Over the past 3 years, there has been a growing interest in clinical research regarding the potential involvement of intestinal flora in thyroid cancer (TC). This review delves into the intricate connection between intestinal flora and TC, focusing on the particular intestinal flora that is directly linked to the disease and identifying which may be able to predict potential microbial markers of TC. In order to shed light on the inflammatory pathways connected to the onset of TC, we investigated the impact of intestinal flora on immune modulation and the connection between chronic inflammation when investigating the role of intestinal flora in the pathogenesis of TC. Furthermore, the potential role of intestinal flora metabolites in the regulation of thyroid function was clarified by exploring the effects of short-chain fatty acids and lipopolysaccharide on thyroid hormone synthesis and metabolism. Based on these findings, we further explore the effects of probiotics, prebiotics, postbiotics, vitamins, and trace elements.

Cancer cachexia, a multifactorial syndrome characterized by body weight loss, muscle, and adipose tissue wasting, affects patients with cancer. Over time, the definition of cachexia has been modified, including inflammation as one of the main causal factors. Evidence has suggested that a range of proinflammatory mediators may be involved in the regulation of intracellular signaling, resulting in enhanced resting energy expenditure, metabolic changes, and muscle atrophy, all of which are typical features of cachexia. Physiologically speaking, however, inflammation is a response aimed at facing potentially damaging events. Along this line, its induction in the cancer hosts could be an attempt to restore the physiological homeostasis. Interesting observations have shown that cytokines such as interleukins 4 and 6 could improve muscle wasting, supporting the view that the same mediator may exert pro- or anti-inflammatory activity depending on the immune cells involved as well as on the tissue metabolic demand. In conclusion, whether inflammation is crucial to the occurrence of cachexia or just one contributor among others, is still unclear. Indeed, while inflammation is a trigger of cachexia, the alterations of energy and protein metabolism and of the hormonal homeostasis occurring in cachexia likely act as inflammatory stimuli on their own. Whether the causative role prevails over the compensatory one likely depends on the tumor type and stage, patient lifestyle, the presence of comorbidities, and the response to anticancer treatments paving the way to a holistic, personalized approach to cancer cachexia.

The composite dietary antioxidant index (CDAI), reflecting total dietary intake of antioxidant vitamins, may indicate overall antioxidant capacity. This study examined its association with the risk of probable sarcopenia, defined by handgrip strength, in older adults.

Participants aged over 60 from the UK Biobank (N = 22,921) and National Health and Nutrition Evaluation Surveys (NHANES) 2011-2014 (N = 2,641) cohorts were categorized into probable sarcopenia and non-probable sarcopenia groups. Multivariable logistic regression models assessed the associations between CDAI (both continuous and quartile) and its components (vitamin A, vitamin C, vitamin E, and carotene) with probable sarcopenia risk in cohorts, with sex subgroup and sensitivity analyses to validate results.

The median (interquartile range) of CDAI was -0.39 (-1.88, 1.45) in the UK Biobank and -0.57 (-1.60, 0.84) in NHANES, respectively. A higher CDAI was significantly associated with a lower risk of probable sarcopenia in both cohorts. Specifically, each one-unit increase in CDAI was associated with a 2% decrease in the odds of probable sarcopenia in the UK Biobank (OR = 0.98, 95% CI = 0.97-0.998, p = 0.027) and a 13.5% decrease in NHANES (OR = 0.865, 95% CI = 0.75-0.997, p = 0.045), after full adjustment under the Sarcopenia Definition and Outcomes Consortium (SDOC) criteria. In quartile analyses, the risk of probable sarcopenia tended to decrease across higher CDAI quartiles, although the dose-response trend was not strictly linear. In the UK Biobank, multivariable-adjusted odds ratios (95% CIs) across increasing CDAI quartiles were: Q1 (reference), Q2 = 0.87 (0.78-0.97), Q3 = 0.91 (0.81-1.01), and Q4 = 0.86 (0.77-0.96). In NHANES, the trend was more pronounced: Q1 (reference), Q2 = 0.47 (0.24-0.94), Q3 = 0.39 (0.19-0.82), and Q4 = 0.46 (0.22-0.95). Additionally, higher dietary intake of carotene, one of the key antioxidant components, was independently associated with a lower risk of probable sarcopenia in both cohorts. Subgroup analyses indicated an inverse association between CDAI and probable sarcopenia risk in females across both cohorts, whereas no significant association was observed in males. Sensitivity analyses confirmed the robustness of these findings.

Increased dietary intake of antioxidant vitamins may reduce the risk of probable sarcopenia in older adults, emphasizing the need for targeted prevention strategies. Further research on underlying mechanisms and sex differences is warranted.

Gastric cancer (GC)，the fourth leading cause of cancer-related deaths globally and thus early detection, is considered critical for diagnosis and treatment of this disease. It is well known that measurement of microRNA (miRNA) may serve as diagnostic and prognostic biomarker for GC. The aim of this study was to determine whether miR-30c was present in patients with gastric cancer and to correlate relative expression with patient survival. A total of 162 GC patients and 150 healthy controls were recruited. miR-30c levels were quantified in serum using quantitative real-time PCR(QRT-PCR). The sensitivity and specificity of circulating miR-30c was compared to carbohydrate antigen (CA) CA72-4, CA19-9, and carcinoembryonic antigen (CEA), 3 known markers associated with GC. QRT-PCR demonstrated downregulation of gene expression of miR-30c in GC patients. Downregulation of miR-30c gene expression was significantly correlated with stage of cancer, lymphatic metastasis, and distal metastasis. The sensitivity to detect GC of miR-30c, CA72-4, CA19-9, and CEA in serum of GC was 80%, 43%, 21%, and 42%, respectively, while specificity was 89%, 57%, 30%, and 78% respectively. Kaplan-Meier survival analysis showed that the presence of low gene expression of miR-30c was effective in predicting poor prognosis in GC patients. Our data suggest that circulating serum miR-30c concentrations may serve as a reliable biomarker for GC occurrence. (212words).

p53, often referred to as the "guardian of the genome," is a critical regulator of cellular responses to stress. p53 plays a dual role in tumor suppression and immune regulation. In addition to its well-known functions of maintaining genomic stability and inducing apoptosis, p53 orchestrates a complex interaction between innate and adaptive immune responses. This involvement contributes to pathogen clearance, immune surveillance, and immunogenic cell death (ICD). This review explores the influence of p53 on immune dynamics, detailing its effects on macrophages, dendritic cells, natural killer cells (NK), T cells, and B cells. This review explains how mutations in p53 disrupt immune responses, promoting tumor immune evasion, and highlights its regulation of inflammatory cytokines and pattern recognition receptors. Furthermore, p53's role in ICD marks it as a key player in antitumor immunity, which has significant implications for cancer immunotherapy. The review also discusses the role of p53 in inflammation, autoimmune diseases, and chronic infections, revealing its dual function in promoting and suppressing inflammation through interactions with NF-κB signaling. Therapeutically, approaches that target p53, including wild-type p53 reactivation and combination therapies with immune checkpoint inhibitors, show considerable promise. Advances in high-throughput technologies, such as single-cell RNA sequencing and CRISPR screens, provide new insights into the immunological functions of p53, including its role in microbiome-immune interactions and immune senescence. This comprehensive review highlights the importance of incorporating immunological insights from p53 into innovative therapeutic strategies, addressing existing knowledge gaps, and paving the way for personalized medicine.

Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts and certain tumor cells, making it a promising therapeutic target for various malignancies. This study evaluated the efficacy and safety of 177Lu-Evans blue-FAP inhibitor (177Lu-LNC1004) radioligand therapy (RLT) for treating end-stage metastatic tumors.

This single-arm, single-center, phase II trial included 28 patients with progressive metastatic malignancies (11 types) and high FAP expression (defined as a maximum standardized uptake value ≥10 in >50% of tumors) who had exhausted all approved therapies, screened between June 2022 and April 2024. Patients were scheduled to receive four 177Lu-LNC1004 RLT cycles at 3.33 GBq/cycle every 6 weeks. The primary endpoint was post-RLT radiologic response. The secondary endpoints were progression-free survival (PFS), overall survival (OS), dosimetry, and safety.

Eastern Cooperative Oncology Group scores >2 were observed in 68% of patients. Overall, 63 177Lu-LNC1004 RLT cycles were performed, with 19 (68%) patients undergoing ≥2 cycles. Disease control was achieved in 13 (13/28, 46%) patients, with 4 and 9 patients demonstrating partial response and stable disease, respectively, and associated with improved PFS and OS (P < 0.001). The mean absorbed dose in tumors was 4.69 ± 3.83 Gy/GBq (1.18-25.03 Gy/GBq). Treatment-related grade 3/4 hematotoxicity was observed in six (21%) patients, with thrombocytopenia, leukopenia, and neutropenia most prevalent. No grade 3/4 hepatotoxicity or nephrotoxicity was observed.

FAP-directed RLT using 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated with an acceptable toxicity profile. Nearly half of patients achieved disease control, which was associated with prolonged PFS and OS.

The progression of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer is accompanied by a reduction in the immune response. The objectives of the study were to determine whether colposcopic lesion area is associated with serum levels of cytokines IL (interleukin) -1, IL-6, IL-8, IL-10, IL-12 and TNF-α in precursor lesions of cervical cancer.

The study population comprised patients with high-grade squamous intraepithelial lesion who had undergone colposcopy, cervical biopsy, and measurements of serum cytokines by ELISA (Enzyme-Linked Immunosorbent Assay). Genotyping for HPV (human papillomavirus) 16, 18, 45 and 52 was performed by PCR (Polymerase Chain Reaction). ROC (Receiver Operating Characteristic) curves were calculated to determine whether there existed a cut-off value for serum cytokines in patients with colposcopic lesion area smaller vs larger than 1 cm2. For cytokines with significant results, these cut-off values were used to perform the multivariable analysis.

There were 71 patients with CIN 2/3. ROC curves were calculated to verify a cut-off value for serum cytokine levels that could be used to distinguish between lesion areas <1 cm2 vs ≥1 cm2. Values with statistical significance were IL-1 >13.3 pg/mL and IL-12 ≤349.6 pg/mL. In the multivariable analysis, the independent variables associated with colposcopic lesion area greater than 1cm2 were IL-1>13.3 pg/mL and IL-12 ≤349.6 pg/mL [OR (95% CI) = 10.10 (1.50-67.96); OR (95% CI)=10.70 (1.17-97.45), respectively].

Although CIN 2/3 is a local uterine cervix lesion, there is a systemic immunological response. Our results are unprecedented and could be the target of new important studies in public health and cervical cancer prevention.

It is important to explore whether there are antagonistic and synergistic effects between different strains of Lactobacillus when developing mixed Lactobacillus strain products. In this study, we investigated the antagonistic and symbiotic effects of co-cultured Lactobacillus strains, as well as their amelioratory effects on lipopolysaccharide (LPS)-induced inflammation and oxidative stress in RAW264.7 cells. The Lactobacillus strains tested in this paper showed no antagonism. Co-culture of Lactiplantibacillus plantarum Y44 and L. plantarum AKS-WS9 was found to show inhibiting effects on the growth of Escherichia coli and Staphylococcus aureus. Additionally, the co-cultured Lactiplantibacillus plantarum Y44 and L. plantarum AKS-WS9 relieved inflammation in RAW264.7 cells induced by LPS by inhibiting the activation of NF-κB and P38 signaling pathways and down-regulating the expression of pro-inflammatory cytokines NO, ROS, iNOs and TNF-α. And the co-cultured Lactobacillus strains activated the Nrf2 signaling pathway in the LPS-induced RAW264.7 cells to promote the expression of antioxidant enzymes in response to oxidative stress. There was a difference in intracellular and extracellular metabolites between single or co-cultured Lactobacillus strains, and the co-cultured Lactobacillus strains significantly increased extracellular metabolites 4-chlorobenzaldehyde, psoromic acid, and 2-dodecylbenzenesulfonic acid and intracellular metabolites 9(S)-HODE, pyocyanin, and LysoPA. We inferred that the better antibacterial and anti-inflammatory ability of the co-cultured Lactobacillus strains were related to the changes in the metabolites of the co-cultured Lactobacillus strains. The co-cultured L. plantarum Y44 and L. plantarum AKS-WS9 strains exhibited better anti-inflammatory abilities and had the potential to alleviate the symptoms of inflammatory diseases as mixed probiotics.

Cigarette smoke (CS) is a driver of many respiratory diseases, including chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Tobacco causes oxidative stress, impaired phagocytosis of alveolar macrophages (AMs), and alterations in gene expression in the lungs of smokers. MicroRNAs (miRNAs) are small non-coding RNAs that influence several regulatory pathways. Previously, we monitored the expressions of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p, and 106a-5p in AMs derived from the bronchoalveolar lavage (BAL) of subjects with NSCLC, COPD, and smoker and non-smoker control groups. Here, we investigated the capability of CS conditionate media to modulate the abovementioned miRNAs in primary AMs obtained in the same 43 sex-matched subjects. The expressions of has-miR-34a-5p, 17-5p, 16-5p, 106a-5p, 223-5p, and 20a-5p were assessed before and after in vitro CS exposure by RT-PCR. In addition, a comprehensive bioinformatic analysis of miRNAs KEGGS and PPI linked to inflammation was performed. Distinct and common miRNA expression profiles were identified in response to CS, suggesting their possible role in smoking-related diseases. It is worth noting that, following exposure to CS, the expression levels of hsa-miR-34a-5p and 17-5p in both smokers and non-smokers, 106a-5p in non-smokers, and 20a-5p in smokers, shifted towards those found in individuals with COPD, suggesting them as a risk factor in developing this lung condition. Moreover, CS-focused sub-analysis identified miRNA which exhibited CS-dependent pattern and modulated mRNA involved in the immune system or AMs property regulation. In conclusion, our study uncovered miRNA signatures in AMs exposed to CS, indicating that CS might modify epigenetic patterns that contribute to macrophage activation and lung disease onset and progression.

Determining the relationships between miRNA expression, target genes, and cancer development is critical to cancer research. The possibility of correlating miRNA expression with plant or artificial ones provides prerequisites for cancer treatment. Based on the broad database of human miRNA expression for all cancer types, we grade human miRNAs by their expression level. The identified deficient miRNAs are compared with their target genes for coincidences in their expression directions. The replacement of human miRNAs is proposed to be implemented, using plant miRNAs closest to the human-deficient ones. Such plant substitutes are identified by analyzing the average complementarity of all human under-expressed miRNAs. It was established that the number of downregulated miRNAs is almost 2.5 times greater than that of upregulated miRNAs. There is no significant correlation between the expression of miRNA and genes, implying many other expression regulation mechanisms exist. Working on the organization of experimental verification of the obtained statistical studies, we present significant regularities that provide grounds for considering some plant microRNAs as possible means of compensating for insufficient expression of regulatory microRNAs in humans and animals in a wide range of oncological diseases.

A significant number of deaths and disabilities worldwide are brought on by inflammatory lung diseases. Many inflammatory lung disorders, including chronic respiratory emphysema, resistant asthma, resistance to steroids, and coronavirus-infected lung infections, have severe variants for which there are no viable treatments; as a result, new treatment alternatives are needed. Here, we emphasize how oxidative imbalance contributes to the emergence of provocative lung problems that are challenging to treat. Endogenic antioxidant systems are not enough to avert free radical-mediated damage due to the induced overproduction of ROS. Pro-inflammatory mediators are then produced due to intracellular signaling events, which can harm the tissue and worsen the inflammatory response. Overproduction of ROS causes oxidative stress, which causes lung damage and various disease conditions. Invasive microorganisms or hazardous substances that are inhaled repeatedly can cause an excessive amount of ROS to be produced. By starting signal transduction pathways, increased ROS generation during inflammation may cause recurrent DNA damage and apoptosis and activate proto-oncogenes. This review provides information about new targets for conducting research in related domains or target factors to prevent, control, or treat such inflammatory oxidative stress-induced inflammatory lung disorders.

Cancer has consistently been the leading cause of death worldwide, with head and neck cancer (HNC) being one of the top ten causes of cancer-related death. Nasopharyngeal carcinoma (NPC), in particular, is a cancer that is unique to East Asia. Numerous studies have shown that the Epstein-Barr virus (EBV) DNA load and the systemic immune inflammation (SII) index can serve as prognostic indicators for NPC patients. However, no studies have compared different predictive models of inflammatory factors. This study combines the SII and the EBV virus load in patients with stage I to IV NPC and compares different inflammatory factor models to determine the best predictive model.

We reviewed 240 patients with stage I to IV NPC who were diagnosed between January 2016 and July 2023. We collected data from adult patients who were diagnosed with NPC and included those who completed the definitive staging workup and treatment in this analysis. We tested various inflammatory markers and the EBV DNA load via Cox regression for survival analysis.

We found that the EBV viral load, the SII, and the SIRI are related to the severity of nasopharyngeal cancer. In the univariate Cox regression analysis, clinical stage, EBV virus load (HR: 2.15, 95 % CI: 1.19-3.90), NLR (2.37, 1.29-4.34), PLR (2.7, 1.06-6.87), SIRI (2.02, 1.11-3.68), and SII (2.45, 1.251-4.89) were prognostic factors for overall survival. In the multivariate analysis, after adjusting for sex, age and clinical stage, a higher EBV virus load and SII were associated with a worse prognosis (HR: 4.71, 1.95-11.41).

The combination of the EBV viral load and the SII was a better predictor of NPC prognosis.

Opisthorchis felineus, Opisthorchis viverrini, and Clonorchis sinensis (family Opisthorchiidae) are parasitic flatworms that pose serious threats to humans in certain countries and cause opisthorchiasis/clonorchiasis. Opisthorchiid flukes parasitize the biliary tract of the host, causing cholangitis, cholecystitis, cholelithiasis and cholangiocarcinoma. In this review, we primarily focus on recent microRNAs (miRNAs) studies of opisthorchiid flukes and their definitive hosts. Many miRNAs are conserved and expressed in a developmentally stage specific manner in the three opisthorchiid flukes, which play important roles in the growth and development of Opisthorchiidae spp., as well as host-pathogen interactions. Some miRNAs might be potential biomarkers related to carcinogenesis of cholangiocarcinoma. Therefore, this review provides the basis for further investigating the roles of miRNAs in opisthorchiid flukes and their definitive hosts, as well as promoting the development of novel approaches to prevent and treat opisthorchiasis/clonorchiasis.

Drug-carrying nanoparticles can be recognized and captured by macrophages and cleared away by the immune system, resulting in reduced drug efficacy and representing the main drawbacks. Biomimetic nanoparticles, which are coated with cell membranes from natural resources, have been applied to address this problem. This type of nanoparticle maintains some specific biological activities, allowing them to carry drugs reaching designated tissues effectively and have a longer time in circulation. This review article aims to summarize recent progress on biomimetic nanoparticles based on cell membranes. In this paper, we have introduced the classification of biomimetic nanoparticles, their preparation and characterization, and their applications in inflammatory diseases and malignant tumors. We have also analyzed the shortcomings and prospects of this technology, hoping to provide some clues for basic researchers and clinicians engaged in this field.

Rheumatoid arthritis (RA) and osteoporosis (OP) are considered to be complex diseases. In recent studies, a positive association between RA and OP has been reported triggering growing research interest. This study aims to investigate the drugs related to critical genes in RA and OP, using bioinformatics approaches, toward drug repurposing.

RA and OP genes were identified. The RA-OP PPI network was constructed and analyzed using the STRING and Cytoscape, respectively. Hub genes and modules were extracted and enriched Gene Ontology, through the WebGestalt and g:Profiler. The identification of the drugs related to critical genes using the DGIDB, and extracted the miRNAs using miRWalk and miRNet.

By network clustering, five significant modules were obtained that have important roles in the immune system. IL6, TNF, IL1B, STAT3, TGFB1, TP53, HIF1A, CCL2, IL10, and MMP9 were found as the top 10 hub genes in the RA-OP network. Hub genes were shown to have implications in inflammatory response, significant functions in cytokine receptor binding, and localized mostly in extracellular space. By investigating the drugs related to hub genes, 16 drugs were identified as repurposing candidate drugs. The 10 drugs included Hydroxychloroquine, Infliximab, Adalimumab, Etanercept, Certolizumab, Cyclosporine, Diacerein, Gevokizumab, Canakinumab, and Olokizumab proposed for OP. Also, six drugs including Pirfenidone, Pentoxifylline, Vadimezan, Rilonacept, Metelimumab, and Siltuximab have important roles in inflammatory control and were proposed for both RA and OP.

The results of the present study can provide novel insights into the pathogenesis and treatment of RA and OP.

Genetic factors underlying lymphocyte telomere length (LTL) may provide insights into genomic stability and integrity, with direct links to susceptibility to cancer recurrence. Polymorphisms in telomere-associated genes are strongly associated with LTL and cancer risk, while few large studies have explored the associations between LTL-related polymorphisms and recurrence risk of non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC). Totally 1403 non-OPHNSCC patients were recruited and genotyped for 16 LTL-related polymorphisms identified by genome-wide association studies. Univariate and multivariate analyzes were performed to evaluate associations between the polymorphisms and non-OPHNSCC recurrence risk. Patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes exhibited shorter DFS than those with the rs755017 AA, rs2487999 CC, rs2736108 CC, or s6772228 TT genotypes, respectively (all log-rank p < 0.05). Multivariable analysis confirmed an increased risk of recurrence for patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes (adjusted hazard ratio [aHR]: 1.66, 95% confidence interval [CI]: 1.32-2.07; aHR: 1.77, 95% CI: 1.41-2.23; aHR: 1.56, 95% CI: 1.22-1.99; aHR: 1.52, 95% CI: 1.20-1.93, respectively). Further stratified analysis revealed stronger associations between these genotypes and recurrence risk in ever-smokers and patients undergoing chemoradiotherapy. The similar but particularly pronounced results were observed for the combined risk genotypes of the four significant polymorphisms. This is the first large study on non-OPHNSCC patients showing that LTL-related polymorphisms may modify risk of non-OPHNSCC recurrence individually and jointly, particularly when analyzed in the context of smoking status and personized treatment. Larger studies are needed to validate these results.

Hypoxia, a critical feature during cancer development, leads to the stabilization and activation of the hypoxia-inducible factor 1-alpha (HIF-1α) to drive the expression of many target genes which in turn can promote many aspects of breast cancer biology, mainly metastasis and resistance to therapy. MicroRNAs are known to modulate the expression of many genes involved in breast cancer tumorigenesis. In this study, we examined the regulatory effect of miRNAs on HIF1α expression.

MCF-7 and MDA-MB-231 were cultivated under normoxia or hypoxia conditions. TaqMan-Low Density Array (TLDA) was used to characterize the miRNA signatures. Wild-Type (WT) or mutated fragments of HIF-1α 3'UTR containing the miR-138 potential target site were cloned downstream of the Renilla luciferase gene in the psiCHECK-1 plasmid. Luciferase assays were then carried out. A lentiviral vector containing copGFP as a reporter gene was prepared and transduced into MCF-7 and MDA-MB-231 cells to assess the effect of identified deregulated miRNAs on HIF-1α expression.

Under hypoxic conditions, MCF-7 cells showed deregulated expression for 12 miRNAs. In the case of MDA-MB-231 cells, 16 miRNAs were deregulated in response to hypoxia. Interestingly, miR-138 that was downregulated in both MCF-7 and MDA-MB-231 cells cultivated under hypoxic conditions appeared to have a binding site in 3'UTR of HIF-1α. Moreover, our results indicated that miR-138 could down regulate HIF-1α expression, upon binding directly to its 3'UTR.

Interestingly, our data highlights miR-138 as a potential therapeutic target to reduce HIF-1α expression and subsequently restrain breast cancer invasion and metastasis.

Testicular dysfunction is a common adverse effect of cisplatin (CIS) administration as a chemotherapeutic drug. The current study has outlined the role of micro-RNAs (miR-155 and 34c) in CIS-induced testicular dysfunction and evaluated the protective effect of N-acetyl cysteine (NAC) and/or l-arginine (LA). Seven groups of Albino rats were used for this study. The control (C) group received physiological saline; the CIS group was injected CIS (7 mg/kg IP, once) on day 21 of the experiment; the NAC group was administered NAC (150 mg/kg intragastric, for 28 days); and the LA group was injected LA (50 mg/kg IP, for 28 days). NAC+CIS, LA+CIS, and NAC+LA+CIS groups received the above regime. CIS significantly reduced serum testosterone, LH, and FSH concentrations with decline of testicular enzyme activities. CIS caused significant elevation in testicular oxidative-stress biomarkers, inflammation-associated cytokines, and apoptosis markers, along with overexpression of miR-155 and low miR-34c expression. Additionally, marked testicular degenerative changes were observed in the examined histological section; a significant decrease in the expression of PCNA with significant increase in expressions of F4/80 and BAX was confirmed. The administration of NAC or LA upregulated testicular functions and improved histopathological and immunohistochemical changes as well as miRNA expression compared with the CIS-administered group. Rats receiving both NAC and LA showed a more significant ameliorative effect compared with groups receiving NAC or LA alone. In conclusion, NAC or LA showed an ameliorative effect against CIS-induced testicular toxicity and dysfunction through the regulation of antioxidant, anti-inflammatory, and antiapoptotic markers and via modulating miR-155 and miR-34c expression.

Obesity has emerged as an important global health challenge, significantly influencing the incidence and progression of various cancers. This comprehensive review elucidates the complex relationship between obesity and oncogenesis, focusing particularly on the role of dysregulated signaling pathways as central mediators of this association. We delve into the contributions of obesity-induced alterations in key signaling cascades, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/β-catenin to carcinogenesis. These alterations facilitate unchecked cellular proliferation, chronic inflammation and apoptosis resistance. Epidemiological evidence links obesity with increased cancer susceptibility and adverse prognostic outcomes, with pronounced risks for specific cancers such as breast, colorectal, endometrial and hepatic malignancies. This review synthesizes data from both animal and clinical studies to underscore the pivotal role of disrupted signaling pathways in shaping innovative therapeutic strategies. We highlight the critical importance of lifestyle modifications in obesity management and cancer risk mitigation, stressing the benefits of dietary changes, physical activity, and behavioral interventions. Moreover, we examine targeted pharmacological strategies addressing aberrant pathways in obesity-related tumors and discuss the integration of cutting-edge treatments, including immunotherapy and precision medicine, into clinical practice.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports a role of the immune system, mainly played by alveolar macrophages (AMs), in key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore their involvement in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine the expressions of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, a bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group, suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insights for diagnosis or pharmacological treatment.

Breast cancer (BrC) is a highly prevalent tumour among women. The high incidence and mortality rate of BrC prompts researchers to search for new markers that will provide information on the possible impact of the therapy on the risk of cancer-related events. This study aimed to investigate whether the level of advanced oxidation protein products (AOPPs) may have a potential impact on disease-free (DFS) and overall survival (OS) in BrC patients with early-stage cancer. Additionally, we tried to assess the relationship between AOPPs and angiogenic parameters. In this study, the pre- and post-treatment AOPP levels were examined in the serum of 70 newly diagnosed BrC women. The receiver operating characteristic curve identified pre- and post-treatment AOPPs to be above 9.37 μM and 10.39 μM, respectively, as the best cut-off values to predict the risk of cancer relapse. Additionally, Kaplan-Meier survival analysis indicated that pre- and post-treatment AOPPs above 9.37 μM and 10.39 μM were associated with significantly poorer OS. The uni- and multivariate Cox regression analysis highlighted that lower levels of pre- and post-treatment AOPPs were associated with a longer duration without relapse or cancer-related death. A positive correlation between concentrations of pre-treatment AOPPs and vascular endothelial growth factor A, and negative correlations with levels of soluble forms of vascular endothelial growth factor receptor type 1 and 2, were found. In conclusion, AOPPs appear to have an important role in predicting cancer-related events and may potentially serve as a simple prognostic marker in clinical practice.

Several clinical trials and experimental studies have recently shown that vitamin K (VK) supplementation benefits the human body. Specifically, VK participates in coagulation and is associated with cellular senescence and cancer. VK has a potential anticancer effect in various cancers, such as pancreatic and prostate cancers. Through anti-inflammatory and antioxidant effects, VK can prevent senescence and inhibit cancer metastasis. Therefore, cancer prognosis can be improved by preventing cellular senescence. In addition, VK can inhibit the proliferation, growth, and differentiation of cancer cells through various mechanisms, including induction of c-myc and c-fos genes, regulation of B-cell lymphoma-2 (Bcl-2) and p21 genes, and angiogenesis inhibition. This review aims to discuss the relationship among VK, cellular senescence, and cancer metastasis and thus may improve comprehension of the specific functions of VK in human health. The potential application of VK as an adjuvant therapy for cancer (or in combination with traditional chemotherapy drugs or other vitamins) has also been highlighted.

Low-grade chronic inflammation contributes to both aging and the pathogenesis of age-related diseases. White adipose tissue (WAT) in obese individuals exhibits chronic inflammation, which is associated with obesity-related disorders. Aging exacerbates obesity-related inflammation in WAT; however, the molecular mechanisms underlying chronic inflammation and its exacerbation by aging remain unclear. Age-related decline in activity of the proteasome, a multisubunit proteolytic complex, has been implicated in age-related diseases. This study employed a mouse model with decreased proteasomal function that exhibits age-related phenotypes to investigate the impact of adipocyte senescence on WAT inflammation. Transgenic mice expressing proteasomal subunit β5t with weak chymotrypsin-like activity experience reduced lifespan and develop age-related phenotypes. Mice fed with a high-fat diet and experiencing proteasomal dysfunction exhibited increased WAT inflammation, increased infiltration of proinflammatory M1-like macrophages, and increased proinflammatory adipocytokine-like monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and tumor necrosis factor-α, which are all associated with activation of endoplasmic reticulum (ER) stress-related pathways. Impaired proteasomal activity also activated ER stress-related molecules and induced expression of proinflammatory adipocytokines in adipocyte-like cells differentiated from 3T3-L1 cells. Collective evidence suggests that impaired proteasomal activity increases ER stress and that subsequent inflammatory pathways play pivotal roles in WAT inflammation. Because proteasomal function declines with age, age-related proteasome impairment may be involved in obesity-related inflammation among elderly individuals.

Inflammation is a multifaceted biological and pathophysiological response to injuries, infections, toxins, and inflammatory mechanisms that plays a central role in the progression of various diseases. MicroRNAs (miRNAs) are tiny, 19-25 nucleotides long, non-coding RNAs that regulate gene expression via post-transcriptional repression. In this review, we highlight the recent findings related to the significant roles of miRNAs in regulating various inflammatory cascades and immunological processes in the context of many lifestyle-related diseases such as diabetes, cardiovascular diseases, cancer, etc. We also converse on how miRNAs can have a dual impact on inflammatory responses, suggesting that regulation of their functions for therapeutic purposes may be disease-specific.

Studies show that Epstein-Barr virus (EBV) infection can play a role in malignancy and increase the risk of gastric cancer (GC). The objective of this research was to pinpoint genes whose expression may be influenced by EBV and play a role in the development of GC.

Candidate genes potentially susceptible to expression modulation in the presence of EBV were identified through the analysis of GSE185627 and GSE51575 datasets. The association of candidate genes with GC and the survival rate of patients was investigated based on the cancer genome atlas (TCGA) data. Also, pathways related to candidate genes were examined through the MsigDB database. The PPI network was used to identify Hub genes. To corroborate the obtained results, we utilized the RT-qPCR method, employing GC samples from both EBV + and EBV-cases, as well as adjacent normal samples.

Our results showed that genes upregulated by the EBV in the GC cell line, as well as in EBV + samples, are significantly linked to pathways involving the immune response, inflammation, and the P53 pathway. Conversely, genes downregulated by EBV are closely linked to pathways involving cell proliferation and mTORC1. Examining the candidate genes revealed that a considerable portion of genes susceptible to downregulation under the influence of EBV exhibit oncogenic roles based on TCGA data. Moreover, some of these genes are associated with an unfavorable prognosis. Protein-protein interaction network analysis of candidate genes highlighted IFI44L and OAS2 as potential hub genes in the EBV-GC axis. Our RT-qPCR results further validated these findings, demonstrating that the expression levels of IFI44L and OAS2 were higher in EBV + samples compared to both healthy and EBV-samples.

Our study underscores the capacity of EBV to exert regulatory control over genes associated with GC malignancy. In addition to its inflammatory effects, EBV elicits transcriptomic changes that appear to attenuate the progression of GC.

In the setting of pronounced inflammation, changes in the epithelium may overlap with neoplasia, often rendering it impossible to establish a diagnosis with certainty in daily clinical practice. Here, we discuss the underlying molecular mechanisms driving tissue response during persistent inflammatory signaling along with the potential association with cancer in the gastrointestinal tract, pancreas, extrahepatic bile ducts, and liver. We highlight the histopathological challenges encountered in the diagnosis of chronic inflammation in routine practice and pinpoint tissue-based biomarkers that could complement morphology to differentiate reactive from dysplastic or cancerous lesions. We refer to the advantages and limitations of existing biomarkers employing immunohistochemistry and point to promising new markers, including the generation of novel antibodies targeting mutant proteins, miRNAs, and array assays. Advancements in experimental models, including mouse and 3D models, have improved our understanding of tissue response. The integration of digital pathology along with artificial intelligence may also complement routine visual inspections. Navigating through tissue responses in various chronic inflammatory contexts will help us develop novel and reliable biomarkers that will improve diagnostic decisions and ultimately patient treatment.

Chemical agents can cause cancer in animals by damaging their DNA, mutating their genes, and modifying their epigenetic signatures. Carcinogen-induced preclinical cancer models are useful for understanding carcinogen-induced human cancers, as they can reproduce the diversity and complexity of tumor types, as well as the interactions with the host environment. However, these models also have some drawbacks that limit their applicability and validity. For instance, some chemicals may be more effective or toxic in animals than in humans, and the tumors may differ in their genetics and phenotypes. Some chemicals may also affect normal cells and tissues, such as by causing oxidative stress, inflammation, and cell death, which may alter the tumor behavior and response to therapy. Furthermore, some chemicals may have variable effects depending on the exposure conditions, such as dose, route, and duration, as well as the animal characteristics, such as genetics and hormones. Therefore, these models should be carefully chosen, validated, and standardized, and the results should be cautiously interpreted and compared with other models. This review covers the main features of chemically induced cancer models, such as genetic and epigenetic changes, tumor environment, angiogenesis, invasion and metastasis, and immune response. We also address the pros and cons of these models and the current and future challenges for their improvement. This review offers a comprehensive overview of the state of the art of carcinogen-induced cancer models and provides new perspectives for cancer research.

1, 3, 4-oxadiazole and its derivatives have significant anti-inflammatory and antimicrobial property. Their precise mechanism of action is not known but it is postulated that they act by inhibiting the biosynthesis of certain prostaglandins. 1, 3, 4-oxadiazoles are a class of heterocyclic compounds with wide variety of biological and pharmacological activities. They have been reported to possess analgesic, antimicrobial, antipyretic and anti-inflammatory properties. These compounds are also active against a number of other inflammatory conditions such as arthritis, gout etc. A wide variety of these compounds have been synthesized and some of them are under clinical trials. In this review article, anti-inflammatory and antimicrobial activity of the 1, 3, 4- oxadiazole shall be discussed.

Despite being the subject of multiple cancer studies, nothing is known about miR-597-5p's role in colitis-associated colorectal cancer (CAC). We intend to explore how miR-597-5p influences the growth and development of CAC. In order to construct a CAC model, mice were stimulated with azoxymethane (AOM)/dextran sulfate sodium (DSS). The in situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) was used for the detection of miR-597-5p expression. The protein expression of CXCL5 was determined by western blotting, immunohistochemistry and enzyme-linked immuno sorbent assay (ELISA). The histologic colitis score and hematoxylin and eosin (HE) staining were used to evaluate degree of damage to colonic tissues. The proportion of macrophages detected in colon tumors was also measured using flow cytometry. The transwell test was employed to assess macrophage migration. It was found that the miR-597-5p and its target CXCL5 had a negative correlation. MiR-597-5p expression was decreased, while CXCL5 expression was raised in CAC tissues. In AOM/DSS-induced mice, miR-597-5p deficiency in intestinal epithelial cells resulted in decreasing colon length as well as increasing tumor numbers and histologic colitis score, which was reversed by CXCL5 inhibition. MiR-597-5p deficiency facilitated macrophage recruitment in AOM/DSS-induced mice and promoted macrophage migration in vitro, which were reversed by CXCL5 inhibition. Deficiency of miR-597-5p aggravated macrophage recruitment and tumorigenesis in a mouse CAC model, suggesting that miR-597-5p agonists may have an anti-inflammatory therapeutic effect in inflammatory bowel diseases and reduce the risk of developing CAC.

Introduction: Poor oral hygiene is linked to high risks of many systemic diseases, including cancers. Oral dysbiosis is closely associated with poor oral hygiene, causing tooth loss, gingivitis, and periodontitis. We provide a summary of studies and discuss the risk factors for oesophageal squamous cell carcinoma (ESCC) from a microbial perspective in this review.Methods: A literature search of studies published before December 31, 2022 from PubMed, Web of Science, and The Cochrane Library was performed. The search strategies included the following keywords: (1) oral care, oral health, oral hygiene, dental health, dental hygiene, tooth loss, teeth loss, tooth absence, missing teeth, edentulism, tooth brushing, mouthwash, and tooth cleaning; (2) esophageal, esophagus, oesophagus, and oesophageal; (3) cancer, carcinoma, tumor, and neoplasm.Discussion: Poor oral health, indicated by infrequent tooth brushing, chronic periodontitis, and tooth loss, has been associated with an increased risk of squamous dysplasia and ESCC. Oral microbial diversity and composition are profoundly dysregulated during oesophageal tumorigenesis. Similar to the oral microbiota, the oesophageal microbiota varies distinctly in multiple bacterial taxa in ESCC and gastric cardia adenocarcinoma, both of which have high co-occurrence rates in the "Oesophageal Cancer Belt". In addition, the potential roles of oncogenic viruses in ESCC have also been discussed. We also briefly explore the potential mechanisms underlying the tumor-promoting role of dysregulated microbiota for the development of therapeutic targeting strategies.Conclusion: Poor oral health is an established risk indicator of ESCC. The dysbiosis of microbiota in upper gastrointestinal tract that highly resembles the oral microbial ecosystem but with distinct features at individual sites contributes to the development and progression of ESCC.

To develop and validate a prognostic nomogram based on baseline nutritional and inflammatory parameters for risk stratification in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving chemotherapy combination programmed death-1 (PD-1) inhibitor.

This retrospective study analyzed 131 patients with dmNPC (88 and 43 in the training and validation cohorts, respectively) between March 2017 and November 2020. All these patients received chemotherapy combined with PD-1 inhibitor treatment. We identified independent risk factors using univariate and multivariate Cox regression analyses and established a nomogram to predict the progression-free survival (PFS). The predictive accuracy of the nomogram was evaluated and independently validated.

Baseline nutritional risk index (NRI), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), uric acid (UA), and post-treatment Epstein-Barr virus (EBV) DNA were used to develop a nomogram that could divide patients into favorable- and unfavorable-prognosis groups. The median PFS (mPFS) was significantly longer in the favorable-prognosis group compared to the unfavorable-prognosis group (35.10 months [95% CI: 27.36-42.84] vs. 7.23 months [95% CI: 6.50-7.97]; p = 0.001). All results were confirmed in the validation cohort.

The proposed model improved the prognostic risk stratification for patients with dmNPC undergoing chemotherapy combined with PD-1 inhibitor treatment.

This study aimed to examine the association of circulating senescence-associated secretory phenotype proteins, secreted by senescent cells, with indicators of women's ovarian reserve.

This secondary analysis of cross-sectional baseline survey data was undertaken by the Korean Genome and Epidemiology Study Cardiovascular Disease Association Study. A total of 223 women (aged 40-82 y), without any history of oophorectomy, hysterectomy, or other medical conditions that could lower the ovarian reserve, were enrolled in this analysis. Chronological age (years), menopausal status, and serum anti-müllerian hormone (ng/mL) level were used to assess the associations among biological aging, accelerated menopausal aging, and ovarian reserve.

Of the 223 women participants (53.4 ± 11.0 y), 147 (46.4 ± 3.9 y) and 76 (67.0 ± 6.9 y) were premenopausal and postmenopausal, respectively. Serum levels of senescence-associated secretory phenotype proteins were generally higher in postmenopausal, than in premenopausal, women. In the analyses adjusted for chronological age and body mass index, 17 senescence-associated secretory phenotype proteins were associated with menopausal status. However, in premenopausal women, no association trends with the level of anti-müllerian hormone were detected for a total of 28 senescence-associated secretory phenotype proteins.

In a cohort of middle-aged/older women, the level of circulating senescence-associated secretory phenotype proteins indicated chronological age and menopausal status. Yet, serum levels of senescence-associated secretory phenotype protein potentially have limited predictive value for ascertaining ovarian reserve in premenopausal women.

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men. The use of IL-17A and its receptor IL-17RA as prognostic markers for PCa has shown promising results. We analyzed the clinical data of 77 patients with PCa after radical prostatectomy with lymphadenectomy and lymph node metastasis (LN+). We assessed the expression levels of IL-17A and IL-17RA in cancer cells in prostate and, for the first time, also in LN+. Prostate IL-17A expression positively correlated with BMI (p = 0.028). In LN+, the expression of IL-17A was positively correlated with the percentage of affected lymph nodes (p = 0.006) and EAU risk groups (p = 0.001). Additionally, in the group with high IL-17A expression in LN+, the extracapsular extension (ECE) of the prostate was significantly more frequent (p = 0.033). Also, significant correlations with the level of IL-17RA expression was found-expression was higher in prostate than in LN+ (p = 0.009); in LN+, expression positively correlated with the EAU risk group (p = 0.045), and in the group of high expression in LN+ ECE of lymph nodes was detected significantly more often (p = 0.009). Our findings support the potential role of IL-17A and IL-17RA as PCa markers; however, further studies are needed to determine their roles and potential clinical applications.

Recurrent pregnancy loss is defined as the loss of two or more pregnancies and is a distressing condition for couples.

To investigate the relationship between variants in the candidate susceptibility genes and epigenetic factors to identify risk factors for idiopathic recurrent pregnancy loss (iRPL).

A systematic literature search was performed using PubMed, Google Scholar, ScienceDirect, and Scopus databases. Insilico analysis was carried out using ShinyGO and STRING software.

Research papers examining the association between variations in genetic and epigenetic factors and iRPL.

Data were independently extracted by two authors.

In total, 83 research papers were finally selected for the present study. Among all the genes involved in the pathogenesis of recurrent pregnancy loss, polymorphisms in IL superfamily genes, VEGF, ESR, and MTHFR were the most investigated.

Polymorphisms in angiogenesis, immune tolerance, and thrombophilia pathway genes, which occur independently or synergistically, may lead to various complications during fetal development. Identification of multi-allele risk variants and epigenetic factors in women will be helpful in the identification of high-risk pregnancies.

Prospero CRD42021287315.

Eight previously undescribed lanostane triterpenoids and nine known ones were identified from the fruiting bodies of Ganoderma lingzhi S.H. Wu, Y. Cao & Y.C. Dai. Their structures were determined based on spectroscopic data and quantum chemical calculations. Structurally, ganoderane GL-1, featuring a hydrogenated tetramethyls-phenanthraquinone, represents the first example in lanostane nor-triterpenoid group. Biologically, ganoderanes GL-2 and GL-3, distinguished by the presence of a rare "1,11-epoxy" moiety, exhibited significant inhibition against nitric oxide production induced by lipopolysaccharide in RAW264.7 macrophage cells, while ganoderanes GL-4 and GL-8 exhibited bifunctional activities of anti-proliferation and anti-inflammation.

Malignant mesothelioma (MM) is a cancer caused mainly by asbestos exposure, and is aggressive and incurable. This study aimed to identify differential metabolites and metabolic pathways involved in the pathogenesis and diagnosis of malignant mesothelioma.

By using gas chromatography-mass spectrometry (GC-MS), this study examined the plasma metabolic profile of human malignant mesothelioma. We performed univariate and multivariate analyses and pathway analyses to identify differential metabolites, enriched metabolism pathways, and potential metabolic targets. The area under the receiver-operating curve (AUC) criterion was used to identify possible plasma biomarkers.

Using samples from MM (n = 19) and healthy control (n = 22) participants, 20 metabolites were annotated. Seven metabolic pathways were disrupted, involving alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; butanoate and histidine metabolism; beta-alanine metabolism; and pentose phosphate metabolic pathway. The AUC was used to identify potential plasma biomarkers. Using a threshold of AUC = 0.9, five metabolites were identified, including xanthurenic acid, (s)-3,4-hydroxybutyric acid, D-arabinose, gluconic acid, and beta-d-glucopyranuronic acid.

To the best of our knowledge, this is the first report of a plasma metabolomics analysis using GC-MS analyses of Asian MM patients. Our identification of these metabolic abnormalities is critical for identifying plasma biomarkers in patients with MM. However, additional research using a larger population is needed to validate our findings.

The Composite Dietary Antioxidant Index (CDAI), a composite score of multiple dietary antioxidants (including vitamin A, C, and E, selenium, zinc, and carotenoids), represents an individual's comprehensive dietary antioxidant intake profile. CDAI was developed based on its combined effect on pro-inflammatory markers Tumor Necrosis Factor-α (TNF-α) and anti-inflammatory effects of Interleukin-1β (IL-1β), which are associated with many health outcomes, including depression, all-cause mortality, colorectal cancer, etc. Handgrip strength is used as a simple measure of muscle strength, not only is it highly correlated with overall muscle strength, but also serves as a diagnostic tool for many adverse health outcomes, including sarcopenia and frailty syndromes.

The association between CDAI and Handgrip strength (HGS) is currently unclear. This study investigated the association between CDAI (including its components) and HGS in 6,019 American adults.

The research data were selected from the 2011-2014 National Health and Nutrition Survey (NHANES), and a total of 6,019 American adults were screened and included. A weighted generalized linear regression model was used to evaluate CDAI (including its components) and HGS.

(1) CDAI was significantly positively correlated with HGS (β = 0.009, 0.005∼0.013, P < 0.001), and the trend test showed that compared with the lowest quartile of CDAI, the highest quartile of CDAI was positively correlated with HGS (β = 0.084, 0.042∼0.126, P = 0.002) and significant in trend test (P for trend < 0.0100). Gender subgroup analysis showed that male CDAI was significantly positively correlated with HGS (β = 0.015, 0.007∼0.023, P = 0.002), and the trend test showed that compared with the lowest quartile of CDAI, the highest quartile of CDAI was positively correlated with HGS (β = 0.131, 0.049∼0.213, P = 0.006) and the trend test was significant (P for trend < 0.0100). There was no correlation between female CDAI and HGS, and the trend test was not statistically significant (P > 0.05). (2) The intake of dietary vitamin E, Zinc and Selenium showed a significant positive correlation with HGS (β = 0.004, 0.002∼0.007, P = 0.006; β = 0.007, 0.004∼0.009, P < 0.001; β = 0.001, 0.001∼0.001, P < 0.001), vitamin A, vitamin C and carotenoid were significantly associated with HGS in the Crude Model, but this significant association disappeared in the complete model with the increase of control variables. Gender subgroup analysis showed that in model 3, male dietary intake levels of vitamin E, Zinc, and Selenium were significantly positively correlated with HGS (β = 0.005, 0.002∼0.009, P = 0.011; β = 0.007, 0.004∼0.011, P = 0.001; β = 0.001, 0.001∼0.001, P = 0.004), the rest of the indicators had no significant correlation with HGS. Among the female subjects, dietary zinc intake was significantly positively correlated with HGS (β = 0.005, 0.001∼0.008, P = 0.008), and there was no significant correlation between other indicators and HGS (P > 0.05).

There was an association between the CDAI and HGS, but there was a gender difference, and there was an association between the CDAI and HGS in male, but the association was not significant in female. Intake of the dietary antioxidants vitamin E, selenium, and zinc was associated with HGS in male, but only zinc was associated with HGS among dietary antioxidants in female.

Programmed death-1 (PD-1) blockade promotes combination therapy in advanced non-small cell lung cancer (NSCLC), hypofractionated radiotherapy (HFRT) and chemotherapy combined with immunotherapy improves the outcome of prognosis in advanced NSCLC, while effective biomarkers to follow prognostic efficacy are still to be found.

We enrolled 44 NSCLC patients with HFRT combined with PD-1 blockade, 13 patients with chemotherapy combined with immunotherapy, additionally collected tissue samples from 8 patients with earlystage NSCLC without therapy, and peripheral whole blood from 16 healthy donors, detected the expression differences of cytokines Interleukin 6 (IL-6), Interleukin 8 (IL-8) and Interleukin 17A (IL-17A) in the peripheral plasma and tissues by flow cytometry, immunofluorescence, and real-time fluorescence quantitative PCR. Cultured peripheral blood mononuclear cell (PBMC) and tumor-infiltrating T cells with recombinant human IL-8 in vitro to observe the changes of immune memory T cell subtypes and apoptosis.

Our results show that IL-6, IL-8, and IL-17A are highly expressed in advanced NSCLC, high levels of IL-8 are significantly associated with poor prognosis in advanced NSCLC patients treated with HFRT + PD1 blockade, high circulating IL-8 in NSCLC increased apoptosis of effector memory RA (TemRA; CD45RA⁺CCR7^-) T cell subsets and CD8⁺ T cell subsets in tissues, resulting in decreased peripheral TemRA and stem cell-like memory T cells (TSCM: CD45RA ⁺CCR7 ⁺ CD95 ⁺) in tissue.

We suggest that IL-8 can impair immune memory function in NSCLC. It is a useful biomarker to evaluate the efficacy of HFRT + PD1 blockade in advanced NSCLC. Further exploration of easily available plasma biomarkers for personalized treatment of NSCLC is required.