming an inflammatory microenvironment that sustains psoriatic inflammation. Homeostasis of these tissue-resident T cells is supported by fibroblasts, the primary structural cells in the dermis. In psoriasis, there is increased expression of matrix metalloproteinase 2 (MMP2), mediating structural alterations in skin tissues and modulating inflammation. Additionally, the CD100–plexin-B2 (PLXNB2) axis is known to enhance psoriasis inflammation via keratinocytes, and CD103 levels are associated with the severity of psoriasis upon relapse. Objectives To elucidate the role of fibroblasts and the MMP2–CD100 axis in modulating psoriasis inflammation. Methods CD100 expression and function in psoriasis were assessed using immunofluorescence, enzyme-linked immunosorbent assay, single-cell transcriptome sequencing, cellular interaction analyses and quantitative reverse transcriptase polymerase chain reaction. CD8+ T cells from people with psoriasis were isolated using magnetic beads, to investigate the regulatory effect of MMP2 on CD100 expression on their membranes. Single-cell transcriptome sequencing, spatial transcriptome sequencing, mimetic timing analysis, immunofluorescence and flow cytometry were used to determine the origin of MMP2 and its impact on CD103+ CD8+ T cells. The hypotheses were further validated in vivo using MMP2 and CD100 inhibitors. Results Soluble CD100 (sCD100) was significantly upregulated in both psoriatic lesions and peripheral blood, amplifying psoriasis inflammation by promoting the production of inflammatory cytokines by keratinocytes, fibroblasts and endothelial cells via the sCD100–PLXNB2 axis. Fibroblasts that highly expressed MMP2 (MMP2hi) exacerbated psoriasis symptoms by facilitating CD100 shedding from CD8+ T-cell membranes. Additionally, it was shown that fibroblasts enhance the upregulation of the CD8+ T-cell residency factor CD103 in co-cultures with CD8+ T cells. Inhibitors targeting MMP2 and CD100 were effective in reducing inflammation in an imiquimod-induced psoriasis model. Conclusions Our findings underscore the pivotal role of MMP2hi fibroblasts in the amplification and recurrence of inflammatory responses in psoriasis. These fibroblasts augment psoriasis inflammation through the CD100–PLXNB2 axis by facilitating CD100 shedding on CD8+ T-cell membranes and by upregulating CD103, thereby enhancing CD8+ T-cell residency. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter required for excitation/inhibition balance is synthesized by the glutamic acid decarboxylases (GADs) in GABAergic neurons. The levels and activity of GADs are strongly correlated with GABA and neural transmission. Dysregulation of GADs and GABA is associated with various neurological disorders. The study used psoralidin, found in the seeds of Psoralea corylifolia, to investigate its effect on GAD levels and regulatory mechanisms in primary cortical neurons. Psoralidin reduced GAD67 through transcriptional regulation. The reduction was not mediated by the N-methyl-D-aspartate receptor. Additionally, psoralidin attenuated the formation of inhibitory synapses in primary hippocampal neurons. [ABSTRACT FROM AUTHOR]

Globally, there is a move towards using local, native species for ecotoxicological risk assessments. Anthropogenic stressors from urban, agricultural, and industrial activities can impact the health of receiving ecosystems. Biomarkers can provide valuable insights as early warning signals of the potential environmental impacts of stressors. The aim of this study was to develop biomarkers in the green-lipped mussel (Perna canaliculus), a potential bioindicator of environmental health for coastal marine ecosystems in New Zealand. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays targeting the expression of genes involved in oxidative stress, xenobiotic transfer, membrane transportation, cellular and DNA response/repair, and endocrine disruption were developed and validated for P. canaliculus. We found significant modulation of genes associated with oxidative stress, xenobiotic transfer, membrane transport, endocrine disruption, and genotoxicity in P. canaliculus following 48-hour exposures to copper and benzo[α]pyrene. These results demonstrate the potential of P. canaliculus as a bioindicator species for environmental risk assessment. The gene expression assays showed potential as early indicators of exposure to the chemicals tested but require additional validation to assess their ability to predict effects at higher levels of biological organisation. [ABSTRACT FROM AUTHOR]

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Introduction: Spermatogenesis is the primary process of sperm production occuring in seminiferous tubules. Spermatogonial stem cells (SSCs) have the ability for self-renewal, differentiation, and the transmission of genetic information to subsequent generations. KLF4 and POU5F1 are transcription factors expressed in a wide range of tissues and play key roles in such processes as apoptosis, differentiation, proliferation, and cellular development. The present study aimed to assess the expression levels of KLF4 and POU5F1 genes in mouse embryonic stem cells (mESCs), spermatogonial stem cells (SSCs), embryonic-like stem cells (ES-like), and testicular cells, and identify the signaling pathways associated with them in the process of spermatogenesis. Materials & Methods: In this experimental study, spermatogonial cells were extracted from mouse testes using enzymatic digestion method and cultured in GSC medium containing FGF, EGF, and GDNF. Thereafter, the expression of KLF4 and POU5F1 genes was examined in mESCs, SSCs, ES-like, and testicular cells was investigated using immunocytochemistry, immunohistochemistry, and reverse transcription-polymerase chain reaction methods, and protein-protein interactions and signaling pathways were evaluated using bioinformatics methods. Results: The KLF4 and POU5F1 genes exhibited positive expression in ES-like cells and testicular cells. The assessment of KLF4 mRNA and POU5F1 mRNA expression levels demonstrated that KLF4 expression is higher in mESCs and ES-like cells compared to other cells, while POU5F1 expression is higher in SSCs. Both KLF4 and POU5F1 are considered essential and powerful genes that share a common class and function. Conclusion: The findings of this study indicated that KLF4 and POU5F1 play crucial roles in the proper development of sperm and are present in various types of cells, including mESCs, SSCs, ES-like cells, and testicular cells. These factors are key components of sexual stem cells and contribute to stem cell proliferation, making them potential diagnostic markers for these cell lines. [ABSTRACT FROM AUTHOR]

Numerous marine sponge bioactive compounds exhibit diverse pharmacological properties. This study investigated the ethyl acetate extract of Amphimedon chloros for its effects on breast cancer cells (MDA-MB-231), focusing on the expression of key genes involved in apoptosis and cell cycle regulation, including Bax, Cyclin D, caspase 3, p21, C-myc, and Bcl2. The extract's chemical profile was analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS), identifying fourteen compounds such as zamamidine (11.4%), keramamine (10.2%), and methoxyhexadecanoate (9.1%). Cytotoxicity and anticancer activity were assessed on MDA-MB-231 cells and human periodontal ligament fibroblasts (HPLFs). The IC50 of the extract against MDA-MB-231 cells was 3.0 µg/mL, indicating significant cytotoxicity, while it did not affect fibroblast viability at concentrations ranging from 50-200 µg/mL. RT-PCR (Real Time-Polymerase Chain Reaction) analysis revealed that the extract increased the expression of Bax, p21, and caspase 3, and decreased the levels of Bcl2 and Cyclin D in MDA-MB-231 cells. These findings suggest that the extract may inhibit cancer cell proliferation by interfering with growth factors signaling pathways, such as PI3K/Akt (Phosphoinositide 3-Kinase/Protein Kinase B) and MAPK (Mitogen-Activated Protein Kinase). The increase in Bax and p21 expression indicates enhanced apoptosis, while the drastic reduction in c-Myc expression points to potential cell cycle arrest. The results support the potential of A. chloros as an anticancer agent, with selective cytotoxicity towards cancer cells and significant modulation of apoptotic and cell cycle-related genes. [ABSTRACT FROM AUTHOR]

Purpose: Psoriasis is an immune-related disorder characterized by silver scales, epidermis thickness, and itching. She-Chuang-Si-Wu-Tang (SSWT), a traditional Chinese medicine decoction, has been used clinically for 400 years. Although it benefits psoriasis treatment, the mechanism of action is still unclear. This study explores SSWT's molecular mechanism in treating psoriasis through network pharmacology analysis and experiments. Methods: We identified relevant SSWT and psoriasis targets using network pharmacology and conducted SSWT quality control with high-performance liquid chromatography (HPLC). A mouse model of psoriasis was established using imiquimod (IMQ), with the drug administered continuously for seven days, spanning an eight-day period. During the experiment, we observed spontaneous scratching behaviors and assessed the Psoriasis Area and Severity Index (PASI) scores. At the conclusion of the experiment, we examined skin tissue pathology under an optical microscope and measured epidermal thickness. Additionally, we used enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure interleukin (IL)-23, IL-17A, IL-17F, and interferon (IFN)-γ levels in the mice's serum and their mRNA expression in the skin. Western blot analysis was conducted to assess protein levels related to signaling pathways. Results: Results indicate that SSWT may target IL-17 signaling pathways and T helper (Th) 17 cell differentiation, as predicted by network pharmacology. SSWT significantly improved the PASI and Baker scores, reduced epidermal thickness, and decreased spontaneous scratching in IMQ-induced mice. Additionally, SSWT treatment significantly lowered the concentrations of inflammatory factors in the serum and skin lesions, as well as mRNA expression levels, compared to the IMQ group. Furthermore, SSWT significantly inhibited the phosphorylation of both the signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) pathways. Conclusion: In summary, this study unveiled the potential anti-psoriatic mechanism of SSWT, offering new evidence for its clinical application. [ABSTRACT FROM AUTHOR]

Background: It has been established that Spalt-Like Transcription Factor 4 (SALL4) promotes Colorectal Cancer (CRC) cell proliferation. Furthermore, Amphiregulin (AREG) is crucially involved in cancer cell proliferation and therapeutic resistance regulation. In this regard, this study aimed to establish whether SALL4 affects the radiosensitization of CRC cells via AREG expression regulation. Methods: Transcriptome sequencing and the Human Transcription Factor Database (HumanTFDB) were used to identify the potential SALL4 targets. The dual-luciferase reporter analysis was used to confirm the SALL4-induced AREG activation. Western Blot (WB) and Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) assays were used to examine the effect of X-ray irradiation on SALL4 and AREG expression. The AREG-KD (Knockdown) stable cell lines were created through lentiviral infection. Cell proliferation was tracked using Cell Counting Kit 8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine (EdU)-incorporation assays. Cell cycle and apoptosis were examined through flow cytometry. The cells were exposed to a controlled X-ray radiation dose (6 Gy) for imaging purposes. Results: SALL4 could bound to the AREG promoter, enhancing AREG expression. Furthermore, irradiation upregulated SALL4 and AREG in CRC cells. Additionally, AREG knockdown in CRC cells led to reduced DNA replication efficiency, suppressed cell proliferation, increased DNA damage, and enhanced G1 phase arrest and apoptosis following irradiation. On the other hand, AREG overexpression reversed the inhibitory effects of SALL4 downregulation on AREG expression. Conclusion: In CRC cells, SALL4 downregulation suppressed AREG expression, regulating CRC cell radiosensitivity via the PI3K-AKT pathway, thus presenting a potential therapeutic pathway for CRC treatment using Radiotherapy (RT). [ABSTRACT FROM AUTHOR]

The high isoflavones content of soybeans is an important breeding goal due to the demonstrated benefits of isoflavones to human health and their association with plant resistance. In this study, quantitative trait loci (QTL) mapping for soybean isoflavone aglycones, including daidzin, glycerin, and genistin, and total isoflavones content was performed in a population of 178 F2:6 recombinant inbred lines (RILs) which was generated from a cross between varieties Jinong 17 and Jinong 18. A genetic linkage map covering 1248 cM was constructed using the simple sequence repeat (SSR) molecular markers. The results revealed 22 isoflavone-related QTLs, 5 for daidzin, 7 for genistin, 6 for glycerin, and 4 for total isoflavone content. Seven of these represented new QTLs. All QTL regions contained 6462 genes, of which 58 have been annotated for flavonoid synthesis. Using public databases, three candidate genes, namely Glyma.11G164400, Glyma.16G158400, and Glyma.19G217700, were subsequently identified. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated that the three genes exhibited specific, high expression in soybean seeds and a positive correlation with flavonoid content. These findings might be helpful in the efforts to breed new soybean varieties with improved isoflavone composition and content. [ABSTRACT FROM AUTHOR]

To investigate the effects of a Brazil nut-enriched diet on the wall thickness and the left ventricular chamber diameter of the heart, and lipid peroxidation in a CKD-induced model. Male Wistar rats at 12 weeks of age were divided into two groups (n=16/group): the Nx group, which underwent 5/6 nephrectomy, and the Sham group, as a control. After 5 weeks, the groups were subdivided according to diet (n=8/group): the Nx and Sham groups received a control diet; the Nx5% and Sham5% groups received a diet enriched with 5 % Brazil nuts for 8 weeks. The left ventricular thickening and chamber diameter were determined. Plasma biochemical parameters were evaluated. Analysis of thiobarbituric acid reactive substances (TBARS) and antioxidant enzyme activity was performed in the plasma and the left ventricle (LV). LV mRNA expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by reverse transcription-polymerase chain reaction. The Nx5% group showed a remodeled LV wall with decreased thickness compared to the Nx group (p=0.016). Furthermore, LV TBARS concentration was reduced in the Nx5% group (p=0.0064). In addition, the Nx5% group showed an increase in plasma GPx activity (p=0.0431). No significant results were found concerning the LV mRNA expression of NF-κB and Nrf2 genes. A Brazil nut-enriched diet decreased LV thickness and LV TBARS concentration and increased GPx activity in a 5/6 nephrectomy experimental model, making it a promising adjuvant therapy to improve antioxidant status and cardiovascular outcomes in chronic kidney disease. [ABSTRACT FROM AUTHOR]

The detection of genetic alterations in patients with acute leukemias is essential for the targeting of more specific and effective therapies. Therefore, the aim of this study was to compare the sensitivity of Nested-PCR and RT-qPCR techniques in the detection of genetic alterations in patients with acute leukemias. This study included samples from 117 patients treated at the Fortaleza General Hospital. All samples were submitted to analysis using the Nested-PCR and the RT-qPCR techniques. Acute Myeloid Leukemia (AML) patients' samples were submitted to the analysis of the following alterations: FLT3-ITD, RUNX1::RUNX1T1, CBFB::MYH11 and PML::RARA; meanwhile, BCR::ABL1, TCF3::PBX1, KMT2A::AFF1, ETV6::RUNX1, and STIL::TAL1 fusions were investigated in the Acute Lymphoblastic Leukemia (ALL) patients' samples. Throughout the study, 77 patients were diagnosed with AML and 40 with ALL. Among the 77 AML patients, FLT3-ITD, RUNX1::RUNX1T1, PML::RARA, and CBFB::MYH11 were detected in 4, 7, 10 and 8 patients, respectively. Among the 40 ALL patients, the presence of 23 patients with BCR::ABL1 translocation and 9 patients with TCF3::PBX1 translocation was observed through the RT-qPCR methodology. Overall, the present study demonstrated that the RT-qPCR technique presented a higher sensitivity when compared to the Nested-PCR technique at the time of diagnosis of the acute leukemia samples studied. [ABSTRACT FROM AUTHOR]

Bone loss is a major burden for society and impacts people's health all over the world. In a changing world looking toward a more conscious use of raw materials, efforts are being made to increasingly consider new promising biomaterials that account for, on one side, the ability to provide specific functional biological activities and, on the other, the feature of being well tolerated. In this regard, the use of phenolic compounds in the field of bone-related bioengineering shows a rising interest in the development of medical solutions aimed at taking advantage of the multiple beneficial properties of these plant molecules. In this work, the anti-bacterial and anti-inflammatory power of a biphasic calcium phosphate synthetic bone filler coated with a mixture of phenolic compounds was investigated by evaluating the minimal inhibitory concentration (MIC) value against Streptococcus mutans and Porphyromonas gingivalis and the expression of genes involved in inflammation and autophagy by real-time reverse transcription polymerase chain reaction (RT-qPCR) on J774a.1 murine macrophage cells. Results show a MIC of 0.8 μg/mL, a neat anti-inflammatory effect, and induction of autophagy key genes compared to a ceramic bone filler. In conclusion, functionalization with a polyphenol-rich extract confers to a ceramic bone filler anti-bacterial and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Gliomas are the most prevalent primary malignant brain tumors worldwide. Growing evidences indicate that circular RNAs (circRNAs) play an important role in the regulation of biological behavior of tumors. We aimed to investigate the role and mechanism of circVCAN in glioma. RNase R treatment was utilized to assess the cyclic properties of circVCAN. CircVCAN, miR‐488‐3p, and myocyte enhancer factor 2C (MEF2C) levels in glioma tissues and cells were detected by reverse transcription real‐time polymerase chain reaction (RT‐qPCR), and the localization of them in glioma cells was determined with fluorescence in situ hybridization. Furthermore, a variety of biologically functional assessments were used to validate the role of circVCAN in glioma. The regulatory mechanisms of circVCAN, miR‐488‐3p, and MEF2C were further confirmed by double luciferase reporter gene assay, RNA immunoprecipitation and RNA pull‐down assay, and the binding of MEF2C to JAGGED1 was revealed by chromatin immunoprecipitation. Additionally, a xenograft tumor model was constructed to demonstrate the effect of circVCAN on tumor growth in vivo. Our results indicated that circVCAN was more stable than its linear RNA and was significantly upregulated in gliomas. CircVCAN overexpression stimulated glioma cells to proliferate and metastasize, but circVCAN silencing exerted the opposite effect. Meanwhile, silencing circVCAN inhibited tumor growth in vivo. Moreover, we found that circVCAN interacted with miR‐488‐3p to regulate MEF2C expression, and miR‐488‐3p inhibition or MEF2C overexpression reversed the inhibitory effect on malignant bio‐behaviors mediated by circVCAN knockdown in glioma cells. MEF2C promoted the transcription of JAGGED1, and circVCAN knockdown reduced the binding between MEF2C and JAGGED1. Collectively, circVCAN is a carcinogenic circRNA in glioma, and the circVCAN/miR‐488‐3p/MEF2C‐JAGGED1 axis could serve as a potential target for the management of glioma. [ABSTRACT FROM AUTHOR]

Objective: The effect of continuous topical oxygen therapy (cTOT) on Pseudomonas aeruginosa biofilm gene transcription profiles following inoculation onto porcine skin, using a customised molecular assay was determined. Method: Sterilised porcine skin explants were inoculated with Pseudomonas aeruginosa in triplicate: 0 hours as negative control; 24 hours cTOT device on; 24 hours cTOT device off. The oxygen delivery system of the cTOT device was applied to the inoculated tissue and covered with a semi-occlusive dressing. All samples were incubated at 37±2°C for 24 hours, with the 0 hours negative control inoculated porcine skin samples recovered immediately. Planktonic suspensions and porcine skin biopsy samples were taken at 0 hours and 24 hours. Samples were processed and quantifiably assessed using gene specific reverse transcription-quantitative polymerase chain reaction assays for a panel of eight Pseudomonas aeruginosa genes (16S, pelA, pslA, rsaL, pcrV, pscQ, acpP, cbrA) associated with biofilm formation, quorum sensing, protein secretion/translocation and metabolism. Results: Transcriptional upregulation of pelA, pcrV and acpP, responsible for intracellular adhesion, needletip protein production for type-3 secretion systems and fatty acid synthesis during proliferation, respectively, was observed when the cTOT device was switched on compared to when the device was switched off. Data suggest increased metabolic activity within bacterial cells following cTOT treatment. Conclusion: cTOT is an adjunctive therapy that supports faster healing and pain reduction in non-healing hypoxic wounds. Oxygen has previously been shown to increase susceptibility of biofilms to antibiotics through enhancing metabolism. Observed gene expression changes highlighted the impact of cTOT on biofilms, potentially influencing antimicrobial treatment success in wounds. Further in vitro and clinical investigations are warranted. [ABSTRACT FROM AUTHOR]

Background: Considering that few studies have investigated the differences in clinical, laboratory, and imaging symptoms of patients with coronavirus disease 2019 (COVID-19) during different peaks of the disease in Iran, the present study compares the patients who were admitted to the COVID-19 departments of Imam Reza Hospital during the first, second, and third peaks of the disease. Methods: In this cross-sectional study, data were collected by reviewing the files of patients with a definite diagnosis of COVID- 19 based on the RT-PCR test in Imam Reza Hospital in Mashhad. The patients were divided into three groups based on the time of admission: The first peak from March 2020 to June 2020, the second peak from July to September 2020, and the third peak from October to December 2020. The variables evaluated in this study included demographic information, clinical signs and symptoms, and laboratory and radiological findings. Descriptive qualitative data were reported using frequency tables, while quantitative descriptive data were reported using measures of central tendency and dispersion. A comparison of qualitative data among the three peaks was conducted using the chi-square test, while for quantitative data, the ANOVA test was used followed by appropriate post-hoc tests. Results: A total of 561 patients with an average age of 58.90 ± 16.80 years were included in the study, of which 336 (59.9%) were male. Regarding underlying diseases, significant differences were found in age (P < 0.001), smoking (P < 0.001), diabetes (P = 0.003), high blood pressure (P < 0.001), asthma (P = 0.025), and ischemic heart disease (P < 0.001). For vital signs, significant differences were observed in heart rate (P < 0.001), respiration rate (P < 0.001), diastolic blood pressure (P = 0.010), and SPO2 (P < 0.001). In clinical characteristics, significant differences were found in fever (P < 0.001), nausea (P = 0.011), vomiting (P = 0.031), headache (P < 0.001), weakness (P < 0.001), and sore throat (P < 0.001). In laboratory characteristics, significant differences were observed in white blood cell (WBC) count (P = 0.024), neutrophil percentage (P < 0.001), lymphocyte percentage (P < 0.001), and C-reactive protein (CRP) (P = 0.001). The CT score values of the patients were significantly different between the three peaks. Patient mortality was significantly different across the three peaks. Less than 15% of hospitalized patients died in the first peak, while over 24% died in the second peak and nearly 40% of inpatients died in the third peak. In our study, the first and third surges and the second and third surges had different mortalities. Conclusions: The third and first peaks had the highest and lowest mortality rates, respectively. Underlying diseases and unstable vital signs were more common in the second and third peaks. Patients in the second peak had significantly higher CT scores compared to the other peaks. [ABSTRACT FROM AUTHOR]

Background The 2022 African Cup of Nations (AFCON) took place in Cameroon from January 9th to February 5th, 2022, including Garoua in the north. We aimed to measure the impact of this event on the local COVID-19 epidemic given the implementation of a preventive strategy based on a health pass. Methods All players, staff and fans involved in the AFCON event were screened with PCR tests. Symptomatic cases were also continuously monitored in the general population and screened for variants of concern. Daily numbers of confirmed cases were compared to neighboring countries numbers retrieved from a public domain source. Results In total, 1479 and 2481 tests were performed in the general population and on asymptomatic AFCON attendees, respectively. From the latter, 12.5% were PCR-positive; 97% were infected with Omicron, with no significant difference compared to the passive program (G-test, P value = 0.162). Surveillance indicated the AFCON did not increase the number of symptomatic PCR-positive cases in the general population compared to neighboring countries. Conclusions Though the COVID-19 epidemic was fueled by asymptomatic cases infected with the Omicron variant at the time, the non-therapeutic preventive measures implemented for AFCON mitigated an increase in the epidemic in the local population. [ABSTRACT FROM AUTHOR]

Myocardial fibrosis (MF), which is an inevitable pathological manifestation of many cardiovascular diseases in the terminal stage, often contributes to severe cardiac dysfunction and sudden death. Morroniside (MOR) is the main active component of Cornus officinalis with a variety of biological activities. This study was designed to explore the efficacy of MOR in MF and to investigate its pharmacological mechanism. The viability of MOR-treated human cardiac fibroblast (HCF) cells with or without Angiotensin II (AngII) induction was assessed with Cell Counting Kit-8 (CCK-8). The migration of AngII-induced HCF cells was appraised with a transwell assay. Gelatin zymography analysis was adopted to evaluate the activities of MMP2 and MMP9, while immunofluorescence assay was applied for the estimation of Collagen I and Collagen III. By means of western blot, the expressions of migration-, fibrosis-, and p38/c-Jun N-terminal kinase (JNK) signal pathway-related proteins were resolved. The transfection efficacy of oe-Kruppel-like factor 5 (KLF5) was examined with reverse transcription-quantitative PCR (RT-qPCR) and western blot. In this study, it was found that MOR treatment inhibited AngII-induced hyperproliferation, migration, and fibrosis of HCF cells, accompanied with decreased activities of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), connective tissue growth factor (CTGF), Fibronectin, and α-SMA, which were all reversed by KLF5 overexpression. Collectively, MOR exerted protective effects on MF by blocking p38/JNK signal pathway through the downregulation of KLF5. [ABSTRACT FROM AUTHOR]

Background & Objective: The study aims to determine the adverse effects of a mild COVID-19 infection on maternal and neonatal outcomes in pregnant women living in the eastern part of Tehran. Materials & Methods: In this prospective cohort study, we followed two groups of pregnant women until term and their pregnancy and neonatal outcomes. RT-PCR (reverse transcriptase polymerase chain reaction) positive tests of nasopharyngeal swabs were confirmed in one group, where at least three signs and symptoms associated with COVID-19, and/or chest CT scans identified highly specific findings for the disease were present. The control group is composed of healthy pregnant women tested negative for COVID-19. Results: The study included 319 pregnant women (108 with mild COVID-19 infection and 211 healthy). A higher percentage of mothers with mild COVID-19 infection had preterm births (47.9% vs. 30%, p=0.007), and their neonates required hospitalization more often (45.8% vs. 22.6%, p<0.001). PTB was positively associated with maternal hypertension (relative risk (RR): 5.40), mild COVID-19 infection (RR: 2.05), and older age (RR: 1.05). Among the risk factors for neonatal hospitalization, PTB (RR: 5.94), maternal hypertension (RR: 2.74), and mild COVID-19 infection during pregnancy (RR: 2.57) were significant. Conclusion: The outcomes of pregnancy are significantly impacted by maternal infection with COVID-19, even if it is mild. Preterm births are more likely to happen in mothers with mild COVID-19 infection, and neonates need more hospitalizations. [ABSTRACT FROM AUTHOR]

Insufficient milk supply is a widespread issue faced by women globally and associated with a higher risk of health problems in infants and mothers. Hemerocallis citrina Baron, commonly known as daylily, is a perennial edible plant often used in traditional Asian cuisine to promote lactation. However, the active compound(s) and mechanism of its lactation-promoting effect remain unclear. This study aimed to confirm the traditional use of daylily in promoting lactation and investigate its potential active components and underlying molecular mechanisms. Our results showed that the aqueous extracts of H. citrina Baroni (HAE) significantly enhanced milk production, and the serum levels of lactation-related hormones, and promoted mammary gland development in lactating rats, as well as increased the levels of milk components in bovine mammary epithelial cells (BMECs) (p < 0.05). UHPLC-Q-Exactive Orbitrap-MS analysis revealed that hexamethylquercetin (HQ) is the representative flavonoid component in HAE, accounting for 42.66% of the total flavonoids. An integrated network pharmacology and molecular docking analysis suggested that HQ may be the potential active flavonoid in HAE that promotes lactation, possibly supporting lactation by binding to key target proteins such as STAT5A, PIK3CA, IGF1R, TP53, CCND1, BCL2, INS, AR, and DLD. Cell experiments further demonstrated that HQ could promote cell proliferation and the synthesis of milk proteins, lactose, and milk fat in BMECs. Transcriptomic analysis combined with a quantitative reverse transcription polymerase chain reaction (RT-qPCR) revealed that both HAE and HQ exert a lactation-promoting function mainly through regulating the expression of key genes in the PI3K-Akt signaling pathway. [ABSTRACT FROM AUTHOR]

KIAA1429 is an important 'writer' of the N6‐methyladenine (m6A) modification, which is involved in tumour progression. This study was conducted to explore the mechanism of action of KIAA1429 in colon adenocarcinoma (COAD). KIAA1429‐silenced COAD cell and xenograft tumour models were constructed, and the function of KIAA1429 was explored through a series of in vivo and in vitro assays. The downstream mechanisms of KIAA1429 were explored using transcriptome sequencing. Dimethyloxalylglycine (DMOG), an activator of HIF‐1α, was used for feedback verification. The expression of KIAA1429 in COAD tumour tissues and cells was elevated, and KIAA1429 exhibited differential expression at different stages of the tumour. Silencing of KIAA1429 inhibited the proliferation, migration, and invasion of HT29 and HCT116 cells. The expression levels of NLRP3, GSDMD and Caspase‐1 were decreased in KIAA1429‐silenced HT29 cells, indicating the pyroptotic activity was inhibited. Additionally, KIAA1429 silencing inhibited the growth of tumour xenograft. Transcriptome sequencing and reverse transcription quantitative polymerase chain reaction revealed that after KIAA1429 silencing, the expression of AKR1C1, AKR1C2, AKR1C3 and RDH8 was elevated, and the expression of VIRMA, GINS1, VBP1 and ARF3 was decreased. In HT29 cells, KIAA1429 silencing blocked the HIF‐1 signalling pathway, accompanied by the decrease in AKT1 and HIF‐1α protein levels. The activation of HIF‐1 signalling pathway, mediated by DMOG, reversed the antitumour role of KIAA1429 silencing. KIAA1429 silencing inhibits COAD development by blocking the HIF‐1 signalling pathway. [ABSTRACT FROM AUTHOR]

3,5,7‐Trihydroxy‐2‐phenylchromen‐4‐one (THF) possesses a diverse range of pharmacological activities. Evidence suggests that THF exerts anticancer activity by distinct mechanisms of action. This study explores the anticancer potential of THF in human lung (A549) and skin (A431) cancer cells by employing different antiproliferative assays. 3‐(4,5‐Dimethylthiazol‐2‐yl)−2,5‐diphenyltetrazolium bromide, neutral red uptake, sulphorhodamine B, and cell motility assays were used to confirm the anticancer potential of THF. Cell target‐based and quantitative reverse transcription polymerase chain reaction (qRT‐PCR) assays were used to explore the effect of THF on the initiation, promotion and progression phase biomarkers of carcinogenesis. THF suppresses the activity of lipoxygenase‐5 up to ~40% in both A549 and A431 cells and up to ~50% hyaluronidase activity in A549 cells. qRT‐PCR assay reveals that THF inhibits the activity of phosphatidyl inositol‐3 kinase/protein kinase B/mammalian target of rapamycin in both cell lines, which is responsible for the initiation of cancer. It also arrests the G2/M phase of the cell cycle in A431 cells and increases the sub‐diploid population in both A549 and A431 cell lines which leads to cell death. Annexin V‐FITC assay confirmed that THF induces apoptosis and necrosis in A431 and A549 cell lines. Further investigation revealed that THF not only enhances reactive oxygen species production but also modulates mitochondrial membrane potential in both cell lines. It significantly inhibits S‐180 tumour formation at 5 and 10 mg/kg bw, i.p. dose. An acute skin toxicity study on mice showed that erythema and edema scores are within the acceptable range, besides acceptable drug‐likeness properties and non‐toxic effects on human erythrocytes. Conclusively, THF showed potent anticancer activity on skin and lung carcinoma cell lines, suppressed the level of the biomarkers and inhibited tumour growth in mice. Highlights: 3,5,7‐Trihydroxy‐2‐phenylchromen‐4‐one (THF) shows antiproliferative potential on A431 and A549 cancer cell lines.THF downregulates carcinogenesis biomarkers of the promotion and progression phase.THF arrests the cell cycle phase and disrupts mitochondrial membrane potential.THF inhibits S‐180 tumour growth in mice. THF inhibits the initiation, promotion, and progression biomarkers of carcinogenesis process. [ABSTRACT FROM AUTHOR]

The involvement of let‐7 in the occurrence and progression of various cancers has been well‐documented. However, the precise molecular mechanisms underlying its impact on oral cancer development remain unclear. In this study, we aimed to elucidate the role of let‐7 in oral cancer progression and investigate its underlying molecular mechanisms. The expression of let‐7 and high mobility group A2 (HMGA2) mRNA was assessed using the quantitative reverse transcription polymerase chain reaction. Western blot analysis was employed to detect the expression of key proteins in the PI3K/AKT signaling pathway as well as HMGA2 protein levels. The targeting relationship between let‐7 and HMGA2 was predicted through bioinformatics methods and confirmed via luciferase reporter gene assay. The effects of let‐7 and HMGA2 on the functionality of oral cancer cells were evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, colony formation assay, Transwell assay, wound healing assay, and Annexin V/PI apoptosis assay. Additionally, the impact of let‐7 on the growth of oral cancer cells in vivo was investigated by inducing subcutaneous tumor formation in nude mice. Let‐7 effectively suppresses the proliferation, migration, and invasion of oral cancer cells by inhibiting the activation of the PI3K/AKT signaling pathway. HMGA2, a downstream target gene of let‐7, exhibits high expression in oral cancer. However, overexpression of HMGA2 diminishes the inhibitory effects induced by let‐7 overexpression on the proliferation, migration, and invasion of oral cancer cells. The occurrence and progression of oral cancer cells are inhibited by Let‐7 through the downregulation of HMGA2, potentially mediated by the inhibition of PI3K/AKT signaling pathway activation. [ABSTRACT FROM AUTHOR]

Background and Objectives: The steady spread of dengue virus (DENV) poses a profound public health threat worldwide. Reverse transcription real-time polymerase chain reaction (RT2-PCR) has been increasingly recognized as a reference method for the diagnosis of acute dengue infection. The goal of this study was to assess the diagnostic accuracy of five different RT2-PCR kits for the detection of DENV in a historically processed set of sera samples. Materials and Methods: In this retrospective study, 25 sera samples from routinely processed unique adult patients with a known DENV status (previously tested in both molecular and serological assays) were tested in parallel using four conventional (RealStar Dengue PCR Kit 3.0, Clonit'ngo Zika, Dengue & Chikungunya, BioPerfectus Zika Virus/Dengue Virus/Chikungunya Virus Real Time PCR Kit and Novaplex Tropical fever virus) and one sample-to-result (STANDARD M10 Arbovirus Panel) RT2-PCR assays. Additionally, an end-point dilution analysis was conducted in quintuplicate on six serial dilutions of an RNA preparation obtained from a culture-grown DENV serotype 1 strain for a total of 150 tests. Results: The overall accuracy of the evaluated tests ranged from 84% to 100%. In particular, the sensitivity of three conventional RT2-PCR assays (RealStar, Clonit'ngo and Novaplex) was 100% (95% CI: 79.6–100%), while it was lower (73.3%; 95% CI: 48.1–89.1%) for the BioPerfectus kit. The sample-to-result STANDARD M10 panel performed comparatively well, showing a sensitivity of 92.9% (95% CI: 68.5–98.7%). No false positive results were registered in any assay. The end-point dilution analysis suggested that the RealStar kit had the lowest limit of detection. Conclusions: Available RT2-PCR kits for the detection of DENV are highly specific and generally sensitive and, therefore, their implementation in diagnostic pathways is advisable. [ABSTRACT FROM AUTHOR]

A total of 490 diarrhoeic samples from calves aged between 0 and 6 months were screened for the presence of different G- and P-genotypes of rotavirus circulating in bovines in the Kashmir Valley. Of the 490 diarrhoeic samples, Group A rotavirus was detected in 68 (13.87%) samples by polymerase chain reaction (PCR) followed by RNA-PAGE. Genotyping analysis revealed G10, G6, G3, P[11] and P[5] to be the predominant types. The most common types of combinations detected were G10P[11] (27.90%) and G6P[11] (20.60%). The prevalence rate of G10 and P[11] decreased from 60% to 36.76% and 100%–69.11%, respectively. Genotypes G6, G3, P[1] and P[5], which were not previously reported, were detected and unusual combinations such as G6P[11], G3P[11], G10P[5], G3P[5], G6P[1], G6P[5], G6+G8P[11] were also observed for the first time. Fluctuations in the predominant types, emergence of new types and possible genetic reassortment events suggest an unstable epidemiological situation and the need for continuous surveillance of the circulating types to ensure the suitability of the vaccination programme. The present data suggests G10, G6, P[11] and P[5] genotypes could be incorporated in the polyvalent vaccine to offer increased protection against bovine rotavirus infection in India. [ABSTRACT FROM AUTHOR]

Apple pomace is the residue left after apples are squeezed. The majority of pomace produced worldwide is produced by the apple manufacturing industry, however, most of the pomace produced by the industry is discarded. Apple pomace contains functional ingredients, such as polyphenols and triterpenoids, and exerts several beneficial effects on human health; however, studies on its cosmetic effects on the skin are lacking. Therefore, herein, we investigated the effects of apple pomace extract (APE) on human skin fibroblasts (HSFs) in vitro. When HSFs were cultured with the extract for 72 h, the number of HSFs increased at concentrations of 10 and 20 µg/mL. Transcriptome analysis and reverse transcription-quantitative PCR results revealed that the extract upregulated the expression of hyaluronan synthase (HAS) 1, HAS2, and HAS3 and downregulated the expression of HYAL1, a gene encoding the hyaluronan-degrading enzyme, in HSFs. Additionally, enzyme-linked immunosorbent assay revealed increased amounts of factors related to skin extracellular matrix, such as type I collagen and hyaluronic acid, secreted in the culture supernatant. The western blotting results suggested that the extract induced extracellular signal-regulated kinase and protein kinase B phosphorylation in HSFs. Additionally, several GO_Terms related to mitosis were detected in the Gene Ontology analysis. This is the first study to show that APE induces the proliferation of HSFs and production of factors related to skin anti-aging. [ABSTRACT FROM AUTHOR]