High Mortality Worldwide Research Articles

Integrated Metabolomics and Lipidomics Approach for the Study of Metabolic Network and Early Diagnosis in Cerebral Infarction.

Cerebral infarction (CI) remains a major cause of high mortality and long-term disability worldwide. The exploration of biomarkers and pathogenesis is crucial for the early diagnosis of CI. Although the understanding of metabolic perturbations underlying CI has increased in recent years, the relationship between altered metabolites and disease pathogenesis has only been partially elucidated and requires further investigation. In this study, we performed an integrated metabolomics and lipidomics analysis on 59 healthy subjects and 47 CI patients. Ultimately, 49 metabolite and 68 lipid biomarkers were identified and enriched in 24 disturbed pathways. The metabolic network revealed a significant interaction between altered lipids and other metabolites. Using receiver operating characteristic curve (ROC) analysis, a panel of three polar metabolites and seven lipids was optimized in the training set, which included taurine, oleoylcarnitine, creatinine, PE(22:6/P-18:0), Cer 34:2, GlcCer(d18:0/18:0), DG 44:0, LysoPC(16:0), 22:6-OH/LysoPC, and TAG58:7-FA22:4. Subsequently, a support vector machine (SVM) model was constructed and validated, which showed excellent predictive ability in the validation set. Thereby, the integrated metabolomics and lipidomics approach could contribute to a comprehensive understanding of the metabolic dyshomeostasis associated with the pathogenesis of underlying CI. The present research may promote a deeper understanding and early diagnosis of CI in the clinic. All raw data were deposited in PRIDE (PXD036199).

Neutrophils in pancreatic cancer: Potential therapeutic targets

Pancreatic cancer is a digestive system malignancy and poses a high mortality worldwide. Traditionally, neutrophils have been thought to play a role in acute inflammation. In contrast, their importance during tumor diseases has been less well studied. Generally, neutrophils are recruited into the tumor microenvironment and exert inflammation and tumor-promoting effects. As an essential part of the tumor microenvironment, neutrophils play diverse roles in pancreatic cancer, such as angiogenesis, progression, metastasis and immunosuppression. Additionally, neutrophils can be a new potential therapeutic target in cancer. Inhibitors of cytokines, chemokines and neutrophil extracellular traps can exert antitumor effects. In this review, we describe the role of neutrophils in the development and progression of pancreatic cancer, discuss their potential as therapeutic targets, and aim to provide ideas for improving the prognosis of patients with this malignant tumor disease.

Plasma Cell-Free DNA as a Novel Biomarker for the Diagnosis and Monitoring of Atherosclerosis.

Atherosclerosis (AS) is the leading cause of cardiovascular diseases (CVDs) with a high rate of mortality worldwide. Plasma cell-free DNA (cfDNA), mainly originating from apoptosis, necrosis, and active secretion, has been recognized as a promising biomarker for the diagnosis and prognosis of multiple cancers, whereas there are no reports about cfDNA in CVDs. Here, we found an increased quantity and decreased integrity of cfDNA (cfDI) in the serum from AS patients compared with normal controls. Moreover, the reduced cfDI is inversely correlated with serum LDL levels, carotid plaque size, and carotid plaque thickness in the progression of AS. Consistently, in vivo experiments confirmed that the release and cleavage of cfDNA were increased concomitantly with the development and progression of AS in ApoE−/− mice. Our study sheds light on the potential of cfDNA and cfDI as molecular biomarkers for detecting and monitoring AS.

Qualitative Phytochemical Screening and Antibacterial Effect of Averrhoa bilimbi Fruit Extracts Against Selected Bacteria

Introduction: Most diseases involving bacterial infections have caused high mortality and morbidity rates worldwide. However, the misuse of synthetic antibiotics in treatments has not only caused adverse effects on patients but also led to the emergence of antibiotic-resistant bacteria. The escalating issue of antimicrobial resistance has led to the urgent need for new antimicrobial agents originating from natural resources. Thus, this study was conducted to determine the antibacterial activity of ethyl acetate and aqueous extracts of Averrhoa bilimbi fruits against selected bacteria. Methods: The antimicrobial susceptibility testing (AST) and minimum inhibitory concentration (MIC) by disc diffusion method and microdilution broth method were respectively performed to evaluate the antibacterial activity of the A. bilimbi extract against gram-positive Staphylococcus aureus (ATCC 25923) and Bacillus cereus (ATCC 14579), as well as gram-negative bacteria (Escherichia coli (ATCC 25922) and Salmonella typhimurium (ATCC 13311)). Results: Initial screening for ethyl acetate and aqueous extracts showed inhibition against all microbes with the most significant effects on B. cereus at 16 and 11.67±1.15 mm, respectively. With MIC value of 7.81 mg/ml, the lowest concentration of ethyl acetate extract was required by S. aureus and B. cereus to inhibit their growth. For aqueous extract, the lowest MIC value of 31.25 mg/ml was observed to inhibit E. coli. Moreover, A. bilimbi fruit extracts also contain alkaloids, flavonoids, phenols, terpenoids, tannins, and reducing sugars responsible for antibacterial activities. Conclusion: Therefore, A. bilimbi fruit extract with its potential antibacterial properties can be used as an alternative therapy to combat infectious diseases initiated by the selected pathogens.

A cell free biomembrane platform for multimodal study of influenza virus hemagglutinin and for evaluation of entry-inhibitors against hemagglutinin.

Seasonal periodic pandemics and epidemics caused by Influenza A viruses (IAVs) are associated with high morbidity and mortality worldwide. They are frequent and unpredictable in severity so there is a need for biophysical platforms that can be used to provide both mechanistic insights into influenza virulence and its potential treatment by anti-IAV agents. Host membrane viral association through the glycoprotein hemagglutinin (HA) of IAVs is one of the primary steps in infection. HA is thus a potential target for drug discovery and development against influenza. Deconvolution of the multivalent interactions of HA at the interfaces of the host cell membrane can help unravel therapeutic targets. In this contribution, we reported the effect of a multivalent HA glycoprotein association on various glycosphingolipid receptors (GD1a, GM3, GM1) doped asymmetrically into an artificial host membrane spanned across an aqueous filled microcavity array. The extent of HA association and its impact on membrane resistance, capacitance, and diffusivity was measured using highly sensitive electrochemical impedance spectroscopy (EIS) and fluorescence lifetime correlation spectroscopy (FLCS). Furthermore, we investigated the inhibition of the influenza HA glycoprotein association with the host mimetic surface by natural and synthetic sialic acid-based inhibitors (sialic acid, Siaα2,3-GalOMe, FB127, 3-sialyl lactose) using electrochemical impedance spectroscopy and observe that while all inhibit, they do not prevent host binding. Overall, the work demonstrates the platform provides a label-free screening platform for the biophysical evaluation of new inhibitors in the development of potential therapeutics for IAV infection prevention and treatment.

Evaluation of risk factors associated with SARS-CoV-2 transmission

Objective Coronavirus disease 2019 (COVID-19) has caused high morbidity and mortality worldwide. Since there is not enough evidence of risk factors of SARS-CoV-2 transmission, this study aimed to evaluate them. Methods This survey-based study was conducted across 66 countries from May to November 2020 among suspected and confirmed individuals with COVID-19. The stepwise AIC method was utilized to determine the optimal multivariable logistic regression to explore predictive factors of SARS-CoV-2 transmission. Results Among 2372 respondents who participated in the study, there were 1172 valid responses. The profession of non-healthcare-worker (OR: 1.77, 95%CI: 1.04–3.00, p = .032), history of SARS-CoV or MERS-CoV infection (OR: 4.78, 95%CI: 2.34–9.63, p < .001), higher frequency of contact with colleagues (OR: 1.17, 95%CI: 1.01–1.37, p = .041), and habit of hugging when greeting (OR: 1.25, 95%CI: 1.00–1.56, p = .049) were associated with an increased risk of contracting COVID-19. Current smokers had a lower likelihood of having COVID-19 compared to former smokers (OR: 5.41, 95%CI: 1.93–17.49, p = .002) or non-smokers (OR: 3.69, 95%CI: 1.48–11.11, p = .01). Conclusions Our study suggests several risk factors for SARS-CoV-2 transmission including the profession of non-healthcare workers, history of other coronavirus infections, frequent close contact with colleagues, the habit of hugging when greeting, and smoking status.

Deep-Learning-Based Stroke Screening Using Skeleton Data from Neurological Examination Videos.

According to the Korea Institute for Health and Social Affairs, in 2017, the elderly, aged 65 or older, had an average of 2.7 chronic diseases per person. The concern for the medical welfare of the elderly is increasing due to a low birth rate, an aging population, and the lack of medical personnel. The demand for services that take user age, cognitive capacity, and difficulty into account is rising. As a result, there is an increased demand for smart healthcare systems that can lower hospital admissions and offer patients individualized care. This has motivated us to develop an AI system that can easily screen and manage neurological diseases through videos. As neurological diseases can be diagnosed by visual analysis to some extent, in this study, we set out to estimate the possibility of a person having a neurological disease from videos. Among neurological diseases, we focus on stroke because it is a common condition in the elderly population and results in high mortality and morbidity worldwide. The proposed method consists of three steps: (1) transforming neurological examination videos into landmark data, (2) converting the landmark data into recurrence plots, and (3) estimating the possibility of a stroke using deep neural networks. Major features, such as the hand, face, pupil, and body movements of a person are extracted from test videos taken under several neurological examination protocols using deep-learning-based landmark extractors. Sequences of these landmark data are then converted into recurrence plots, which can be interpreted as images. These images can be fed into convolutional neural networks to classify stroke using feature-fusion techniques. A case study of the application of a disease screening test to assess the capability of the proposed method is presented.

Comparison of vaccination efficacy using live or ultraviolet-inactivated influenza viruses introduced by different routes in a mouse model.

Influenza is a major cause of highly contagious respiratory illness resulting in high mortality and morbidity worldwide. Annual vaccination is an effective way to prevent infection and complication from constantly mutating influenza strains. Vaccination utilizes preemptive inoculation with live virus, live attenuated virus, inactivated virus, or virus segments for optimal immune activation. The route of administration also affects the efficacy of the vaccination. Here, we evaluated the effects of inoculation with ultraviolet (UV)-inactivated or live influenza A virus strains and compared their effectiveness and cross protection when intraperitoneal and intramuscular routes of administration were used in mice. Intramuscular or intraperitoneal inoculation with UV-inactivated Influenza A/WSN/1933 provided some protection against intranasal challenge with a lethal dose of live Influenza A/WSN/1933 but only when a high dose of the virus was used in the inoculation. By contrast, inoculation with a low dose of live virus via either route provided complete protection against the same intranasal challenge. Intraperitoneal inoculation with live or UV-inactivated Influenza A/Philippines/2/1982 and intramuscular inoculation with UV-inactivated Influenza A/Philippines/2/1982 failed to produce cross-reactive antibodies against Influenza A/WSN/1933. Intramuscular inoculation with live Influenza A/Philippines/2/1982 induced small amounts of cross-reactive antibodies but could not suppress the cytokine storm produced upon intranasal challenge with Influenza A/WSN/1993. None of the tested inoculation conditions provided observable cross protection against intranasal challenge with a different influenza strain. Taken together, vaccination efficacy was affected by the state and dose of the vaccine virus and the route of administration. These results provide practical data for the development of effective vaccines against influenza virus.

Andrographolide Induces G2/M Cell Cycle Arrest and Apoptosis in Human Glioblastoma DBTRG-05MG Cell Line via ERK1/2 /c-Myc/p53 Signaling Pathway.

Human glioblastoma multiforme (GBM) is one of the most malignant brain tumors, with a high mortality rate worldwide. Conventional GBM treatment is now challenged by the presence of the blood–brain barrier (BBB), drug resistance, and post-treatment adverse effects. Hence, developing bioactive compounds isolated from plant species and identifying molecular pathways in facilitating effective treatment has become crucial in GBM. Based on pharmacodynamic studies, andrographolide has sparked the interest of cancer researchers, who believe it may alleviate difficulties in GBM therapy; however, it still requires further study. Andrographolide is a bicyclic diterpene lactone derived from Andrographis paniculata (Burm.f.) Wallich ex Nees that has anticancer properties in various cancer cell lines. The present study aimed to evaluate andrographolide’s anticancer effectiveness and potential molecular pathways using a DBTRG-05MG cell line. The antiproliferative activity of andrographolide was determined using the WST-1 assay, while scratch assay and clonogenic assay were used to evaluate andrographolide’s effectiveness against the cancer cell line by examining cell migration and colony formation. Flowcytometry was also used to examine the apoptosis and cell cycle arrest induced by andrographolide. The mRNA and protein expression level involved in the ERK1/2/c-Myc/p53 signaling pathway was then assessed using qRT-PCR and Western blot. The protein–protein interaction between c-Myc and p53 was determined by a reciprocal experiment of the co-immunoprecipitation (co-IP) using DBTRG-05MG total cell lysate. Andrographolide significantly reduced the viability of DBTRG-05MG cell lines in a concentration- and time-dependent manner. In addition, scratch and clonogenic assays confirmed the effectiveness of andrographolide in reducing cell migration and colony formation of DBTRG-05MG, respectively. Andrographolide also promoted cell cycle arrest in the G2/M phase, followed by apoptosis in the DBTRG-05MG cell line, by inducing ERK1/2, c-Myc, and p53 expression at the mRNA level. Western blot results demonstrated that c-Myc overexpression also increased the production of the anti-apoptotic protein p53. Our findings revealed that c-Myc and p53 positively interact in triggering the apoptotic signaling pathway. This study successfully discovered the involvement of ERK1/2/c-Myc/p53 in the suppression of the DBTRG-05MG cell line via cell cycle arrest followed by the apoptosis signaling pathway following andrographolide treatment.

Identification of bromodomain-containing proteins prognostic value and expression significance based on a genomic landscape analysis of ovarian serous cystadenocarcinoma.

BackgroundOvarian serous cystadenocarcinoma (OSC), a common gynecologic tumor, is characterized by high mortality worldwide. Bromodomain (BRD)-containing proteins are a series of evolutionarily conserved proteins that bind to acetylated Lys residues of histones to regulate the transcription of multiple genes. The ectopic expression of BRDs is often observed in multiple cancer types, but the role of BRDs in OSC is still unclear.MethodsWe performed the differential expression, GO enrichment, GSEA, immune infiltration, risk model, subtype classification, stemness feature, DNA alteration, and epigenetic modification analysis for these BRDs based on multiple public databases.ResultsMost BRDs were dysregulated in OSC tissues compared to normal ovary tissues. These BRDs were positively correlated with each other in OSC patients. Gene alteration and epigenetic modification were significant for the dysregulation of BRDs in OSC patients. GO enrichment suggested that BRDs played key roles in histone acetylation, viral carcinogenesis, and transcription coactivator activity. Two molecular subtypes were classified by BRDs for OSC, which were significantly correlated with stemness features, m6A methylation, ferroptosis, drug sensitivity, and immune infiltration. The risk model constructed by LASSO regression with BRDs performed moderately well in prognostic predictions for OSC patients. Moreover, BRPF1 plays a significant role in these BRDs for the development and progression of OSC patients.ConclusionBRDs are potential targets and biomarkers for OSC patients, especially BRPF1.

RBM3 interacts with Raptor to regulate autophagy and protect cardiomyocytes from ischemia-reperfusion-induced injury.

Acute myocardial infarction (AMI) is a common disease with high morbidity and mortality worldwide. However, postinfarction pathogenesis remains unclear, and it is particularly important to identify new therapeutic targets. The RNA-binding motif protein RBM3 (also known as cold-inducible protein) is known to promote translation and is associated with tumor proliferation and neuroprotection. However, little is known about the biological effects of RBM3 on myocardial infarction. In the present study, we found that RBM3 expression was significantly upregulated in ischemia-reperfusion (I/R) condition and downregulation of RBM3 inhibited autophagy and promoted apoptosis in cardiomyocytes. We confirmed that RBM3 interacts with Raptor to regulate the autophagy pathway. Taken together, these findings illustrate the protective effects of RBM3 against I/R-induced myocardial apoptosis through the autophagy pathway.

Saffron Extract Attenuates Anxiogenic Effect and Improves Cognitive Behavior in an Adult Zebrafish Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) has the highest mortality rates worldwide, yet effective treatment remains unavailable. TBI causes inflammatory responses, endoplasmic reticulum stress, disruption of the blood–brain barrier and neurodegeneration that lead to loss of cognition, memory and motor skills. Saffron (Crocus sativus L.) is known for its anti-inflammatory and neuroprotective effects, which makes it a potential candidate for TBI treatment. Zebrafish (Danio rerio) shares a high degree of genetic homology and cell signaling pathways with mammals. Its active neuro-regenerative function makes it an excellent model organism for TBI therapeutic drug identification. The objective of this study was to assess the effect of saffron administration to a TBI zebrafish model by investigating behavioral outcomes such as anxiety, fear and memory skills using a series of behavioral tests. Saffron exhibited anxiolytic effect on anxiety-like behaviors, and showed prevention of fear inhibition observed after TBI. It improved learning and enhanced memory performance. These results suggest that saffron could be a novel therapeutic enhancer for neural repair and regeneration of networks post-TBI.

COMPARATIVE ANALYSIS OF RAPID IMMUNOCHROMATOGRAPHIC TEST (ICT) AND ENZYME LINKED IMMUNO SORBENT ASSAY (ELISA) TESTS TO DETECT ANTI-HCV ANTIBODY AMONG PATIENTS UNDERGOING HAEMODIALYSIS

Introduction: Over the years HCV infection has proved to be one of the leading causes of public health issue as a result of high morbidity and mortality rate worldwide. Hence prevention or early detection has proved to be of great use to tackle the disease. Since the introduction of rapid screening assays, they have been used widely worldwide. Hence this study was conducted to compare rapid ICT test with ELISA for the effective detection of anti-HCV antibodies in patients on haemodialysis (HD). Material and methods: A total of 109 HD patients suffering from chronic kidney disease were recruited. This study was conducted from July 2019 to March 2022. Sera of all the patients was tested for anti HCV antibodies by rapid ICT and further tested by ELISA. Results: In our study results obtained show that the seroprevalence of anti-HCV was 26.6% i.e. 29 patients via rapid ICT and 35.8% i.e. 39 patients via ELISA depicting a signicant difference of sensitivity and specicity of ELISA over ICT testing. Conclusion: The results indicated that the rapid ICTkits for HCV have a limited efciency and should be backed by superior supplemental methods like ELISAand PCR where possible.

КЛИНИЧЕСКИЕ ИСХОДЫ COVID-19 СРЕДИ ЛИЦ, ЖИВУЩИХ С ВИРУСОМ ИММУНОДЕФИЦИТА ЧЕЛОВЕКА

Abstract. Introduction. Since the early 1980s, the world has experienced an epidemic of human immunodeficiency virus infection. After that, in 2019 healthcare system faced a pandemic of infection caused by the emergence of a new coronavirus SARS-CoV-2, which caused high morbidity and mortality worldwide. Data on the incidence, course, and outcomes of COVID-19 in people living with human immunodeficiency virus are limited. Aim. The aim of the study is to examine data from publications on clinical outcomes of COVID-19 in people living with human immunodeficiency virus. Material and methods. A thorough literature search was carried out using the MEDLINE, Embase, Scopus databases, 21 sources were selected and analyzed. Results and discussion. Publication data do not indicate that people living with human immunodeficiency virus are more susceptible to COVID-19 than the general population. As in the general population, older age and the presence of comorbidities worsen the prognosis in patients with human immunodeficiency virus and COVID-19. A number of authors note higher mortality rates from COVID-19 infection in HIV-infected patients of African and Asian descent. Well-controlled human immunodeficiency virus infection does not change the clinical presentation or worsen the clinical outcome of hospitalization for COVID-19 infection in HIV-infected patients. Patients with human immunodeficiency virus in the advanced stages of the disease may show less severe symptoms of COVID-19 infection due to a reduction in the severity of immune responses. Conclusion. Clinical outcomes of COVID-19 in patients with and without human immunodeficiency virus coinfection are comparable. The high-risk group for COVID-19 includes human immunodeficiency virus patients with pre-existing comorbidities and individuals in older age groups. Controlled human immunodeficiency virus patients with an undetectable viral load have a better prognosis than uncontrolled patients.

Interferon Gamma Release Assay Request Indications: From Laboratory to Clinical Perspective

Tuberculosis is a re-emerging infectious disease that causes high morbidity and mortality worldwide and remains a major health threat in many parts of the world. With the increase in the incidence of HIV-positive/AIDS patients and immunocompromised individuals, accurate and timely diagnosis of latent TB (LTB) and active TB (ATB) has gained great importance. The aim of this study was to investigate the rationale lying behind interferon gamma release assay (IGRA) requests for patients applying to various clinics of a tertiary care hospital. In the study, 2905 IGRA tests requested in two years period were analyzed retrospectively. The IGRA test positivity rates were recorded and analyzed by linking with the requesting departments and indications. IGRA test positivity was determined in 503 cases (17.31%). IGRA test positivity rates were above 20% in samples sent from general surgery, pulmonology, nephrology, and transplantation departments, respectively. At all, 54.17% of the cases from whom IGRA requests were made constituted the first group of "pre-treatment investigation", and the positivity rate in this group was 12.96%. The positivity rate was highest [163 (28.69%)] in the patient group from whom the test was requested with the suspicion of TB. As a conclusion, until today, there is no study in which IGRA test requests are evaluated in terms of clinics. In this respect, this study is thought to be important. It is also desired to highlight that it is important for each country to develop its specific guidelines, country specific indications for IGRA test requests. Multi-centered studies are also essential for a global suggestion.

Bioinformatics based structural analysis of Cytochrome P450 genes in Candida tropicalis

Cytochrome P450 is a superfamily of enzymes that contain heme as a cofactor that functions as monooxygenases. These proteins are responsible for the oxidation of fatty acids, steroids, and xenobiotics, and the synthesis and breakdown of various hormones. Candida tropicalis has been identified as the leading cause of Candidemia, a bloodstream infection that contributes to the high mortality rate worldwide. So far, no research has reported a detailed study of the cytochrome P450 genes in the genome of Candida tropicalis. Hence, a detailed analysis involving the identification and characterisation of cytochrome P450 genes from the Candida tropicalis genome would provide valuable information about the evolutionary history and functions of the Cytochrome P450 gene family. In this study, 32 Cytochrome P450 genes were identified in Candida tropicalis, which were further grouped into four clades. The results show that most cytochrome P450 families in Candida tropicalis have a close phylogenetic relationship. And diversity might have mainly been a result of gene duplication. Clans and family groupings, alongside their putative functions and subcellular localisation, also showed the possible relationship between the genes’ cellular location and their functions. The results obtained from this study pave the way for a broader and more detailed analysis of the specific functions of each of the Cytochrome P450 genes in Candida tropicalis, as well as possible ways of altering their functions to find a way of curbing/eradicating the negative effect of Candida tropicalis and its contribution to the high rate of mortality worldwide.

Clinical Prognosis of Lung Cancer in Patients with Moderate Chronic Kidney Disease.

Simple SummaryLung cancer has a high incidence and mortality rate worldwide. In addition, lung cancer develops commonly in the elderly, and it is necessary to consider comorbidities when planning treatment. Chronic kidney disease (CKD) is a common comorbidity in patients with lung cancer. However, there are conflicting results regarding its effect on the clinical prognosis of lung cancer, and only insufficient evidence for treatment of lung cancer according to renal function. In this retrospective multicenter study, we evaluate clinical course and prognostic factors of lung cancer according to the renal function of moderate CKD patients.The clinical outcomes of patients with lung cancer coexisting with chronic kidney disease (CKD) are reported to have been conflicting. There is insufficient evidence for treatment and prognosis of lung cancer according to renal function in patients with CKD. We evaluate clinical course and prognostic factors of lung cancer according to the renal function of moderate CKD patients. A retrospective, multicenter study of lung cancer patients with moderate CKD was performed. Moderate CKD was defined as having an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. CKD was classified as stage 3, stage 4, and stage 5 according to eGFR. The cumulative mortality of lung cancer was calculated by competing risks survival analysis, and the risk factors were evaluated by the Cox-proportional hazards model. Among the lung cancer patients with moderate CKD (n = 181), median overall survival (OS) was 11.1 (4.2–31.3) months for stage 3 CKD patients, 6.0 (1.8–16.3) months for stage 4 CKD patients, and 4.7 (2.1–40.1) months for stage 5 CKD patients (p = 0.060), respectively. In a subgroup analysis, CKD stage was associated with an increased mortality in early-stage non-small cell lung cancer (NSCLC). Cox regression analysis revealed that age ≥ 75 years (adjusted hazard ratio (aHR), 1.581; 95% confidence interval (CI), 1.082–2.310), Charlson comorbidity index (aHR, 1.669; 95% CI, 10.69–2.605), and stage IV NSCLC (aHR, 2.395; 95% CI, 1.512–3.796) were associated with increased mortality risk, whereas adenocarcinoma (aHR, 0.580; 95% CI, 0.352–0.956) and stage 3 CKD (aHR, 0.598; 95% CI, 0.399–0.895) were associated with decreased mortality risk. In conclusion, the mortality risk of patients with lung cancer was lower in stage 3 CKD compared with stage 4 or 5 CKD. In addition, in the early stages of NSCLC, the CKD stage affected the prognosis, but not in the advanced stage NSCLC.

Establishment and characterization of chemotherapy-enriched sphere-forming cells with stemness phenotypes as a new cell line (BAG50) of gastric carcinoma.

Gastric cancer is a malignancy with a high mortality rate worldwide. Cancer stem cells (CSCs) are a small subpopulation of tumor cells that possess the tumor-initiating ability, self-renewal capacity, and high resistance to conventional therapies. Due to the diversity and complexity of human tumors, new cell lines are urgently needed to supply clinically and physiologically relevant cancer models. Here, we report establishing a novel cell line (BAG50) with stemness properties. Chemotherapy-enriched sphere-forming cells with CSC properties isolated from a patient with GC were cultured in a serum-containing medium and passaged for up to 51 passages. The colony-forming ability and tumor-forming capacity of BAG50 cells were evaluated in vitro and in vivo. mRNA upregulation of stemness-related transcriptional factors using real-time PCR as well as expression of CSC markers using flow cytometry was investigated. Finally, STR profiling and chromosome studies were performed. BAG50 cells formed floating spheroid colonies in a serum-free medium. Subcutaneous injection of these cells generated xenograft tumors in nude mice. Pluripotency markers (SOX-2, OCT4, and Cripto-1) in them were upregulated compared with normal gastric cells. The majority of them expressed CSC markers of CD44, CD54, and EpCAM, and stemness marker of oct-4. STR profiling showed a unique DNA fingerprint. Karyotype also demonstrated multiple aneuploidies and chromosomal translocations. We suggested that the highly tumorigenic BAG50 cell line with stem cell-like phenotypes may provide a valuable in vitro tool to support new diagnostic, prognostic, and predictive biomarkers as well as the development of more effective treatment strategies.

Transmembrane and coiled-coil domains 3 is a diagnostic biomarker for predicting immune checkpoint blockade efficacy in hepatocellular carcinoma.

Liver hepatocellular carcinoma (LIHC) is a malignancy with a high mortality and morbidity rate worldwide. However, the pathogenesis of LIHC has still not been thoroughly studied. Transmembrane and coiled-coil domains 3 (TMCO3) encodes a monovalent cation, a member of the proton transducer 2 (CPA2) family of transporter proteins. In the present study, TMCO3 expression and its relationship with cancer prognosis, as well as its immunological role in LIHC were studied by bioinformatic analysis. We found the significant overexpression of TMCO3 in LIHC in the TCGA, HCCDB, and GEO databases. In LIHC patients, high TMCO3 expression was related to poorer overall survival (OS) and TMCO3 had good predictive accuracy for prognosis. Moreover, TMCO3 was linked to the infiltrates of certain immune cells in LIHC. The correlation of TMCO3 with immune checkpoints was also revealed. Moreover, patients with LIHC with low TMCO3 expression showed a better response to immune checkpoint blockade (ICB) than those with LIHC with high TMCO3 expression. GO and KEGG enrichment analyses indicated that TMCO3 was probably involved in the microtubule cytoskeleton organization involved in mitosis, small GTPase mediated signal transduction, and TGF-β pathway. In conclusion, TMCO3 may be a potential biomarker for LIHC prognosis and immunotherapy.

Magnolol as a Potential Anticancer Agent: A Proposed Mechanistic Insight.

Cancer is a serious disease with high mortality and morbidity worldwide. Natural products have served as a major source for developing new anticancer drugs during recent decades. Magnolol, a representative natural phenolic lignan isolated from Magnolia officinali, has attracted considerable attention for its anticancer properties in recent years. Accumulating preclinical studies have demonstrated the tremendous therapeutic potential of magnolol via a wide range of pharmacological mechanisms against cancer. In this review, we summarized the latest advances in preclinical studies investigating anticancer properties of magnolol and described the important signaling pathways explaining its underlying mechanisms. Magnolol was capable of inhibiting cancer growth and metastasis against various cancer types. Magnolol exerted anticancer effects through inhibiting proliferation, inducing cell cycle arrest, provoking apoptosis, restraining migration and invasion, and suppressing angiogenesis. Multiple signaling pathways were also involved in the pharmacological actions of magnolol against cancer, such as PI3K/Akt/mTOR signaling, MAPK signaling and NF-κB signaling. Based on this existing evidence summarized in the review, we have conclusively confirmed magnolol had a multi-target anticancer effect against heterogeneous cancer disease. It is promising to develop magnolol as a drug candidate for cancer therapy in the future.