High Mortality Worldwide Research Articles

Therapeutic Potential of Chinese Herbal Medicine and Underlying Mechanism for the Treatment of Myocardial Infarction.

Myocardial infarction (MI) is a prevalent disease with high mortality rates worldwide. The course of MI is intricate and variable, necessitating personalized treatment strategies based on different mechanisms. However, variety of postoperative complications and rejections, such as heart failure, arrhythmias, cardiac rupture, and left ventricular thrombus, contribute to a poor prognosis. Despite the inclusion of antiplatelet agents and statins in the conventional treatment regimen, their clinical applicability is constrained by potential adverse effects and limited efficacy. Additionally, the mechanisms leading to MI are complex and diverse. Therefore, the development of novel compounds for MI treatment. The use of traditional Chinese medicine (TCM) in the prevention and treatment of cardiovascular diseases, including MI, is grounded in its profound historical background, comprehensive theoretical system, and accumulated knowledge. An increasing number of contemporary evidence-based medical studies have demonstrated that TCM plays a significant role in alleviating symptoms and improving the quality of life for MI patients. Chinese herbal formulations and active ingredients can intervene in the pathological process of MI through key factors such as inflammation, oxidative stress, apoptosis, ferroptosis, pyroptosis, myocardial fibrosis, angiogenesis, and autophagy. This article critically reviews existing herbal formulations from an evidence-based medicine perspective, evaluating their research status and potential clinical applications. Additionally, it explores recent advancements in the use of herbal medicines and their components for the prevention and treatment of MI, offering detailed insights into their mechanisms of action.

Mechanisms of microRNA Regulation of the Epithelial–Mesenchymal Transition (EMT) in Lung Cancer

Lung cancer remains the cancer with the highest mortality worldwide, largely due to a limited understanding of the precise molecular mechanisms that drive its progression. microRNAs (miRNAs) have emerged as crucial regulators of lung cancer progression by influencing key cellular processes, notably the epithelial–mesenchymal transition (EMT). EMT is a complex and potentially reversible process where epithelial cells lose their polarity and adhesion, reorganize their cytoskeleton, and transition to a mesenchymal phenotype, enhancing their migratory and invasive capacities. While EMT plays an essential role in normal physiological contexts such as tissue development and wound healing, it is also a critical mechanism underlying the progression and metastasis of lung cancer. This review aims to summarize the latest research findings on the role of endogenous and exosome-derived microRNAs in regulating EMT in lung cancer, focusing on studies conducted over the past five years. It also provides an overview of EMT’s essential molecular mechanisms to better understand how miRNAs regulate EMT in lung cancer.

Knockdown of Inhibin Beta A Reversed the Epithelial Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance and Enhanced the Therapeutic Effect of Radiotherapy in Non-Small Cell Lung Cancer.

Lung cancer is a malignant tumor with the highest mortality rate worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately half of all lung cancer cases. Inhibin beta A (INHBA) is a ligand of the transforming growth factor-beta superfamily. This study aimed to analyze the function of INHBA in NSCLC resistance cells. Gene Expression Omnibus and The Cancer Genome Atlas databases were used to identify differentially expressed genes (DEGs) in NSCLC resistance cells and patients. DEGs were further analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. A colony formation assay was performed to determine cell growth. Cell migration and invasion were tested by Transwell assay. Epithelial-mesenchymal transition (EMT)-related genes were analyzed using qRT-PCR and Western blot analysis. Using bioinformatics tools, INHBA was demonstrated to be overexpressed in NSCLC resistant cells and patients. Gefitinib treatment affected NSCLC resistant cells. Additionally, INHBA silencing or X-ray treatment suppressed the growth and metastasis of NSCLC resistant cells. Moreover, the combined application of INHBA silencing and X-ray treatment enhances the therapeutic effects. Moreover, EMT has been confirmed to occur in NSCLC resistant cell lines. Both INHBA silencing and X-ray treatment inhibited EMT development. This study demonstrated that INHBA silencing ameliorates EGFR-TKI resistance and enhances the therapeutic effect of radiotherapy in NSCLC.

Exploring the dual role of endoplasmic reticulum stress in urological cancers: Implications for tumor progression and cell death interactions

AbstractThe endoplasmic reticulum (ER) is crucial for maintaining calcium balance, lipid biosynthesis, and protein folding. Disruptions in ER homeostasis, often due to the accumulation of misfolded or unfolded proteins, lead to ER stress, which plays a significant role in various diseases, especially cancer. Urological cancers, which account for high male mortality worldwide, pose a persistent challenge due to their incurability and tendency to develop drug resistance. Among the numerous dysregulated biological mechanisms, ER stress is a key factor in the progression and treatment response of these cancers. This review highlights the dual role of aberrant ER stress activation in urologic cancers, affecting both tumor growth and therapeutic outcomes. While ER stress can support tumor growth through pro‐survival autophagy, it primarily inhibits cancer progression via apoptosis and pro‐death autophagy. Interestingly, ER stress can paradoxically aid cancer progression through mechanisms such as exosome‐mediated immune evasion. Additionally, the review examines how pharmacological interventions, particularly with phytochemicals, can stimulate ER stress‐mediated tumor suppression. Key regulators, including PERK, IRE1α, and ATF6, are discussed for their roles in upregulating CHOP levels and triggering apoptosis. In conclusion, a deeper understanding of ER stress in urological cancers not only clarifies the complex interactions between cellular stress and cancer progression but also provides new opportunities for innovative therapeutic strategies.

Targeting Macrophage Phenotype for Treating Heart Failure: A New Approach.

Heart failure (HF) is a disease with high morbidity and mortality rates worldwide and significantly affects human health. Currently, the treatment options for HF are limited, and there is an urgent need to discover new therapeutic targets and strategies. Macrophages are innate immune cells involved in the development of HF. They play a crucial role in maintaining cardiac homeostasis and regulating cardiac stress. Recently, macrophages have received increasing attention as potential targets for treating HF. With the improvement of technological means, the study of macrophages in HF has made great progress. This article discusses the biological functions of macrophage phagocytosis, immune response, and tissue repair. The polarization, pyroptosis, autophagy, and apoptosis are of macrophages, deeply involved in the pathogenesis of HF. Modulation of the phenotypic changes of macrophages can improve immune-inflammation, myocardial fibrosis, energy metabolism, apoptosis, and angiogenesis in HF.

A Comprehensive Review on the Significance of Cysteine in Various Metabolic Disorders; Particularly CVD, Diabetes, Renal Dysfunction, and Ischemic Stroke.

Metabolic disorders have long been a challenge for medical professionals and are a leading cause of mortality in adults. Diabetes, cardiovascular disorders (CVD), renal dysfunction, and ischemic stroke are the most prevalent ailments contributing to a high mortality rate worldwide. Reactive oxygen species are one of the leading factors that act as a fundamental root cause of metabolic syndrome. All of these disorders have their respective treatments, which, to some degree, sabotage the pathological worsening of the disease and an inevitable death. However, they pose a perilous health hazard to humankind. Cysteine, a functional amino acid shows promise for the prevention and treatment of metabolic disorders, such as CVD, Diabetes mellitus, renal dysfunction, and ischemic stroke. In this review, we explored whether cysteine can eradicate reactive oxygen species and subsequently prevent and treat these diseases.

Genetic selection for lung adenocarcinoma: a statistical approach based on pathological genetic data

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC), with high morbidity and mortality worldwide, posing a serious threat to human health. Due to the complex molecular mechanism of lung adenocarcinoma, which involves a variety of genetic and environmental factors, this makes early diagnosis and treatment a major challenge. This research aims to identify the key pathogenic genes of lung adenocarcinoma to solve the challenges in early diagnosis and treatment. In this paper, three differential analysis methods, limma, DESeq2 and edgeR, were used to select 3315 differential genes. Then, combined with Lasso regression and XGboost algorithm, the pathological gene data were analyzed in depth, and through these advanced statistical and machine learning techniques, the genes related to lung adenocarcinoma were screened from a large number of gene expression data, and 17 characteristic genes of the highest importance were found GO enrichment analysis and KEGG enrichment analysis were performed on these characteristic genes to clarify the biological functions of the genes. Finally, 8 significant pathogenic genes were identified by Cox survival analysis. The expression levels of these genes are closely related to the prognosis of lung adenocarcinoma patients, providing a new perspective for understanding the disease mechanism. The conclusions of this study not only improve the understanding of the molecular mechanism of lung adenocarcinoma, but also provide potential biomarkers for clinical diagnosis and treatment. The discovery of these genes is expected to promote the development of early diagnosis technology and guide the formulation of personalized treatment plans, thereby improving the treatment efficacy and quality of life of lung adenocarcinoma patients. In the future, these genes may become key targets for the development of new drugs and therapeutic strategies.

Epidemiological characteristics and meteorological factors of acute respiratory infections (ARIs) in hospitalized children in eastern Guangdong, China

Acute respiratory infections (ARIs) are the most common issue in pediatric clinical practice. They pose a significant public threat, with high morbidity and mortality rates worldwide. Aiming at understanding the epidemiological characteristics of respiratory pathogens and their risk factors among children in eastern Guangdong, China. Samples obtained from 15,993 children hospitalized with ARIs in eastern Guangdong Province were tested for 14 pathogens via multiplex polymerase chain reaction (PCR) from May 2019 to July 2023. The number of hospitalizations for ARIs was correlated with pathogens, age, meteorological parameters, and the pandemic of COVID-19. The data were analyzed by different statistical methods. Among all the samples, the positive rate with ARIs accounted for 68.94% (11,026/15,993) in hospitalized patients. Cytomegalovirus (CMV) (24.49%), Streptococcus pneumoniae (SP) (20.54%), and Respiratory Syncytial Virus (RSV) (14.16%) were the top three pathogens with the greatest infection rates. Among hospitalized patients, there were more single infections in pediatric patients (40.91%, P < 0.001). Compared with bacterial infection and mixed infection, the detection rate of virus infection was higher in pediatric (36.04%, P < 0.001). Age-related increases in Mycoplasma pneumoniae (MP) infection (r = 0.729, P < 0.001) and decreases in RSV infection were observed (r = 0.88, P < 0.001). The virus infection peaked at six months, and the bacterial infection and mixed infection peaked at 1–3 years. Viral pathogens are on the rise in the post-pandemic era. The prevalence of SP infection was more influenced by the Air Quality Index (AQI), RSV infections were more clearly influenced by temperature, and Influenza A virus (IAV) infections were more strongly correlated with both the AQI and relative humidity (P < 0.001). This study highlights the need of keeping an eye on monitoring meteorological factors in assessing hospitalizations for pediatric ARIs in eastern Guangdong, China, especially RSV- and SP-associated hospitalizations.

The first prevalence and antifungal susceptibility profile of Candida infections in Palestine, 2022

BackgroundCandida spp. are the most common cause of opportunistic fungal infections and are associated with a high mortality rate worldwide. In Palestine, the prevalence of Candida spp. infections remains elusive.MethodsWe performed our study at two hospitals in Palestine (Istishari Arab Hospital, and Najah National University Hospital). All patients diagnosed with candidiasis during the year 2022 have participated in the study. The prevalence of Candida spp., their distribution, and the activity of selected antifungals against Candida pathogens were assessed. In combination with phenotypic properties, Candida isolates were identified and tested for antifungal susceptibility using the colorimetric VITEK-2 Compact system.ResultsOur results showed that the prevalence of Candida spp. among infected samples was 11.6%. A total of eleven different Candida spp. were identified. Among these isolates, C. albicans (46.54%) was the most frequent, followed by C. glabrata (16.14%), C. tropicalis (13.83%), C. parapsilosis (4.82%), C. krusei (3.56%), C. dubliniensis (2.09%), C. ciferrii (1.67%), C. lusitaniae (0.83%), C. guilliermondii (0.62%), C. kefyer (0.41%) and C. spherica (0.20%). Among C. albicans, all isolates were 100% susceptible to fluconazole and micafungin. The susceptibility rates to Amphotericin B and flucytosine were 95% and 99%, respectively. The susceptibility rates of non-albicans Candida spp. (NAC) to fluconazole, voriconazole, amphotericine B, caspofungin, flucytosine and micafungin were 70%, 99%, 97%, ,72%, 92% and 100%, respectively. The incidence of Candida infections was higher in the intensive care unit and surgery department as compared to other hospital departments.ConclusionsFour pathogens are responsible for the most invasive infections: C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis. A notable characteristic of this study was the high frequency of NAC species which were often more resistant to antifungal agents. A quick and accurate system like Vitek 2 compact was suggested for the careful species identification of clinical isolates of Candida. We suggest that continued surveillance of species distribution and susceptibility to antifungals will enhance future burden estimates and assist in evaluating preventative measures’ effectiveness.

Invasive Fungal Infections in Immunocompromised Conditions: Emphasis on COVID-19.

The COVID-19 pandemic caused death of 6 million lives globally, primarily from respiratory failure, but also a significant number from invasive fungal co-infections in these patients, owing to the immune dysfunction in hospitalized patients. Such complications occurred more often in critically ill, hospitalized patients particularly those admitted in intensive care units and were reported as the major reason associated with a high mortality rate worldwide. Fungal pathogens most commonly associated with COVID-19 patients comprise members of the Mucorales (such as Rhizopus, Mucor, and Lichtheimia), as well as genera Aspergillus and Candida. In India, the prevalence rate of mucormycosis is relatively high than aspergillosis and candidiasis, and the predisposing risk factors associated with such infections included uncontrolled diabetes, underlying lung disease, leukopenia, neutropenia, malignancies and prolonged steroid therapy. However, co-infection with other fungi, including Alternariaand Scedosporium was also sporadically reported. These devastating invasive fungal infections are associated with differential mortality (high-low) and morbidity rates even after active management. The diagnosis of such infections is often challenging due to lack of sensitivity in contemporary diagnostic methods and poses an enormous challenge to healthcare experts. Thus, the role of early and accurate diagnosis, and management of such fungal infections, is vital in preventing life-threatening situations. Hence, this review focusses primarily on the epidemiology, predisposing risk factors, host environment, diagnosis and treatment of the most common medically important invasive fungal infections in immunocompromised conditions associated with COVID-19.

Colorectal Cancer: aggressive presentations among young Nigerian adults

Colorectal Cancer (CRC) is the fourth most common cancer contributing to high morbidity and mortality worldwide. CRC is very common in the Western world with typical peculiarities how- ever, the black population has a different pattern of presentations since polyps and other pre-malignant lesions are relatively uncom- mon as compared to the Caucasians. This is a cross-sectional descriptive study of patients referred for colonoscopy evaluation at Aminu Kano Teaching Hospital, Kano, Nigeria. Sixty patients with colonic diseases were consecutively recruited during the study period. Colorectal cancer accounted for 11.7% of the study population with a M:F ratio of 2.5:1. Significantly, 57.14% of the patients were within 50 years of age. Over 70% of the patients were diagnosed with aggressive variant CRC. Constipation, fatigue, and weight loss were the dominant presenting symptoms, and predominantly left-sided colonic tumours were seen in 85% of the study population. For reasons that require further investiga- tions, the African population develops more aggressive variants of CRC at younger ages and it has a worse prognosis.

LncRNA-SNHG16 Protects Against Oxidative Stress-Induced Vascular Endothelial Cell Injury in Cardiovascular Diseases by Regulating the miR-23a-3p-GLS-Glutamine Metabolism Axis.

Cardiovascular diseases are disorders of the heart and vascular system that cause high mortality rates worldwide. Vascular endothelial cell (VEC) injury caused by oxidative stress (OS) is an important event in the development of various cardiovascular diseases, including ischemic heart disease. This study aimed to investigate the critical roles and molecular mechanisms of long non-coding RNA (lncRNA) SNHG16 in regulating vascular endothelial cell injury under oxidative stress. We demonstrated that SNHG16 was significantly downregulated and miRNA-23a-3p was notably induced in human vascular endothelial cells under OS. Overexpressing SNHG16 or silencing miR-23a-3p effectively mitigated the OS-induced VEC injury. Additionally, glutamine metabolism of VECs was suppressed under OS. SNHG16 protected the OS-suppressed glutamine metabolism, while miR-23a-3p functioned oppositely in VECs. Furthermore, SNHG16 downregulated miR-23a-3p by sponging miR-23a-3p, which direct targeted the glutamine metabolism enzyme, GLS. Finally, restoring miR-23a-3p in SNHG16-overexpressing VECs successfully reversed the protective effect of SNHG16 on vascular endothelial cell injury under OS. In summary, our results revealed the roles and molecular mechanisms of the SNHG16-mediated protection against VEC injury under OS by modulating the miR-23a-3p-GLS pathway.

Pachymic acid promotes ferroptosis and inhibits gastric cancer progression by suppressing the PDGFRB-mediated PI3K/Akt pathway

Gastric cancer (GC) is a common malignant tumour with high incidence and mortality rates worldwide. Despite current treatment modalities, including surgical resection and chemotherapy, challenges such as postoperative recurrence, metastasis and drug resistance persist. Therefore, investigating the feasibility and mechanism of traditional Chinese medicine in treating gastric cancer is crucial for discovering new anti-gastric cancer drugs or adjuvant therapies. Pachymic acid (PA) is a natural triterpenoid found in the traditional Chinese medicinal herb Poria cocos (PC) (Schw. Wolf). Recent studies have reported its inhibitory effects on various cancer cells, including liver, cervical, breast and gastric cancer. Our in vitro and in vivo experiments confirmed that PA inhibits the proliferation, migration and invasion of gastric cancer cells. The treatment of gastric cancer cells with various death inhibitors revealed that PA may suppress gastric cancer progression by inducing ferroptosis. Malondialdehyde, Fe2+, reactive oxygen species and glutathione assays were performed to validate the effects of PA on ferroptosis in gastric cancer. High-throughput sequencing combined with analysis of the TCGA database identified PDGFRB as a potential downstream target of PA. In vivo experiments indicated that the PDGFRB overexpression could counteract the antitumour effects of PA, while ferroptosis induced by the PI3K/Akt signalling pathway may play a key role in this process. This study provides initial evidence that PA, through its interaction with PDGFRB, alters the PI3K/Akt signalling pathway, leading to ferroptosis in gastric cancer cells, thus manifesting its antitumour properties. This discovery holds promise for the development of novel therapeutic strategies for gastric cancer patients.

TRPM8 overexpression suppresses hepatocellular carcinoma progression and improves survival by modulating the RTP3/STAT3 pathway.

Hepatocellular carcinoma (HCC) is a malignant tumour associated with high morbidity and mortality rates worldwide. Recently, TRPM8 was reported to play an important role in tumour progression. However, the precise role of TRPM8 in HCC remains unclear. In this study, we explored the expression levels, molecular functions and underlying mechanisms of TRPM8 in HCC. Tissue samples were used to analyse the expression of TRPM8 to assess its diagnostic value for prognosis. Cell Counting Kit-8, EdU and colony formation assays were performed to evaluate the effects of TRPM8 on cell proliferation, whereas the Transwell assay was used to assess cell migration and invasion. The role of TRPM8 invivo was evaluated using a mouse subcutaneous xenograft tumour model. We performed PPI network analyses to understand the possible mechanisms of TRPM8 action. TRPM8 expression was decreased in HCC tissues and was correlated with histological grade and poor patient prognosis. Functionally, TRPM8 repressed the proliferation and metastasis of HCC cells both invitro and invivo by modulating the RTP3/STAT3 signalling pathway. Our findings underscore the critical role of the TRPM8-RTP3-STAT3 axis in maintaining the malignant progression of HCC. Moreover, our study demonstrates that AD80 is involved in anti-tumour processes by upregulating the expression of TRPM8.

Ligand-based pharmacophore modeling, virtual screening, and molecular dynamics simulations of Pfhsp90 fingerprints in Plasmodium malaria treatment

The World Health Organization (WHO) documents malaria as one of the leading causes of high morbidity and mortality worldwide. The disease affects millions and kills thousands of people annually. Efforts to reduce the global burden of malaria have prompted the WHO to recommend prevention strategies such as using antimalarial drugs. However, these strategies have been ineffective because of antimalarial drug resistance. The only efficacious malaria treatment is Artemisinin-based Combination Therapy (ACT). However, the extended ACT clearance times, linked to the emergence of artemisinin monotherapy resistance recorded most recently in Africa and the Great Mekong region, pose a danger to its efficacy. Therefore, better efficacious antimalarial drugs are required. Since P. falciparum heat shock protein 90 (PfHsp90) is a well-characterized malaria drug target, this study uses it to discover more efficacious antimalarial drugs. An in silico approach was used to discover PfHsp90 inhibitors with pharmacological properties against Plasmodium malaria using a molecular dynamics simulation (MDS) and hierarchical virtual screening. Geldanamycin (GDM), a well-known anti-PfHsp90 compound, was used to identify PfHsp90 inhibitors with pharmacological properties against Plasmodium malaria by screening it against the ZINC20 database via the ZINCPHARMER web server. This virtual screening process resulted in 17 hits. These ZINCPHARMER hits were subjected to drug-likeness and pharmacokinetics properties analysis in the SwissADME web server, and nine of them satisfied the requirements. The nine ZINC20 compounds were docked with PfHsp90 using the PyRx software version 0.8 to understand their interactions. From the molecular docking results, ZINC09060002 (−8.2 kcal/mol), ZINC72133064 (−7.8 kcal/mol), ZINC72163401 (−7.7 kcal/mol), ZINC72358537 (−8.1 kcal/mol), and ZINC72358557 (−7.6 kcal/mol) had better binding affinities to PfHsp90 than GDM (−7.5 kcal/mol). The stability of these molecularly docked protein–inhibitor complexes was assessed through MDS using GROMACS 2022. ZINC72163401, ZINC72358537, and ZINC72358557 formed stable complexes with PfHsp90. The lead compounds were subjected to in vitro validation for their inhibitory capability. They showed promising inhibition of parasite growth with IC50 values ranging between 200 and 400 ng/mL. In this regard, the three PfHsp90 inhibitors can be further developed as potential antimalarial drugs. However, further structural optimization studies and clinical (in vivo) tests are necessary to ascertain the antimalarial activity of these compounds in humans.

Survivability of low pathogenic avian influenza virus in aqueous poultry manure fertilizer

Avian influenza has been a growing problem in the United States for decades. Low pathogenic avian influenza (LPAI) virus causes low morbidity, while highly pathogenic avian influenza (HPAI) has a devastating effect on the poultry industry causing high morbidity and mortality worldwide. Manure from large and small poultry operations is spread on crop fields as a fertilizer. During an outbreak of avian influenza in a farm it is critical to adequately process the manure to kill the virus before its use in agriculture. Aqueous extraction of poultry manure at high temperature (55-65°C) is an attractive method for treatment of poultry manure, which extracts the nutrients and kills harmful microbes from the manure. The end product is a nutrient rich liquid that can be safely applied to fields or used in hydroponic operations, with nutrients that are more bioavailable to the plant compared to dry litter. However, we do not know whether aqueous high temperature extraction processes completely kill avian influenza virus present in the manure. Our aim in this study was to determine the competence of the aqueous extraction of poultry manure on avian influenza virus inactivation. We optimized the procedure using a LPAI virus isolate in a biosafety level 2 cabinet. Our data indicated that LPAI virus including the hemagglutinin protein of the virus were completely destroyed when the poultry manure was processed by aqueous extraction at temperatures ≥ 55°C for one hour. Future research will identify the conditions required for inactivating HPAI virus using this optimized procedure by performing the study in a BSL3 facility.

MRNA expression profile and prognostic values of the CDHR family genes in lung adenocarcinoma

Lung adenocarcinoma (LUAD), the predominant subtype of lung cancer, has a high incidence and annual mortality worldwide. Members of the cadherin-related (CDHR) family are associated with many malignant tumor types. However, their role and clinical significance in LUAD have not been clarified. We analyzed the association of CDHRs mRNA expression profiles with prognostic significance, immune infiltration, and potential biological functional signatures in several public databases. We constructed a co-expressed mRNA network, and performed an intrinsic molecular structure and function enrichment analysis. Our results showed that CDHR2 mRNA expression was upregulated in LUAD, whereas CDHR1, CDHR3, CDHR4, and CDHR5 mRNAs were downregulated. Upregulation of CDHR2 mRNA is associated with a poor prognosis in patients with LUAD. Next, the correlation between CDHR family members and immune infiltration was observed. A receiver operating characteristic curve showed that the CDHR family is valuable for diagnosing LUAD. In this study, we found that CDHR2 mRNA expression was upregulated in LUAD. Upregulation of CDHR2 mRNA was associated with a poor prognosis in patients with LUAD.

MFGE8 promotes gastric cancer progression by activating the IL-6/JAK/STAT3 signaling

ObjectiveGastric cancer is malignant cancer with high morbidity and mortality worldwide. Milk fat globule EGF and factor V/VIII domain containing (MFGE8) was involved in many cancers. Nevertheless, the role of MFGE8 in gastric cancer remained indistinct. To probe the role of MFGE8 in gastric cancer and further explore the regulating mechanism. MethodsGEPIA was employed for analysis of MFGE8 expression and survival of gastric cancer patients. MFGE8 expression in gastric cancer was determined by immunohistochemistry, PCR, and western blot. The effect of MFGE8 on gastric cancer cells were evaluated by a series of cell function experiments. The mechanism of MFGE8 on gastric cancer was analyzed by GSEA and verified by in vitro and in vivo experiments. ResultsMFGE8 was over-expressed in gastric cancer. Silence of MFGE8 suppressed cell viability, proliferated ability, migrated and invasive ability, and EMT, but accelerated cell apoptosis. The opposite results were obtained in MFGE8-overexpressed gastric cancer cells. Zinc finger and BTB domain containing 7 A (ZBTB7A) was a transcription factor of MFGE8. ZBTB7A overexpression eliminated the effect of MFGE8 on gastric cancer cells. MFGE8 activated the IL-6/JAK/STAT3 signaling. Inhibition of IL-6/JAK/STAT3 signaling by Stattic (pathway inhibitor) could eliminate the promoting effect of MFGE8 on IL-6/JAK/STAT3 signaling. In addition, MFGE8 shRNA inhibited tumor growth. ConclusionMFGE8 promoted cell proliferation, EMT progress, and tumor growth of gastric cancer by activating the IL-6/JAK/STAT3 signaling.

Identification of Effective Factors and Prediction of Ischemic Heart Disease Using Machine Learning Methods and Data from the Yazd Health Study (YaHS) "

Introduction: Ischemic heart diseases are one of the most common diseases that cause high mortality worldwide. This article has identified various factors affecting heart disease and identified susceptible people using various machine learning methods. Methods: The current research was conducted on the Yazd Health Study (YaHS) database. YaHS was conducted on adults aged 20-70 years who were residents of Yazd Greater Area and collected information on the health and various diseases of nearly 10,000 people in the form of a questionnaire with 300 different questions. In this research, by using the correlation of questions with heart disease, the most important factors of heart disease have been identified. By using the identified factors and machine learning algorithms, susceptible people with heart disease have been identified. Results: The results of the evaluations have shown that factors such as age, family history of heart disease, blood pressure, diabetes, blood cholesterol, stress, anxiety, depression, quality of life, quality of sleep, physical activity, smoking, and diet have an effect on heart disease. Likewise, among the different machine learning methods, the nearest neighbor method, the deep neural network method, and the multi-layer perceptron method with a recall criterion of 99.94%, 99.88%, and 99.11% have performed the best in the identifying sick people, respectively. Conclusion: According to the findings of the research, it can be understood that by controlling factors such as blood pressure, diabetes, blood cholesterol, stress, anxiety, and depression, changing factors such as quality of life, sleep status, physical activity, and eating patterns of people and quitting smoking, it is possible to move towards improving the health of society. On the other hand, the identification of people prone to heart disease using machine learning methods is done faster and at a lower cost than the traditional methods that are done by referring to medical centers and doctors and performing various tests.

Assessing Listeria monocytogenes Growth in Artificially Inoculated Sea-Farmed Product—Raw Sea Bass (Dicentrarchus labrax) Fillet, Produced in Greece

Listeria monocytogenes (Lm) is responsible for listeriosis, a serious foodborne disease, with high hospitalization and mortality rates worldwide. The main cause of listeriosis in humans is the consumption of ready-to-eat (RTE) foods; Commission Regulation (EC) No 2073/2005 establishes microbiological criteria for Lm in RTE foods. Raw fish products are widely consumed, e.g., in sushi and various seafood recipes (e.g., carpaccio, sashimi, maki, nigiri, tartare, etc.), but are not subjected to RTE food safety criteria. The aim of our study was to assess the growth potential of Lm in raw sea bass fillets obtained from a leading aquaculture company in Greece. In order to assess the growth of Lm in raw sea bass fillets, we applied the “challenge test”, a scientific experiment designed to assess the growth of Lm within a specific food product under controlled conditions. According to our results, and taking into consideration the health risk for the listeriosis-vulnerable population, raw fish products utilized in the preparation of RTE foods, including sushi and an array of seafood dishes, should be incorporated in the Category of Safety Criteria of Regulation (EC) No 2073/2005 “Ready-to-eat food able to support the growth of Listeria monocytogenes”.