Oligoribonuclease mediates high adaptability of P. aeruginosa through metabolic conversion.

BACKGROUND: Oligoribonuclease (orn) of P. aeruginosa is a highly conserved exonuclease, which can regulate the global gene expression levels of bacteria through regulation of both the nanoRNA and c-di-GMP. NanoRNA can regulate the expression of the bacterial global genome as a transcription initiator, and c-di-GMP is the most widely second messenger in bacterial cells. OBJECTIVE: This study seeks to elucidate on the regulation by orn on pathogenicity of P. aeruginosa. METHODS: P. aeruginosa with orn deletion was constructed by suicide plasmid homologous recombination method. The possible regulatory process of orn was analyzed by TMT quantitative labeling proteomics. Then experiments were conducted to verify the changes of Δorn on bacterial motility, virulence and biofilm formation. Bacterial pathogenicity was further detected in cell and animal skin trauma models. ELISA detection c-di-GMP concentration and colony aggregation and biofilm formation were observed by scanning electron microscope. RESULTS: orn deletion changed the global metabolism of P. aeruginosa and reduced intracellular energy metabolism. It leads to the disorder of the quorum sensing system, the reduction of bacterial motility and virulence factors pyocyanin and rhamnolipids. But, orn deletion enhanced pathogenicity in vitro and in vivo, a high level of c-di-GMP and biofilm development of P. aeruginosa. CONCLUSION: orn regulates the ability of P. aeruginosa to adapt to the external environment.

Cancer energy reprogramming and the immune responses.

Cancer as an uncontrolled growth of cells due to existing mutation in host cells that may proliferate, induce angiogenesis and sometimes metastasize due to the favorable tumor microenvironment (TME). Since it kills more than any disease, biomedical science does not relent in studying the exact pathogenesis. It was believed to be a problem that lies in the nucleus of the host cells; however, recent oncology findings are shifting attention to the mitochondria as an adjuvant to cancer pathogenesis. The changes in the gene are strongly related to cellular metabolism and metabolic reprogramming. It is now understood that reprogramming the TME will have a direct effect on the immune cells' metabolism. Although there are a number of studies on immune cells' response towards tumor energy reprogramming and cancer progression, there is still no existence with the updated collation of these immune cells' response to distinct energy reprogramming in cancer studies. To this end, this mini review shed some light on cancer energy reprogramming mechanisms and enzyme degradation pathways, the cancer pathogenicity activity series involved with reduced lactate production, the specific immune cell responses due to the energy reprogramming. This study highlighted some prospects and future experiments in harnessing the host immune response towards the altered energy metabolism due to cancer.

The connection between epigenetics and gut microbiota-current perspective.

Both the epigenetic changes and gut microbiota (GM) have attracted a growing interest in establishing effective diagnostics and potential therapeutic strategies for a number of diseases. These disorders include metabolic, central nervous system-related diseases, autoimmune, and gastrointestinal infections (GI). Despite the number of studies, there is no extensive review that connects the epigenetics modifications and GM as biomarkers that could confer effective diagnostics and confer treatment options. To this end, this review hopes to give detailed information on connecting the modifications in epigenetic and GM. An updated and detailed information on the connection between the epigenetics factors and GM that influence diseases are given. In addition, the review showed some associations between the epigenetics to the maternal GM and offspring health. Finally, the limitations of the concept and prospects into this new emerging discipline were also looked into. Although this review elucidated on the maternal diet and response to offspring health with respect to GM and epigenetic modifications, there still exist various limitations to this newly emerging discipline. In addition to integrating complementary multi-omics data, longitudinal sampling will aid with the identification of functional mechanisms that may serve as therapeutic targets. To this end, this review gave a detailed perspective into harnessing disease diagnostics, prevention and treatment options through epigenetics and GM.

The influence of maternal diet on offspring's gut microbiota in early life.

BACKGROUND: The influence of maternal diet on offspring's health is an area of study that is linked to epigenetics. Maternal diet contributes to determining the health status of offspring and maternally linked mechanisms and is a global health challenge that requires attention. The impact of gut microbiota on host metabolism and offspring health is still not established. OBJECTIVE: In this review, we intend to discuss the evidence on the impact of maternal diet and the health of offspring gut microbiota. The paper focuses on the gut microbiome of animal models. It captures the maternal diet and its influence on the offspring's gut microbiota, behavior that is supported by cell experimental results. Both inflammation and immune status of offspring induced by maternal diet are discussed. Finally, this review used predicted biological pathways involved in maternal diet and offspring health, and the influence of maternal diet on gut microbiota and offspring behavior. Obesity, diabetes, asthma and allergies, and neurodegenerative disorders and prospects for maternal diet, and microbiota and offspring health were discussed. CONCLUSION: The review was able to gather that a high-fat diet during pregnancy created a long-lasting metabolic signature on the infant's innate immune system, altering inflammation in the offspring microbiota, which predisposed offspring to obesity and metabolic diseases in adulthood.

Respiratory syncytial virus infection disrupts pulmonary microbiota to induce microglia phenotype shift.

The lung-brain axis is an emerging biological pathway that is being investigated in relation to microbiome medicine. Increasing evidence suggests that pulmonary viral infections can lead to distinct pathological imprints in the brain, so there is a need to explore and understand this mechanism and find possible interventions. This study used respiratory syncytial virus (RSV) infection in mice as a model to establish the potential lung-brain axis phenomenon. We hypothesized that RSV infection could disrupt the lung microbiota, compromise immune barriers, and induce a significant shift in microglia phenotype. One week old mice were randomized into the control, Ampicillin, RSV, and RSV+Ampicillin treated groups (n = 6 each). Seven days after the respective treatments, the mice were anaesthetized. Immunofluorescence and real-time qRT-PCR was used to detect virus. Hematoxylin-eosin staining was used to detect histopathology. Malondialdehyde and superoxide dismutase were used to determine oxidative stress and antioxidant capacity. Real-time qRT-PCR and enzyme-linked immunosorbent assay (ELISA) were used to measure Th differentiation in the lung. Real-time qRT-PCR, ELISA, and confocal immunofluorescence were used to determine the microglia phenotype. 16S DNA technology was used to detect lung microflora. RSV infection induces elevated oxidative stress, reduced antioxidant, and significant dysbacteriosis in the lungs of mice. Pulmonary microbes were found to enhance Th1-type immunoreactivity induced by RSV infection and eventually induced M1-type dominant microglia in the brains of mice. This study was able to establish a correlation between the pulmonary microbiome and brain function. Therefore, we recommend a large sample size study with robust data analysis for the long-term effects of antibiotics and RSV infection on brain physiology.

Gimap5 promoted RSV degradation through interaction with M6PR.

Respiratory syncytial virus (RSV) is one of the main pathogens of viral pneumonia and bronchiolitis in infants and young children and life-threatening diseases among infants and young children. GTPases of the immune-associated protein family (GIMAP) are new family members of immune-associated GTPases. In recent years, much attention has been paid to the function of the GIMAP family in coping with infection and stress. Gimap5 is a member of the GIMAP family, which may be correlated with anti-infectious immunity. RT-qPCR, Western blot, and indirect immunofluorescence (IFA) were used to detect the expression of Gimap5, M6PR and IGF1R(the major RSV receptor). Transmission electron microscopy (TEM) was used to detect the degradation of RSV in Gimap5-overexpressed or -silent cell lines. Computer virtual screening was used to screen small molecule compounds targeting Gimap5 and the anti-RSV effects were explored through in vivo and in vitro experiments. GIMAP5 and M6PR were significantly downregulated after RSV infection. Gimap5 accelerated RSV degradation in lysosomes by interacting with M6PR, and further prevented RSV invasion by downregulating the expression of RSV surface receptor IGF1R. Three small molecule compounds targeting Gimap5 were confirmed to be the agonists of Gimap5. The three compounds effectively inhibited RSV infection and RSV-induced complications. Gimap5 promotes the degradation of RSV and its receptor through interacting with M6PR. Gimap5 agonists can effectively reduce RSV infection and RSV-induced complication in vivo and in vitro, which provides a new choice for the treatment of RSV.

Crosstalk between the lung microbiome and lung cancer.

The human microbiome is a complex ecosystem that mediates interaction between the human host and the environment. All of the human body is colonized by microorganisms. The lung as an organ used to be considered sterile. Recently, however, there has been a growing number of reports with evidence that the lungs are also in a state of carrying bacteria. The pulmonary microbiome is associated with many lung diseases and is increasingly reported in current studies. These include; chronic obstructive pulmonary disease (COPD), asthma, acute chronic respiratory infections, and cancers. These lung diseases are associated with reduced diversity and dysbiosis. It directly or indirectly affects the occurrence and development of lung cancer. Very few microbes directly cause cancer, while many are complicit in cancer growth, usually working through the host's immune system. This review focuses on the correlation between lung microbiota and lung cancer, and investigates the mechanism of action of lung microorganisms on lung cancer, which will provide new and reliable treatments and diagnosis of lung cancer in the future.

The antiviral efficacies of small-molecule inhibitors against respiratory syncytial virus based on the F protein.

OBJECTIVES: Respiratory syncytial virus (RSV) infection is one of the three most common causes of death in the infants, pre-schoolers, immunocompromised patients and elderly individuals due to many complications and lack of specific treatment. During RSV infection, the fusion protein (F protein) mediates the fusion of the virus envelope with the host cell membrane. Therefore, the F protein is an effective target for viral inhibition. METHODS: We identified potential small-molecule inhibitors against RSV-F protein for the treatment of RSV infection using virtual screening and molecular dynamics (MD) simulations. The CCK8 assay was used to determine the cytotoxicity and quantitative RT-PCR and indirect fluorescence assay (IFA) were used to determine the viral replication and RSV-induced inflammation in vitro. An RSV-infected mouse model was established, and viral replication was assayed using real-time quantitative PCR and IFA. Virus-induced complications were also examined using histopathological analysis, airway resistance and the levels of IL-1ß, IL-6 and TNF-α. RESULTS: The top three potential inhibitors against the RSV-F protein were screened from the FDA-approved drug database. Z65, Z85 and Z74 significantly inhibited viral replication and RSV-induced inflammation. They also significantly alleviated RSV infection and RSV-induced complications in vivo. Z65 and Z85 had no cytotoxicity and better anti-RSV effects than Z74. CONCLUSIONS: Z65 and Z85 may be suitable candidates for the treatment of RSV and serve as the basis for the development of new drugs.

Lung-brain axis.

The appreciation of human microbiome is gaining strong grounds in biomedical research. In addition to gut-brain axis, is the lung-brain axis, which is hypothesised to link pulmonary microbes to neurodegenerative disorders and behavioural changes. There is a need for analysis based on emerging studies to map out the prospects for lung-brain axis. In this review, relevant English literature and researches in the field of 'lung-brain axis' is reported. We recommend all the highlighted prospective studies to be integrated with an interdisciplinary approach. This might require conceptual research approaches based on physiology and pathophysiology. Multimodal aspects should include experimental animal units, while exploring the research gaps and making reference to the already existing human data. The overall microbiome medicine is gaining more ground. Aetiological paths and experimental recommendations as per prospective studies in this review will be an important guideline to develop effective treatments for any lung induced neurodegenerative diseases. An in-depth knowledge of the bi-directional communication between host and microbiome in the lung could help treatment to respiratory infections, alleviate stress, anxiety and enhanced neurological effects. The timely prevention and treatment of neurodegenerative diseases requires paradigm shift of the aetiology and more innovative experimentation.Impact statementThe overall microbiome medicine is gaining more ground. An in-depth knowledge of the bi-directional communication between host and microbiome in the lung could confer treatment to respiratory infections, alleviate stress, anxiety and enhanced neurological effects. Based on this review, we recommend all the highlighted prospective studies to be integrated and be given an interdisciplinary approach. This might require conceptual research approaches based on physiology and pathophysiology. Multimodal aspects should include experimental animal units; while exploring the research gaps and making reference to the already existing human data.

Lung-brain axis: Metabolomics and pathological changes in lungs and brain of respiratory syncytial virus-infected mice.

The lung-brain axis is an emerging area of study that got its basis from the gut-brain axis biological pathway. Using Respiratory Synctial Virus (RSV) as the model of respiratory viral pathogen, this study aims to establish some biological pathways. After establishing the mice model, the inflammation in lung and brain were assayed using Hematoxylin-eosin staining, indirect immunofluorescence (IFA), and quantitative reverse-transcription polymerase chain reaction. The biological pathways between lung and brain were detected through metabolomics analysis. In lung, RSV infection promoted epithelial shedding and infiltration of inflammatory cells. Also, RSV immunofluorescence and titerss were significantly increased. Moreover, interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α) were also significantly increased after RSV infection. In brain, the cell structure of hippocampal CA1 area was loose and disordered. Inflammatory cytokines IL-6 and IL-1ß expression in the brain also increased, however, TNF-α expression showed no differences among the control and RSV group. We observed an increased expression of microglia biomarker IBA-1 and decreased neuronal biomarker NeuN. In addition, RSV mRNA expression levels were also increased in the brains. 15 metabolites were found upregulated in the RSV group including nerve-injuring metabolite glutaric acid, hydroxyglutaric acid and Spermine. ɑ-Estradiol increased significantly while normorphine decreased significantly at Day 7 of infection among the RSV group. This study established a mouse model for exploring the pathological changes in lungs and brains. There are many biological pathways between lung and brain, including direct translocation of RSV and metabolite pathway.

Dispersion and utilization of lipid droplets mediates respiratory syncytial virus-induced airway hyperresponsiveness.

BACKGROUND: Respiratory viral infections (RSV) can induce acute asthma attacks, thereby destroying lung function and accelerating the progression of the disease. However, medications in the stable phase of asthma are often not effective for acute attacks induced by viral infections. We aimed to clarify the possible mechanism of viral infection-induced asthma through fatty acid metabolism. METHODS AND RESULTS: The airway resistances, inflammatory injuries, and oxidative stress in the RSV-induced animal models were significantly higher than those in the control group at acute phase (7 days) and chronic phase (28 days). Moreover, the concentrations of the medium- and long-chain fatty acids in lung tissue at (28 days) were significantly increased, including 14:0 (myristic acid), 16:0 (palmitic acid, PA), 18:1 (oleic acid, OA), and 18:2 (linoleic acid, LA) using non-targeted metabonomics. Airway epithelial cells treated with RSV showed the reduced expression of FSP27, RAB8A, and PLIN5, which caused the fusion and growth of lipid droplet (LD), and increased expression of the LD dispersion gene perilipin 2. There was also a decrease in PPARγ expression and an increase in the fatty acid catabolism gene PPARα, causing lipid oxidation, free fatty acid releases, and an upsurge in IL-1, IL-2, IL-4, and IL-6 expression, which could be abrogated by GPR40 inhibitor. Treated mice or epithelial cells with C18 fatty acid exhibited inhibition of epithelial proliferation, increases of inflammation, and oxidative damage. CONCLUSIONS: RSV promoted lipid dispersion and utilization, causing enlarged oxidative injuries and an upsurge in the pro-inflammatory cytokines, leading to the progression of airway hyperresponsiveness (AHR).

Prevalence of menstrual symptoms change and influencing factors among international female students studying in china during acculturation period.

BACKGROUND: A number of previous studies have explored international students' adaptation process with regards to language, lifestyle, food, and environment. However, there have yet been no studies conducted to address the menstrual symptoms challenges faced by international female students during the acculturation period. Thus, this study aims to describe the prevalence of menstrual symptoms change and to explore the influencing factors among international female students studying in China during the acculturation period. METHODS: An online cross sectional study was conducted among international female students studying in China during the acculturation period (defined as the first six months of living in the host country) in Hunan Province of China from March 2019 to July 2019. Menstrual symptoms questionnaire, sociocultural adaptation scale, China higher education student satisfaction scale, perceived stress scale, and Pittsburgh sleep quality index were used for data collection. Descriptive analysis, ANOVA, paired t-test, Pearson correlation, and multivariate linear regressions were used to analyze the data using SPSS 21.0 software. RESULTS: Three hundred and forty-five (97.18%, 345/355) female students from 45 countries fully completed the questionnaire. The mean age of the participants was (26.59 ± 6.439) years. In total, 18.49% of participants had encountered menstrual symptoms change. There were significant differences in the menstrual symptoms score between before arrival and evaluation during the first six months of living in China (t = - 11.700, p = 0.000). The main menstrual symptoms change included cramps (17.68%), irritation (14.78%), abdominal pain (12.46%), fatigue (12.46%), and headaches (9.85%). Cultural adaptation level (ß = 0.198, 95% CI: 0.934, 2.995), sleep quality (ß = 0.166, 95% CI: 0.112, 0.496), perceived stress (ß = 0.193, 95% CI: 0.123, 0.410), time spent in the host environment, (ß = - 0.270, 95% CI: - 3.200, - 1.444) and experience of visiting foreign countries (ß = 0.184, 95% CI: 1.134, 4.125) were significantly correlated with menstrual symptoms change. CONCLUSION: The prevalence of menstrual symptoms change among international female students should not be overlooked when considering menstrual health in this population. Poorer cultural adaptation, poorer sleep quality, higher stress, and lack of overseas living experiences significantly influence the menstrual symptoms of international female students studying in China.

Pathogenicity of Salmonella During Schistosoma-Salmonella Co-infections and the Importance of the Gut Microbiota.

Antibiotic inefficacy in treating bacterial infections is largely studied in the context of developing resistance mechanisms. However, little attention has been paid to combined diseases mechanisms, interspecies pathogenesis and the resulting impact on antimicrobial treatment. This review will consider the co-infections of Salmonella and Schistosoma mansoni. It summarises the protective mechanisms that the pathophysiology of the two infections confer, which leads to an antibiotic protection phenomenon. This review will elucidate the functional characteristics of the gut microbiota in the context of these co-infections, the pathogenicity of these infections in infected mice, and the efficacy of the antibiotics used in treatment of these co-infections over time. Salmonella-Schistosoma interactions and the mechanism for antibiotic protection are not well established. However, antimicrobial drug inefficacy is an existing phenomenon in these co-infections. The treatment of schistosomiasis to ensure the efficacy of antibiotic therapy for bacterial infections should be considered in co-infected patients. Co-infections of Salmonella and Schistosoma mansoni confers the protective mechanisms that give ineffetive treatment of salmonella. The functional characteristics of the gut microbiota in the context of these co-infections influence the pathogenicity of the both pathogens thereby drecreasing immunity and brings changes in gut metabolism.

Th17/IL-17 Axis Regulated by Airway Microbes Get Involved in the Development of Asthma.

PURPOSE OF REVIEW: Bronchial asthma is a common respiratory disease induced by immune imbalance, characterized by chronic non-specific airway inflammation and airway hyperresponsiveness (AHR). Many factors induce asthma, among which respiratory infection is the important cause. In this review, we discuss how respiratory microbes participate in the occurrence and progression of asthma via Th17/IL-17 axis. RECENT FINDINGS: Pathogenesis of asthma has been considered as closely related to the imbalance in number and function of Th1/Th2 in the CD4+ T lymphocyte subsets. Recent studies have shown that Th17 cell and its secretory IL-17 also play an important role in AHR. Respiratory virus, bacteria, fungi, and other respiratory microbial infections can directly or indirectly induce the differentiation of Th17 cell and the production of related cytokines to induce AHR. Respiratory microbial infection can affect the TH17/IL-17A axis through a variety of mechanisms, thereby promoting the occurrence and development of asthma, and these specific mechanisms may provide new effective therapeutic ideas for asthma.

Off­label and unapproved pediatric drug utilization: A meta­analysis.

Despite legislative enforcement on authorized drugs, off-label and unapproved pediatric drug use is prevalent. The present study aimed to assess the global prevalence of off-label and unlicensed prescriptions among hospitalized children via meta-analysis. A comprehensive examination of articles published between 1990 and 2023 from the PubMed, Scopus, Excerpta Medica Database, Web of Science and Google Scholar databases was conducted. Key word-based advanced searches were executed using the aforementioned databases. A total of 45 studies that reported the prescriptions of off-label and unlicensed drugs to pediatric patients were included. The global prevalence of off-label and unlicensed drug prescriptions to children in pediatrics or neonatal departments was 56%. Patient sample sizes varied from 40-13,426, with a range of 240-8,891 total prescriptions issued. Of the 45 studies examined, 22 studies originated from Europe, 13 from Asia, 3 from South America, 3 from Africa, and 2 each from North America and Australia. Africa had the highest prevalence rate at 66%, followed by Asia, South America, North America, Australia and Europe. The present meta-analysis demonstrated that the prevalence of off-label and unlicensed drug prescriptions given to pediatric patients was notably high and geographically diverse. Therefore, drug authorities should standardize pediatric prescription practices in future.

A mini-review-cancer energy reprogramming on drug resistance and immune response.

With the growing interest to harness cancer metabolism and energy reprogramming, this mini review aimed to explain the metabolic programming revealing the mechanisms regarding the treatment resistance. This mini review summarized the prominent cancer metabolic reprogramming on macromolecules. In addition, metabolic reprogramming explaining immune response and treatment resistance as well as energy reprogramming mechanisms are briefly discussed. Finally, some prospects in MR for reversing cancer drug resistance are highlighted.

Current advances in cancer energy metabolism under dietary restriction: a mini review.

The manipulation of the energy or source of food for cancer cells has attracted significant attention in oncology research. Metabolic reprogramming of the immune system allows for a deeper understanding of cancer cell mechanisms, thereby impeding their progression. A more targeted approach is the restriction of cancer cells through dietary restriction (CR), which deprives cancer cells of the preferred energy sources within the tumor microenvironment, thereby enhancing immune cell efficacy. Although there is a plethora of CR strategies that can be employed to impede cancer progression, there is currently no comprehensive review that delineates the specific dietary restrictions that target the diverse metabolic pathways of cancer cells. This mini-review introduces amino acids as anti-cancer agents and discusses the role of dietary interventions in cancer prevention and treatment. It highlights the potential of a ketogenic diet as a therapeutic approach for cancer, elucidating its distinct mechanisms of action in tumor progression. Additionally, the potential of plant-based diets as anti-cancer agents and the role of polyphenols and vitamins in anti-cancer therapy were also discussed, along with some prospective interventions for CR as anti-tumor progression.

High expression of KIFC1 is a poor prognostic biomarker and correlates with TP53 mutation in lung cancer.

The Kinesin Family Member C1 (KIFC1) is highly expressed in a variety of tumors. Since it is linked with tumorigenesis and progression, KIFC1 has emerged as a promising candidate for targeted chemotherapies. Thus, this study aims to find out the association between KIFC1 and lung cancer. The original data were assessed from The Cancer Genome Atlas and Gene Expression Omnibus databases. Compared to normal lung tissues, both mRNA and protein levels of KIFC1 were significantly increased in lung cancer tissues. The upregulation of KIFC1 was significantly correlated with sex, pathological stage, and TMN stage. Survival analysis revealed that increased KIFC1 expression was associated with poor overall survival, first-progression survival and post-progression survival in lung cancer. Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, we observed that KIFC1 upregulation was linked to enrichment of the cell cycle and TP53 signaling pathway. Additionally, the overexpression of KIFC1 was positively correlated with TP53 mutations in lung cancer. Based on real-world cohort results, western blotting and RT-qPCR showed high-KIFC1 expression in lung cancer, which may be related to the malignancy of lung cancer. Finally, experiments in vitro showed that KIFC1 inhibitor could significantly inhibit the proliferation and invasion of lung cancer cells. In conclusion, KIFC1 is a poor prognostic biomarker, and patients with high-KIFC1 levels may benefit from targeted therapy.

Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine.

Energy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, cell fate (proliferation, survival, apoptosis, malignant transformation etc.), and, on the other hand, carcinogenesis, tumor development, progression and metastazing versus anti-cancer protection and cure. The orchestrator is the mitochondria who produce, store and invest energy, conduct intracellular and systemically relevant signals decisive for internal and environmental stress adaptation, and coordinate corresponding processes at cellular and organismal levels. Consequently, the quality of mitochondrial health and homeostasis is a reliable target for health risk assessment at the stage of reversible damage to the health followed by cost-effective personalized protection against health-to-disease transition as well as for targeted protection against the disease progression (secondary care of cancer patients against growing primary tumors and metastatic disease). The energy reprogramming of non-small cell lung cancer (NSCLC) attracts particular attention as clinically relevant and instrumental for the paradigm change from reactive medical services to predictive, preventive and personalized medicine (3PM). This article provides a detailed overview towards mechanisms and biological pathways involving metabolic reprogramming (MR) with respect to inhibiting the synthesis of biomolecules and blocking common NSCLC metabolic pathways as anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules to yield mitochondrial substrates for energy homeostasis and nucleotide synthesis. Histone modification and DNA methylation can predict the onset of diseases, and plasma C7 analysis is an efficient medical service potentially resulting in an optimized healthcare economy in corresponding areas. The MEMP scoring provides the guidance for immunotherapy, prognostic assessment, and anti-cancer drug development. Metabolite sensing mechanisms of nutrients and their derivatives are potential MR-related therapy in NSCLC. Moreover, miR-495-3p reprogramming of sphingolipid rheostat by targeting Sphk1, 22/FOXM1 axis regulation, and A2 receptor antagonist are highly promising therapy strategies. TFEB as a biomarker in predicting immune checkpoint blockade and redox-related lncRNA prognostic signature (redox-LPS) are considered reliable predictive approaches. Finally, exemplified in this article metabolic phenotyping is instrumental for innovative population screening, health risk assessment, predictive multi-level diagnostics, targeted prevention, and treatment algorithms tailored to personalized patient profiles-all are essential pillars in the paradigm change from reactive medical services to 3PM approach in overall management of lung cancers. This article highlights the 3PM relevant innovation focused on energy metabolism as the hub to advance NSCLC management benefiting vulnerable subpopulations, affected patients, and healthcare at large. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00357-5.

A bioinformatics approach to systematically analyze the molecular patterns of monkeypox virus-host cell interactions.

Monkeypox has been spreading worldwide since May 2022, when the World Health Organization (WHO) declared the outbreak a "public health emergency of international concern." The spread of monkeypox has posed a serious threat to the health of people around the world, but few studies have been conducted, and the molecular mechanism of monkeypox after infection remains unclear. We therefore implemented a transcriptome analysis to identify signaling pathways and biomarkers in monkeypox-infected cells to help understand monkeypox-host cell interactions. In this study, datasets GSE36854 and GSE11234 were obtained from GEO. Of these, 84 significantly different genes were identified in the dataset GSE36854, followed by KEGG, GO analysis protein-protein interaction (PPI) construction, and Hub gene extraction. We also analyzed the expression regulation of hub genes and screened for drugs targeting hub genes. The results showed that monkeypox-infected cells significantly activated the cellular immune response. The top 10 hub genes are IER3, IFIT2, IL11, ZC3H12A, EREG, IER2, NFKBIE, FST, IFIT1 and AREG. AP-26113 and itraconazole can be used to counteract the inhibitory effect of monkeypox on IFIT1 and IFIT2 and serve as candidate drugs for the treatment of monkeypox virus infection. IRF1 may also be a transcription factor of IFIT. Our results provide a new entry point for understanding how monkeypox virus interacts with its host.